Farelerde interferon ve steroid uygulamasının karaciğer, dalak ve kemik iliğindeki regülatuvar t-hücrelerine etkisi

Objectives: Regulatory T-cells (T-regs) maintain immune tolerance by affecting other cells of the immune system. They play an important role in autoimmune diseases and the prevention of graft rejection. Steroids suppress the immune system, especially inhibiting cytokine secretion of T-lymphocytes, initiation of the cell- mediated immune response, and stimulation of T-regs. Interferons (IFN) also have immunomodulatory, antiviral, and anti-proliferative effects. They activate macrophages and cytotoxic T-cells and stimulate the differentiation of T-regs. The aim of this study was to evaluate the effects of IFN and steroids on T-regs in the liver, spleen, and bone marrow in a mouse model, and to determine if they exert their immunosuppresive/immunomodulatory effects through T-regs. Materials and Methods: A total of 24 mice were randomly separated into 3 groups and administered an intraperitoneal injection for five days. The control group received 0.1 mL saline every day, the IFN group received IFN-alpha-2b 20,000 IU on the first, third, and fifth days, and only 0.1 mL saline on the other days, and the steroids group received 5 mg/kg dexamethasone in 0.1 mL saline every day. Two days after the end of therapy, each mouse was anesthetized, the portal vein was explored via laparotomy, and 5 mL bovine serum albumin (BSA) was administered through the portal vein. The inferior vena cava was cut to allow BSA perfusion of the liver, and then the mice were sacrificed. The liver, spleen, and bone marrow were removed for analysis. T-regs were identified and counted using flow cytometry. Results: The flow cytometry count results showed no significant difference between the IFN, steroid, and control groups. Conclusion: IFN and steroid use do not seem to affect the quantity of T-regs.Amaç: Regülatuvar T-hücreleri (T-reg) immün sistemde görevli birçok hücre çeşidine etki ederek immünolojik toleransı sağlayan hücrelerdir. Otoimmün hastalıklar, greft rejeksiyonunun önlenmesi ve enfeksiyon hastalıklarında önemli role sahiptirler. Steroidler, immün sistemi baskılarlar; özellikle T-lenfositlerin sitokin salgılamasını ve hücresel immünolojik yanıtın başlamasını önlerler ve T-reg’leri de stimüle ederler. Diğer yandan interferonlar (İFN) immünomodülatör, antiviral ve anti-proliferatif etkiye sahiptirler. Makrofajları ve sitotoksik T-hücrelerini aktive ederler ve T-reg’lerin diferansiyasyonunu uyarırlar. Biz bu çalışmamızda İFN ve steroidin karaciğer, dalak ve kemik iliğindeki T-reg’lere etkisini, bilinen immünosüpresif/immün düzenleyici etkilerini T-reg’ler üzerinden yapıp yapmadıklarını değerlendirmeyi amaçladık. Gereç ve Yöntemler: Bunun için 24 fareye 5 gün boyunca intraperitoneal enjeksiyon yapıldı. Kontrol grubuna 0,1 cc serum fizyolojik her gün uygulandı. İFN grubuna İFN-alfa-2b 20.000 IU 0,1 cc olacak şekilde serum fizyolojik ile sulandırılarak gün aşırı 3 kez diğer günler 0,1 mL serum fizyolojik uygulandı. Steroid grubuna deksametazon 5 mg/kg 0,1 mL olacak şekilde serum fizyolojik ile sulandırılarak her gün uygulandı. Enjeksiyonlar bittikten sonra 2 gün beklendi. Farelere genel anestezi uygulandı, laparotomi yapılıp portal ven açığa çıkarıldı, portal venden 5 mL bovine serum albümin (BSA) verildi, inferior vena kava kesilerek karaciğerin BSA ile perfüzyonu sağlandı, fareler feda edilmiş oldu. Karaciğer, dalak ve kemik ilikleri elde edildikten sonra T-reg’lerin ayrımı yapıldı ve akım sitometrisi ile sayıldı. Bulgular: Akım sitometrisi ile sayımda İFN, steroid ve kontrol grubunda T-reg sayılarında istatiksel olarak anlamlı bir farlılık bulunamadı. Sonuç: Sağlıklı farelerde İFN ve steroid kullanımının karaciğer, dalak ve kemik iliğindeki T-reg’lerin miktarına etki etmediği düşünüldü

Safety and effectiveness of tenofovir alafenamide in the Turkish population: A systematic review

Hepatitis B virus infection is an important public health problem in the world and in Turkey. Nucleoside analogues and pegylated interferon-alpha are used as therapeutic agents in the management of chronic hepatitis B (CHB) infection. With current treatments, the disease is at a controllable point. Unfortunately, although cure studies continue, the cure treatments in the near future will not be an alternative. Tenofovir disoproxil fumarate (TDF) has been used for the treatment of CHB infection since 2008. Beside its high antiviral activity and lack of resistance, long-term use of TDF may lead to a decline in renal functions and bone mineral density. As a prodrug, tenofovir alafamide (TAF) provides considerable reduction (%90) in systemic exposure to tenofovir and has a better safety profile. TAF was used in some special cases (osteoporosis and decreased renal functions) in Turkey. In 2020, TAF was reimbursed for naive and treatment-experienced patients CHB patients. Evidence for the efficacy and safety of TAF continues to accumulate at an accelerating rate, especially following removal of reimbursement restrictions in 2020. In this review, we aim to summarize the real-world evidence obtained about TAF treatment in the last two years in Turkey

Sarcoidosis mimicking lymphoma on positron emission tomography-computed tomography in two patients treated for lymphoma: two case reports

<p>Abstract</p> <p>Introduction</p> <p>Sarcoidosis is a granulomatous disease that mostly involves the lungs. Its association with malignancies has been well documented. Several mechanisms have been proposed that may underlie this concurrence including triggering tumour antigens and defective cellular immunity.</p> <p>Case presentations</p> <p>We briefly review the literature on malignancy associated sarcoidosis and report two female lymphoma patients of 49 and 56 years of age who, during their course of disease, developed sarcoidosis that was misinterpreted as a lymphoma relapse on positron emission tomography-computed tomography.</p> <p>Conclusion</p> <p>We hypothesise that T cell dysfunction and exposure to tumour associated antigens might be the underlying mechanisms of development of sarcoidosis in patients with lymphoma. Positron emission tomography-positive lesions do not always indicate malignancy and therefore a tissue biopsy is always mandatory to confirm the diagnosis.</p

İnfektif endokarditin epidemiyolojik, klinik ve prognostik sonuçları: 90 atağın retrospektif kohortu

To evaluate the epidemiological, clinical, microbiological, and echocardiographic features, as well as the prognosis and long- term outcome of patients with infective endocarditis. Methods: The clinical records and follow-up data of 90 endocarditis episodes in 86 patients diagnosed with definite and possible infec- tive endocarditis according to the modified Duke criteria in a tertiary university hospital, between 1998 and 2016, were reviewed. Results: Fifty-six patients were male (65.1%), and the mean age was 49.9 ± 14.3. Native valve endocarditis constituted 62.2% of the cases, while the remaining patients had prosthetic valve endocarditis. The aortic (34.4%) and mitral (24.4%) valves were infected more frequently. Streptococci (27.7%) and staphylococci (24.4%) were the most frequently isolated microorganisms. Embolic complications (35.5%) were the leading cause of morbidity, followed by valve insufficiency (28.8%) and heart failure (21.1%). Valve replacement surgery was performed in 28 patients (31%). The in-hospital mortality rate was 15.1% (n = 13). Chronic renal failure (P = .042) and degenerative valves (P = .036) were significantly associated with mortality. Among 43 of the 73 cases available for telephonic survey, 36 (83.7%) patients were alive and without disease, with a median follow-up of 52.9 (4-163) months. Twenty-five (69.4%) of these patients were younger than 55 years, and 24 (66.6%) had native valve endocarditis. Conclusion: Underlying cardiac conditions and chronic renal failure increase mortality in infective endocarditis, regardless of the patho- gen. Long-term survival seems promising in cases with native valve endocarditis and in younger patients with low rates of comorbidities.İnfektif endokardit tanısıyla izlenen hastaların epidemiyolojik, klinik, mikrobiyolojik, ekokardiyografik özellikleri, prognozu ve uzun dönem sonuçlarını değerlendirmek. Yöntemler: 1998 ve 2016 yılları arasında bir üniversite hastanesinde modifiye Duke kriterlerine göre kesin ve olası infektif endokardit tanısı konan 86 hastanın 90 endokardit atağının klinik kayıtları ve takip verileri retrospektif olarak incelendi. Bulgular: Çalışmamızda hastaların 56’sı (%65,1) erkek ve ortalama yaş 49,9 ± 14,3 idi. Doğal kapak endokarditi olguların %62,2’sini oluştururken, diğerlerinde protez kapak mevcuttu. En sık aort (%34,4) ve mitral (% 24,4) kapak tutulumu saptandı. Etken olarak strep- tokoklar (%27,7) ve stafilokoklar (%24,4) en sık izole edilen mikroorganizmalardı. Tüm komplikasyonlar içinde embolik komplikasyonlar (%35,5) ilk sırada yer almış, bunu kapak yetmezlikleri (%28,8) ve kalp yetmezliği (%21,1) izlemiştir. Hastaların 28’ine (%31) kapak replasman operasyonu yapılmış ve tüm hastalar içinde 13 hasta (%15,1) hastane takibinde kaybedilmiştir. Mortalite kronik böbrek yetmezliği (P = ,042) ve dejeneratif kapak hastalarında (P = ,036) istatistiksel olarak daha anlamlı bulundu. Taburculuk sonrası prognoz ve uzun dönem sonuçlar değerlendirildiğinde sağ kalan 73 hastanın 43’üne ulaşılabilmiş ve bu hastalardan 36’sının (%83,7) ortalama 52,9 ay (4-163) hayatta ve genel durumlarının iyi olduğu, 25 hastanın (%69,4) <55 yaş, 24’ünün (%66,6) doğal kapak endokarditi tanısıyla izlenmiş olduğu görülmüştür. Sonuç: İnfektif endokardit hastalarında altta yatan kalp hastalıkları ve kronik böbrek yetmezliği patojenden bağımsız olarak mortalit- eyi arttırmaktadır. Doğal kapak endokarditi ve komorbiditeleri daha az olan genç yaş hastalarda ise uzun dönem sağkalım umut verici görünmektedir

Effectiveness and safety of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate single-tablet combination among HIV-infected patients in Turkey: results from a real world setting

Background: Efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil (E/C/F/TDF) in treatment-naïve and experienced patients with HIV infection was demonstrated in phase 3 trials. The primary objective of this study was to evaluate effectiveness and safety of E/C/F/TDF in real world settings. Methods: Retrospective, observational data collected by the Turkish ACTHIV-IST study group between May 2015 and December 2016 were analysed. Results: A total of 387 patients were prescribed E/C/F/TDF; 210 patients with available data at 6th month were eligible; 91.5% were male, and mean age was 35.2 (SD: 10.8) years; 54.0% of males identified themselves as MSM. Sixty-three percent (133) of the study population were treatment-naïve patients, and 37% (77) were treatment experienced. HIV RNA level was below 100 copies/mL in 78.9% of treatment-naïve patients and 89.9% of treatment experienced patients at month 6. Median increase in CD4 T lymphocyte count was 218 copies/mL in treatment-naïve patients and remained stable or increased in treatment experienced patients. Adverse events were observed in 15% of the patients, and the regimen was discontinued in only six patients. Conclusion: Real world data on the effectiveness and safety of E/C/F/TDF is comparable with the phase 3 trial results Adverse events are uncommon and manageable. Keywords: Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate; HIV; effectiveness; safety

A pan-resistant Myroides odoratimimus catheter-related bacteremia in a COVID-19 patient and review of the literature

Myroides spp. are opportunistic environmental Gram-negative bacteria. These affect mostly immunocompromised hosts and generally lead to soft tissue, and urinary tract infections. Bacteremia most commonly develop secondary to soft tissue or catheter related infections and may lead rarely to mortality. Myroides spp. are generally suscetible to fluoroquinolones, piperacillin/tazobactam, trimethoprim/sulfamethoxazole, carbapenems or tetracyclines however, pan-resistant isolates and multiple resistance genes have been reported in clinical isolates of Myroides spp. We report a pan-resistant Myroides odoratimimus bacteremia in a patient with severe COVID-19 ending with fatality and in this context a review of reported Myroides bacteremias are also described. In this study, a 64-year old male patient with history of coronary artery bypass was admitted to ICU with severe COVID-19 pneumonia accompanied by pneumomediastinum and pneumopericardium. Continous renal replacement therapy and extracorporeal membraneous-oxygenation were initiated due to acute renal failure and persistent hypercarbia/hypoxia, respectively. Within four weeks of hospitalization various episodes of bacteremia developed and multiple antibiotics were used. On the 5th week of follow-up, acute phase reactants increased and empirical broad spectrum antibiotics were initiated. Blood culture revealed Gram-negative rods. The patient became hypotensive and despite maximum medical care he was lost due to cardiac arrest. M. odoratimimus was identified by MALDI-TOF and the bacterium was pan-resistant. According to Center for Genomic Epidemiology results the strain was identified as M. odoratimimus PR63039 and the genome analysis revealed antibiotic resistance genes associated with resistance to beta-lactams (bla(OXA-347), bla(MUS-1), bla(EBR-1)), tetracyclines (tetX), sulfonamides (sul2), macrolides (ereD), (ermF)

Immunosuppressive therapy and the risk of hepatitis B reactivation: Consensus report

This consensus report includes expert opinions and recommendations regarding the screening, and if necessary, the follow-up, prophylaxis, and treatment of hepatitis B before the treatment in patients who will undergo immunosuppressive therapy due to the risk of hepatitis B reactivation emergency. To increase awareness regarding the risk of hepatitis B reactivation in immunosuppressive patients, academicians from several university health research and training centers across Turkey came together and discussed the importance of the subject, current status, and issues in accordance with the current literature data and presented solutions

Urinary tract infections in older adults: associated factors for extended-spectrum beta-lactamase production

ObjectiveUrinary tract infections (UTIs) due to extended-spectrum beta-lactamase (ESBL) producing Escherichia coli and Klebsiella pneumoniae are among the leading causes of morbidity and mortality in older adults. Identifying associated factors for ESBL production may contribute to more appropriate empirical treatment.Materials and methodsThis was a prospective observational study. Hospitalized patients of age &gt; 65 with community-onset or hospital-acquired upper UTI due to E. coli or Klebsiella pneumoniae were included. A multivariate analysis was performed.ResultsA total of 97 patients were included. ESBL prevalence among UTIs with E. coli or Klebsiella pneumoniae was 69.1% (n = 67). CRP values at the time of UTI diagnosis were found to be significantly higher in the ESBL-producing group (p = 0.004). The multivariate analysis revealed that male gender (OR: 2.72, CI: 1.02–7.25), prior recurrent UTI (OR: 3.14, CI: 1.21–8.14), and the development of secondary bacteremia (OR: 4.95, CI: 1.03–23.89) were major associated factors for UTI in older adults due to ESBL-producing E. coli and Klebsiella pneumoniae.ConclusionSevere UTI in older men with a history of recurrent UTI may be a warning to the clinician for ESBL production in the setting of high ESBL prevalence. Carbapenems may be prioritized in the empirical treatment of patients with known risk factors for ESBL

Longitudinal analysis of hsa-miR-3163, hsa-miR-124-3p, hsa-miR-548c-3p, and hsa-miR-27a-3p as prognostic biomarkers in HIV-infected patients

IntroductionMicroRNAs (miRNAs), key regulators of cellular pathways, play crucial roles in the pathogenesis of various diseases, including Human Immunodeficiency Virus (HIV). This study aimed to evaluate the expression and diagnostic potential of in silico-identified miRNAs (miR-124-3p, miR-27a-3p, miR-548ac-3p, miR-3163) before and during antiretroviral treatment (ART), together with their correlations with immunological markers (CD4 count, CD4/CD45 ratio) and virological parameters (HIV RNA load).MethodsBlood samples and clinical data of 16 patients were collected at 4 different time points; before the initiation of ART (baseline), 1st, 2nd and 6th months following HIV diagnosis. 16 healthy controls were enrolled to this study. RT-qPCR and ELISA techniques were used to analyze miRNA expression levels while immunological markers (CD4 count and ratio) were assessed by flow cytometry.ResultsmiR-27a-3p expression was significantly increased at 2nd and 6th months of ART (p&lt;0.001). miR-548ac-3p was upregulated at 6th month compared to healthy individuals and ART-naive subjects (p&lt;0.05). miR-124-3p expression was significantly elevated in ART-naive subjects in comparison with healthy controls (p&lt;0.001). Conversely, miR-3163 was downregulated in ART-naive, 1-month, and 2-month ART groups (p&lt;0.001), but returned to normal levels by 6 months. miR-548ac-3p and miR-3163 showed moderate-to-strong positive correlations with CD4 counts (R=0.46, R=0.67; p&lt;0.001). ROC analysis identified miR-3163 as a promising prognostic marker, with an AUC of 0.8561, (95% CI: 0.756–0.9265).DiscussionOur findings highlight the potential of miR-3163 as a robust prognostic biomarker for monitoring HIV progression and optimizing ART strategies. Validation in larger cohorts is warranted to confirm its clinical utility

Low hepatitis B surface antigen and HBV DNA levels predict response to the addition of pegylated interferon to entecavir in hepatitis B e antigen positive chronic hepatitis B

Background: Various treatment combinations of peginterferon (PEG‐IFN) and nucleos(t)ide analogues have been evaluated for chronic hepatitis B (CHB), but the optimal regimen remains unclear. Aims: To study whether PEG‐IFN add‐on increases response compared to entecavir (ETV) monotherapy, and whether the duration of ETV pretreatment influences response. Methods: Response was evaluated in HBeAg positive patients previously treated in two randomized controlled trials. Patients received ETV pretreatment for at least 24 weeks and were then allocated to 24‐48 weeks of ETV+PEG‐IFN add‐on, or continued ETV monotherapy. Response was defined as HBeAg loss combined with HBV DNA <200 IU/mL 48 weeks after discontinuing PEG‐IFN. Results: Of 234 patients, 118 were assigned PEG‐IFN add‐on and 116 continued ETV monotherapy. Response was observed in 38/118 (33%) patients treated with add‐on therapy and in 23/116 (20%) with monotherapy (P = 0.03). The highest response to add‐on therapy compared to monotherapy was observed in PEG‐IFN naive patients with HBsAg levels below 4000 IU/mL and HBV DNA levels below 50 IU/mL at randomization (70% vs 34%; P = 0.01). Above the cut‐off levels, response was low and not significantly different between treatment groups. Duration of ETV pretreatment was associated with HBsAg and HBV DNA levels (both P < 0.005), but not with response (P = 0.82). Conclusions: PEG‐IFN add‐on to ETV therapy was associated with higher response compared to ETV monotherapy in patients with HBeAg positive CHB. Response doubled in PEG‐IFN naive patients with HBsAg below 4000 IU/mL and HBV DNA below 50 IU/mL, and therefore identifies them as the best candidates for PEG‐IFN add‐on (Identifiers: NCT00877760, NCT01532843)