Mikaelyan Institute of Surgery

Familial Mediterranean Fever (FMF) is a genetic disorder with complex inheritance patterns and genotype-phenotype associations, and it is highly prevalent in Armenia. FMF typically follows an autosomal recessive inheritance pattern (OMIM: 249100), though it can occasionally display a rare dominant inheritance pattern with variable penetrance (OMIM։134610). The disease is caused by mutations in the MEFV gene, which encodes the pyrin protein. While the 26 most prevalent mutations account for nearly 99% of all FMF cases, more than 60 pathogenic mutations have been identified. In this study, we aimed to develop an affordable nanopore sequencing method for full-length MEFV gene mutation detection to aid in the diagnosis and screening of FMF. We employed a multiplex amplicon sequencing approach, allowing for the processing of up to 12 samples on both Flow cells and Flongle flow cells. The results demonstrated near-complete concordance between nanopore variant calling and qPCR genotypes. Moreover, nanopore sequencing identified additional variants, which were confirmed by whole exome sequencing. Additionally, intronic and UTR variants were detected. Our findings demonstrate the feasibility of full-gene nanopore sequencing for detecting FMF-associated pathogenic variants. The method is cost-effective, with costs comparable to those of the qPCR test, making it particularly suitable for settings with limited laboratory infrastructure. Further clinical validation using larger sample cohorts will be necessary.

Abstract Aim This study, wave 2 of the International Sexual Health and Reproductive Health (I-SHARE) study, aims to explore the prevalence and correlates of online harassment in 10 countries including low- and middle-income countries. Subject and methods Data were collected through the I-SHARE-2 survey from March 2021 to July 2022, in 10 countries ( N = 2860) during the COVID-19 pandemic. Results Overall, 30% of participants reported that they believed online harassment was happening more frequently than before COVID-19; 20% of participants reported having received unsolicited advances, 17% reported having received unsolicited obscene images or videos, and 7% reported that someone had shared a photo or video of them doing something humiliating or embarrassing without permission. This perceived increase in online harassment during the pandemic was potentially due to more online behavior amid lockdowns. A mixed-effects logistic regression revealed that people identifying as gender/sexual minority, people with worse economic situations, and people living in a country with lower gender inequality had higher odds of experiencing online harassment. Conclusion These results align with prior research, emphasizing the vulnerability of minorities to online harassment. Our study findings have implications for the development of interventions to decrease online harassment.

AimsInflammation has emerged as a potential key pathophysiological mechanism in heart failure (HF) in general and acute HF (AHF) specifically, with inflammatory biomarkers shown to be highly predictive of adverse outcomes in these patients. The CORTAHF study builds on both these data and the fact that steroid burst therapy has been shown to be effective in the treatment of respiratory diseases and COVID‐19. Our hypothesis is that in patients with AHF and elevated C‐reactive protein (CRP) levels without symptoms or signs of infection, a 7‐day course of steroid therapy will lead to reduced inflammation and short‐term improvement in quality of life and a reduced risk of worsening HF (WHF) events.Methods and resultsThe study, which is currently ongoing, will include 100 patients with AHF ages 18–85, regardless of ejection fraction, screened within 12 h of presentation. Patients will be included who have NT‐proBNP > 1500 pg/mL and CRP > 20 mg/L at screening. Exclusion criteria include haemodynamic instability and symptoms and signs of infection. After signed consent, eligible patients will be randomized according to a central randomization scheme stratified by centre 1:1 to either treatment once daily for 7 days with 40 mg prednisone orally or to standard care. Patients will be assessed at study day 2, day 4 or at discharge if earlier, and at days 7 and 31 at the hospital; and at day 91 through a telephone follow‐up. The primary endpoint is the change in CRP level from baseline to day 7, estimated from a mixed model for repeated measures (MMRM) including all measured timepoints, in patients without a major protocol violation. Secondary endpoints include the time to the first event of WHF adverse event, readmission for HF, or death through day 91; and changes to day 7 in EQ‐5D visual analogue scale score and utility index. Additional clinical and laboratory measures will be assessed.ConclusionsThe results of the study will add to the knowledge of the role of inflammation in AHF and potentially inform the design of larger studies with possibly longer duration of anti‐inflammatory therapies in AHF.

Background: About 200 new ovarian cancer cases per year are diagnosed in Armenia, an upper-middle-income country. This study aims to summarize the survival outcomes of relapsed ovarian cancer patients in Armenia based on the type of relapse, risk factors, and the choice of systemic treatment. Methods: A retrospective case-control study including 228 patients with relapsed ovarian cancer from 3 different institutions. Results: The median age of the patients was 55. The median follow-up from the relapse and primary diagnosis was 21 and 48 months. The incidence of platinum-sensitive relapse was 81.6% (186), while platinum-resistant relapse was seen only in 18.4% (42) patients. Median survival of the patients starting from the primary diagnosis in the platinum-sensitive compared to the platinum-resistant group was 54 versus 25 months (p < 0.001), and median survival after relapse: was 25 versus 13 months, respectively 3- and 5-year survival in these groups were: 31.2% vs. 23.8%, and 15.1% vs. 9.5%, respectively (p = 0,113). Conclusions: Overall, despite new therapeutic approaches, ovarian cancer continues to be one of the deadly malignant diseases in women, especially, in developing countries with a lack of resources, where, in fact, the main available systemic treatment for the majority of patients remains chemo-therapy. Low survival rates emphasize the urgent need for more research on this group of patients with poor outcomes.

BackgroundAs considerable evidence indicates viruses play an important role in the pathogenesis of inflammatory rheumatic diseases as environmental factors. The most prominent pathogenic viruses which have been proposed in the triggering and initiation of autoimmune diseases include Parvovirus B19, Epstein-Barr-virus (EBV), Cytomegalovirus (CMV), Herpes virus-6, HTLV-1, Hepatitis A and C virus, and Rubella virus1. It is possible that COVID-19 infection is also a trigger. Because SARS-CoV-2 infection can break immune tolerance and trigger autoimmune responses, it is also likely to induce clinical autoimmunity2.ObjectivesFind out a possible association between Covid-19 infection and development of IMDs.MethodsWe analyzed data of 21 patients (Male 4 /19 %/, female 17 /81%/, mean age 45.5 ± 13,9 years), who were admitted to Rheumatology department of “Mikayelyan” University Hospital after Covid -19 infection with newly diagnosed IMDs from June till December 2021. All of included had never had such kind of disorder before. EULAR/ACR criteria were used for diagnosis and assessment of disease activity.ResultsAfter SARS-CoV-2 infection some patients presented with preserved fever, high levels of CRP and ESR, had rash and arthritis. Particularly, 3 (14.3%) developed systemic lupus erythematosus, 3(14.3%) – antiphospholipid syndrome, 4 (19%) – rheumatoid arthritis, 2(9.5%) - spondyloarthritis, 3 (14.3%) - sarcoidosis, 4 (19%) - erythema nodosum, 1 (4.8%) - small-vessel vasculitis, 1 (4.8%) - undifferentiated arthritis, and 1(4.8%) - Tietze syndrome. 11 (52.4%) experienced severe course of Covid-19 with pneumonia and respiratory failure, in 10 (47.6%) patients the course of disease was mild. We’ve found a significant association between severe course of Covid-19 and development of erythema nodosum. (p< 0.05). Also an association between female gender and severe course of Covid-19 was determined (p<0,05).ConclusionIn acute progression of the COVID-19 along with development of antiviral immunity, a dysregulated response of immune system may occur, represented by the marked cytokine release syndrome, macrophage activation, and systemic hyperinflammation.3We analyzed the data of patients who didn’t have any typical symptom of rheumatic diseases before coronavirus infection, therefor, on our opinion, virus played an important role to induce clinical autoimmunity and autoinflammation and subsequently – IMDs. Possibly, Covid-19 infection may be included in the group of trigger viruses forReferences[1]Ehrenfeld M, Tincani A, Andreoli L, Cattalini M, Greenbaum A, Kanduc D, Alijotas-Reig J, Zinserling V, Semenova N, Amital H, Shoenfeld Y. Covid-19 and autoimmunity. Autoimmun Rev. 2020 Aug;19(8):102597. doi: 10.1016/j.autrev.2020.102597. Epub 2020 Jun 11. PMID: 32535093; PMCID: PMC7289100.[2]Liu Y, Sawalha AH, Lu Q. COVID-19 and autoimmune diseases. Curr Opin Rheumatol. 2021 Mar 1;33(2):155-162. doi: 10.1097/BOR.0000000000000776. PMID: 33332890; PMCID: PMC7880581.[3]Novelli L, Motta F, De Santis M, Ansari AA, Gershwin ME, Selmi C. The JANUS of chronic inflammatory and autoimmune diseases onset during COVID-19 - A systematic review of the literature. J Autoimmun. 2021 Feb;117:102592. doi: 10.1016/j.jaut.2020.102592. Epub 2020 Dec 14. PMID: 33401171; PMCID: PMC7833462.Disclosure of InterestsNone declared

Doğu Anadolu Bölgesi, dağlık bir bölge oluşu ya da iklimsel elverişsizliğine rağmen önemli bir güzergâh veya önemli bir mesken konumunda olmuştur. Tarih öncesi çağlardan beri sürekli yerleşim görmüş, çoğu büyük kültürün, krallığın ve devletin odak noktası olmayı başarmıştır. Özellikle Kalkolitik Çağ sonlarında başladığı düşünülen büyük göçler ve bunun devamında gelen kültürler bölgeyi anayurtları gibi kullanmaya devam etmiştir. Aynı şekilde Muş Bölgesi içinde geçerli olan bu göç dalgaları sadece yüzey araştırmaları ile belirlenirken, Tepeköy Höyük kazıları ile bu veriler belgelenmiştir. Tepeköy, Muş Bölgesinde yapılan tabakalı ilk höyük kazısı olması açısından önemlidir. Höyükte yapılan kazılar sonucu; Orta Çağ, Demir Çağ ve Tunç Çağı tabakalarına ulaşılmıştır. Özellikle Erken Tunç Çağı (ETÇ) ve Orta Tunç Çağı (OTÇ) kültürlerinin çok iyi izlenebildiği yerleşimde hem mimari hem de buluntular açısından zengin özellikler görülebilmektedir. Demir Çağlarının Erken ve Orta Demir (Urartu) Dönemleri’ne ait veriler sunması açısından da oldukça önemli bir höyüktür. Erken Transkafkasya Kültürü ile başlayan ve günümüze kadar sürekli kullanılan höyük hem Muş Bölgesi hem de Doğu Anadolu Bölgesi tarihi için çok önemli veriler sağlamaktadır. Tabakalanması, mimari öğeleri ve diğer buluntu grupları ile birlikte birçok soruya cevap vermektedir.

Aims Ileal intubation and biopsy are considered as a main method for diagnosis of IBD, enteropathy and etc, nevertheless there is no definite recommendation for routinely ileal intubation during colonoscopy in patients without IBD suspicion. The aim of this study was to evaluate necessity of terminal ileum intubation during endoscopy among patients with GI complaints but without IBD suspicion.

Introduction: The vascular territory of an occluded large intracranial vessel can be reliably identified by CT or MR perfusion imaging. Furthermore, prior studies have shown that perfusion imaging can reliably predict the specific vessel that is occluded in anterior circulation large vessel strokes. We evaluated whether perfusion imaging can predict the specific vessel occlusion (vertebral, basilar, or posterior cerebral) in posterior circulation strokes. Hypothesis: We hypothesized that the occluded vessel could be inferred from the perfusion imaging results in &gt;80% of patients with an acute stroke due to large vessel occlusion in the posterior circulation using the simultaneous CTA or MRA as the gold standard. Furthermore, the inter-rater agreement between a vascular neurologist and a neuroradiologist would be &gt; 90%. Agreement Coefficients (AC1) were determined. Methods: From a multicenter cohort of consecutive patients with posterior circulation stroke, we included patients with documented occlusion of the Basilar Artery (BA) posterior cerebral Artery (PCA) or vertebral artery (VA) who had perfusion imaging (MRI or CT) processed by RAPID software. Perfusion images were evaluated blinded to the angiography or any other brain imaging results. The primary outcome measure was agreement on LVO location based on the CTA/MRA results. Results: 74 patients were eligible: age 63±2, female 32%, median NIHSS 15 (IQR 5-24). The distribution of large vessel occlusions on CTA/MRA was BA (74%), PCA (14%) and VA (12%). Perfusion imaging was able to correctly predict the occluded vessel in 63 (85%), AC1 = 0.82 (95% CI 0.72-0.92), p&lt;0.001. Interrater agreement (n=41) was high [AC1 = 0.94 (95% CI 0.87-1.0), p &lt; 0.001]. Conclusion: Perfusion imaging can predict the site of vessel occlusion (vertebral, basilar, or posterior cerebral) in posterior circulation strokes with good accuracy and high inter-rater agreement.

Aim : to study the anticonvulsant and psychotropic activities and side effects of pufemid, pyrathidine and compound N3012 developed at the Institute of Fine Organic Chemistry of the National Academy of Sciences. Materials and methods . Anticonvulsant activities were tested using the following models of experimental seizures: maximum electric shock, corazol, camphor, thiosemicarbazide, picrotoxin, strychnine, amigdala-kindling convulsions. The psychotropic activities of the tested compounds were investigated using the “elevated plus maze”, “electroshock retrograde amnesia”, and the “open field” models. The neurotoxicity of the compounds was assessed by the level of impaired motor coordination in the “rotating rod” test and in the “grid climbing” test. Results . Pufemid, pyrathidine, and compound N3212 demonstrated high anticonvulsant activity that was superior to the reference antiepileptic drugs; in addition, the tested compounds had low toxicity and high indicators of therapeutic and protective effects. Pufemid, pyrathidine and compound N3212 showed psychotropic activities: e. g., compound N3212 had anxiolytic and nootropic effects. Conclusion . The tested compounds – pufemid, pyrathidine and compound N3212 – are highly efficient and low-toxic substances and are, therefore, promising for further preclinical and clinical studies as anti-epileptic drugs with psychotropic activities.