మెడికల్ సైన్సెస్‌లో పరిశోధన మరియు నివేదికలు

To evaluate and consider an alternative surgical technique for huge horizontal strabismus of more than fifty-five prism diopter (55> PDs) instead of the traditional technique and to improve that the muscles are spontaneously reattached without suture.

Methods and Material:

A retrospective case-series on forty cases at different hospitals, non-suture surgery was done in both eyes under local anesthesia which is more than 14 years old children. We documented forty cases, thirty-six primary strabismus patients (Exotropia-Esotropia) and only 4 secondary cases were re-operated. All patients were evaluated after surgery clinically with good results, images were taken preoperatively and postoperatively. The follow-up visit was conducted after the first month and then every 6 months for up to 3 years.

By coincidence twenty years ago I lost a patient with loose adjustable suture after the recession of both medial rectus surgeries for ten days and He came back with good ocular motility and there was no need to readjust the suture !!...then. I observed ten cases of the loose adjustable suture during the first week of surgery (a loose adjustable suture is a loop created from the disinserted muscle to the original insertion of it out of conjunctival incision margins)

Introduction:

Huge squint is a grey zone for most surgeons and there are no clear surgical rules as to which type of technique you may use for the squint surgery, and frequently re-operation is the option when operations fail many times. The protocol of the classical strabismus surgery is determined mostly by changing the mechanical actions of the horizontal muscles by resections or recessions and on how many muscles you operated. Far from this concept the check ligaments and intermuscular membrane play a role, or there is a neurological supranuclear pathway that controls the ocular muscle movement including the pathway in the brainstem and cerebellum and their connection to utricles and saccules of the inner ear and visual cortex and posterior cingulate cortex. Indication indicates a cause for strabismus may lie with the input providing to the visual cortex. This allows for strabismus to happen without the direct impairment of any cranial nerves (or) extraocular muscles.

All patients had an oral and written agreement and the patient’s privacy was preserved. The surgical technique was as follows: under local anesthesia drops and subconjunctival (lidocaine 2%) injection 0.5 ml to 1ml with adrenaline near the muscle, (for children light general anesthesia were also done). We injected all patients with Atropine by an anesthesiologist through Intramuscular (IM) or intravenous (IV) 1 mL/0.5 mg, eight (8 mm) conjunctival and tenon’s wound incision was done over the insertion of the muscle, and by muscle hook losing the muscle was done from the eyeball carefully than by the Mosquito clamps held the muscle prior to severing to avoid bleeding, full myectomy 2 mm from insertion was done no cutting of check ligament, no suture in the situation. I asked the patient to move his eyes to left and right after every step of surgery to estimate and to see whether he need tractional suture or need some dissection (not more than two mm) (traction suture is U shape 5-0 suture from the limbus to the outer canthal area in the opposite direction of the strabismus was performed for one or two weeks and for one or two muscle as needed to adjust the final position of the eye), the conjunctival incision is closed by bipolar diathermy. Orbital CT scan was performed within hours after the surgery to evaluate the adjustment of the muscles and confirm that it is in place and did not slip and that was due to saving the check ligament and the intermuscular membrane and tenon capsule, and also there was no resection to the antagonist's muscles. Essentially, I used the Krimsky test to calculate the degree of strabismus, and some extreme cases by the Hirschberg test. the number of each case of those made, the type of strabismus, the preoperational degree, the procedure and other techniques, outcome, and the distance of resection

Results:

38 (95%) out of 40 cases, were successful and less than 10 PD with good ocular motility within one month. We found that under-correction only in 2 cases (5%). No overcorrection, one case re-operated (because she lost tractional suture early and became orthotropic. The other patient refused reoperation. The other procedure tractional suture (62%) was done, with no major complications during or after the surgeries, no persistent diplopia in the central 30° field, outcomes were documented by figures and video.

Discussion:

The main point is to say that the ocular muscles are reattaching spontaneously after free myectomy, I found a similar like myectomy technique has been done in 1983 by Prof. Caleb Gonzalez of bilateral sixth nerve palsy with strabismus fixus, disinsertion, and myectomy of OU medial rectus and released it in the orbit without sutures and also many others in last two century (18th - 19th) did like this technique and I found that too many American doctors were doing like this procedure in the 19-century, as Samuel David Gross, and James Bolton, and they published it with good results. Also, an important study (myectomy of large-angle strabismus in patients with Graves’ ophthalmopathy) is done by dr. Liao SL and others at -Eye (Lond) Jur. 2017- and they said in conclusion that “complete rectus muscle myectomy technique is effective and predictable” also don’t forget that the inferior oblique is attached again to the sclera after myectomy. Also, on 9/20/2018 the “journal of pediatric ophthalmology and strabismus” published a nice original article in post-natal monkeys about “spontaneous reattachment of the medial rectus after free tenotomy” if we considered our success rate 98% While the best rate ranges from 68% to 85% when we were using the traditional techniques, residual or recurrent strabismus was a common problem found after large-angle strabismus operations.

Conclusion:

This technique is remarkable in our ophthalmic field because it did not interrupt the natural integrity of the normal ocular motility, it is simpler, with a high success rate, requires a shorter time, under local anesthesia for adult, without suturing, much more efficient, with lesser complications, and shorter learning curve, the horizontal muscles spontaneous reattach and adjust after surgery.

Note: This work is partly presented at World Eye and Vision Congress December 09-10, 2019 Dubai, UAE

To compare the efficacy of half-dose photodynamic therapy (PDT) and one-third-dose PDT in treatment in chronic or recurrence Central Serous Chorioretinopathy (CSC).

Methods:

A retrospective review of chronic or recurrence CSC patients, who were treated with half-dose or one-third dose PDT for 12 months follow-up. Best-Corrected Visual Acuity (BCVA), Central Retinal Thickness (CRT), and resolution of Subretinal Fluid (SRF) at baseline, 1, 3, 6, and 12 months’ post-PDT were assessed.

Introduction:

Central serous chorioretinopathy (CSC) is characterized by an accumulation of subretinal fluid (SRF) in the posterior pole and is a common condition in middle-aged men with a so-called A-type personality. Although acute CSC could be resolved spontaneously, approximately half of the patients have recurrence or persistence of SRF and require treatment. To treat CSC is generally used Laser photocoagulation (LP). However, CSC with subfoveal or parafoveal leakage points and chronic CSC with broad and indistinct leakage is difficult to treat with LP because of the complication of scotoma.4 Choroidal neovascularization (CNV) is also known as a serious complication of LP.

Recently, photodynamic therapy (PDT) with verteporfin has been exposed to be effective in reducing SRF and improving visual acuity for chronic CSC. The post-PDT problems such as secondary CNV, pigmentary variations of the retinal pigment epithelium (RPE), and persistent choriocapillaris hypoperfusion have been informed. To reduce these side effects and to obtain the maximum effects, half-dose verteporfin PDT has been led successfully in chronic CSC without serious complications. However, the optimal dosage of verteporfin required to treat chronic CSC has not been established. The lowest dose of verteporfin required to treat acute CSC successfully was reported to be 30% of the conventional dosage. Thus, the purpose of this study was to prospectively compare the results of half-dose verteporfin for 3 mg/m2 PDT (1/2 PDT) with those of one-third-dose verteporfin (2 mg/m2) PDT (1/3 PDT) for chronic CSC. The primary outcome measure was the disappearance rate of SRF. Secondary outcome measures were the changes in best-corrected visual acuity (BCVA) and central retinal sensitivity. In addition, we studied the changes in the anatomical structure of the choroid after PDT to find the factors associated with the resolution of SRF.

Study design and patient recruitment:

This study was a prospective, non-randomized, consecutive, open-label case series conducted in the Department of Ophthalmology, Nagoya University Graduate School of Medicine. Sixteen eyes of 16 patients with chronic CSC were recruited from July 2009 to January 2010. The first ten patients received 1/2 PDT and the next six patients received 1/3 PDT. Because there was no previous report that showed the effects of 1/3 PDT on chronic CSC, we set the number of patients in the 1/3 PDT group (n=6) lesser than that of the 1/2 PDT group for n=10. CSC was diagnosed if SRF caused by idiopathic leakage from the RPE was present at the macula. Leakage from the RPE was detected by fluorescein angiography. Indocyanine green angiography (ICGA) was used to confirm the presence of choroidal vascular hyperpermeability.

The inclusion criteria were the following:

• Presence of SRF involving the foveal region persisting for 3 months or more.
• Leakage from the subfoveal, parafovea is difficulty to treat the LP
• BCVA between 35 and 85 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters.
• Age between 20 and 70 years.

The exclusion criteria were as follows:

• Focal thermal LP to treat CSC or previous PDT
• CNV or another maculopathy
• Choroidopathy that may affect the choroidal thickness
• Previous intravitreal injections of anti-vascular endothelial growth factor drugs
• Intake of medication such as corticosteroids, adrenergic agonists, or adrenergic antagonists.

Photodynamic therapy:

When performing 1/2 PDT and 1/3 PDT, only the dosage of verteporfin was changed from the conventional PDT recommended by the Age-Related Macular Degeneration with Photodynamic Therapy investigation.21 In 1/2 PDT 3 mg/m2 of verteporfin was infused, and in 1/3 PDT 2 mg/m2 of verteporfin was infused. After treatment, patients were instructed to avoid strong light for 5 days.

Results:

Half-dose and one-third dose PDT received 46 eyes and 20 eyes, respectively. The study displays the non-inferiority of the one-third-dose PDT compared with half-dose PDT in BCVA improvement (0.10±0.04 vs. 0.17±0.04 Log Mar, P=0.293) and CRT improvement (125.6±24.6 vs. 139.1±16.54 µm, P=0.652) at 12 months follow-up. The SRF recurrence rates of was significantly higher in one-third-dose of PDT related to half-dose PDT (40.0% vs. 15.2%, P=0.027) at 12 months follow-up.

At 1 month, 7 eyes (70%) in the 1/2 PDT group had complete resolution of SRF compared with 2 eyes (33%) in the 1/3 PDT group. At 3 months, all 10 eyes (100%) in the 1/2 PDT group had complete resolution of SRF, and the same 2 eyes (33%) in the 1/3 PDT group maintained the complete resolution. The SRF disappearance rate of the 1/2 PDT group was significantly greater than that of the 1/3 PDT group at 3 months (P=0.008).

Conclusion:

One-third-dose PDT was non-inferiority in BCVA and CRT upgrading when compared with half-dose PDT. This study presented one-third-dose PDT which was a higher recurrence rate of disease.

As CSC is a benign disorder and patients usually have a good baseline visual function, it is important to seek the best PDT protocol in order to obtain the maximum effect and the minimum complications. Half-dose PDT has been conducted to chronic CSC with relative safety, but treatment with verteporfin at less than 50% of the conventional dosage has not been attempted for chronic CSC. Previous studies have shown that cytotoxicity and vascular damage associated with PDT are dose-dependent. The mechanism of the action of PDT in CSC has not been fully understood, but the changes in choroidal structures after PDT in this study provide a useful clue.

Note: This work is partly presented at World Eye and Vision Congress December 09-10, 2019 Dubai, UAE

Artificial intelligence (AI) implementation in medicine will increase the efficiency of medical services. Appropriate program implementation in ophthalmology is recommended to avoid, prevent, or treat the socio-economic issues caused by blindness and visual impairment. Artificial Intelligence (AI) will help medical specialists evaluate at the highest possible standards any medical condition offering the most complex and accurate medical information in the most rapid way. The complex geometric-physicochemical quantitative information offered by Magnetic Resonance Imaging (MRI) on the qualitative anatomical bio physiology and/or pathophysiology of the eye covers the main eye structures: Cornea, aqueous humor, ciliary body, lens, vitreous humor, sclera, optic nerve, and three retinal layers. Implementation of AI-based MRI techniques in ophthalmology could, therefore, play a crucial role in reducing the present socio-economic burden caused by eye disease.

Objective:

To develop a disease management approach for the direct and immediate implementation of AI MRI

Methods:

Relations between particular quantitative MRI limitations available in the works and the corresponding physio-anatomy were made to figure the human MRI physio-anatomical state chart (hMRI_PASC). Pathology can be assessed using the relative-to-normal (RN) values of each MRI parameter for corresponding control-normal (CN) and disease-affected (DA) regions, based on the equation: RN_Parameter(%)=multiply(100,divide(subtract(ParameterDA, ParameterCN), (ParameterCN))). The RN_Parameter 50% absolute value threshold for the selected MRI parameters was used to define a medical state severity staging scale (MCSSS). The disease management plan is presented for a scenario of DA human MRI organ model, the eye, using the hMRI_PASC, and MCSSS.

Artificial intelligence (AI) is considered the third eye for medical specialists and has a promising perspective field for medical imaging, offering the most complex and accurate information to patients and medical specialists in the most rapid way through the most performance of medical evaluations. AI-based imaging is needed to reduce the socio-economic burden caused by disease and improve the efficiency in radiology departments. The current situation of AI in medical imaging has been analyzed recently and the future directions have been suggested. Wandell et al., Benson et al., Jiang et al., and Dumoulin et al., have already made some steps in these directions and developed complex AI algorithms for image analyses. Strategies for data management to support reproducible research, the influence of feedback in intelligence processes, and algorithms for more rapid MRI data acquisition were also evaluated. Many Artificial intelligence developments are suitable for MRI due to the wealth of qualitative and quantitative pathophysiological info offered for any organ in the human body and the low imaging invasiveness.

The brain, prostate, heart, breast, and eye are the human organs most frequently evaluated using multiparametric MRI in recent years. Software developers need simple specifications for explainable MRI to implement these developments in AI-based clinical radiology. Conditions for reasonable MRI were obtained from complex correlations between the geometric-physicochemical MRI parameters and the consistent pathophysiology to evaluate the rat brain. A generalization of this approach combined with the already available clinical AI-based strategies for medical diagnosis in dermatology and cardiology was made to assess the clinical MRI data available in the literature and grow in the human MRI physio-anatomical state chart (hMRI_PASC) and the medical condition performance scale (MCSSS) for AI-based disease administration. These results can be presented directly and immediately in software for AI-based clinical ocular MRI.

Findings:

Detailed MRI physio-anatomical characteristics were defined based on the analyses of the MRI parameters evaluated. The complex disease staging scale was built using the relative-to-normal values calculated for the normal subjects and the MRI physio-anatomy defined. A scenario for AI-based ocular MRI is also presented.

Results:

The specifications relevant for the diagnosis of a medical condition detected are presented in the hMRI_PASC . The IDE MCSSS presented was used to detect bio-physiological changes in the regions-of-interest, produced by external agent infiltration, changes in the dynamics of the 1H nuclei in water molecules, and/or elastic deformations. Infiltration of blood or T1 and/or T2 lengthening or shortening agents, macromolecules, calcifications, and iron particles through broken blood vessels or broken blood vessels and blood-to-tissue barriers can be detected using MRI. The dynamics of the 1H nuclei in water molecules can be assessed with diffusion and flow-sensitive MRI techniques applied to different regions of the human body. Inflammation, constriction, or stiffness of regions can be detected in MRI elastography studies. The geometric-physicochemical parameters in Table 1 were used to analyse the physiological IDE status of a region-of-interest based on the hMRI_PASC.

Discussion:

Results in this study can easily and immediately be implemented in AI-based ocular MRI and demonstrate the feasibility of introducing AI-based analysis of ocular MRI scans. This could potentially support a program for the prevention and treatment of eye disease.

The research has developed and described here has 3 main compatibility areas:

•           human anatomy

•           medical procedure

•           imaging technique

The hMRI_PASC and MCSSS in this study have universal human body applicability. The strategy for disease management is explained with an ocular MRI example, but it can be generalized to any organ. The research method developed in this study can be further developed to integrate all imaging techniques used at present in radiology. A similar method to that presented here might be used to develop AI-based medical imaging strategies and spread the MCSSS for MRI in this study to:

• Ultrasonography

• Computed tomography

• Positron emission tomography

• Laser or infrared medical imaging

Example: The research method presented in this study is compatible with many medical procedures: diagnosis, prognosis, response to therapy, and surgery, for example. After the generalization to these 3 main compatibility areas has been achieved, software developers can integrate the research method in software for general human body AI-based medical imaging.

Note: This work is partly presented at World Eye and Vision Congress December 09-10, 2019 Dubai, UAE

Introduction:

Idiopathic Intracranial Hypertension (IIH), also referred to as benign intracranial hypertension, is a disorder generally affecting overweight women of childbearing age. Idiopathic intracranial hypertension has been considered an analysis of exclusion, particularly if no cranial neuropathies or papilloedema have been noticed. Measurement of the Optic Nerve Sheath Diameter (ONSD) using a CT scan can run a solution for this condition, as it has been used as a non-invasive way of ICP monitoring since the mid-1990s. Another rapid non-invasive method for the evaluation of patients with IIH is Optical Coherence Tomography (OCT). Spectral-domain OCT offers reliable thickness and measurements of the optic nerve head and retina and can constantly demonstrate structural variations due to papilloedema. This study included 40 patients (aged ≥18 years) presented with headache and fulfilled modified Dandy criteria for IIH. Idiopathic intracranial hypertension (IIH) is defined -according to modified Dandy criteria- as the presence of clinical signs and symptoms of increased intracranial pressure including headache, nausea, vomiting, transient visual disturbances like mild visual loss, papilledema, and unilateral or bilateral 6th cranial nerve paresis and is generally affecting overweight women in the childbearing period.

Normal neuroimaging is important for diagnosis excepting for empty sella turcica. Idiopathic intracranial hypertension is measured as a diagnosis of exclusion, particularly when no cranial neuropathies or papilloedema have been determined. If a patient is complaining of only persistent severe headache, then the diagnosis is delayed as in such cases lumbar puncture and a head CT scan for these patients is regularly negative, putting the clinicians in a diagnostic challenge. Measurement of the optic nerve sheath diameter (ONSD) using orbit CT scan can provide a solution in this case, as It is considered as a non-invasive method of intracranial pressure (ICP) based on that the presence of enlarged ONSD specifies the elevated ICP.

Aim of the work: is to evaluate the usage of optic nerve sheath diameter (ONSD) measured by computed tomography and Spectral-domain OCT for the detection of elevated intracranial pressure (ICP) in patients with IIH as an alternative to lumbar puncture.

Methods:

We collected and analyzed data on the following variables: ONSD in the middle third of the intraorbital path (the point where the ophthalmic artery crosses the optic nerve served as an anatomical landmark); Our patients underwent spectral-domain OCT (SD-OCT) scanning dual-beam Spectralis laser tracking tomography Spectralis, using a commercially available device (3D OCT-1000; Topcon Corp., Tokyo, Japan). The scanning protocol involved the acquisition of a 6×6 mm cube scan of the Optic Nerve Head (ONH) and macula with a scan density of 512×128 pixels. Ethical statement this prospective study was conducted according to international guidelines approved by the Research Ethics Committee. Informed consent was obtained from all patients prior to the study. We followed the ethical principles of the Declaration of Helsinki during the preparation of this study.

Study population: This study included 40 female patients (aged ≥18 years) presented with headache and fulfilled modified Dandy criteria for IIH. Patients were recruited from the Neurology Outpatient Clinic and Neurology inpatients ward of Zagazig University Hospitals. During history taking, complaints that were usual for raised ICP (headache, nausea, vomiting, etc.) were detected and all patients were generally and neurologically examined. Routine lab and plain chest X-rays were done to exclude patients with end-organ failure. Also, patients with known ophthalmological disorders such as glaucoma, hypertensive or diabetic retinopathy, patients with migraine, or those having contraindications for IV contrast-enhanced CT were excluded. All patients underwent an initial non-contrast head CT scan. All patients with suspected IIH were examined by an ophthalmologist, even if they did not report any visual symptoms. Patients who complained of headaches associated with tinnitus and dizziness were also examined.

Results:

Our study involved 40 female patients with a clinical-radiological analysis of IIH with their age range from 22 to 42 years, their main complaints were visual complaints as blurred vision and transient visual obscurations in 16 patients (40%), and headache in 15 patients (37.5%), while 9 patients (22.5%) had both complaints. The ONSD was nearly in the same range in both eyes (4-10 mm for right and 4- 11 mm for left) when measured by CT with contrast at the crossing point of the ophthalmic artery. More than 82% (33) of patients diagnosed by OCT have papilloedema while 17% (7) of patients not. There was a statistically significant relationship between the ONSD by OCT in both right and left sides with the diagnosis of IIH (P =0.003 for right, P= 0.001 for left) while there was no significant relation between pseudotumor cerebri (PTC) and patient's age (P= 0.921). The estimated statistical cut-off value of ONSD was 5.5 mm with a sensitivity of 84.4% and specificity to diagnose optic nerve thickening by 100% on the left side and 85.7% in the right side.

DISCUSSION:

The diagnosis of IIH is mainly made by the measurement of raised intracranial pressure (ICP). This is considered critical as the early diagnosis and treatment of the increased pressure can protect against optic nerve damage. Lumbar puncture, as a diagnostic tool for the detection of IIH, is considered accurate but its performance is limited in patients with obesity, thrombocytopenia, bleeding tendencies or those on regular anticoagulants and also considered as an invasive procedure that carries the risk of post-spinal tap headache, nerve root irritation, spinal subdural hematoma, and infection.

Conclusion:

The addition of OCT to ONSD by CT+C can increase its diagnostic ability for the cases with IIH, which may reduce the need for invasive diagnostic techniques like LP.

Note: This work is partly presented at World Eye and Vision Congress December 09-10, 2019 Dubai, UAE

Cornea collagen crosslinking has emerged as a highly successful treatment for keratoconus and post-LASIK ectasia. The use of topical concerted riboflavin explanation, along with a calibrated ultraviolet light source has been shown to successfully cross-link and stiffen the cornea align storm and arrest and in most cases, reduce the effect of corn steepening in several degenerative cornea conditions including keratoconus and post-refractive surgery ectasia.

Cornea cross-linking with the Avedro profitable UV light source and focused topical riboflavin explanation produced in a standard dose is usually accepted and was FDA accepted in the USA in 2016 as a treatment for Keratoconus and post-refractive surgery ectasia.  The high financial treatment cost, along with the high cost of the Avedro machine, has limited ophthalmologist’s and patient’s contact with this new effective treatment.

We report cases at three separate institutions where patients, either on the own or under the suggestion of their ophthalmologist ingested high doses of dietary riboflavin (Vitamin B2) and were bare to 15 minutes per day of direct sunlight and noted within 6 months to experience a significant amount of cornea flattening by both topographic and keratometric capacities.  No adverse effects were observed or reported in patients taking up to 1500 mg of dietary riboflavin per day and spending 15 minutes daily outdoors walking briskly facing the sun without sunglasses.

Case 1:

In February of 2012, patient 1, a 63-year-old Caucasian woman, was seen at Evergreen Eye Center in Federal Way, Washington for blurred vision after undergoing successful cataract surgery with a premium IOL. Prior treatment with LASIK surgery in both eyes for myopia was reported pre-operatively. Residual astigmatism in both eyes following her premium IOL surgery reduced uncorrected vision to less than 20/40 in each eye at her three months follow up exam. After informed consent, the patient underwent additional successful keratorefractive “touch-up” surgery (LASEK) six months following her cataract operations, and visual acuity improved to 20/25 uncorrected in both eyes. Twelve months later she was noted to have signs of cornea ectasia on topography in both eyes, including with the rule astigmatism and a characteristic early “lobster claw” appearance with best-corrected acuity decreasing to 20/40 OD and 20/30 OS.

The patient returned six months later noting that her vision had greatly improved, and she was noted to have 20/25 best-corrected visual acuity with keratometric and topographical flattening of 1.5 diopters on topography. When questioned about her treatment the patient remarked that she had followed her EyeMD’s suggestion of taking dietary riboflavin but stated that she felt “if 50 mg was good, I thought 500 mg would be better.” She continued to follow up for 48 months maintaining excellent vision with no progression or worsening of her post-refractive surgery cornea ectasia.

Case 2:

Because of the initial positive results of this first patient, several additional post-refractive and keratoconus patients were treated at Evergreen Eye Center, Federal Way, Washington, and most recently at University of Missouri Department of Ophthalmology, Columbia, Missouri as part of an IRB and FDA approved investigation.

After informed consent and in compliance with the patient rights found in the Declaration of Helsinki, 11 additional patients have been enrolled in a prospective randomized, controlled study at the Department of Ophthalmology, University of Missouri – Columbia School of Medicine, taking 100 mg or 400 mg dietary riboflavin and walking briskly outdoors facing the sun without sunglasses for 15 minutes daily.

Case 3:

A 35-year-old clinical dietician with a history of progressive keratoconus reported to her cornea specialist at the Department of the Ophthalmology University of Tennessee – Memphis, that she had taken “mega-doses” of riboflavin after examination about its high tolerability and low risk of side effects. When seen by her cornea specialist, (A.S.), the patient was found to have 2.17 diopters OD and 1.33 diopters OS of cornea flattening on topography compared to her pre-treatment K average findings.

Discussion:

In 2016, we submitted Institutional Review Board (IRB) application for a high dose dietary riboflavin and direct sunlight exposure study in the treatment of keratoconus and post-refractive surgery cornea ectasia, which was approved for patient enrollment in 2016 and has recruited 11 patients to date with a minimum of 6 months follow up at University of Missouri Department of Ophthalmology. Prior to initiating our IRB and FDA approved and NIH registered study, several patients with keratoconus, post radial keratotomy and post LASIK ectasia were treated at Evergreen Eye Center with a minimum of 24 months follow up with our initial patient now at 60 months follow up.

Conclusion:

We conclude that high-dose dietary riboflavin may have a place in the conduct of keratoconus and post-refractive surgery kerectasia as an economical another or adjunctive form of action.  It may be especially useful in pediatric and pregnant patients who are more likely to regress after commercial cross-linking therapy.

Note: This work is partly presented at World Eye and Vision Congress September 06-08, 2018 Dubai, UAE

We developed a technology to provide simultaneous VIS-OCT and AF of the retina and a reference standard target at the intermediate retinal imaging plane with a single broadband visible light source. Then both OCT and AF images are made from the same group of photons the OCT probe light capabilities attenuation by the same ocular layers. The technology is able to eliminate the variable pre-RPE attenuation factor in AF imaging using the concurrently acquired VIS-OCT image. To quantitatively bridge the OCT and AF detection schemes thus eliminate the effects of illumination power and detector sensitivity, a normal reference target with known reflectivity and fluorescence efficacy was implemented into the system. Using the standard reference, similar to the one used by Deloris AF and reflectance signals are normalized to a known reference value that is independent of the exposure power and detection gain.

Introduction

Lipofuscin, a by-product of the visual cycle of photoreceptors, is the major source of the fundus auto fluorescence (FAF) in the Retinal Pigment Epithelium (RPE). The lipofuscin accumulates with aging and in certain pathological disorders and is thus a biomarker for degenerative retinal diseases. Therefore, the quantification of lipofuscin is important in the diagnosis, progression monitoring, and treatment evaluation. Lipofuscin quantification is challenging because the light is attenuated by the media anterior to the RPE which is subject to inter-individual and intra-individual differences. Further, various illumination power and detection sensitivity of different imaging systems can also affect the readings of the detected FAF.

FAF imaging has been used in ophthalmology clinics for many years. For example, hyper auto fluorescence is positively linked with the development of AMD and Stargardt’s macular dystrophy. In the case of geographic atrophy (GA), the late stage of dry AMD, advanced RPE alterations exhibit clinically recognizable patterns of hyper auto fluorescence, which is positively correlated with the rate of GA progression and can be evaluated semi-automatically with newly advanced software by non-expert graders.

However, the currently available technologies are not capable to measure standardized FAF intensity. The measured FAF signal by the currently available technologies could be affected by the excitation light intensity, detector sensitivity, and gain of the instrument used.

In addition, and importantly, signals are attenuated by the ocular tissues anterior to the RPE, especially by the lens, and the attenuation cannot be measured directly. The ocular properties of tissues anterior to the RPE could be significantly different among individuals, and it changes over time in the same person. Thus, it is difficult to compare images obtained by the currently available technologies from the same person over time, or from different individuals, which hinders the clinical usefulness of FAF images. It is a challenge to obtain the absolute intensity of FAF.

Methods:

Imaging system:

The system consists of two spectral-domain OCTs in the NIR and visible spectrum, respectively. The NIR-OCT is used only for alignment to reduce visible light exposure and avoid additional bleaching effects to the fluorophores. The VIS-OCT consists of a supercontinuum laser (SC, model: EXB-6, SuperK EXTREME, NKT Photonics, Denmark) with a variable band-pass filter (selected center wavelength: 480 nm, bandwidth: 30 nm). The output VIS light is coupled into the source arm of a single-mode optical fiber-based Michelson interferometer. The NIR-OCT uses a superluminescent diode as the light source (SLD-37-HP, center wavelength: 840 nm, bandwidth: 50 nm, Superlum, Russia). The NIR light is coupled to another fiber-based Michelson interferometer after passing through an optical-fiber isolator. After exiting the optical fibers in the sample arms, both the NIR and VIS light are collimated and combined by two dichroic mirrors (DM1: DMLP505, Thorlabs, and DM2: NT43-955, Edmund Optics). The combined light beam is scanned and delivered to the eye by a combination of a relay lens (L1, f = 75 mm, achromatic) and an ocular lens (L2, Volk lens, 60D).

Results:

In the phantom experiments, we first investigated the influence of detector sensitivity of the system on the AF signal detection. The fluorescent intensities were measured at different detector gains (by varying the detector control voltage) to verify the capability of the technique for cancelling the effects of detector sensitivity. The averaged FAF signals measured from the model eye and signals from the reference fluorescent target (RAF) were plotted against the OD values of the ND filters. At a given gain, the logarithm of the fluorescent signals from the master reference in the model eye linearly decreases with the OD values of the ND filters at a slope of −2, which agrees with the round-trip attenuation of light through the ND filter and the listed transmission data of the ND filters. The signals from the standard fluorescent reference target are independent of the attenuation of the ND filters and remain constant. The measured signal intensities of FAF and RAF decreased with the PMT control voltage accordingly.

Discussion:

We have demonstrated that the VIS-OCT based multimodal imaging technology is capable to obtain both OCT reflectance and AF images simultaneously. The intensities of the OCT reflectance from the RPE can serve as an internal reference to compensate signal attenuation by ocular tissues anterior to the RPE, including melanin in the RPE cells. The OCT and fluorescence signal intensities from the two reference standards placed in the intermediate retinal imaging plane can be used to not only eliminate the effects of light source fluctuation and detector sensitivity for OCT and AF imaging but also quantify the FAF signal to a value that is proportional to the absolute concentration of lipofuscin.

Conclusion:

We have developed a new multimodal imaging system with two reference targets placed in the intermediate retinal imaging plane for quantitative imaging of RPE lipofuscin. The system employs a single light source to acquire AF and VIS-OCT images of the retina

simultaneously. Since the same group of photons is responsible for both AF and OCT imaging, the OCT image intensities can be used to compensate signal attenuation by media anterior to the RPE, including melanin in RPE cells.

Note: This work is partly presented at World Eye and Vision Congress September 06-08, 2018 Dubai, UAE

The increase in older people wishing to live alone in their own homes has increased studies of monitoring systems to improve the quality of life of older people, their families and carers. The aim of the communication is to present the results of the evaluation of the degree of acceptability and satisfaction with the Senior Monitoring application. At the end of the study, an acceptability scale was passed to the 11 elderly participants (six women and five men) with an average age of 68 years and a standard deviation of 8 years. The scale consists of six Likert items with five response categories that assess two dimensions: usability and satisfaction. The average usability was 12.18 points (SD = 1.99) and the average satisfaction was 12.91 points (SD = 2.21); quite high values. As a qualitative assessment, several people expressed the wish that the device would be able to place the person away from home. The Senior Monitoring application has been evaluated satisfactorily by the study participants. New studies are opened in the use of conversational devices that allow the evaluation of aspects such as loneliness, depression, well-being through the analysis of behavioral data collected at home through conversational devices. This devices can be able to connected with bluetooth and wifi through internet, they can also be used to track physical activity,the conversional devices can help in tracking their mental health, and well being. The elderly behavior monitoring system used magnetic switches to record movement in rooms, infrared sensors to detect activities, and sound sensors to determine the types of activities.

The Senior Monitoring application has been evaluated satisfactorily by the study participants. New studies are opened in the use of conversational devices that allow the evaluation of aspects such as loneliness, depression, well-being through the analysis of behavioral data collected at home through conversational devices. The bed-exit detection system can detect the person is in the bed or starts counting time when the elderly totally gets up and leaves the bed. The toilet alarm system can keep recording the time that elder in the room. If the suspecious activity are observed, the monitoring system will signal an alert to caregivers who can check the real condition of the elder people and help them to get of the trouble immediatly,the time for treatment can be fastend Experiments were conducted and the results could illustrate the effectiveness and instantaneity of this system, the accuracy of the Systrem was around 98% it not long until we achieve the 100% accuracy the present growth rate of the information technology.This system is gaining the popularity in 21sr centuary due the increased population of old age people, according to the statistics the population of elders might surpass the mid aged people by the mid centuary and Some emergencies in the daily life of the elderly, including tumbling or falling off the bed, are difficult to be found and handled in time. This consequently delays the time for treatment.hence it is very critical to develope such kind of system so that elderly people can live in good health in their remaining years,apart from constant monitering from Docters and nurses, it has become difficult for the care givers to take care of elderly with this kind of system it willl be easy to track the Elderly activity, even tough being away from home for work or any stituation where they had to stay away from them.To improve the living quality of the elderlythe research on comprehensive indoor monitoring system for daily activities anf the behaviour of older people in their homes is of great importance. And is in the growing demand, experiments were conducted and the results could illustrate the effectiveness and instantaneity of this system. This kind of system can be also used in Nursing homes and at the hospitals apart from the domestic utilitya nd is becoming the popular option, therefore reducing the pressure of contioues observation and giving good care to the old aged people and the patients . Ensuring well-being of the elderly and provide them support when required is of special concern.

Elderly care at home is a matter of great concern if the elderly live alone, unforeseen problematic circumstances might occur that affect their well-being. Technologies that assist the elderly in independent living are essential for enhancing care in a cost-effective and reliable manner to be taken into account while designing such systems are also pointed out. This research work is an attempt to get insight into differing types of ambient-sensor-based elderly monitoring technologies within the home. With the aim of adopting these technologies, research works, and their outcomes are reported. Elderly behavior monitoring technology could also be a promising field, especially for long-term elderly care ,monitoring technologies should be taken to subsequent level with more detailed studies that evaluate and demonstrate their potential to contribute to prolonging the independent living of elderly people assisted living technologies will be needed in the future to take care of elderly people and help them to live independently.

This work is partly presenting in 12^th International Conference on Geriatrics Nursing, Gerontology and Aging on December 09-10, 2020 held at Paris, France.

Nuclear receptor related-1 (Nurr1) orphan receptor has emerged as a promising contender in ameliorating Parkinson’s disease, thus finding a suitable activator of Nurr1 receptor is an attracting target for treating PD. Meanwhile, the deregulation of autophagy, along with other processes such as; inflammation, apoptosis and mitochondrial dysfunction is believed to contribute to the pathogenesis of the disease. The aim of this study is to explore the neuroprotective effect of cilostazol and hydroxychloroquine in rotenone-induced PD model in rats. Both drugs managed to enhance the dopaminergic neurons functionality and integrity as depicted by the increase in the striatal tyrosine hydroxylase content, as well as the improved locomotion and muscle coordination in rotarod and open field. However, this improvement was opposed by hydroxychloroquine induced autophagic inhibition as manifested by enhancing both LC3-II and P62 levels possibly through the prominent decline in sirtuin 1 level and enhanced apoptosis evidenced by cytochrome C and caspase-3 elevation. In conclusion, cilostazol could be a promising candidate for PD treatment through modulating Nurr1 expression, as well as SIRT-1/autophagy, and GSK-3β/apoptosis cross-regulation. Where, hydroxychloroquine successfully ameliorated PD motor dysfunction in spite of the fact that both autophagy and apoptosis were deregulated through Nurr1 modulation.

The nuclear orphan receptor (Nurr1) has recently received a perceivable solicitude as a target for the therapeutic intervention against PD. Meanwhile, the dysregulation of autophagy, along with other processes is believed to contribute massively to PD pathophysiology. Hydroxychloroquine, a hydroxy derivative of chloroquine, is an antimalarial agent which is also used as an anti-rheumatic drug. The neuroprotective potential of hydroxychloroquine and chloroquine remained controversial until recently a study showed that chloroquine exhibited an antiparkinsonian activity through Nurr1 modulation. The aim of this work is to identify whether the less toxic derivative, hydroxychloroquine, could show a similar pattern. In rat rotenone model, hydroxychloroquine effectively boosted Nurr-1 expression, exhibited an anti-inflammatory effect as verified by hindering certain pro-inflammatory cytokines and successfully reduced GSK-3β activity. Consequently, an increase in the striatal tyrosine hydroxylase content, as well as improved locomotion and muscle coordination was shown. However, this improvement was opposed by hydroxychloroquine induced autophagic inhibition as manifested by enhancing both LC3-II and P62 levels possibly through the prominent decline in sirtuin 1 level and elevated apoptotic biomarkers. In conclusion, hydroxychloroquine successfully ameliorated PD motor dysfunction in spite of the fact that both autophagy and apoptosis were deregulated through Nurr1 modulation.

Parkinson’s disease (PD) is a chronic progressive, yet incurable neurological disorder affecting mainly the elder population . The most prominent hallmark of the disorder is dopaminergic neurons degeneration in the substantia nigra pars compacta (sNpc) and subsequent exhaustion of the dopamine content (DA) in the striatum . This depletion in DA results in the cardinal motor manifestations afflicting PD patient including tremors, rigidity and bradykinesia among others. The pathogenesis of the disorder is intricate as several interconnected factors influence the disease including; apoptosis, abnormal protein aggregates, inflammation and mitochondrial dysfunction . Thus finding a suitable agent that amends these complex interrelated factors remains a challenge.

The orphan nuclear receptor (Nurr1) up-regulation is proved to preserve the dopaminergic neurons functionality and integrity in the sNpc thus, it can be considered as a pivotal target for the intervention against PD. This receptor was shown to trigger tyrosine hydroxylase (TH) transcription along with other genes crucial for dopamine synthesis and normal development of dopaminergic neurons. Moreover, pro-inflammatory cytokines release was mitigated by Nurr1 expression

in astrocytes and microglia, an effect that could protect the dopaminergic neurons against inflammation induced neuronal death.Noteworthy showed that treatment with rotenone, a known pesticide used to induce symptoms resembling PD, was associated with a heightened inflammatory response and release of inflammatory cytokines such as interleukin 1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) mediated by nuclear factor-kappa B (NF-κB), an effect that was associated with Nurr1 down-regulation. Thus, drugs activating Nurr1 over- expression have received a perceivable interest as potential candidates providing protection against PD.Lately, activated glycogen synthase kinase-3 beta (GSK-3β) has been PD is characterized by the accumulation of abnormal protein aggregates preceding the neurological damage. One of the natural physiological procedures responsible for removing those aggregates is autophagy. Accordingly, autophagy dysregulation is believed to contribute massively to PD pathogenesis.The neurotoxic pesticide rotenone was found to result in autophagic flux inhibition through lysosomal dysfunction, an effect that could be reversed by autophagic activators providing a protective effect against rotenone cytotoxicity. On the other hand, dopaminergic cell death in PD is proved to be a direct result of an enhanced apoptosis.Previous reports showed that dopaminergic neurons may survive and their function and morphology could be preserved after using apoptosis inhibitors.Therefore, it is of an utmost importance to keep normal balanced cell death mechanisms to maintain the normal homeostasis without causing irreparable damage. Hydroxychloroquine (HCQ), a chloroquine hydroxy-derivative, is an anti-malarial and anti-rheumatic drug.HCQ neuroprotective potential is still questionable. A previous study failed to prove HCQ efficacy against Alzheimer’s disease.On the other hand, a recent study suggested that some anti-malarial drugs including chloroquine succeeded in ameliorating PD motor disturbances in 6-OHDA-treated rats.Moreover, HCQ managed to alleviate neurological sarcoidosis manifestations, an effect that could support the claims around its neuroprotective potential. Hence, this study aims to unveil the discrepancy regarding the possible Nurr1 mediated neuroprotective effects of hydroxychloroquine versus autophagy and apoptosis dysregulation, in a rat model of PD. claimed to participate significantly in pathogenic mechanisms of neurodegenerative diseases including, PD and Alzheimer's disease.It was shown that GSK-3β regulates various components of the complex network involved in PD such as, inflammation and abnormal protein aggregates formation.Hence, GSK-3β inhibition can exhibit a beneficial outcome in PD treatment. Normal turnover of proteins and cells within an organism is controlled by various processes including, apoptosis and autophagy

Keywords: Nurr-1, Rotenone, Parkinson’s disease, Autophagy, Tyrosine hydroxylase. GSK-3β LC3-II Nurr1 Rotenone SIRT-1 Hydroxychloroquine.

This work is partly presenting in 2nd International Conference on Molecular Pathology and Genomics on December 09-10, 2020 held at Paris, France

Background : ”Multiparametric flow cytometry (MFC)’' is a powerful tool for the diagnosis of hematological malignancies and has been useful for the classification of chronic lymphoproliferative disorders (CLPD) according to the WHO criteria. Following the purpose of Flow Cytometry , the aim of this report was to standardize the minimum requirements to achieve an accurate diagnosis in CLPDs, considering the different economic possibilities of the laboratories in our country. Most laboratories in India work with 4-fluorescence flow cytometers, which is why this study has been proposed 4-color monoclonal antibody (MoAb) panels .

Multiparametric flow cytometry (MFC) is a powerful tool for the diagnosis of hematological malignancies and has been useful for the classification of chronic lymphoproliferative disorders (CLPD) according to the WHO criteria. Following the purposes of the Brazilian Group of Flow Cytometry (GBCFLUX), the aim of this report was to standardize the minimum requirements to achieve an accurate diagnosis in CLPDs, considering the different economic possibilities of the laboratories in our country. Most laboratories in Brazil work with 4-fluorescence flow cytometers, which is why the GBCFLUX CLPD Committee has proposed 4-color monoclonal antibody (MoAb) panels.

Key terms: chronic lymphoproliferative disorders; flow cytometry; monoclonal antibody panel; lymphoma; multiple myeloma, Flow cytometry principles, Flow cytometry in hematology, immunophenotype characterization, immunophenotype characterization, Immunophenotype characterization for chronic lymphoproliferative disorders

Methods/Results: Panels for screening and diagnosis in B, T and NK lymphoproliferative disorders were developed based on the normal differentiation pathways of these cells and the most frequent phenotypic aberrations. Important markers for prognosis and for minimal residual disease (MRD) evaluation were also included. The MoAb panels presented here were designed based on the diagnostic expertise of the participating laboratories and an extensive literature review.

Conclusion: The 4-color panels presented to aid in the diagnosis of lymphoproliferative neoplasms by Flow Cytometry aim to provide clinical laboratories with a systematic, step-wise, cost-effective, and reproducible approach to obtain an accurate immunophenotypic diagnosis of the most frequent of these disorders.

Panels for screening and diagnosis in B, T and NK lymphoproliferative disorders were developed based on the normal differentiation pathways of these cells and the most frequent phenotypic aberrations. Important markers for prognosis and for minimal residual disease (MRD) evaluation were also included. The MoAb panels presented here were designed based on the diagnostic expertise of the participating laboratories and an extensive literature review.

Conclusion: The 4-color panels presented to aid in the diagnosis of lymphoproliferative neoplasms by GBCFLUX aim to provide clinical laboratories with a systematic, step-wise, cost-effective, and reproducible approach to obtain an accurate immunophenotypic diagnosis of the most frequent of these disorders. © 2016 International Clinical Cytometry Society.

Introduction

In modern diagnostics, flow cytometry has an important place as one of the basic and irreplaceable tools for diagnosis, classification, monitoring and prediction of malignant hematological disease . The extreme complexity of these diseases, on one hand, and the availability of the different therapeutic protocols for the different types of these diseases on the other, makes accurate and precise diagnosis imperative. Contributing to this is the fact that the World Health Organization (WHO), in the Classification of Tumours of Hemopoietic and Lymphoid Tissues, suggests a multiparametric approach in diagnosing these diseases; basic parameters required are morphological, immunophenotypic and genetic analysis for each entity of the disease, in addition to a detailed history of the disease and clinical examination. The clinical picture and cell morphology, as a well-known and traditionally-used means of examination, are insufficient in many cases; quite often, because of a similar clinical presentation and cell morphology, it is not possible to draw a diagnostic conclusion based on these findings or a wrong diagnosis may be reached in some cases.

Flow cytometry principles

Flow cytometry is a powerful technology that simultaneously measures many aspects of single particles, usually cells. Any suspended particle or cell from 0.2–150 μm is suitable for analysis. However, it can also measure soluble molecules if trapped onto a particulate surface and bound by fluorochromes. Virtually any component or function of a cell can be measured if the fluorescent probe can be made to detect it.

Sample preparation should provide a homogeneous suspension of cells with monoclonal antibodies conjugated with fluorochromes of a different emission spectrum. Depending on the sample, it most often includes incubation, erythrocyte lysis, centrifugation, washing and fixation.

Becoming more available in clinical laboratories, a wide range of clinical applications of flow cytometry are constantly expanding and the most common among them are in, for example, lymphoma and leukemia diagnosis, stem cell enumeration for transplantation, estimation of minimal residual disease, paroxysmal nocturnal hemoglobinuria diagnosis, immunodeficiencies, HIV infection.

Flow cytometry in hematology

Flow cytometric immunophenotyping enables examination of the phenotype of the separate cells in the suspension and summarizing of the results, which gives data about the presence or absence of antigen expression as well as the expression intensity [5]. Hence, an immunophenotypic pattern is obtained on the cell population of interest for the examined disease. Meanwhile, there are no separate antigens specific for the particular disease. Instead, their mutual relation is observed and analysed, which makes the analysis of the flow cytometry results very demanding and complex, but usually very useful and precise owing to the huge amount of data that can be collected from the cells [6]. Therefore, flow cytometry helps with determining the cell line, the degree of cell maturity, abnormal patterns of expression and provides a detailed immunophenotype of the pathological cell population [7]. From information on all the aforementioned factors, a diagnostic conclusion is drawn if there is a phenotype characteristic for some disease. In the case of an atypical phenotype, the disease is assigned to the appropriate group and additional tests should be done to gain a precise diagnosis (such as immunohistochemical, FISH, molecular tests).

immunophenotype characterization.

The antibody panel for the analysis of the sample to be tested by flow cytometry depends, to a large extent, on the available information of other findings made for that patient. According to the Bethesda Group recommendations from 2006, which were aimed at regulating a more systematic approach in this field (and are still valid today), before sending a sample to flow cytometry, a detailed history of the disease, clinical examination, microscopic examination of cell morphology, and other laboratory tests should be carried out, and based on this, diagnosis or differential diagnosis determined. In this way significant rationalization and cost reduction can be achieved.

Immunophenotype characterization for chronic lymphoproliferative disorders

For both of the two major groups of malignant hematologic diseases, those derived from mature and from immature cells, flow cytometry is of a great importance. Neoplasms of mature lymphoid cells, according to the WHO Classification, include chronic lymphoid leukemia and non-Hodgkin’s lymphoma. Their basic characteristic is that they have an immunophenotype similar to mature lymphoid cells and, accordingly, they show an absence of immaturity indicators (CD34, TdT). According to the origin, in relation to the cell line, they can be divided into T, B and NK neoplasms.

In most cases of CLL, cell morphology is characteristic and typical for this disease. However, in a number of cases, flow cytometry has a huge and decisive significance for diagnosis (Fig. 3) [13]. CLL and MCL share many morphological and immunophenotypic features [14]. As a result of their partial overlap, a differential diagnosis of MCL is most considered when making a diagnosis of CLL. Because of the different therapeutic approach and prognoses of the diseases, their diagnostic differentiation is very important. For that purpose cyclin D1 testing is recommended [15, 16]. Unlike the other chronic lymphoproliferations, HCL cells do not match any stage of the normal lymphoid cells development. Morphologically typical HCL cells have fine, hair-like, cytoplasmic projections, which are sometimes difficult to find in the peripheral blood smear. Because of this and a very specific immunophenotype, flow cytometry is essential for HCL diagnosis.

Advantages

The possibility of combining more antibodies in the same tube and analysing their interactions on the population of interest for the given disease is the greatest advantage of multiparametric flow cytometry, which involves simultaneously collecting and analysing a large amount of data from cells or particles.

Considerations

Comprehensive analysis involves considering possible causes of false-positive or false-negative results, thus avoiding an incomplete or incorrect interpretation of flow cytometry data.

Other difficulties, such as non-standardized methods, particularly the issue of regulation in cytometry, different antibody panels, cut-off values, analysis subjectivity – recommended visual approach, result analysis complexity, report form, etc., are the subject of work by various associations dealing with cytometry in order to achieve harmonization.

This work is partly presenting in 2nd International Conference on Molecular Pathology and Genomics on December 09-10, 2020, held at Paris, France

Background: The clinical value of plasma circulating cell-free DNA (cfDNA)integrity as diagnostic biomarker in the patients with HCV related hepatocellular

carcinoma (HCC) was investigated and correlated with the commonly usedmarker alpha fetoprotein (AFP).

Aim of the work: To assess the plasmacirculating cell free DNA integrity versus AFP as a biomarker fordiagnosis of hepatocellularcarcinoma using ALU 115 and ALU 247 sequences.

“Context Hepatitis C virus (HCV) is a common blood-borne pathogen that relies heavily on nucleic acid testing for confirmation of infection. Nucleic acid tests are invaluable for the diagnosis of HCV infection and provide critical prognostic information for guiding treatment and measuring the response to antiviral therapy”.

Context hepatitis C virus (HCV) may be a common blood-borne infectious agent that depends heavily on macromolecule testing for confirmation of infection. macromolecule tests ar valuable for the designation of HCV infection and supply essential prognostic data for guiding treatment and measurement the response to antiviral therapy”.

“Objective To review the presently obtainable molecular diagnostic tests for HCV, their clinical applications, and the way these tests shed lightweight on the explanation of HCV”,

“Evidence Acquisition Search of MEDLINE (1966 to July 2006), article reference lists, and national meeting abstracts for the designation and applications of molecular diagnostic tests for HCV. Studies were hand-picked on the idea of clinical relevance”.

“Evidence Synthesis Qualitative macromolecule tests have low limits of detection (<50 IU HCV RNA/mL) and ar used for confirmation of HCV infection and for screening blood donations. hepatitis C virus genotype take a look at results give necessary prognostic data associated with therapeutic response and ar habitually used for choosing treatment regimens. Quantitative HCV ribonucleic acid testing provides prognostic data concerning probability of treatment response and plays a vital role in observation the antiviral response to treatment. Sustained medicine response is outlined as testing negative for HCV ribonucleic acid half-dozen months once halt of medical aid. Recent studies counsel that the speed of response to medical aid is additionally necessary. for instance, conversion to associate HCV ribonucleic acid negative take a look at result once four weeks of medical aid constitutes a rapidvirological response and may be a robust predictor of treatment success. Patients WHO haven't had associate earlyvirological response, outlined as a minimum of a 2-log decline in HCV ribonucleic acid once twelve weeks of medical aid, ar unlikely to reply with an extra thirty six weeks of medical aid, and may stop therapy”.

Conclusions :

“A sensitive macromolecule take a look at ought to be accustomed make sure all cases of acute or chronic HCV infection. A genotype take a look at and quantitative HCV ribonucleic acid take a look at ought to be performed on all patients before medical aid to best assess chance of response and to assist in choice of applicable therapeutic program. observation HCV ribonucleic acid throughout treatment provides necessary data on probability of sustained medicine response. identical form of quantitative HCV ribonucleic acid take a look at ought to be used throughout a patient's treatment course”.

“Chronic hepatitis C virus (HCV) infection happens often within the us and worldwide. The Centers for unwellness management and bar estimates that a minimum of three.2 million persons within the us ar inveterately infected.1 within the one990s, a minimum of ten 000 deaths annually were directly thanks to hepatitis C, with a projection of a multiplication of the infectious disease C–related deaths by 2020.1,2Chronic hepatitis C is a vital and rising think about hepatoma and is currently the leading indication for liver transplantation.3 sadly, HCV infection is commonly underdiagnosed. over five hundredth of individuals at highest risk for HCV ar infected however ar unaware of their unwellness, resulting in unfold of the infection and lost treatment opportunities”.

“Molecular medicine techniques play a key role in designation and observation of treatment. as a result of it's troublesome to culture the virus, molecular techniques were instrumental in initial distinctive HCV, creating it one among the primary pathogens to be known strictly by molecular medicine.5 hepatitis C viral infection is confirmed by the detection of microorganism ribonucleic acid through macromolecule tests (NATs), and these tests ar accustomed monitor the response to antiviral medical aid. we have a tendency to review presently obtainable molecular diagnostic tests for HCV, their clinical applications, and the way these tests shed lightweight on the explanation and best management of hepatitis C. Readers ar brought up a previous review during this series for a a lot of general summary of the clinical management of hepatitis C.6”

“Evidence acquisition”

“We searched the MEDLINE info from 1966 to July 2006 for English-language articles victimization the subsequent search terms: HCV, infectious disease C/diagnosis, infectious disease C/virology, hepacivirus/physiology, infectious disease C/treatment, enzyme chain reaction/methods, enzyme chain reaction/standards, enzyme chain reaction, sensitivity and specificity, accuracy, genotype, virus replication. we have a tendency to more reviewed meeting abstracts from the 2006 yank Association for the Study of disease and also the European Association for the Study of the Liver for relevant articles. we have a tendency to based mostly our recommendations on laboratory designation and analysis on the 2002 National Institutes of Health agreement tips, the 2004 yank Association for the Study of disease observe tips, and also the 2003 Centers for unwellness management and bar Screening and Testing tips.7-9”

“Evidence synthesis”

Natural History of HCV Infection

“Among patients exposed to HCV, 15 August 1945 to four-hundredth can clear the infection inside half-dozen months10,11 (Figure 1). The remaining hour to eighty fifth of patients WHO still have detectable HCV ribonucleic acid for six months ar thought-about to be inveterately infected.8 A minority of inveterately infected patients can have persistently traditional aminoalkanoic acid transaminase (ALT) levels.13 As a result, ALT levels and a positive HCV medical science result aren't adequate for the designation of chronic HCV; instead, detection of HCV ribonucleic acid is needed to ascertain the designation. Results from longitudinal viraemia studies have indicated that spontaneous resolution of chronic HCV infections happens at a rate of zero.50% to 0.74% per person-year annually.14,15Unfortunately, up to twenty of people with chronic hepatitis C eventually develop liver cirrhosis of the liver, which can be sophisticated by hepatoma, internal organ decompensation, or death”.

Subjects and Methods:

It was a comparative study on eighty patientsrecruited from Cairo UniversityHospital Endemic medication department throughout the amount from Gregorian calendar month 2018 to September 2018. They were divided into 2 groups: forty HCC patients and 40HCV connected liver cirrhosis of the liver patients.AFP was measured by accelerator luminescence. Genetic analysis for determination of cfDNA integritywas done by analysingALU a hundred and fifteen and ALU 247 sequencesusing SYBR inexperienced based mostly period PCR.

Results:

HCV connected HCC patients had lower plasma cfDNA integrity than thosewith HCV connected liver cirrhosis of the liver patients (p price < zero.005). Also, there was a

statistical important correlational statistics between foetoprotein (measured by chemiluminescence) and plasma cfDNAintegrity with r price = -0.54 (P price <0.001). The AUCs for detection of HCCby cfDNA integrity and foetoprotein were zero.965 (P price < zero.001) and 0.886 (P < 0.001),respectively.

Conclusion: The results of this study prompt that the plasma cfDNA integritycan be used as a possible early marker for HCC among the HCV patients.Keywords: circulating cell-free DNA; cfDNA; integrity; hepatocellular carcinoma.

This work is partly presenting in 2nd International Conference on Molecular Pathology and Genomics on December 09-10, 2020 held at Paris, France.

Introduction: The revolutionary advances made in molecular biology are occurring in such a rate that it is drastically changing the methods of diagnosis of disease. However practicing as a pathologist in Kathmandu University Hospital (KUH), we have huge limitations.

Precision medicine aims to focus on meeting patient requirements accurately,optimizing patient outcomes, and reducing under-/overdiagnosis and therapy. We aim to offera fresh perspective on accuracy driven “age-old precision medicine” and illustrate how newercase-based blended learning ecosystems (CBBLE) can strengthen the bridge between age-old precisionapproaches with modern technology and omics-driven approaches. Methodology: We present aseries of cases and examine the role of precision medicine within a “case-based blended learningecosystem” (CBBLE) as a practicable tool to reduce overdiagnosis and overtreatment. We illustratedthe workflow of our CBBLE through case-based narratives from global students of CBBLE in highand low resource settings as is reflected in global health. Results: Four micro-narratives based oncollective past experiences were generated to explain concepts of age-old patient-centered scientificaccuracy and precision and four macro-narratives were collected from individual learners in ourCBBLE. Insights gathered from a critical appraisal and thematic analysis of the narratives werediscussed. Discussion and conclusion: Case-based narratives from the individual learners in ourCBBLE amply illustrate their journeys beginning with “age-old precision thinking” in low-resourcesettings and progressing to “omics-driven” high-resource precision medicine setups to demonstratehow the approaches, used judiciously, might reduce the current pandemic of over-/underdiagnosisand over-/undertreatment.

The term “Precision Medicine” was first coined by Clayton Christensen in his book the“Innovator’s Prescription”, published in 2009 [1]. According to the early definition given by theInstitute of Precision Medicine, “Precision medicine is targeted, individualized care that is tailored toeach patient based on his or her specific genetic profile and medical history” [2].While the above definitions allow us to assume that precision medicine is focused on meetingpatients’ requirements accurately, we need to review the scientific nature of accuracy, precision andtheir relationship with each other to put things in perspective. This is essential toward optimizingpatient requirements and outcomes, minimizing damage to the healthcare ecosystem by reducingunder-overdiagnosis and therapy. To quote from Thomas (2014), “The healthcare ‘system’ is nowbetter understood as an ‘ecosystem’ of interconnected stakeholders, each one charged with a missionto improve the quality of care while lowering its cost. To ensure patient safety and quality care whilerealizing savings, these stakeholders are building new relationships—often outside the four walls ofthe hospital” [3].

We illustrate the above concepts with micro case studies below:“An elderly patient from a country endemic with tuberculosis presented with a chronic cough andweight loss. A lung pathology was detected on imaging that was not amenable to further biopsyefforts as a result of unavailable resources. He was started on empirical treatment for tuberculosisafter sending a sputum for acid-fast bacillus (AFB) and culture.”In tuberculosis endemic countries, physicians often treat empirically for tuberculosis in suspiciouslung pathologies, although lung malignancy is a close differential in such situations. In the abovepatient’s context, physicians were being obviously imprecise in starting treatment for tuberculosisempirically even when the tuberculosis bacilli was undetectable. This is an acceptable standardpractice with established protocols for treating sputum-negative tuberculosis utilized globally by manycountries that are endemic for tuberculosi

“The idea of sharing and learning around patients has been alive since the beginning of medicine,when physicians would present their cases to a large audience to primarily learn from the inputs ofother physicians.” With the invention of the printing press, instead of restricting themselves to verbalface-to-face case presentations, many physicians published their cases in journals and slowly the medicalfraternity started naming those published diseases after their first authors. “In this way, case reportingbecame a gainful activity not only in terms of scientific advancement towards patient benefits, but alsoas an important instrument of physician fame.” We have utilized this case reporting model to help ourpatients and to train our medical students about disease and patient experience

Healthcare 2018,6, 78 5 of 17By reporting cases, this model allows more engagement both from patients and medical studentsto reach a precise and accurate diagnosis, and also helps as an educational tool.

Objectives: To study the molecular tests performed in KUH, the challenges faced and to explore the additional possibilities in the field of Molecular pathology.

Materials and methods: The cases and problems faced in Molecular tests by the doctors, and technicians are discussed, analysed and reported.

Results: The molecular tests currently being performed in KUH are PCR and Immunohistochemistry (IHC). PCR test functioning since 1 year is performed especially for HPV detection and for diagnosing Tuberculosis. Total PCR cases sent are average 10 per day. Among 580 cancer case in a  year, 34 needed IHC for conformation. Only 4 are performed IHC.

Discussion: Use of Molecular pathology tests is at its infancy in KUH. IHC is very difficult to continue because of the cost and hence the scarcity of the cases. The antibody once opened has very short life that aids in increasing the cost. So the patients who can afford are sent abroad. However Kathmandu University have nine affiliated colleges. If we can have standard Molecular diagnosis lab then we can collect the cases from almost all of them which can reduce the cost.

Conclusion: There's frequent diagnosis of cancer cases in KUH and in affiliated colleges, KUH can be made the hub for Molecular diagnosis in Nepal.

This work partly presenting in 2nd International Conference on Molecular Pathology and Genomics on December 09-10, 2020 held at Paris, France.

The dynamic interactions of cancer cells with their microenvironment consisting of stromal cells (cellular part) and extracellular matrix (ECM) components (non-cellular) is essential to stimulate the heterogeneity of cancer cell, clonal evolution and to increase the multidrug resistance ending in cancer cell progression and metastasis. The reciprocal cell-cell/ECM interaction and tumor cell hijacking of non-malignant cells force stromal cells to lose their function and acquire new phenotypes that promote development and invasion of tumor cells. Understanding the underlying cellular and molecular mechanisms governing these interactions can be used as a novel strategy to indirectly disrupt cancer cell interplay and contribute to the development of efficient and safe therapeutic strategies to fight cancer. Furthermore, the tumor-derived circulating materials can also be used as cancer diagnostic tools to precisely predict and monitor the outcome of therapy. This review evaluates such potentials in various advanced cancer models, with a focus on 3D systems as well as lab-on-chip devices.

The process of tumor formation and progression is influenced by two factors, namely genetic/epigenetic changes in the tumor cells and the rearrangement of the components of the tumor microenvironment (TME) through mutual and dynamic crosstalk [1]. TME consists of tumor cells, tumor stromal cells including stromal fibroblasts, endothelial cells and immune cells like microglia, macrophages and lymphocytes and the non-cellular components of extracellular matrix such as collagen, fibronectin, hyaluronan, laminin, among others [2, 3]. As the heart of TME, tumor cells control the function of cellular and non-cellular components through complex signaling networks to use the non-malignant cells to work for their own benefit. The consequence of such crosstalks is reflected in tumor formation and maintenance as well as deficient response to therapy and multi-drug resistance (MDR). The non-malignant cells in the TME are known to promote tumorigenesis in all phases of cancer development and metastasis [4, 5].

The source of intercellular communication is a complex network of cytokines, chemokines, growth factors, inflammatory mediators and matrix remodeling enzymes, but other fascinating mechanisms of interaction are now emerging. These include circulating tumor cells (CTCs), exosomes, cell-free DNA (cfDNA) and apoptotic bodies as novel horizontal gene transfer (HGT) mediators derived from tumor cells and delivering information to distant target cells including tumor cells and/or normal cells [6, 7].

Recent advances in tumor biology have shown that a comprehensive analysis of the multiple exchanges between tumor cells and their neighboring microenvironment is essential to understand the different underlying mechanisms of tumor growth and metastasis [8]. The loss of tissue integrity, carcinogenesis and further progress occurs as a consequence of reciprocal interactions between tumor cells with non-cellular (ECM) and cellular components of the TME [9, 10]. Therefore, on the other side of the argument, interactions in reactive non-neoplastic cells, genetically-altered tumor cells, and ECM control the majority of the stages of tumorigenesis effectively including clonal evolution, cancer heterogeneity, epithelial-mesenchymal-transition (EMT), migration, invasion, development of metastasis, neovascularization, apoptosis and chemotherapeutic drug resistance [11,12,13,14].

Due to the compelling role of TME in malignancy, many efforts are focused on this area [15, 16]. That is, a better understanding of the ways in which TME affects cancer progression is expected to make new targets available for the cancer cell isolation and cancer treatment. This can be achieved by interfering with the complex crosstalks established between cancer cells, host cells, and their surrounding ECM [10].

The recapitulating of TME is an important challenge in the development of experimental cancer models. In order to develop a reliable tool for personalized cancer therapy and drug development, it is essential to preserve the key characteristics of the original tumor. Recent advances on three dimensional (3D) platforms through the use of lab-on-chip and microfluidic devices [17] have provided an enormous opportunity to better stimulate the function and biology of TME and to bridge the translational gap between preclinical and clinical settings [18].

In this review, we look into the molecular interactions between cancer cells and their microenvironment and evaluate the effect of such interactions on the fate of cancer cells. The effect of tumor-derived circulating materials as novel cancer theranostics are also highlighted. To this end, we review the feasibility of implementing an innovative strategy pattern based on the interruption of these crosstalks to build an effective anti-cancer approach.

The cornerstone of the current review compared to the previous ones is its comprehensiveness. Previous reviews in this area are focused, for example, on recapitulating the gradual process of cancer metastasis by discussing advanced biomaterials and microtechnologies [19]. Also, they may highlight the mechanics of tumor metastasis [20]. And most of them only discussed a limited number of players/strategies such as anti-angiogenic therapies or targeting ECM yet fail to discuss the newly formed gadgets of cell-cell interactions such as cfDNA, apoptotic bodies, CTCs as well as exosomes [21, 22]. This review also evaluates the potential of disrupting tumor cells interactions in various cancer settings, in particular the newly emerging cancer models including 3D models and microfluidic platforms that allow to study different aspects of cancer cell behavior and biology, similar to the physiological environment in which they naturally occur.

I am working with my Team on Epigenetics. We have many papers regarding our work on Epigenetic. Our work is basically on DNA methylation. We are on ongoing Clinical phase I and Phase IIa Trials Regarding Anti UPAR and SAM ( hypermethylating agent) We are also working on development of DNA methylation signature or tumor markers for breast and Prostatic cancer. DNA methylation till now seems very promising regarding its Diagnostic Therapeutic and prognostic implication.

 I want to discuss Epigenetics focused on DNA methylation.

In my talk I want to focus on the following:

Why Patients metastasize even on hormonal therapy.

Functions of uPA-uPAR System

uPA/uPAR as a Focal Point in Tumor Progression

System to assess uPAR/PAI expression

Development of uPA/uPAR Targeted Therapeutics

ATN-658 is a fully humanized anti-uPAR antibody

uPA Promoter Methylation

Epigenetic regulation of gene transcription. DNA Methylation

Hypermethylating agents; S-adenosylmethionine (SAM)

Effect of SAM on Osteosarcoma metastasis in vivo

Early Non-invasive Biomarkers of Breast and Prostate Cancer

Development of “epigenetic signature” for patients with breast, prostate and other common cancers.

Validation of identified “epigenetic signature” in a large cohort of patients in multi-centre trial.

Comparison of identified “epigenetic signature” in patients with different ethnic, racial and geographical background.

Approval and marketing of identified approach for clinical use in normal and high risk subjects with various malignancies. 

This work is partly presenting in 2nd International Conference on Molecular Pathology and Genomics on December 09-10, 2020 held at Paris, France.

Vibrio vulnificus is a gram-negative bacterium that thrives in high-salt environments. V. vulnificus infections disproportionately affect males and old patients, especially those with underlying conditions such as liver disease, diabetes and immune disorders. Severe wound infections are often characterized by necrotizing skin and soft-tissue infection, including fasciitis and gangrene. Taiwan is situated in a subtropical region. The residents usually introduce seawater to cultivate seafood for a living. The mortality rate of patients with wound infection and septic shock can be as high as 90%. The patient might die within 24-36 hours. This article describes the care experience of a female 72-year-old with hypertension but without any high-risk disease. She suffered from sudden onset of right hand swelling after cleaning Tilapia 12 hours. Tigecycline 100mg was administrated after admission, sepsis and rapidly progressive necrotizing fasciitis was noticed. Continuous Tigecycline and wound care with sterile distilled water dressing were treated, fasciotomy and debridement was done on Day 3. The wound culture yielded Vibrio vulnificus. FIR (Far-Infrared Ray) energy radiation was done and the necrotic wound was dressed with Aqual-Ag+ Extra for comfortable reason. The patient was hospitalized for 15 days and three times of debridement, FTSG was performed after injury 28 days. She was prevented from amputation or surrounding tissue damage. These interventions are beneficial to maintaining a patient's life, symptom relief and lowering the mortality rate.syNecrotizing fasciitis due to Vibrio vulnificus can produce an overwhelming toxic shock-like syndrome that results in rapid deterioration and death. It is markedly associated with chronic liver disease such as cirrhosis caused by chronic hepatitis B or C infection. Other high-risk conditions that predispose to severe infection with Vibrio vulnificus include hemochromatosis, current malignancy, AIDS and other immunocompromised states, and achlorhydria. As yet, no superantigen has been implicated as a cause of this form of necrotizing fasciitis. The current literature suggests that host factors play a large role in the fulminant nature of the disease in these susceptible patients . Exposure to the organism usually occurs through ingestion of shellfish or inoculation via traumatic injury in marine environments. It is likely that our patient either could have ingested raw shellfish or was exposed while preparing seafood at his place of employment. Vibrio vulnificus is a halophilic, motile, comma-shaped, gram-negative bacillus from the family Vibrionaceae. It is associated with warm coastal waters such as the Gulf of Mexico and is seen during the warmer months, generally from mid-May to mid-September. The organism is isolated in high concentrations from shellfish (especially oysters), and during the summer months, it can be seen in concentrations as high as 10³ to 10⁴ CFU per gram of tissue . In some epidemiologic studies, greater than 50% of shellfish and 11% of crabs harbor the organism during warmer months. Of 422 cases of Vibrio vulnificus infection reported to the CDC over a 9-year period, 43% were primary septicemia, 45% were wound infections, 5% were gastroenteritis, and in 7%, the source could not be determined. The overall case fatality rate is 25%, and infection is estimated to result in 90% of all deaths related to the ingestion of seafood. Primary septicemia is seen without an apparent source of inoculation and is attributed to the ingestion of contaminated shellfish, with blood-borne dissemination through the gastrointestinal tract, particularly in patients with cirrhosis.

Note- This Work is partly presenting at 12^th International Conference on Geriatrics Nursing, Gerontology and Aging on December 09-10, 2020 held at Paris, France.

Background:  A case of extensive nasal polyposis with rarely aggressive recurrent nature and its management is presented.

Case:  A 64-year-old female patient complained of recurrence of nasal polyps. The patient presented with multiple large polypoid lesion protruding from the both nostril, which had been treated with thermal ablations for more than four times. Biopsy under local anaesthesia was performed, showing findings consistent with nonspecific inflammation.  Minimally procedure with microinjection of Triamcinolone Acetonide through nasoscope under local anaesthesia was performed at the comprehensive clinic layer by layer in a sequential time-point fashion, and the polypoid masses were medically ablated one after the other in the next three weeks. Postoperative follow-up has shown no evidence of recurrence after 3 months.

Keywords: Anosmia, Blindness, Mucocele, Paranasal sinuses, Pyocele

Introduction: Mucocele of the paranasal sinus is an incessant, growing, mucosa-lined injury portrayed by mucous retention.1 The aggregation of mucous emission and possible auxiliary bacterial disease may bring about the development of a pyocele.1,2 This clinical condition tends to distend and disintegrate the sinus hard dividers coming about, when the circle is included, in serious neuro-ophthalmic complications.3

Frontal and foremost ethmoidal sinuses are the commonest locales for mucocele or mucopyocele while the back ethmoidal, sphenoidal and maxillary sinuses are seldom involved.2,4–6 Multiple paranasal sinuses might be included yet respective pansinus mucopyocele is rare.6 Nasal polyps, contaminations, tumors (particularly frontal osteoma), past facial injury and intranasal medical procedures causing ostia blockage have been accounted for as prominent reasons for mucocele.7,8

This mucocele may get tainted and turn into a pyocele. The disease animates creation of cytokines [interleukin 1 (IL-1) and tumor rot factor (TNF)] from lymphocytes and monocytes, and builds combination of prostaglandin (PGE2) and collagenase from fibroblast of the bodily fluid lining.9

Lund and Milroy et al showed and announced a high amount of cytokines (IL-1, IL-6, and TNF), PGE2 and collagenase between the covering of the mucocele and sinus wall.9–11 This is answerable for the resorption and pulverization of the sinus divider, taking into consideration the development of the mucocele.

Case:  A 64-year-old female patient complained of recurrence of nasal polyps. The patient presented with multiple large polypoid lesion protruding from the both nostril, which had been treated with thermal ablations for more than four times. Center with a two year history of dynamic reciprocal nasal blockage and nasal mass. There was related intermittent mucoid nasal release, hyponasal discourse and loss of impression of smell. There was no epistaxis, neck growing, cheek or dental side effects. Two months before introduction, she created dynamic respective visual disability, more regrettable in the left eye. There was related migraine however no neck torment, heaving, or neurologic deficiencies. She had experienced the surgery, 8 years already, of two-sided outside fronto-ethmoidectomy, nasal freedom and reciprocal intranasal sub-par meatal antrostomy for respective multi-sinusitis with nasal polyposis. Histology report affirmed constant provocative polyp.

Assessment uncovered a young lady with hyponasal discourse and a slight level of mouth relaxing. She was not febrile and had no critical fringe lymph hub amplification. There was telecanthus and two-sided mended Lynch-Howarth entry point scars. Nasal assessment uncovered inflammed various polypoidal mass sores secured by mucopurulent discharges distending from and totally annihilating the correct nasal depression.

The mass was firm, touchy to contact however didn't seep on contact and seemed to emerge from the correct horizontal nasal divider. The left nasal depression additionally had a pale polypoidal mass secured with mucopurulent emissions. The mass was non-touchy, had no contact draining and seemed to emerge from the sidelong mass of left nasal. Assessment of the throat uncovered a granular back pharyngeal divider, and postnasal mucoid release.

Otoscopy uncovered unblemished however dull tympanic layer respectively. The neck seemed ordinary. The neuro-ophthalmic assessment uncovered left non-hub proptosis and visual sharpness of nil light discernment in the two eyes at 3 meters. A clinical conclusion of interminable rhinosinusitis with nasal polyposis was made.

The computed tomographic (CT) output of the paranasal sinuses and cerebrum uncovered broad blended thickness injuries inside all the paranasal sinuses. There was gross extension of the left frontal sinus whose extraordinarily sclerotic back divider caused checked pressure of the left frontal flap of the cerebrum. Comparative sores filled both nasal depressions

The surgery was completed at a time and included reciprocal nasal polypectomy, two-sided intranasal antrostomy, and two-sided fronto-ethmoido-sphenoidectomy by means of respective fronto-nasal-orbital craniotomy. Remaking of Cranio-facial bone imperfections was encouraged utilizing a titanium skull clasp, the CraniovFixR (B Braun, Aesculap, Germany)

The employable discoveries were two-sided polypoidal intranasal masses, respective deformities in the supero-average dividers of the circles speaking with the ethmoidal sinuses straightforwardly, complex mucopyocele in all the paranasal sinuses (Frontal, Ethmoidal, Sphenoidal, and maxillary sinuses) and sclerotic development of their dividers. The histology of the example affirmed ceaseless provocative polyp

Postoperatively, she developed cerebrospinal liquid (CSF) rhinorrhea on the fourth postoperative day and this was effectively dealt with sequential lumbar CSF seepage. The constant postoperative issues were respective visual deficiency and anosmia.

Discussion: This case report presents some significant purposes of significance in clinical practice in a creating nation. The first is the significant expense of a preventable two-sided visual deficiency that this patient keeps on paying for her postponement in introduction for treatment of an in any case considerate treatable sore. Another point is the excellence, and consequently the basic of interdisciplinary endeavors between skull base neurosurgeons and ENT specialists where neurological medical procedure and otorhinolaryngology meet in cases this way.

The presentation of paranasal sinus mucocele is generally unilateral; bilaterality is rare indeed. Our patient represents one of such rare occurrences of bilaterality. This might have happened due to the associated recurrent bilateral nasal polyposis or the previous bilateral intranasal surgery which this patient had.

The old conventional intranasal surgical line of attack which does not employ the use of the current modern progressive surgical tools like nasal endoscopes to aid visualization of intranasal structures, has the great potential of inadvertently damaging or removing the thin bone of the orbit (lamina papyracea) and optic nerve with a possibility of damage to these structures.^12-13

The current gold standard of imaging the paranasal sinuses is the CT scan which is very good at recognizing any sinus mucocele and any other pathological changes within the paranasal sinus cavities.^9,11 Mucocele is confirmed as a homogenous smooth walled mass, expanding the sinus, with thinning or loss of the cortical bone altogether. There may be confirmation of new bone formation or sclerosis (Figure 1), as the mucopyocele may initiate a process of bone resorption and expansion.¹¹

Conclusion: Nasal polyps manifests typically in an aggressive recurrence manner. Since thermal ablation has been intolerant after multiple times, we managed it under local medical ablation with Triamcinolone Acetonide at the clinic, suggesting minimally invasive management on complex nasal polyps is feasible in the clinical setting. 

Note: This work is partly presenting at 11^th International Conference on Clinical and Medical Case Reports on September 14-15, 2020 held at Vienna, Austria

Background: Myocarditis is an acute infectious or immunologically mediated syndrome causing inflammation of the heart muscle. Around half of all cases are idiopathic (Karjalainen et al. 1983). Possible complications include syncope, arrhythmia and heart failure.

Presentation: 65 year old man with background hyperlipidaemia was presented with chest pain and palpitation. Initial ECG was monomorphic VT. Patient was haemodynamically stable. Subsequently, VT was approaching 240 bpm. Decision was made to proceed with cardioversion and sinus rhythm was restored. Electrolyte disturbance was excluded and angiogram was performed which did not show any flow limiting coronary artery disease. Cardiac MR had demonstrated normal left ventricular function with patchy mid wall epicardial mid gadolinium enhancement, consistent with a diagnosis of likely myocarditis although nonspecific cardiomyopathy could not be excluded. Being SVT with aberrancy a differential in view of regular broad complex tachycardia, EP study was subsequently performed and had confirmed VT. The patient then underwent ICD implantation and discharged well.

ECG: to be displayed on poster

Discussion: The mechanisms for ventricular arrhythmias during myocardial inflammation are unknown. Endo - myocardial biopsy is not necessary for the diagnosis of myocarditis. MRI should be performed in patients resuscitated from sudden cardiac death, to rule out myocardial inflammation. Although it is difficult to establish the exact prognosis, it is suggested that the prognosis of patients with resuscitated sudden cardiac death in the onset of acute myocarditis is favourable, arrhythmias usually being self-limited with no recurrences that follow the acute phase.

1 Introduction

Myocarditis is a typical cardiovascular ailment that is recognized in up to 9% of routine after death examinations.[1] It can give heterogeneous clinical appearances from vague side effects to a quickly breaking down heart capacity and perilous arrhythmias.[2] In patients with a considerate course of the infection, the heart capacity may totally recoup or advance to constant enlarged cardiomyopathy.[3] Long-term line up studies[4–6] of patients with a past filled with intense myocarditis frequently have a 5-or 6-year follow-up period, and those investigations investigated the relationship of the improvement of interminable expanded cardiomyopathy and the danger of abrupt cardiovascular passing. Other long haul examines were restricted to a specific etiology of the myocarditis and recognizable proof of the drawn out indicators of the mortality utilizing a few boundaries from analytic studies.[4,7] However, the frequency of new-beginning ventricular tachycardia (VT) during a 10-year follow-up period particularly in patients who recouped from intense myocarditis with no obvious clinical cardiovascular (CV) sequelae is by and by obscure. Furthermore, no examination has had the option to show the general mortality chance in these patients during the long haul development. The motivation behind this examination was to explore the relationship between intense myocarditis and the frequency of VT and mortality during the long haul follow-up period from the National Health Insurance Research Database (NHIRD) of Taiwan.

2 Methods

2.1 Study design and participants

This examination was a populace based review companion study. From January 1, 2000 to December 31, 2004, a sum of 13,250 patients matured 18 years and more established, who were determined to have myocarditis, were distinguished from the NHIRD as indicated by the International Classification of Diseases, ninth Revision—Clinical Modification (ICD9-CM) codes (422). The conclusion of myocarditis must be recorded twice in the outpatient records or if nothing else once in the inpatient records. On a similar list date, a similar number of wellbeing controls without earlier auxiliary coronary illness, coordinated by the sex, history of hypertension (HTN), diabetes mellitus (DM), ceaseless obstructive aspiratory ailment (COPD), constant kidney sickness (CKD), hyperlipidemia, and thyroid malady, were chosen to be the benchmark group for each examination persistent. Patients who were determined to have ischemic coronary illness, cardiovascular breakdown, valvular coronary illness, inborn coronary illness, unmistakable cardiogenic stun requiring vasopressors at the underlying introduction had a past filled with ventricular arrhythmia or past implantable cardioverter defibrillator (ICD) implantation, and those with foundational incendiary infections known to be related with myocardial contribution were prohibited from the investigation. The comorbid states of every individual were recovered from the clinical cases database dependent on the ICD9-CM codes.

2.2 Database

This examination utilized the Taiwan NHIRD to decide the danger of ventricular tachycardia (VT) and CV demise in patients with myocarditis during the long haul development (from 2000 to 2011). The Taiwan Collaboration Center of Health Information Application, Ministry of Health and Welfare, gave the whole datasets utilized in this investigation. The Taiwan's National Health Insurance (NHI) program selected 23 million individuals, which secured 99% of the nation's populace and contained information on use of all NHI assets, including outpatient visits, clinic care, endorsed drugs, and the National Death Registry. It contained all the clinical cases information for 1000,000 recipients, who were haphazardly examined from the 25.68 million enrollees under the NHI program. These arbitrary examples have been affirmed by the NHRI to be illustrative of the Taiwanese populace. The convention was checked on and affirmed by the Research Ethics Committee of National Taiwan University Hospital (NTUH-Rec Number: 201305044W [Institutional Review Board reference]). Moreover, we got consent for the rights from the National Research Institute for the Department of Health and the Health Promotion Administration, Ministry of Health and Welfare.

2.3 Study endpoints during the follow-up

The follow-up period ended when subjects developed a new VT, died or lived after 31 December 2011. The primary endpoints were the time for the development of new-onset VT and the time for CV death / all-cause mortality during follow-up. Death has been confirmed by reference to the Taiwan National Death Register. The time for implantation of an ICD was investigated as a secondary endpoint.

2.4 Statistical analysis

The ordinarily appropriated consistent factors were introduced as the mean qualities and standard deviation and were looked at utilizing a Student t test. The non-ordinarily appropriated factors were looked at utilizing the Mann–Whitney U test. Frequencies were looked at utilizing the chi-square test. The occurrence paces of CV occasions were determined as the quantity of cases per 100,000 man long periods of development. So as to limit the effect of the puzzling elements on the clinical attributes, we utilized the penchant investigation and coordinating procedure. We coordinated the sets balanced with indistinguishable penchant scores with a 0.01 caliper width for the sex, HTN, DM, CKD, COPD, hyperlipidemia, and thyroid malady.

The occasion free endurance bend was plotted utilizing the Kaplan–Meier strategy with the measurable centrality analyzed by the log-rank test. The Cox relative risks relapse was utilized to look at the danger proportions (HR) with 95% certainty stretches (CIs) for the results. Potential confounders were balanced by means of 3 models. Model 1: age and sex; Model 2: Model 1 or more HTN, DM, COPD, CKD, hyperlipidemia, and thyroid sickness; Model 3: Model 2 or more drugs, including angiotensin-changing over chemical inhibitors (ACEis), angiotensin receptor II blockers (ARBs), and beta-blockers (BBs). The degree of factual criticalness was set at a 2-followed alpha level <0.05. The examinations were performed with SAS adaptation 9.3 programming (SAS Institute, Cary, NC).

3 Results

3.1 Patient characteristics

An aggregate of 13,250 patients with a past filled with myocarditis and 13,250 solid controls without an earlier history of auxiliary coronary illness were recognized as the examination populace with a mean follow-up of 10.4 ± 2.94 years (interquartile run: 12, 10.19–12). The attributes of the examination populace are appeared in Table 1. The gauge qualities of the two populaces didn't altogether vary aside from the age wherein the patients with myocarditis were more youthful than the solid associate (myocarditis gathering, 43 ± 27 years of age versus sound accomplice, 44 ± 26 years of age, P < .01). What's more, the utilization of antihypertensive drugs, especially ACEis, ARBs, and BBs, were fundamentally more regular in the myocarditis bunch than in the solid partners (ACEi: 15.11% patients with myocarditis versus 0.01% sound associates, P < .001; ARB: 3.97% versus 0.02%, P < .001; BB: 16.96% versus 0.04%, P < .001).

3.2 Incidence of events

The patients with myocarditis had a higher occurrence of new beginning VT occasions than the sound controls (5.40% [519 per 100,000 man year] in myocarditis bunch versus 0.47% [43 per 100,000 man year] in solid controls; balanced HR: 16.06, 95% CI: 12.37–20.86; P < .001). Higher occurrences of CV demise (6.52% versus 3.18%; balanced HR: 2.42, 95% CI: 2.14–2.73; P < .001; Table 2) and all-cause mortality (24.5% versus 18.9%; balanced HR: 1.41, 95% CI: 1.33–1.49; P < .001) were additionally noted in the myocarditis bunch than the sound associate. The frequency of ICD implantations was additionally fundamentally higher in the myocarditis gathering (0.13% versus 0.02%; balanced HR: 12.07, 95% CI: 2.74–53.08, P < .001) than the solid control populace subsequent to changing for multivariate confounders including the sex, age, basic comorbidities, and drugs (Table 2).

3.3 Event-free survival

The Kaplan–Meier occasion free endurance bends for new-beginning VT occasions, CV demise, all-cause mortality, and ICD implantations contrasting patients and without myocarditis are appeared in Fig. 1A–D. There were critical contrasts in the new-beginning VT occasions, CV passing, and all-cause mortality between the two gatherings (Fig. 1A–C) with the myocarditis bunches indicating expanded new-beginning VT occasions and diminished endurance contrasted with the sound controls. Also, the general hazard for mortality (Fig. 1C) for the two gatherings was at first comparable (from record occasion up to catch up of 5 years). In any case, 5 years ahead throughout the development, the Kaplan–Meier bend showed a disparity in the endurance bend between the myocarditis gathering and sound controls, wherein the myocarditis bunch had a fundamentally expanded generally speaking mortality hazard (log rank P < .001), while the solid controls' mortality chance continued as before. The hazard for the ICD implantations was likewise essentially higher in the myocarditis bunch than in the solid controls during long haul development (log rank P < .001).

3.4 Predictors of the occurrence of ventricular arrhythmias

The qualities of the patients with myocarditis who grew new-beginning VT during the follow-up are appeared in Table 3. The individuals who created VT were for the most part guys (with VT, 55.30% versus without VT, 47.20%, P < .001), had DM (10.20% versus 7.17%, P = .01), CKD (2.51% versus 0.45%, P < .001), hyperlipidemia (14.30% versus 4.25%, P < .001), and an altogether lesser utilization of ACEis (4.05% versus 15.7%, P < .001), ARBs (2.23% versus 4.07%, P < .001), and BBs (4.89% versus 17.7%, P < .001). A multivariable Cox corresponding risk relapse examination uncovered that the free indicators that were fundamentally connected with new-beginning VT occasions in patients with a past filled with myocarditis had a more established age (balanced HR: 1.003, 95% CI: 1.00–1.006, P = .04), male sex (balanced HR: 1.33, 95% CI: 1.15–1.54, P < .001), nearness of DM (balanced HR: 1.40, 95% CI: 1.09–1.79, P = .01), CKD (balanced HR: 2.91, 95% CI: 1.81–4.68, P < .001), hyperlipidemia (balanced HR: 3.05, 95% CI: 2.46–3.78, P < .001), and lesser utilization of ACEis (balanced HR: 0.25, 95% CI: 0.17–0.37, P < .001), ARBs (balanced HR: 0.53, 95% CI: 0.32–0.88, P = .01), and BBs (balanced HR: 0.26, 95% CI: 0.19–0.37, P < .001).

4 Discussion

4.1 Main findings

The main findings of the study are as follows. First, from the national database, this study suggested a higher incidence of life-threatening VT, mortality, and ICD implantations during the very long-term follow-up in patients with a history of acute myocarditis, after adjusting for the multivariate confounders. Second, the predictors of new-onset of VT were a younger age, male gender, presence of DM, CKD, hyperlipidemia, and a lesser use of ACEis, ARBs, and BBs. Third, the concomitant use of ACEis, ARBs, and BBs may provide a protective role from life-threatening VT during the long-term follow-up in patients with a previous history of myocarditis.

4.2 Compared with the previous findings

Myocarditis adds to the worldwide weight of CV malady basically through unexpected heart demise and expanded cardiomyopathy. Exact populace based appraisals of the myocarditis occurrence and pervasiveness are not legitimately accessible in any world region.[8] The long haul line up concentrates in patients with intense myocarditis with saved left ventricle systolic capacity for the most part centered around recognizing the indicators of the advancement of expanded cardiomyopathy,[5] which is the most well-known long haul sequela.[9]

In this examination, we found that patients with a background marked by intense myocarditis had a 12-overlap increment in new-beginning VT during the exceptionally long haul follow-up contrasted with the solid populace without auxiliary coronary illness. This investigation likewise indicated that those with a background marked by myocarditis had a 2-crease and 1.33-overlay increment in the CV mortality and all-cause mortality, separately. The general endurance for the two gatherings was at first comparative as portrayed in the Kaplan–Meier bend (Fig. 1C). Nonetheless, throughout the development, especially 5 years forward, the endurance bend began to dynamically decrease in the myocarditis bunch with an altogether expanded danger of generally speaking mortality (25%) contrasted with the solid companion (19%). Past investigations have announced that intense myocarditis, however patients may at first present less ill,[4] causes significant mortality with a 21% 1-year death rate after the introduction of myocarditis.[5,9] These mortalities were because of ceaseless expanded cardiomyopathy auxiliary to an interminable myocardial incendiary procedure. Up until this point, no examination has had the option to show the drawn out generally speaking mortality chance for patients who have recouped from intense myocarditis with no obvious clinical CV sequelae. Our investigation demonstrated that those gatherings of patients have an essentially diminished long haul endurance. Regardless of whether mysterious tenacious irritation assumes a job in adding to the general long haul mortality in those patients, this qualification can't be made dependent on the clinical grounds alone; consequently, further investigation is suggested. Furthermore, this investigation indicated that these patients have a 3-crease expanded danger of ICD implantations with an altogether more noteworthy expanded mortality than in the sound accomplice. The patients who may have required essential counteraction for ICD implantations may show a higher CV mortality. In view of the Taiwan NHI, ICD implantations are shown distinctly for optional counteraction and not for essential avoidance of VT occasions. This might be one reason to clarify the high death rate in this examination. This investigation demonstrated that the VT may happen 5 to 10 years after the file occasion of myocarditis, and the auxiliary counteraction procedure may put these patients in danger for VT Events

4.3 Potential mechanism of VTs.

In spite of the fact that VT is an exceptional starting indication of myocarditis, it regularly creates during the long haul development, however hardly any investigations have announced this.[10] The component of VT might be ascribed to the incessant myocardial fiery procedure optional to pathogenic autoimmunity that may proceed significantly after myocardial recovery.[11,12] The instrument of arrhythmogenesis is by all accounts the arrangement of small scale reemergence circuits, supported by myocyte injury and substitution fibrosis[13] and activated action primarily due to the proarrhythmic impacts of cytokines which may proceed even without clear inflammation.[12] the earth encompassing the myocytes could likewise impact the electrophysiological properties of the myocardium, prompting the marvel known as electrical remodeling.[13] These progressions may totally or in part turn around after the recuperating of the incendiary procedure. In any case, the specific span and degree of this procedure are obscure see that the characteristic history of VTs in myocarditis has not been enough studied and documented.

4.4 Predictors of VTs

Besides, our investigation demonstrated that a more seasoned age, male sexual orientation, nearness of DM, CKD, hyperlipidemia, and lesser utilization of ACEis, ARBs, and BBs were recognized as free hazard factors for growing new-beginning VT in patients with a background marked by myocarditis in the long haul development. In our examination, 55% of patients with a background marked by myocarditis who had VT were men. In spite of the fact that the specific physiologic system that triggers this wonder isn't clear, all things considered, men have a more noteworthy affinity to ventricular arrhythmias than women.[14] Numerous investigations in everyone have called attention to that men experience a higher pace of ventricular arrhythmias and unexpected passing contrasted with women.[14] The distinctions in the electrophysiologic properties identified with sex hormones may, in any event to some extent, clarify the sexual orientation explicitness penchant to ventricular arrhythmias.[15]

DM,[16] CKD,[17] and hyperlipidemia[18] may separately or through and through cover to build the myocardial defenselessness to ventricular arrhythmias. Increments in the proinflammatory cytokines, fiery go betweens, and responsive oxygen species during the illness procedure effectsly affect the myocardium bringing about myocardial fibrosis. This gives an extra substrate to an expanded electrical flimsiness and unsettling influences in the repolarization.[19] Contrary as far as anyone is concerned that HTN is a hazard factor for unexpected heart passing brought about by ventricular tachycardia and fibrillation, our investigation demonstrated that the nearness of HTN in these gathering of patients have no huge prescient effect on the drawn out hazard for VT occasions. Be that as it may, the admission of antihypertensive meds endorsed for HTN in these patients, especially, ACEis, ARBs, and BBs may have given security from a drawn out hazard for VT occasions. Studies have indicated that the redesigning of the ventricle that frequently happens both in intense (i.e., myocarditis) and ceaseless (i.e., HTN and cardiomyopathy) clinical conditions[19] may proceed for quite a long time and years after the underlying affront, paying little mind to the etiology. This renovating can bring about an expansion in the powerlessness of creating ventricular arrhythmias. Past examinations have exhibited the job of a pharmacologic treatment, especially with ACEis, ARBs, aldosterone enemies, and BBs, in turning around or easing back down the maladaptive ventricular remodeling,[20] just as their job in the anticipation and treatment of ventricular arrhythmias. This may clarify the defensive job of these meds in our investigation patients.

The mix of an activating occasion and a defenseless myocardium has been advancing as an essential electrophysiological idea for the component of the commencement of a conceivably deadly arrhythmia. In any case, much is still to be clarified from the connection of the drawn out danger of ventricular tachycardia in myocarditis and these free hazard factors.

4.5 Clinical Implications

The normal history of myocarditis is as changed as its clinical introduction. The aftereffects of this investigation may have some significant clinical ramifications. Our discoveries propose that quite a long while after affirmation for myocarditis, expanding occasions of new-beginning VT and mortality could be seen in these patients. This infers firmly checked outpatient follow-up visits might be essential so as to give ideal administration systems to forestall the turn of events or control of DM, CKD, and hyperlipidemia, particularly among more youthful guys. Moreover, this examination additionally demonstrated the defensive job of ACEis, ARBs, and BBs in forestalling future VT occasions in those patients. Therefore, for persistent who has a background marked by myocarditis, these prescriptions might be endorsed to invert or hinder maladaptive ventricular renovating in these patients.[20]

4.6 Study limitations

The current investigation indicated the drawn out endurance contrast between patients with a past filled with myocarditis and the solid populace without basic coronary illness. In any case, there were a few constraints to our investigation. Initially, the analysis of myocarditis depended on the ICD-9 codes and was not additionally affirmed with endomyocardial biopsy results. In this manner, the indicative precision of myocarditis can't be completely settled. Second, our information did exclude all the different treatments that patients may have gotten over the 10-year follow-up period. We could just record for the utilization of ACEis, ARBs, and BBs in our examination populace. Finally, in spite of the fact that we balanced for confounders utilizing the Cox corresponding risk relapse investigation, the review idea of this examination constrains a portion of the ends that we can get from the information. Future investigations are prescribed to show the causality of the free indicators for new-beginning VT during the long haul line up in patients with a background marked by intense myocarditis.

5 Conclusion

As far as we could possibly know, the current examination speaks to the longest line up period in patients with a past filled with myocarditis. The aftereffects of this examination propose a higher occurrence of dangerous VT and mortality during a long haul line up in patients with a background marked by intense myocarditis. It likewise proposes that ACEis, ARBs, and BBs may assume a defensive job in forestalling future VT occasions in these patients. Along these lines, future work should concentrate on an inside and out hazard definition of VT in myocarditis patients.

Note: This work is partly presented at 31st European Heart and Heart Failure Congress June on 18-19, 2020 held at Paris, France

Peripartum cardiomyopathy, in itself, is a rare condition. Often undiagnosed early, most cases are those already with complications, usually in decompensated heart failure. The symptoms are not recognized promptly because of the close resemblance to the normal spectrum of pregnancy. In rare occasions, this form of cardiomyopathy can be the etiology of stroke.

A 33 year old female G5P4, known hyperthyroid, admitted in labor and delivered to a live baby boy, with no complications. On the 12th hour postpartum, noted sudden onset of right-sided body weakness. Imaging showed infarct of varying ages on the left frontal lobe. Suspecting a probable embolic origin, electrocardiogram revealed sinus tachycardia but 2D echocardiogram showed global hypokinesia with ejection fraction of 30%. During ICU stay, the patient had difficulty breathing with concomitant desaturations, associated with tachycardia. With a background of hyperthyroidism, thyroid storm was also entertained, thus, the debate regarding the etiology of heart failure secondary to thyrotoxic heart disease versus peripartum cardiomyopathy was raised. Currently, there are no related literature regarding the incidence of all entities occurring in the same setting. 

The case presented a gray area in stroke in the spectrum of pregnancy, peripartum cardiomyopathy and hyperthyroidism because the incidence of these in the same setting is rare. It is unfortunate that the patient already suffered the devastating consequence leading to morbidity on diagnosis. The importance of a high index of suspicion and prompt diagnosis are keys, as well as adherence to medications and patient education, to guide proper management and prevent complications.

Introduction

Peripartum cardiomyopathy (PPCM) is a rare cause of cardiomyopathy that occurs during late pregnancy or early postpartum periods. This condition can be life-threatening and is characterized by severe left ventricular dysfunction and heart failure. [1][2][3] [3]

PPCM is not a specific entity. In 2010 , the European Society for Cardiology identified PPCM as an idiopathic cardiomyopathy with the following characteristics:

• Development of heart failure towards the end of pregnancy or the postpartum period.
• Absence of another identifiable cause for heart failure.
• Left ventricular systolic dysfunction with left ventricle (LV) ejection fraction almost always less than 45 percent. The LV may or may not be extended.

Etiology

The etiology behind PPCM is as yet muddled. Connection with eclampsia and hypertension during pregnancy has been found. In any case, the fundamental component is muddled. Hazard factors for PPCM are African drop, age, pregnancy-related hypertension issue, multiparity, different developments, stoutness, constant hypertension, and delayed utilized of tocolytics. A few examinations have been proposed different theoretical instruments identified with the improvement of PPCM.[4][5] This will be clarified in the pathophysiology segment.

Epidemiology

The occurrence of PPCM is dubious, maybe due to the misdiagnosis of this character. In spite of this, the accessible data from various investigations has indicated that PPCM differs geologically. In the United States, the frequency has been accounted for to be as low as 1 case for each 4,000 live births in examination with the higher rate in Nigeria of 1 case in each 100 live births.

Ladies more established than 25 years with a mean age of 30 years were discovered bound to create PPCM. Other significant components identified with the nearness of PPCM incorporate hypertensive issue related with pregnancy, the nearness of iron deficiency, and African drop.

In the other hand, Hispanic ladies are the ethnicity with the least PCCM frequency. [6][7]

Pathophysiology

The etiology behind PPCM is as yet hazy yet is likely multifactorial. In the writing, potential factors that may add to the etiology of PPCM have been assessed.

Huge hemodynamic changes happen during pregnancy. There is an expansion in preload optional to the increment in red cell mass and blood volume. This likewise builds the cardiovascular yield by 20% to 30% because of an expansion in pulse and stroke volume by 15% to 25%. Every one of these progressions present during the first and second trimester, the second when the patient with basic coronary illness will create manifestations. Contrasted and PPCM, these side effects create during the peripartum. Consequently, it isn't evident that hemodynamic anxieties are the primary purpose behind PPCM.[8][7]

Different etiologies, for example, myocarditis has been speculated because of the nearness of viral genomes in biopsy of patients with PPCM as echovirus, Coxsackie, and parvovirus B19. An error among different investigations exists, and therefore, the explicitness of this discoveries is poor, and further examinations are essential.

Studies have improved our comprehension of the etiology of PPCM as the job of a harmful hormonal condition that produces in late pregnancy and the relationship with hereditary variables that can add to the advancement of PPCM.

Critical hormonal changes happen toward the finish of pregnancy. Prolactins levels increment during late pregnancy and in the puerperium stage. A few experts have been contemplating the impact of prolactin digestion in the mouse model of PPCM. One of these models had a knockout articulation of STAT3; a chemical was found in the myocardium of patients with end-stage cardiovascular breakdown auxiliary to PPCM. This catalyst shields the heart from receptive oxygen species that, when expanded, creates by a component not known the emission of a peptidase known as cathepsin D that cleavage prolactin into an angiostatic N-terminal 16 kDA prolactin section that advances apoptosis in endothelial cells and cardiomyocytes apoptosis.

Hereditary factors likewise have been involved in the etiology of PPCM. Proof of bunch of families with PPCM has been watched, and it is conceivable that the statement of the qualities with the harmful condition during late pregnancy because of oxidative pressure can expand the weakness of PPCM. A few investigations have recognized transformations in certain patients with PPCM.

A professional fiery state may assume a job in the advancement of PPCM. Expanded degrees of cytokines, for example, TNF-alpha and interleukin-6 have been found in patients with PPCM and cardiovascular breakdown.

Worry for an immune system reaction as a potential reason for PPCM has been depicted, particularly on the grounds that elevated levels of antibodies against certain heart tissue could be the reason immune system myocarditis as the etiology behind PPCM. The proof supporting this hypothesis depends on another hypothesis that depicted changes in the resistant arrangement of the mother during pregnancy (immunosuppression) driving the mother's body presented to antigens from the baby that can cause age of an insusceptible reaction after pregnancy when the invulnerable framework recuperates.

Histopathology

In heart examples found in the post-mortem examination of ladies with a past filled with PPCM, seems, by all accounts, to be pale, heavier and enlarged. In the hearts with cardiovascular brokenness, variable nearness of wall painting thrombi has been found. Inside the heart, the valves look ordinary and the coronary vessels are patent more often than not except if know history of ischemia exists. Pericardial emission is once in a while found. In the minute perspective on the heart, proof of interstitial edema and cell expanding, fibrosis, and hypertrophy is every now and again found in the myocardium with frequently territories of bounteous assortment of eosinophils.

Expanded the quantity of glycogen and mitochondrias is generally found in myocardial cells assessed with electron microscopy.

History and Physical

PPCM will introduce following 36 weeks of development, and most of cases is found in the main month after conveyance. A prior introduction can happen in patients with fundamental heart comorbidities as valvular or ischemic cardiomyopathy.

Introduction of PPCM can change contingent upon the level of the sickness right now of introduction. Indications identified with cardiovascular breakdown and identified with pregnancy are paroxysmal nighttime dyspnea, pedal edema, orthopnea, and dyspnea on effort. Different manifestations incorporated a dry hack, palpitations, increment of stomach circumference, dazedness, and chest torment.

Discoveries in the physical test like jugular venous expansions, uprooted apical motivation, third heart sound, and mitral spewing forth mumbles are normal.

Evaluation

The analysis of PPCM requires a high list of doubt dependent on the three clinical measures since manifestations are like those identified with physiopathologic changes auxiliary to pregnancy. PPCM is a conclusion of rejection, and point by point examination is required to preclude other progressively regular reasons for cardiomyopathy. [1][9]

Beginning assessment comprises of routine blood work to assess for different reasons for those side effects, for example, iron deficiency, electrolyte variations from the norm, endocrine conditions as thyroid brokenness, and renal or liver brokenness. Height of cerebrum natriuretic peptide (BNP) is usually discovered raised in patients with cardiovascular breakdown and patients with PPCM.

Radiography of the chest can be a piece of the underlying assessment, indicating cardiomegaly as well as aspiratory edema. These discoveries are vague for PPCM yet reminiscent of cardiovascular breakdown.

Cardiovascular examinations, for example, an electrocardiogram and echocardiogram are a piece of the underlying assessment.

Electrocardiographic discoveries can be vague. The regular discoveries are sinus tachycardia, supraventricular tachycardia (counting atrial fibrillation or vacillate), and every so often ventricular tachycardia. ST portion and T wave irregularities have been accounted for yet are vague. Widening of chambers by electrocardiogram can be available as well. In spite of this vague discoveries, QRS prolongation of more prominent than 120 milliseconds is identified with expanded mortality in patients with PPCM. Echocardiography is the principle study to assess the life systems and usefulness of the heart in patients with suspected PPCM. Assessment of the left ventricular launch portion (LVEF) is critical to preclude PPCM, as a feature of the standards requires a LVEF under 45%. Echocardiography additionally assesses for different reasons for cardiovascular breakdown such valvular maladies or some other auxiliary variations from the norm. Expansion of the ventricles and chambers can be available, and LV blood clot or atrial apoplexy can be found.

Further cardiovascular testing should be possible with heart MRI; this methodology can assist with diagnosing different reasons for cardiovascular breakdown not related with PPCM and can decide the volume of the chambers and ventricular capacity in a more exact manner than echocardiography. A further job of cardiovascular MRI in PPCM is to be resolved.

Heart catheterization is just for chosen patients. Left heart catheterization is shown in patients with doubt of ischemic cardiomyopathy. Right heart catheterization is less every now and again utilized for the assessment of PPCM. Echocardiographic boundaries for chamber weight can be utilized at first, and if further evaluation is fundamental or patient disease is extreme and progressively precise estimation is required, a correct heart catheterization can help with these circumstances.

Endomyocardial biopsy isn't prescribed and is for the most part used to assess for infiltrative maladies that can be causing the bombing heart.

Right now, there is a particular test for finding of PPCM.

Treatment / Management

The underlying clinical administration of PPCM is like different reasons for cardiovascular breakdown with the uncommon regard for how the condition can influence the pregnancy. Extra remedial contemplations for this populace may incorporate arrhythmia the executives, anticoagulation treatment, mechanical help, and investigational therapies.[10][11][12]

As a feature of the objective of treatment for patients with PPCM, enhancing the preload or volume status is done through suitable diuresis and keeping an equalization of intra-and extravascular volume. Liquid limitation is basic to accomplish this objective. Prepartum PCCM has unique contemplations for treatment because of reactions of prescription that may cross the placenta and influence the baby. For instance, utilization of diuretics during pregnancy ought to be done cautiously and in exceptionally low portions as they may hinder perfusion of the placenta and cause likely damage to the hatchling. Both hydrochlorothiazide and furosemide are sheltered during pregnancy and lactation, with close observing for diuresis and at low dosages. Deficient information exist about potassium-saving diuretics for PPCM during pregnancy.

Angiotensin-changing over protein (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are contraindicated during pregnancy because of the notable teratogenic impacts whenever administrated during pregnancy. Both of these drugs can be utilized after conveyance, yet breastfeeding is contraindicated.

Beta-blockers can be utilized with alert during pregnancy (beta-1 particular specialists are liked) and are contraindicated during breastfeeding in light of the fact that this is discharged in the breastmilk. Carvedilol is a joined beta-blocker with an extra alpha-barricade impact that permits a diminishing of the afterload and is compelling in the treatment of PPCM.

Hydralazine, a vasodilator, is sheltered during pregnancy. A nitroglycerin dribble can be utilized to oversee afterload in the intense setting. Nitroprusside is contraindicated during pregnancy for worry of cyanide's harmfulness.

In sick patients with hemodynamic flimsiness, the utilization of inotropes may be fundamental. Utilization of inotropes, for example, dobutamine, dopamine, and milrinone is limited for this basic circumstance with close checking and with quick weaning off prescription if conceivable.

Digoxin is another medication that can be utilized for the treatment of PPCM. It is protected during pregnancy and can be utilized when the ionotropic and chronotropic impact is fundamental, particularly in the setting of uncontrolled atrial fibrillation.

Anticoagulation treatment in patients with PPCM is dubious. As a general suggestion, patients with PPCM without LV clots or atrial fibrillation ought not be in anticoagulation. Patients with PPCM and atrial fibrillation as well as LV blood clot ought to be anticoagulated as indicated by the rules for anticoagulation and the trimester of pregnancy.

Choices in regards to the utilization of an implantable cardioverter defibrillator (ICD) and heart resynchronization treatment in patients with PPCM ought to think about the characteristic history of these ailments, including the potential for the recuperation of ventricular capacity.

Utilization of mechanical circulatory help has been depicting in patients with fulminant PPCM. Position of left ventricular colleague gadget (LVAD) can be a scaffold for transplant or recuperation.

Trial meds, for example, pentoxifylline, bromocriptine, IVIG, and immunosuppression are still under scrutiny, and vague suggestions exist for these medications.

Differential Diagnosis

PPCM is an exclusion diagnosis. It is necessary to evaluate other causes of heart failure. Pregnancy valves or pre-existing cardiomyopathies that decompensate with pregnancy-related hemodynamic changes, and more symptoms can be seen later in pregnancy.

Prognosis

Recuperation regularly happens three to a half year baby blues however has been portrayed until four years after conveyance.

Good Prognosis Factors

A few elements are related with acceptable anticipation, these include:

Little LV diastolic measurement (under 5.5cm)

LVEF more prominent than 30% to 35% and fractioning of shortening more noteworthy than 20% at the hour of analysis

The nonattendance of troponin rise

The nonattendance of LV blood clot

Non-African American ethnicity

Poor Prognosis Factors

The accompanying components may demonstrate a poor anticipation:

QRS more prominent than 120 milliseconds

Deferred finding

High NYHA class

Multiparity

African plunge

Repeat of PPCM in resulting pregnancies is raised, and the patient ought to be exhorted against further pregnancies and observed intently.

Complications

Maternal complications

Thromboembolism

Arrhythmias

Progressive heart failure

Misdiagnosis as pre-eclampsia

Fetal complications

Fetal distress from hypoxia

Consultations

Anesthesiologist

Internist

High-risk obstetrician

Perinatologist

Deterrence and Patient Education

Patients should be provided with information on the potential for adverse effects during pregnancy. Most patients blame the physician for presenting cardiomyopathy without prior knowledge.

Enhancing Healthcare Team Outcomes

Peripartum cardiomyopathy is an uncommon however intense confusion. The general anticipation relies upon the launch division. Around 50-70% of patients have progressive improvement in ventricular capacity and manifestations by a half year. Be that as it may, embolic occasions convey a mortality of 30%. For ladies who endure, a subsequent pregnancy ought not be attempted if the discharge part is low. Before a subsequent pregnancy, the female ought to be altogether animated with a reverberation or a pressure test. Indeed, even patients with a total recuperation ought to be cautioned that the condition can repeat once more. The planning of conveyance and the executives require an interprofessional approach and individualization of the patient. [13][14] (Level V)

The job of the obstetric medical attendant is basic. These patients need an exhaustive training regarding the matter with the goal that they have practical desires. Most patients never think about that as a pregnancy will be unfavorably influenced, and when cardiomyopathy happens, the patient as well as the family generally accuse the medicinal services suppliers for absence of data.

Throughout the years, numerous rules have opened up on the determination and the executives of peripartum cardiomyopathy. Accordingly, all human services laborers who care for these patients must be all around educated about the treatment. [15][16](Level V)

Outcomes

Ladies with a negligible abatement in discharge part will in general have a decent visualization, yet those with a poor launch division have a high danger of death. What's more, any female who requires a help gadget will in general have antagonistic occasions and a low endurance. A heart transplant isn't generally an alternative in light of an absence of contributors. Much of the time, while the pregnant female may endure, the baby may not. Given this dismal measurements, all human services laborers ought to instruct the patient and family about the confusion and its results. [17][18] (level III)

Note: This work is partly presented at 31st European Heart and Heart Failure Congress June on 18-19, 2020 held at Paris, France

Background:

Patients with congestive heart failure (CHF) are at an increased risk of developing ventricular tachycardia (VT). It is unclear how VT ablation affects CHF outcomes.

Objective:

The goal of this study is to evaluate CHF exacerbations and echocardiogram findings based on location of myocardial scar in patients with Ischemic Cardiomyopathy (ICM) who have undergone VT ablation.

Methods:

This was a selected cohort of consecutive patients with ICM who underwent VT ablation at Minneapolis Veterans Affairs Health Care System between July 2008 and September 2019. CHF outcomes and echocardiogram variables were assessed.

Results:

Seventy-five patients with ICM underwent VT ablation, average age was 67.6 ± 7 years old and 100% male. Inferior wall scar (IWS) was the most prevalent (Figure, Table 1A). On pre-ablation echocardiogram, anterior wall scar (AWS) group overall had a lower mean ejection fraction (EF) of 26%, compared to IWS group of 32% (Table 1B). On post-ablation echocardiogram, patients with AWS had statistically significant (p < 0.03, two-tailed test) lower mean EF of 23% compared to IWS group of 30% (Table 1C). Twenty-five patients had admissions for CHF exacerbation post-ablation, 17 were in the first year after ablation (12 IWS and 5 AWS). Average time from ablation to CHF exacerbation was 2.1 years. Patients with IWS presented earlier with CHF exacerbation compared to AWS group (1.6 vs 1.8 years).

Conclusion:

Patients with ICM and AWS scar had a statistically significant mean lower EF post VT ablation compared to IWS scar group. However, patients with IWS scar had higher rates of admission for CHF exacerbation.

1. Introduction

Sustained ventricular tachyarrhythmia continues to be a significant cause of morbidity and mortality in patients with ischemic cardiomyopathy (ICM) [1]. The placement of implantable cardioverter defibrillator (ICD) is proven to reduce the rates of sudden death and mortality in patients with ICM and reduced ejection fraction [2]. However, the ICD has no effect on the incidence or recurrence of the events. Recurrent ventricular tachyarrhythmias can lead to recurrent shocks and re-hospitalizations, and were proven to be associated with worse overall outcomes [3, 4, 5, 6].

Catheter removal plans to forestall repeat of ventricular tachycardia (VT), in this way in principle, diminishing repetitive ICD stuns and along these lines the requirement for long haul utilization of conceivably harmful antiarrhythmic specialists. Be that as it may, critical debate keeps on existing in regards to its adequacy in patients with ICM. We played out a meta-examination of the accessible randomized clinical preliminaries (RCTs) to think about the job of catheter removal versus customary administration for VT in patients with ICM and ICD implantation.

2. Methods

2.1 Search strategy and study selection

An efficient audit of PubMed, MEDLINE, and Cochrane Central Register of Controlled Trials was performed from January 1990 until to December 2016, with no language limitation, as indicated by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) rules [7]. We utilized the watchwords "ventricular tachycardia"; "ischemic"; "cardiomyopathy"; and "removal" independently and in mix. After qualified examinations were recovered, we screened their lists of sources for any potential missed investigations through the underlying inquiry. Besides, earlier meta-examinations were audited to guarantee the consideration of every single qualified investigation. Studies qualified for consideration were randomized controlled preliminaries contrasting catheter removal versus regular administration (control gathering) for VT in patients with ICM and ICD.

2.2 Data extraction

Two autonomous creators (A.A. furthermore, R.N.) removed complete information on study attributes, patients' socioeconomics, and quality appraisal information. The quantities of occasions for results of enthusiasm for the 2 arms were arranged. The removed information were overhauled by a third creator (M.S.) to guarantee precision. Inconsistencies were settled by agreement among all the creators.

2.3 Assessment of quality and bias

The nature of the included preliminaries and the danger of inclination were evaluated by 2 autonomous analysts (W.M. also, M.S.) utilizing the segments suggested by the Cochrane Collaboration [8], including irregular arrangement age, allotment covering, blinding of members and work force, blinding of result appraisal, deficient result information, specific detailing and different wellsprings of predisposition. Preliminaries were viewed as low potential for inclination if having <2 high-chance parts, and high potential for predisposition if having >4 high-chance segments. The general nature of proof for every result was additionally surveyed utilizing the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) instrument suggested by the Cochrane Handbook for Systematic Reviews of Interventions [8].

2.4 Outcomes

The fundamental result of intrigue surveyed by the present examination was all-cause mortality. Different results of intrigue were cardiovascular mortality; cardiovascular-related hospitalization; VT storm (characterized as at least 3 ICD stuns in a 24 hours period in SMASH-VT and at least 3 in VT scenes in a 24 hours period in VTACH and VANISH); and ICD stuns. Results were accounted for at the longest development

2.5 Statistical analysis

This meta-investigation was performed with a goal to-treat approach. Spellbinding investigations were performed utilizing weighted methods with standard deviations (SD) for consistent factors, and weighted frequencies for straight out factors. The weighted mean follow-up span of every result was determined, utilizing the example size of every preliminary as its weight. We determined the evaluated chance proportions (RR) for the whole result utilizing irregular impact DerSimonian and Laird's model [9]. We likewise played out an affectability investigation fixed-impacts rundown chances proportions (OR) utilizing Peto model [10]. Higgins I2 test [11] was utilized to survey for heterogeneity; where low heterogeneity characterized as I2 < 25%, and high heterogeneity as I2 > 50%. All the p-values were 2-followed with factual essentialness at 0.05. Distribution inclination was determined utilizing the Egger technique [12]. Irregular impact converse difference weighted frequency with 95% certainty stretches (CI) was determined for every result utilizing STATA Metaprop programming. Every single measurable examination were led utilizing STATA 14 (STATA Corporation; College Station, Texas).

3. Results

There were 370 papers in our initial online database scan. Five RCTs met our eligibility requirements for further screening. On a thorough analysis, one RCT [13] was omitted as only an abstract was published and the key outcome of our concern was not stated. Therefore, 4 RCTs [14 , 15, 16, 17] with a total of 521 patients (VT ablation group n = 261; and control group n = 260) were included in the study (Fig.1). A total of 24 patients (9%) were confirmed to have progressed from control to ablation at the end of the follow-up period. The weighted mean age was 66.4 ± 1.7 years in the ablation group , compared to 66.4 ± 2.7 years in the control group, 31.7 ± 10.3 vs 31.9 ± 9.9 for the ejection fraction, and 90.4 per cent vs 91.5 per cent for the beta blocker category. The majority of the included populations were male (95.3 ± 3.6 per cent in the ablation group versus 87.7 ± 5.3 per cent in the control group; p = 0.06). The weighted mean hypertension rate was 70.6 ± 2.1 per cent in the ablation group versus 66.1 ± 21.7 per cent in the control group, while 37.3 ± 9.01 per cent for diabetes mellitus vs 42.2 ± 14.8 per cent in the control group. There were no major variations between the variables listed above.

3.1 Quality and risk of bias of the included trials

According to the Cochrane Collaboration method, both trials were found to be at low risk of bias. The consistency of the evidence for results was further assessed using the GRADE evaluation method and the level of high quality of evidence for all outcomes was achieved. The standard of the included trials is summarized in Supplementary Tables 1 and 2. No reporting bias was found in all outcomes (p = 0.88, 0.68, 0.96, 0.45; and 0.08 for all-cause mortality, cardiovascular mortality, cardiovascular hospitalization, VT earthquake, and ICD shocks, respectively).

3.2 Outcomes

The weighted incidence of mortality was 15 percent (95 percent CI 5–25) in the VT ablation group compared to 17 percent (95 percent CI 6–27) in the control group. At a weighted mean follow-up period of 17.5 ± 8.4 months, VT ablation was correlated with a comparable risk of all-cause mortality (RR 0.94, 95 percent CI, 0.66–1.32, p = 0.70; I2 = 0 percent); and cardiovascular mortality (RR 0.82, 95 % CI, 0.52–1.29, p = 0.39; I2 = 0 per cent) relative to the non-ablation (medical treatment only) category (Fig . 2). However, patients with VT catheter ablation reported less cardiovascular hospitalization (RR 0.72, 95 per cent CI, 0.54–0.96, p = 0.02; I2 = 0 per cent), less VT storm (RR 0.71, 95 per cent CI, 0.52–0.97, p = 0.03; I2 = 0 per cent) and a decreased chance of ICD shock (RR 0.59, 95 per cent CI, 0.34–1.05, p = 0.07; I2 = 72 per cent) compared to the control group (Fig . 3). The mortality rate for the first 30 days after ablation or as specifically linked to the ablation procedure was 0 per cent. Nevertheless, if we consider the two deaths recorded in the ablation arm in the first 6 months of the CALYPSO analysis but not defined as a direct risk of the ablation procedure, this would be 0.8%. No stroke and only one transient ischemic attack (0.4%) was identified as a complication of the ablation procedure.

4. Discussion

In the latest meta-analysis of 4 RCTs with a total of 521 participants, it has been shown that VT catheter ablation in participants with ICM and ICD is associated with a reduced risk of cardiovascular hospitalization, induced by a substantial reduction in VT storm and ICD shock relative to traditional medical care. There was no evidence of superiority in all-cause or cardiovascular mortality between the two groups. It is very important to note that the enrolment criteria in the four studies may not be representative of actual word practice where patients usually have VT ablation for a VT storm or frequent ICD shock and have failed to tolerate the maximum dose of antiarrhythmic drugs. 

Ventricular tachycardia is a potentially fatal tachyarrhythmia that occurs mainly in patients with ICM due to re-entry of partly scarred ventricular myocardium. After the implementation of ICD in 1980[18], multiple studies have shown the mortality advantage of ICD implantation in patients with a history of ICM for primary prevention. It is also one of the recommended treatments for such populations according to the existing guidelines[19]. After ICD placement, recurrences of VT treated with ICD shocks are not uncommon and approximately one of every three patients will receive sufficient shocks for ventricular arrhythmia within 5 years of implantation[20]. Previous studies have shown that ICD shocks are linked to increased risk of hospitalization, heart failure, death and poor quality of life[3,4,21,22]. As a consequence, monitoring of repeated VT storms and ICD shocks after ICD implantation has gained attention over the years through either medical treatment and escalating antiarrhythmic drugs or catheter ablation. Both approaches have been correlated with a positive reduction in VT recurrence in multiple studies and mortality in a few others[15,17,23, 24, 25 , 26]. However, current guidelines recommend catheter ablation of VT in patients with recurrent arrhythmia despite appropriate conventional therapy [27, 28, 29]; data supporting these guidelines were mainly derived from observational studies. In the current meta-analysis, the aim was to analyze the available evidence to compare all approaches, using only RCTs, in order to reduce the possibility of bias associated with observational studies. Only 4 RCTs were identified which compared the two strategies as detailed in Fig. 1 and no clinical trials comparing the two treatments in patients with ischemic cardiomyopathy.

It is worth noting that there were low overall serious complications in the ablation arm. (Table 1)

The 30-day mortality rate directly associated with the VT ablation procedure was zero. Two deaths were reported in the ablation arm of the CALYPSO study in the first 6 months post-ablation, but were not identified as a direct risk of the ablation procedure. Including this yields a mortality rate of 0.8 per cent, far lower than the recorded 5 per cent early mortality rate (within 30 days) in the latest retrospective analysis of 2061 patients with systemic heart disease who underwent VT ablation trial [31]. In such trials, this disparity may be due to the sicker patient population. No symptomatic stroke and only one symptomatic transient ischemic attack (0.4 per cent) have been identified. Post-procedural procedures for anticoagulation were somewhat different between research involving the use of aspirin vs. warfarin and different durations for use of aspirin or warfarin, which typically represent recommendations for anticoagulation after VT ablation in patients of structural heart disease[27].

In the Ventricular Tachycardia Ablation in Coronary Heart Disease (VTACH) research, after 2 years of follow-up, survival free from VT or ventricular fibrillation (VF) was 47% in the ablation community, significantly higher than the control group of 29% (p=0.045), whereas in the SMASH-VT trial, patients in the ablation arm had substantially lower ICD shocks and anti-tachycardia rate relative to the control group (12 % vs 33 %).

The latest Ventricular Tachycardia Ablation versus Escalation of Antiarrhythmic Drugs "VANISH" trial, the largest on the subject to date, was a multicenter study that randomized 259 patients to either ablation versus escalating antiarrhythmic drugs and observed a substantial reduction in the primary composite outcome of death, VT storm and ICD shocks (59.1% in the ablation group vs 68.5% in the escalated therapy group) [14]. Although benefits were seen in the ablation group, the event rate was high in both groups reflecting this high-risk population with an overall well-guarded prognosis. This study did not demonstrate a substantial decrease in hospital admission for cardiac conditions with ablation compared to antiarrhythmic drug therapy (p = 0.25). However, our study has shown that the reduction of VT storm and ICD shocks in the pooled population has resulted in a reduction in cardiovascular hospitalization, indicating a potential benefit in improving quality of life as well as lower health care costs. However, additional studies are needed to address these issues, as potential savings from reduced hospitalizations may be offset by procedural costs. In the VANISH trial, two subgroups tended to benefit more from ablation than the majority of the randomized population in terms of primary outcome: patients on baseline amiodarone relative to non-amiodarone, and patients with dual-chamber ICD compared to single-chamber ICD, with p values for interaction 0.03 and 0.10, respectively. Due to data limitations, we were unable to conduct subgroup analyzes to validate the advantages of these subgroups. Only the SMASH-VT trial reported subgroup analysis by type of ICD and did not show any difference in outcome between single and dual chamber ICDs. It is also important to note that in the VANISH study, all-cause mortality remained high in both groups at a mean follow-up of 27.9 months, with little disparity between ablation and medical treatment groups (27.3 per cent vs. 27.6 per cent). Compared to Patel et al.'s meta-analysis, the reduction in VT storms, ICD shocks and cardiovascular hospitalization that we reported in this study is new [32]. That being said, we were also unable to demonstrate a mortality benefit between the ablation and conventional therapy groups, despite having nearly double the patient number from the previous meta-analysis. It illustrates the lack of adequate care to date for this high-risk patient population. Neither cardiac mortality nor all-cause mortality was different between groups in our current study. VT ablation may have decreased cardiac mortality due to ventricular arrhythmia but did not affect overall cardiac mortality due to heart failure in these high-risk patients. It is also possible that studies conducted to date are undervalued in order to demonstrate a mortality benefit with ablation therapy. As a result, larger randomized trials capable of showing differences in hard clinical outcomes are needed to shed more light on the relative benefits of ablation therapy versus medical management in patients with ICM. Furthermore, whether or not VT ablation in real-life experience can minimize mortality can not be inferred from the VT ablation studies.

5. Limitations

This study was not based on patient-level data, which precludes more robust analysis. Although only randomized trials of the highly selected population were included in this analysis, they had different protocols and inclusion criteria as indicated in the Results section. Operator experience and success rates may have played a role that is not taken into account. The majority of patients were male. The total small number of patients comparing antiarrhythmic drugs to initial VT ablation therapy with short duration of follow-up was included in the analysis. Various approaches have been used for VT ablation between clinical VT ablation studies and mapping VT only versus substrate modification (Table 1) which may lead to different success rates[33]. Current studies did not address the quality of life of patients after VT ablation compared to medical therapy alone.

6. Conclusions:

Ablation of ventricular tachycardia in patients with ICM has been associated with a lower risk of cardiovascular hospitalization, VT storms and ICD shocks compared to medical management and no ablation. Mortality and ablation-related stroke rates were very low. Mortality remained identical in both categories, however.

Note: This work is partly presented at 31st European Heart and Heart Failure Congress June on 18-19, 2020 held at Paris, France

Rheumatic heart disease is one of the most common heart diseases in developing country. One of the most common complications of Rheumatic Heart Disease is Mitral Stenosis which ultimately lead to pulmonary hypertension and heart failure and death. So, PTMC (Percutaneous Transluminal Mitral Commissurotomy) is a well established simple, effective and safe  therapeutic intervention for mitral stenosis.

While many literatures reviewed till date have shown that it takes 3-6 months time period for the reduction of pulmonary artery pressure after PTMC, this study is designed to see the result in pulmonary artery pressure immediately after  procedure.

Method

Total 42 patients with Rheumatic Mitral Stenosis in Cath Lab under Department of Cardiology of Chitwan Medical College from October 1 2018 to August 30 2019 were included in the study. Pulmonary artery pressure was assessed by Right heart catheterization by using multipurpose /pigtail catheter under conscious sedation.

Results

It is a prospective observational study on a total of 42 patients who underwent PTMC, 30 were female and 12 were male. Age ranged from 30 to 61 years with the mean age of 45.36±10 years. The mean mitral valve area increased from 0.87±0.2 cm2 to 1.74±0.17 cm2 whereas Mean Pressure Gradient decreased from 13.59± 7.30 mmHg to 5.15±30 mmHg. Mean Pulmonary Artery Pressure decreased from 41.50 ±16.00 mmHg to 33.50±12.00 mmHg. Similarly, the mean left atrial pressure decreased from 26.57±8.62 mmHg to 15.50±5.95 mmHg whereas, the mean Aortic Pressure increased from 91.43 ±23.02 mmHg  to  98.29±24.92 mmHg . Eighteen (42.85%) patients had an increase in MR by 2 grades but there is no need of immediate mitral valve replacement. During procedure, paroxysmal PSVT was noted in six (14.285%) patients and also local hematoma was observed in five (11.90%) patients.

Conclusion

There is reduction in pulmonary artery pressure immediately post PTMC which is directly correlated with left atrial pressure without significant MR and tachycardia.

This study is limited in terms of single center with small sample size.

Keywords

Atrial electromechanical delayMitral stenosisP-wave dispersionPercutaneous transvenous mitral commissurotomy.

Introduction

Rheumatic mitral stenosis (MS) is a gained dynamic type of valvular coronary illness, portrayed by diffuse thickening of mitral valve pamphlets, combination of commissures and shortening and combination of chordae tendinae. The mix of mitral valve malady and atrial aggravation, auxiliary to rheumatic carditis prompts left atrial (LA) expansion, fibrosis of atrial divider, and disorder of atrial muscle bundles.¹ These basic changes lead to electrical inhomogeneity, non-uniform conduction speeds, and inhomogenous unmanageable periods inside the atrial myocardium.^{2, 3} The resultant electrical dyssynchrony and electromechanical brokenness are related with expanded danger of atrial fibrillation (AF).⁴

A few electrocardiographic and echocardiographic markers mirroring the electrophysiological and electromechanical variations from the norm of atria inclined to create AF have been concentrated with a thought of early distinguishing proof of patients who are vulnerable to create AF. Expanded most extreme P-wave span (Pmax) on surface ECG has been accounted for to be related with left atrial size and danger of creating AF^{.5, 6} P-wave scattering (PWD) is an ECG marker of non-uniform and heterogeneous atrial conduction with ECG leads of various orientation.5 It has been characterized as the distinction among greatest and least P-wave length (Pmax and Pmin). Past examinations have indicated that Pmax and PWD are expanded in patients with rheumatic MS^{.7, 8}

Atrial electromechanical deferral (AEMD) has been characterized as the transient postponement between the identified beginning of electrical action (P-wave on ECG) and the acknowledgment of power in the atrial myocardium (beginning of A′ wave on tissue Doppler imaging (TDI).9 Advances in TDI innovation have encouraged the discovery of atrial mechanical action from various atrial districts with high worldly goals and permitted computation of between and intra-atrial electromechanical delays.^{10, 11, 12} Prolonged AEMD is considered as a novel marker of atrial electromechanical rebuilding and has been related with expanded AF chance in different illness states including MS.^{9, 13, 14, 15}

Percutaneous transvenous mitral commissurotomy (PTMC) is at present the treatment of decision for patients with indicative serious MS and ideal valve morphology. Fruitful PTMC prompts increment in mitral valve zone (MVA), cardiovascular list, and lessening in transmitral diastolic weight inclination, left atrial weight, left atrial volume, and aspiratory supply route pressures.^{16, 17} It likewise prompts continued improvement in the practical class of the patients.^{18, 19} Recent examinations have exhibited that decrease in left atrial weight and help of ceaseless stretch after PTMC turns around left atrial heading subordinate conduction variations from the norm, along these lines expanding the odds of MS patients holding their typical sinus rhythm.^{20, 21, 22} This investigation was led with a point of contemplating the quick impact of effective PTMC on between and intra-atrial electromechanical deferrals and PWD in patients with extreme rheumatic MS, in ordinary sinus cadence. As far as we could possibly know, there is just a single such investigation distributed in writing so far.²³

2. Methods

2.1. Study design                                                                                                  

This was a hospital-based prospective, non-randomized, observational study.

2.2. Study population

The examination populace included 25 continuous patients conceded in our emergency clinic with suggestive extreme MS [NYHA class II–IV, MVA of ≤1 cm2 by planimetry, pressure half time (PHT) ≥ 220 ms, as well as mean transmitral diastolic slope (MDG) of ≥10 mmHg],^{24, 25, 26} in typical sinus beat, with ideal valve morphology (Wilkins' score ≤ 8, no or mellow mitral spewing forth, and no commissural calcification or LA thrombus)27, ²⁸ who experienced a fruitful PTMC (quick post-procedural MVA of ≥1.5 cm2 or ≥50% expansion from pre-procedural MVA, and close to direct mitral disgorging after the procedure).^{29, 30} Exclusion models included: (I) Documented history or peri-procedural event of AF or some other supported arrhythmia. (ii) Significant contribution of valves other than mitral valve (aortic valve, aspiratory valve, tricuspid valve) or proof of mitral annular calcification on echocardiography. (iii) Known history or clinical proof of coronary supply route ailment, essential cardiomyopathy, left ventricular (LV) brokenness, conduction variations from the norm, pericarditis, thyroid brokenness, iron deficiency, renal disappointment (serum creatinine of >1.5 mg/dl), pneumonic illness, hypertensive cardiovascular sickness, fundamental fiery malady. (iv) Exposure to any known cardiotoxin (for example doxorubicin chemotherapy, ethanol, and so forth.), electrolyte unevenness, utilization of drugs known to influence atrial conduction (for example digitalis, antiarrythmic medications), and patients on pacemakers. (v) Clinical or lab proof of rheumatic movement in going before a half year. (vi) Indiscernible P-waves in multiple leads on the pattern 12-lead ECG. (vii) Past history of any mitral valve mediation (PTMC, shut mitral valvotomy, open mitral valvotomy) or other heart medical procedures.

2.3. Consent and ethical issues

After describing the analysis in depth, informed consent was obtained from each patient. The report was completed by the Committee on Institutional Ethics.

2.4. Pre-procedural evaluation

A detailed clinical history was collected and a thorough physical examination of each patient was conducted upon admission. Baseline tests, including full blood count, serum biochemistry, coagulation profile, serum electrolytes, and chest X-ray, were conducted one day prior to the operation.

2.5. Electrocardiogram (ECG)

On the morning of the day of technique, a 12-lead surface ECG of every patient in recumbent situation at a paper speed of 50 mm/s and 20 mm/mV was gotten to figure the pre-procedural P-wave terms and PWD. The P-wave terms were estimated physically, by an examiner blinded to the clinical subtleties of the patient, utilizing calipers and amplifying focal point (ten times amplification) to characterize the electrocardiographic redirections. The beginning of the P-wave was characterized as the intersection between the isoelectric line and the start of P-wave diversion. The counterbalance of P-wave was characterized as the intersection between the finish of the P-wave avoidance and the isoelectric line. The time inward between the beginning and counterbalance of P-wave was the P-wave term. In every ECG lead, P-wave term was estimated for three back to back P-waves and the mean of three estimations was viewed as the P-wave length of that lead. P-wave span was estimated in each of the 12-ECG leads. Patients with confused P-waves in multiple leads on the pattern 12-lead ECG were rejected from the examination. The longest P-wave length estimated on any of the 12 ECG leads was characterized as the P most extreme (Pmax) and the briefest P-wave span on any lead was characterized as the P least (Pmin). The contrast among Pmax and Pmin was determined and characterized as PWD = Pmax − Pmin. After 24–48 h of the effective PTMC strategy, a comparable ECG was acquired to figure the post-procedural Pmax, Pmin, and PWD.

2.6. Echocardiography

A far reaching pre-procedural echocardiographic assessment of every patient was done in the first part of the day of the day of technique, utilizing an industrially accessible heart ultrasound scanner furnished with 2.5 and 3.5 MHz transducers (Aloka, Prosound, SSD α-110, South Korea), by an accomplished cardiologist who was blinded to the clinical subtleties and aftereffects of different examinations of the patient. Every patient was inspected in the left parallel decubitus and prostrate situation by precordial 2-dimensional, M-mode, Doppler, and tissue Doppler echocardiography as indicated by the rules of American Society of Echocardiography.^{31, 32} During the echocardiographic assessment, a 1-lead ECG was recorded constantly. A normal of three sequential cycles was investigated for every parameter. Left ventricular end-systolic and end-diastolic breadths (LVIDS and LVIDD) and left atrial (LA) end-systolic distance across were estimated by M-mode imaging in the parasternal long pivot see. LV end-systolic volume (LVESV), LV end-diastolic volume (LVEDV), and discharge part (LVEF) were assessed by Simpson's standard in the apical 4-chamber see. MS was evaluated by estimation of MVA by 2D planimetry in parasternal short hub see and by the weight half time technique in the apical 4-chamber see utilizing nonstop wave (CW) Doppler.25, 26 Peak and mean transmitral diastolic weight angles (PDG and MDG) were estimated by ceaseless wave Doppler in the apical four chamber see. Mitral valve morphology and the sub-valvular mechanical assembly were evaluated by 2D imaging, and Wilkins' score was calculated.^{27, 28} Pulmonary supply route systolic weight (PASP) was determined by including the assessed right atrial strain to {(tricuspid disgorging velocity)2 × 4}, estimated by ceaseless wave Doppler in the apical four chamber view.33 Color stream Doppler imaging was utilized to distinguish and measure the seriousness of mitral spewing forth as indicated by the rules of the American Society of Echocardiography.³⁴

LA volume was determined by the changed Simpson's strategy from the apical four chamber see at end systole, and was amended for body surface region (BSA).³⁵

For the appraisal of between and intra-atrial electromechanical postponements, tissue Doppler echocardiography was performed by enacting the TDI method of a similar machine. TDI was finished with transducer frequencies of 3.5–4 MHz, modifying the ghastly heartbeat Doppler signal channels until a Nyquist cutoff of 15–20 cm/s was reached and utilizing the insignificant optical increase. The screen clear speed was set at 50–100 mm/s to advance the otherworldly showcase of myocardial velocities.^{9, 10, 11, 12, 13, 14,} 15 In the apical four chamber see, the beat Doppler test volume was put at the degree of LV horizontal mitral annulus (Fig. 1), septal mitral annulus (Fig. 2), and right ventricular (RV) tricuspid annulus (Fig. 3). Unique exertion was made to adjust the beat wave cursor so as to keep the Doppler point of rate as near 0° as conceivable to the heading of these dividers. Time span from the beginning of P-wave on surface ECG to the start recently diastolic wave (A′ wave) on TDI, named as PA′, was acquired from horizontal mitral annulus (), septal mitral annulus (), and RV tricuspid annulus (), respectively.^{9, 10, 11, 12, 13, 14, 15} The contrast between sidelong PA′ and tricuspid PA′ () was characterized as between atrial electromechanical deferral (AEMD); distinction between septal PA′ and tricuspid PA′ () was characterized as right intra-atrial electromechanical postponement (R-IAEMD); and the contrast between parallel PA′ and septal PA′ () was characterized as left intra-atrial electromechanical postponement (L-IAEMD).^{9, 10, 11, 12, 13, 14, 15}

Following the PTMC strategy, a recurrent echocardiogram was performed to survey the post-procedural MVA, nearness and seriousness of mitral spewing forth, pinnacle and mean transmitral diastolic weight inclinations, PASP, and to characterize the accomplishment of method as portrayed previously.29, 30 All patients, in whom PTMC was fruitful, experienced a rehash echocardiographic assessment 24–48 h after the methodology for the estimation of post-procedural LA width; LV measurements, volumes and EF; LA volume; and between and intra-atrial electromechanical postponements.

2.7. PTMC procedure

PTMC was conducted using a typical trans-septic procedure using an Inoue balloon.36 Pre-and post-procedural catheterization data were not included in this analysis.

2.8. Collection and recording of data

All patient data, including demographic, clinical, medical, pre-and post-procedural electromechanical parameters, procedural outcomes, complications, and discharge diagnosis, were recorded in a specially pre-designed patient record form.

2.9. Statistical analysis

Factual examination was performed by SPSS programming bundle (form 20.0, SPSS Inc, Chicago, Illinois, USA). Every single persistent variable were communicated as mean ± SD, and unmitigated factors were accounted for as recurrence and rates. Pearson's connection coefficients were utilized to evaluate the quality of connection between persistent factors. Matched t-test was utilized to consider the distinction of methods for different nonstop factors. Measurable importance was characterized as a p estimation of <0.05.

3. Results

The underlying investigation populace included 30 patients of suggestive extreme MS, in typical sinus mood, who satisfied the other consideration models before the method. Out of these, 5 patients were prohibited from the examination after PTMC (2 patients didn't give assent for the investigation, 1 patient had a fizzled trans-septal cut, 1 patient created extreme post-procedural mitral disgorging, and 1 patient created peri-procedural AF which returned to sinus musicality after DC cardioversion). Last investigation test comprised of the staying 25 patients. Quick procedural achievement rate was 93.3% (peri-procedural AF was not viewed as a procedural disappointment).

3.1. Patient characteristics

The median age of the patients was 34.1 years, from 21 to 45 years. Of the 25 patients enrolled in the study sample, 7 (28%) were male, while 18 (72%) were female. The mean body surface of the patients was 1.45 m2, ranging from 1.29 m2 to 1.75 m2.

3.2. Pre-PTMC parameters

3.2.1. Routine echocardiographic parameters  

Pattern echocardiographic parameters of the patients were as per the following: LA breadth – 4.82 ± 0.51 cm; LVIDD – 4.39 ± 0.34 cm; LVIDS – 2.73 ± 0.36 cm; LVEDV – 60.99 ± 10.79 ml/m2; LVESV – 19.37 ± 5.77 ml/m2; LVEF – 68.52 ± 5.48%; Wilkins score – 6.04 ± 1.27; MVA-2D – 0.74 ± 0.13 cm2; MVA-PHT – 0.79 ± 0.14 cm2; PDG – 27.76 ± 6.25 mmHg; MDG – 15.60 ± 4.23 mmHg; PASP – 58.68 ± 13.14 mmHg; and LA volume – 79.0 ± 12.30 ml/m2.

3.2.2. P-wave durations and PWD

Pattern P-wave spans were: Pmax – 136.40 ± 13.19 ms; and Pmin – 91.60 ± 12.48 ms. PWD was 44.80 ± 5.86 ms.

3.2.3. PA′ stretches, Inter-and Intra-atrial electromechanical postponements

Standard PA′ stretches were: – 44.96 ± 5.57 ms; – 106.24 ± 18.48 ms; and – 32.48 ± 4.81 ms. Between and intra-atrial electromechanical postponements were: AEMD – 73.76 ± 15.67 ms; R-IAEMD – 12.48 ± 2.66 ms; and L-IAEMD – 61.28 ± 14.27 ms.

3.3. Pearson correlation analysis of inter- and intra-atrial electromechanical delays (Table 1)

AEMD and L-IAEMD indicated a positive connection with age, LA breadth, Wilkins score, PDG, MDG, PASP, LA volume, Pmax, and Pmin. AEMD and L-IAEMD were contrarily corresponded with MVA. AEMD and L-IAEMD didn't show any noteworthy relationship with PWD. R-IAEMD demonstrated a positive connection with age, LA distance across, and LA volume.

3.4. Impact of PTMC on various parameters

3.4.1. Routine echocardiographic parameters (Table 2)

Immediately after PTMC, there was a statistically significant decrease in LA diameter, LA length, PDG, MDG, and PASP. Statistically significant changes were observed in MVA-2D, MVA-PHT, LVIDD, and LVEDV.

3.4.2. P-wave durations and PWD (Table 3)

There was no change in Pmax, Pmin, and PWD in the immediate post-PTMC phase

3.4.3. PA′ intervals, inter- and intra-atrial electromechanical delays (Table 4)

Statistically significant reductions in,, intervals, AEMD, R-IAEMD and L-IAEMD were observed in the immediate post-PTMC phase.

4. Discussion

The primary discoveries of our examination were:

1. Effective PTMC prompted a measurably noteworthy decline in between and intra-atrial electromechanical postponements.

2. There was no adjustment in P-wave terms or P-wave scattering following PTMC.

3. Between and intra-atrial electromechanical deferrals indicated a solid positive connection with P-wave terms yet not with PWD.

In rheumatic MS, the left atrial life structures, physiology, and electrophysiology are antagonistically influenced optional to expanded left atrial afterload and direct inclusion of left chamber by rheumatic carditis.1, 2, 3, 37 These progressions are related with an expanded danger of improvement of AF which fundamentally builds the drawn out mortality and dreariness of these patients.4, 37, 38

Presented first in 1984 by Inoue et al.,36 PTMC has at present become the treatment of decision in patients with moderate to extreme MS, with good valve morphology, who are indicative or have new beginning AF or noteworthy aspiratory hypertension.39 Over the previous three decades, broad clinical experience has set up the security and adequacy of this methodology in both short and long term.16, 17, 18, 19, 27, 28, 29, 30 Some investigations have indicated that PTMC favorably affects long haul frequency of AF in MS patients.20, 40 In the current examination, we not just portrayed the demonstrated intense hemodynamic advantages of PTMC yet in addition showed its positive impact on novel parameters of left atrial electromechanical rebuilding. We additionally depicted the connection of these parameters with one another and with different clinical and hemodynamic factors.

Our investigation, in consistency with the past entrenched examinations, exhibited noteworthy increment in MVA, LV end-diastolic measurements and end-diastolic volumes, and huge lessening in LA distance across, trans-mitral diastolic weight slopes and PASP following PTMC.16, 17, 18, 19, 27, 28, 29, 30

Expanded Pmax and PWD are notable ECG markers of non-uniform and heterogeneous atrial conduction.13 Various examinations have exhibited their relationship with left atrial size and danger of creating AF.5, 6 Previous examinations have additionally indicated that PWD is expanded in patients with rheumatic MS.7, 8 In an investigation led on patients with mellow to direct MS, Guntekin et al. exhibited that Pmax and PWD increment dynamically as per the movement of MS.41 They likewise indicated that Pmax, Pmin, and PWD were altogether related with MVA, mean mitral slope, LA size, and PASP. In like manner, we likewise found that benchmark Pmax and Pmin had a noteworthy relationship with these parameters. Moreover, we additionally exhibited that Pmax and Pmin had positive relationship with age, Wilkins score, and left atrial volume. These discoveries propose that expanding age and more prominent contortion of mitral valve contraption (reminiscent of more prominent rheumatic action process) and bigger LA volume are related with progressively extreme basic changes in the left chamber, prompting more noteworthy electrical inhomogeneity, non-uniform conduction speeds, and inhomogeneous stubborn periods inside the atrial myocardium, which shows on the ECG as expanded P-wave span. These perceptions are bolstered by the discoveries of Kabukcu et al., who recommended that AF is a marker of boundless rheumatic harm in patients with MS.42 Although PWD was drawn out in our patients, we didn't locate any huge relationship among's PWD and different parameters. Rezaian et al. have additionally mentioned a comparative objective fact in the past.43 They credited this finding to the way that dominant part of the patients in their examination had mellow MS and a generous extent of them were on beta blockers (known to diminish PWD).8 Since we prohibited the patients with non-extreme MS and those taking beta blockers from our investigation, these reasons couldn't clarify our discovering, which needs further explanation. Besides, we didn't watch any adjustment in P-wave terms and PWD in the prompt post-PTMC period. While a few creators have shown an intense abatement in these parameters after effective PTMC,7 others have discovered that such relapse happens to some degree late (≥6 months) after the procedure.44 We accept that surface ECG appearances of deferred and heterogeneous atrial conduction may set aside effort to determine after fruitful alleviation of MS. This needs affirmation on development.

AEMD is a novel, basic, and modest option in contrast to obtrusive electrophysiological reads for evaluating atrial electromechanical remodeling.9, 10, 11, 12, 13, 14, 15 Recent examinations have uncovered that AEMD is delayed in patients with paroxysmal AF and other illness states related with expanded danger of AF.9, 10, 11, 12, 13, 14, 15 These investigations demonstrated that drawn out AEMD appears to reflect atrial renovating for an arrhythmogenic substrate. Ozer et al. exhibited that AEMD is drawn out in patients with MS and is corresponded with PWD.13 They additionally demonstrated that AEMD is connected with left atrial size yet not with the seriousness of MS. Our examination uncovered that AEMD was emphatically connected with age, LA distance across, Wilkins score, trans-mitral weight inclinations, aspiratory supply route pressure, LA volume, Pmax, and Pmin. In spite of the fact that AEMD had a positive connection with PWD, this was not factually huge in our examination. Also, AEMD indicated a negative relationship with MVA. This was as opposed to the perception made by Ozer et al.13 This disparity could halfway be clarified by the reality our patients had progressively extreme MS contrasted with those remembered for that review (MVA – 0.74 ± 0.13 cm2 versus 1.5 ± 0.36 cm2). Univariate relationships of L-IAEMD were like those of AEMD, while R-IAEMD was emphatically connected with age, LA distance across, and LA volume. These discoveries recommend that like P-wave term and PWD, between and intra-atrial electromechanical postponements are markers of left atrial redesigning in patients with MS and drag out dynamically with expanding age, seriousness of MS, and left atrial volumes. Moreover, a solid positive connection between's these electrocardiographic and echocardiographic parameters proposes their reciprocal job in distinguishing patients at expanded danger of creating AF.

We likewise exhibited a noteworthy diminishing in AEMD, L-IAEMD, and R-IAEMD following effective PTMC. Till date, there is just one distributed investigation that has exhibited such a finding.23 Since we didn't watch any comparing decreases in P-wave lengths and PWD, it might demonstrate that TDI is better than surface ECG in mirroring the progressions in atrial electrical milieu after alleviation of MS. Such a hypothesis needs approval by obtrusive electrophysiological contemplates. Another intriguing finding of our investigation was that R-IAEMD added to 17% of the absolute AEMD before PTMC and this commitment expanded to 19% after PTMC. Consequently, in spite of the way that both R-IAEMD and L-IAEMD diminished altogether after PTMC, the decrease altogether AEMD was inferable principally to the reduction in L-IAEMD. This can be intelligently disclosed to be an outcome of decrease in left atrial size and weight following help of MS. The expanded commitment of R-IAEMD to the all out AEMD after PTMC could be estimated to be optional to right atrial volume over-burden because of left to right interatrial shunt over the gained atrial septal deformity. Regardless of whether this commitment changes after the deformity persuades fixed should be tended to in the long haul development.

5. Limitations

The primary constraints of our examination were as per the following:

(I) This examination was completed at a solitary community and the investigation test was moderately little.

(ii) We just examined the quick effect of fruitful PTMC on the electrocardiographic and echocardiographic markers of AF hazard. We by and by don't have any long haul follow-up information of these patients as far as the adjustments in these parameters and their real prescient incentive as to the danger of improvement of AF. Long haul imminent examinations in bigger gatherings of patients are required to come to such complete end results.

(iii) We estimated the conduction times just with TDI and didn't utilize the best quality level, for example electrophysiological study to approve our outcomes.

(iv) At last, it is very much perceived that the improvement of clinical AF is mind boggling and depends on substrate as well as on different factors, for example, triggers and initiators. The impact of inversion of stretch on these different components was not tended to by this investigation.

6. Conclusion

Successful PTMC has a favorable early effect on inter-and intra-atrial electromechanical delays, which are considered to be novel criteria for atrial electromechanical remodeling in MS patients. Prospective large-scale studies are required to confirm whether the change in these markers translates into reduced long-term risk of AF.

Note: This work is partly presented at 31^st European Heart and Heart Failure Congress June on 18-19, 2020 held at Paris, France

Objectives: The association between disorder and depression is well-established. Peripheral arterial disease arises from atherosclerosis like other disorder , but unlike other disorder , it impairs ambulation and lower extremity function. Given peripheral arterial disease's unique characteristics and underrepresentation in psychological state research, we aimed to: (a) assess the prevalence of depression or depressive symptoms among peripheral arterial disease patients compared to arteria coronaria disease rates, (b) assess whether an independent association between peripheral arterial disease and depression exists, and (c) identify associated factors which will be targeted for intervention.
Depressive symptoms are known to compromise health status in cardiac disease, but this relationship has not been described in peripheral artery disease (PAD). Depressive symptoms (PHQ-9) and disease-specific health status (Peripheral Artery Questionnaire, PAQ) were assessed in 242 PAD patients undergoing percutaneous transluminal angioplasty (PTA) at baseline and 1 year. Patients were classified by baseline and follow-up depression status (moderate-severe depressive symptoms = PHQ ≥ 10). Changes were categorized as no depression/improvement of depression versus persistent/worsened depression. At baseline, 20% of patients were depressed; at 1 year, 17% of patients experienced persistent/worsened depression. Although this group improved on most PAQ subscales, they improved to a significantly lesser degree than those without depressive symptoms or those that improved by 1 year (p-values < 0.05). Baseline depressive symptoms (B(per 5-point increment) = -11.9, 95% CI -15.3, -8.5, p < 0.0001) and changes in depression were independently related to a decrease in 1-year health status (B(per 5-point increment) = -11.7, 95% CI -14.3, -9.2, p < 0.0001). In conclusion, depressive symptoms are related to less improvement in health status 1 year after undergoing a peripheral endovascular revascularization (PER) as compared with those having no depression or whose depressive symptoms improve. Efforts to enhance depression detection and treatment among patients with PAD may improve the health status outcomes of those patients.

Design: This study was based on a systematic review.

Materials and methods: Electronic databases were searched to spot studies that examined peripheral arterial disease and depression or depressive symptoms. Methodological quality was assessed using the Newcastle-Ottawa Scale.

Results: We identified 28 studies. Prevalence of depression or depressive symptoms ranged from 11-48% in 12 cross-sectional studies, and from 3-36% in 16 longitudinal studies, which is like reported arteria coronaria disease rates. Depressed peripheral arterial disease patients were more likely to be female, African American, and have more severe peripheral arterial disease symptoms and more compromised physical function compared to non-depressed patients. There is evidence to suggest that depression exerts a negative influence on walking ability and physical function independently of peripheral arterial disease.

Conclusions: A critical got to address depression in peripheral arterial disease patients, particularly those with characteristics that place them at increased risk. Vascular care providers appear to be the primary contact for assessing depressive symptoms, and once identified, integrated mental health providers may intervene to prevent the worsening of both depression and peripheral arterial disease.

Depression is the most common mental health disorder worldwide,1 and is a leading cause of disability.2 It is significantly more prevalent among people with cardiovascular disease (CVD) than among the general population,3 and clinical guidelines recommend depression screening as a component of CVD assessment.4 Peripheral arterial disease (PAD) is an atherosclerotic disease like coronary artery disease (CAD) and stroke, affecting over 200 million people worldwide.5 Unlike other CVD, however, PAD comprises a range of progressive vascular syndromes characterized by lower extremity (LE) pain and impaired walking ability, and is a frequent cause of amputations.⁶

Introduction: The burden of depression in CVD and its associated morbidity and mortality are well-established in a large body of research.^7,8 Nevertheless, the vast majority of published studies either do not include PAD in their estimates, or mention it only in passing. This may in part be due to PAD pathophysiology; approximately 50% of people with PAD report being asymptomatic prior to an acute ischemic event,⁹ suggesting that PAD is also widely under-recognized and underdiagnosed.^10,11 To date, the magnitude of an association between depression and PAD remains unknown.

Aims:

We aimed to evaluate the prevalence of depression and depressive-type symptoms in patients with PAD and compare this to the prevalence among patients with CAD. We further sought to assess the evidence for an independent association between depression and clinical outcomes among patients with PAD. Finally, we attempted to identify factors that may influence the PAD-depression association.

Abbreviations:

PAD: peripheral arterial disease

ABI: ankle-brachial index

BDI: Beck Depression Inventory

BFI-44: Big Five Inventory

Note: This work is partly presented at 25^th World Cardiology Conference July 01-02, 2019 held at Osaka, Japan.

17 year old girl presented to hospital with history of high fever and worsening of shortness of breath which she had for 3 months. On examination  she had a pan systolic murmur best heard  at apex, elevated  JVP  and  a  mild  tender  hepatomegaly  was  found.  ECG  was  normal  and  CXR  showed biatrial  dilatation  and  pulmonary  congestion.  transthoracic   2D  echocardium  followed  by   TOE performed and showed EF> 50% dilated LA with large LA myxoma with a central hypoechoic area measuring 32mm x  60 mm. it is attached to IAS and highly mobile. There was grade II MR. There is  significant  TR  with  TRPG  of  94mmHg  with  severe  pulmonary  hypertension.  RA,RV  mildly dilated and TAPSE 15. Patient underwent surgical excision of left atrial myxoma next day. on day 2 post  surgery  TRPG  was  28mmHg.The  cause  of  pulmonary  hypertension  in  left  atrial  myxoma patients is due to mitral stenosis like pathology of the myxoma. Pulmonary arterial hypertension in these patients were also explained by rise in IL-6 in patient with atrial myxoma. It has shown that IL-6 is a valuable biomarker. Right sided myxomas are rare to develop pulmonary hypertension but it  has  been  described.  The  cause  of  pulmonary  hypertension  in  these  patients  are  mostly  due  to chronic micro thromboembolic phenomenon of the tumour and  associated with cytokines such as IL-6 directly entering the pulmonary circulation.  Because the pulmonary hypertension in right heart myxoma  caused  by  a  chronic  change  in  the  lung  vasculature,  pulmonary  hypertension  may  not resolve after resection of tumour but usually it does in left atrial myxomas.

Myxoma is the most common primary cardiac tumour, found in the left atrium in 75% of cases.1,2 Clinical features range from being asymptomatic to symptoms of mitral stenosis, embolisation and systemic illness.3-5 Pulmonary complications, including pulmonary hypertension,4,6,7 pulmonary infarction8 and lymphadenopathy,9 though uncommon, have been reported. Our patient presented with a pulmonary triad of all the complications mentioned above and all of them resolved immediately following successful excision of the tumour.

We hope to report this case for educational and clinical purposes, due to the unusual combination of pulmonary complications, as well as atrial arrhythmias associated with a left atrial myxoma.

Discussion:

Primary cardiac tumours are rare, with an incidence reported to be below 0.03%.1 By comparison, metastatic involvement of the heart is significantly more frequent and has been reported in up to one in five patients who died of cancer on autopsy.1 Of all the first cardiac tumours, myxoma is that the commonest (70–80%).9 Myxomas tend to be more frequently seen between the third and sixth decades of life, with a female-to-male ratio of 2:1 to 3:1.1,2,10

About 75% of all myxomas occur within the LA and typically originate from the interatrial septum within the fossa ovale region; but a fifth are found within the right atrium, and 5–8% within the ventricles.5 Other locations are reported, though much rarer.1

The size of a myxoma can vary from a couple of millimetres to fifteen cm, with an averaged maximal dimension of three .7 to 5.6 cm.10 Therefore, the myxoma found in our patient was far larger than most reported and, thus, are often classified as giant or colossal.

The clinical features of a cardiac myxoma are associated with its location, size and mobility.

The tumour can present with one or more symptoms of the three categories: outflow obstruction of the mitral valve, embolism and constitutional or systemic symptoms.4,5,12 In our patient, embolism manifested as pulmonary infarction.

The most common symptoms of los angeles myxomas are associated with bicuspid valve obstruction (>60%): dizziness or syncope, palpitations, dyspnoea, cough, pulmonary oedema, or congestive coronary failure . Embolic manifestations are less common (16%). A similar percentage of patients (15%) may present with systemic or constitutional symptoms such as myalgia, muscle weakness, arthralgia, fever, weight loss, fatigue, and even Raynaud syndrome. he detection of it has become more frequent, likely due to the easy access and wide availability of echocardiography.10 The fact that our patient presented to us rather late, and the large myxoma size, suggested an extended period of growth. Hence, he had developed a good range of symptoms along side the pulmonary complications.

Atrial fibrillation has been described as a complication of a LA myxoma,9,10,12 and it are often a consequence of either the myxoma itself or the surgery . In the former case, fibrillation is resolved after a successful operation, but it remains difficult to determine a transparent association between the 2 , although such association is well known between rheumatic mitral stenosis and atrial fibrillation. It would not be illogical to state that the large myxoma in our patient caused significant mitral valve obstruction and lead to the initial atrial fibrillation, and even subsequent atrial flutter after surgery.

Note: This work is partly presented at 25^th World Cardiology Congress July 01-02, 2019 held at Osaka, Japan.

With space flight (SF) significant reductions of serum Mg (P < 0.0001) despite poor serum sensitivity, shown in spacecraft crew members. Mg, a robust antioxidant and calcium blocker; with SF, there's oxidative stress, insulin resistance, inflammatory conditions; in experimental animals significant endothelial injuries to mitochondria, reductions in transferrin and in turn oxidative stress. Inhalation of Lunar iron (Ir) particulate contributes to worry test - hypertension on Earth return (ER): James Irwin’s vital sign (BP) 275/125 after 3 minutes of exercise (ER); Neil Armstrong showed very high diastolic BP 160/135 on ER, consistent with impaired cardiac function. Magnet (M) studies useful on moon; similarly, M studies on Earth wont to quantitate high indoor Ir levels. Since over 90 you look after brakes made from Ir, combination Ir brake dust  inhalation and Mg deficiencies in over 60% U.S. population, may be important factors intensifying worldwide hypertension.

Space flight (SF) and mud inhalation in habitats cause hypertension whereas in SF (alone) there's no consistent hypertension but reduced diurnal vital sign (BP) variation instead. Current pharmaceutical subcutaneous delivery systems are inadequate and there is impairment in the absorption, metabolism, excretion, and deterioration of some pharmaceuticals. Data obtained from the National Aeronautics and Space Administration through the Freedom of Information Act shows that Irwin returned from his 12-day Apollo 15 mission in 1971 and was administered a bicycle stress test. With just three minutes of exercise, his BP was >275/125 torr (heart rate of only 130 beats per minute). There was no acute renal insult. Irwin's apparent spontaneous remission is usually recommended to be associated with the rise of a protective vasodilator, and his atrial natriuretic peptide (ANP) reduced with SF due to reduced plasma volume. With invariable malabsorption and loss of bone/muscle storage sites, there are significant (P < 0.0001) reductions of magnesium (Mg) required for ANP synthesis and release. Reductions of Mg and ANP can trigger pronounced angiotensin (200%), endothelin, and catecholamine elevations (clearly shown in recent years) and harsh cycles between the latter and Mg deficits. There is proteinuria, elevated creatinine, and reduced renal concentrating ability with the potential for progressive inflammatory and oxidative stress-induced renal disease and hypertension with vicious cycles. After SF, animals show myocardial endothelial injuries and increased vascular resistance of extremities in humans. Even without dust, hypertension might eventually develop from renovascular hypertension during very long missions. Without sufficient endothelial protection from pharmaceuticals, a comprehensive gene research program should begin now.

Note: This work is partly presented at 25th World Cardiology Conference July 01-02, 2019 held at Osaka, Japan.

INTRODUCTION: The surprising achievement of numerous immunizations and their great security record alongside the destruction of smallpox are respected among the best open wellbeing accomplishments of the twentieth century. Analysts have contributed (and keep on contributing) essentially toward the innovative work of antibodies around the world. In this article, we talk about a portion of the factual issues that emerge in all periods of antibody advancement, and, where vital, differentiate medicate and immunization clinical preliminaries. An increasingly point by point treatment of this subject is given by Chan et al. (2003).

In the previous three decades, there has been an extraordinary change in our comprehension of the human insusceptible framework and its capacities. While analysts taking a shot at antibody clinical preliminaries are not expected to keep side by side with the most recent advances in cell and atomic immunology, comprehension of the rudiments is basic for legitimate advancement of structure and investigation systems. In like manner, before proceeding onward to factual issues, we give a concise audit of fundamental immunology. For further developed perusing, see Abbas et al. (1997).

Practically all immunizations being used today have been authorized utilizing neutralizer based endpoints. All the more as of late, research has strengthened on creating immunizations that invigorate cell insusceptibility (or both). In any case, whether or not the antibody is planned to prompt humoral or cell insusceptibility, the operational objective of inoculation is the equivalent: to reproduce a microorganism explicit presentation with the goal that the host's insusceptible framework will produce a pool of memory B or potentially T cells to ensure against potential genuine exposures later on. The recreation is practiced by means of vaccination of the host by an antibody that contains either a debilitated variant of the microorganism, or a DNA plasmid or viral vector encoding certain gene(s) of the microorganism, etc.

Understanding the "instrument of activity" of the immunization is basic for distinguishing fitting examination endpoints and measurable investigations in clinical preliminaries. For model, a few T cell-interceded invulnerability based immunizations focused against HIV-1 are as of now being created around the world. Such immunizations may not forestall procurement of HIV-1 disease however will ideally forestall or essentially defer the movement to AIDS among subjects who become contaminated notwithstanding immunization. From a factual point of view, this represents a plenty of difficulties for the structure and investigation of current HIV-1 immunization preliminaries, including the choice of study endpoints.

PRECLINICAL PHASE

Before an antibody can be tried in people, it experiences broad testing in creatures. This is like what is done in the preclinical stage for drugs. In any case, for immunizations there is extra accentuation on the turn of events and approval of bioassays to quantify the immunogenicity of the immunization, i.e., the capacity of the immunization to incite explicit insusceptible reactions. The factual qualities of an perfect measure incorporate exactness, fairness, unwavering quality, reproducibility, accuracy, and toughness. Likewise, a decent examine ought to have elevated levels of explicitness and affectability for the conjectured biomarker of intrigue (counter acting agent level, T cell reaction, and so forth.). Standard measurable devices utilized in test improvement and approval incorporate exemplary plan of trials (e.g., D-ideal factorial structures), straight and nonlinear relapse, the four boundary calculated model, concordance relationship, and difference part models.

Immunizations are progressed to Phase I clinical testing in the event that they are considered to be by and large safe in creatures, and for which a sufficient extent of creatures display a negligibly immunogenic post-inoculation reaction.

PHASE I (CLINICAL SAFETY AND IMMUNOGENICITY)

Stage I antibody clinical preliminaries are little, ordinarily enlisting 30 to 100 human chips in over various investigational focuses. They are normally twofold visually impaired, fake treatment controlled preliminaries that review various dosages or potentially immunization plans of the exploratory immunization. The essential spotlight is on security and averageness, however the preliminaries are intended to likewise give fundamental evaluations of immunogenicity. Note that sedate preliminaries ordinarily select solid subjects in Phase I, however move to the objective populace (patients requiring treatment) in Phase II and past. In differentiate, antibody preliminaries, as anyone might expect, include solid volunteers in all periods of advancement. Exemptions incorporate alleged "remedial immunization" examines, which are not examined here. The measurable difficulties there are significantly more noteworthy, since it is hard to measure and definitively exhibit the advantages of immunization in subjects that are as of now tainted with the microorganism of intrigue.

Security in Phase I is generally summed up utilizing the occurrence of genuine immunization related unfriendly occasions (assuming any), alongside information on infusion site responses, internal heat levels, fundamental unfavorable occasions, and lab measures. The meager condition of security information from an individual Phase I preliminary make them progressively fit for expressive as opposed to formal inferential measurable investigations. The choice to continue to an ensuing preliminary is in this manner dependent on sound clinical judgment, with contribution from a wellbeing assessment board of trustees (if essential), and administrative offices, for example, the Center for Biologics Evaluation and Research (CBER) for U.S.- based preliminaries.

PHASE II/III (CLINICAL IMMUNOGENICITY, EFFICACY AND SAFETY)

After Phase I, there is proceeded with evaluation of the immunogenicity and wellbeing of the a couple of dosages of the immunization chose for additional examination. In any case, the essential center movements toward assessment of antibody viability, and to decide in the event that the biomarker(s) used to propel the immunization past Phase I are corresponded with adequacy. In this area, we examine the key measurable issues experienced in Phase II/III. Strikingly, for sedate clinical preliminaries there is typically a reasonable demarkation between Phase II and Phase III, yet this is less basic for antibody preliminaries.

POST-LICENSURE ISSUES

Stage IV contemplates are directed after licensure to gather extra data on the security, immunogenicity, and additionally adequacy of the immunization to meet administrative responsibilities or post-promoting goals. These incorporate purported crossing over examinations, diligence studies, and post-licensure security contemplates. A portion of the specialist measurable issues are quickly talked about here. Chan et al. (2003) and Halloran (2001) give more detail.

CONCLUDING REMARKS

In this article, we have given an outline of the key measurable issues that emerge in all periods of antibody advancement. We have focused on the significance of understanding the science behind the numbers, including how the immunization is planned to work, just as the bioassays that measure whether the immunization is immunogenic. Since authorized antibodies are regulated to a large number of solid individuals, we have featured the significance of building up immunization security in an enormous number of subjects, and clarified the idea of super adequacy contemplates. At long last, we have noticed the significance of building up that the antibody fabricating process produces immunization parts that summon measurably comparable post-inoculation invulnerable reactions. Ongoing advances in hereditary designing and pharmacogenetics are bringing forth another age of antibody modalities to ensure against HIV/AIDS, malignancy, intestinal sickness, Bacillus anthracis, plague, etc. Improvement of such antibodies will present extra measurable difficulties that will require imaginative idea and innovative arrangements.

NOTE: This work is partly presented at 3^rd International Conference on Vaccines, Immunology and Clinical Trials June 24-25, 2020 held as Online event (WEBINAR)