Search

Growing evidence suggests that the depletion of plasma NAD+ and glutathione (GSH) may play an important role in the development of metabolic disorders. The administration of Combined Metabolic Activators (CMA), consisting of GSH and NAD+ precursors, has been explored as a promising therapeutic strategy to target multiple altered pathways associated with the pathogenesis of the diseases. Although studies have examined the therapeutic effect of CMA that contains N-acetyl-L-cysteine (NAC) as a metabolic activator, a system-wide comparison of the metabolic response to the administration of CMA with NAC and cysteine remains lacking. In this placebo-controlled study, we studied the acute effect of the CMA administration with different metabolic activators, including NAC or cysteine with/without nicotinamide or flush free niacin, and performed longitudinal untargeted-metabolomics profiling of plasma obtained from 70 well-characterized healthy volunteers. The time-series metabolomics data revealed the metabolic pathways affected after the administration of CMAs showed high similarity between CMA containing nicotinamide and NAC or cysteine as metabolic activators. Our analysis also showed that CMA with cysteine is well-tolerated and safe in healthy individuals throughout the study. Last, our study systematically provided insights into a complex and dynamics landscape involved in amino acid, lipid and nicotinamide metabolism, reflecting the metabolic responses to CMA administration containing different metabolic activators. PoLiMeR Innovative Training Network ; SNIC ; ScandiBio Therapeutics ; U.S. Food and Drug Administration ; H2020 Marie Skłodowska-Curie Actions ; National Arts Council - Singapore ; Knut och Alice Wallenbergs Stiftelse ; Chinese Medical Association ; Horizon 2020

Several risk scores have been developed to predict hepatocellular carcinoma (HCC) risk in chronic hepatitis B (CHB) patients. The majority of risk scores are based on pretreatment variables that are no longer considered risk factors for HCC development due to the suppression of hepatitis B virus replication early in the course of potent antiviral treatment in most patients. The PAGE-B score, which is based on platelet levels, age and sex, has been shown to accurately predict HCC risk in CHB patients on antiviral treatment in various populations.We aimed to evaluate the PAGE-B score in predicting HCC risk in Turkish CHB patients on antiviral treatment.In this study, we recruited 742 CHB patients who had been treated with tenofovir disoproxil fumarate or entecavir for ≥ 1 year. Risk groups were determined according to the PAGE-B scores as follows: ≤ 9, low; 10-17, moderate and ≥ 18, high. The cumulative HCC incidences in each risk group were computed using Kaplan-Meier analysis and were compared using the log-rank test. The accuracy of the PAGE-B score in predicting HCC risk was evaluated using a time-dependent area under the receiver operating characteristic (AUROC) curve at all study time points. Univariate and multivariate logistic regression analyses were used to assess the risk factors for HCC development.The mean follow-up time was 54.7 ± 1.2 mo. HCC was diagnosed in 26 patients (3.5%). The cumulative HCC incidences at 1, 3, 5 and 10 years were 0%, 0%, 0% and 0.4% in the PAGE-B low-risk group; 0%, 1.2%, 1.5% and 2.1% in the PAGE-B moderate-risk group; and 5%, 11.7%, 12.5%, and 15% in the PAGE-B high-risk group, respectively (log-rankThe PAGE-B score is a practical tool to predict HCC risk in Turkish patients with CHB and may be helpful to improve surveillance strategies.

Copy number variations (CNVs) are commonly associated with malignancies, including hereditary breast and ovarian cancers. Next generation sequencing (NGS) provides solutions for CNV detection in a single run. This study aimed to compare the accuracy of CNV detection by NGS analyzing tool against Multiplex Ligation Dependent Probe Amplification (MLPA).In total, 1276 cases were studied by targeted NGS panels and 691 cases (61 calls in 58 NGS-CNV positive and 633 NGS-CNV negative cases) were validated by MLPA.Twenty-eight (46%) NGS-CNV positive calls were consistent, whereas 33 (54%) calls showed discordance with MLPA. Two cases were detected as SNV by the NGS and CNV by the MLPA analysis. In total, 2% of the cases showed an MLPA confirmed CNV region inThe diagnostic performance of NGS-CNV analysis is promising; however, the need for confirmation by different methods remains.

BACKGROUND: We aimed to investigate the long-term effects of tenofovir disoproxil fumarate and entecavir treatment on bone mineral density and evaluated the fracture risk assessment tool score in patients with chronic hepatitis B. METHODS: A total of 58 chronic hepatitis B patients treated with tenofovir disoproxil fumarate (n = 40) and entecavir (n = 18) were included in this prospective study from 2012 to 2016. To evaluate bone mineral density, dual-X-ray absorptiometry, fracture risk assessment tool, and laboratory examinations were performed in all patients first at baseline and second at the end of the study. RESULTS: Age, sex, body mass index, fibrosis score, and viral load were similar in both groups. The mean follow-up was 33 months in the tenofovir disoproxil fumarate group and 31 months in the entecavir group. In patients treated with entecavir, there was no statistically significant difference between baseline and second bone mineral density including lumbar spine (L) and total hip T score. In patients treated with tenofovir disoproxil fumarate, there was a significant difference in the second bone mineral density compared with baseline bone mineral density for L3 (P = .033) and the major fracture risk assessment tool score (P = .03). When patients were divided into 3 groups (normal bone mineral density, osteopenic, and osteoporotic), there was a significant increase in the number of osteopenic patients in the total hip T score after tenofovir disoproxil fumarate treatment (P = .034). CONCLUSION: Our results suggest a decrease in the bone mineral density for lumbar spine (L3), an increase in the number of patients with hip osteopenia, and major fracture risk assessment tool score after long-term tenofovir disoproxil fumarate treatment in patients with rechronic hepatitis B.

INTRODUCTION LQTS is of great importance as it is the most common cause of sudden cardiac death in childhood. The diagnosis is made by the prolongation of the QTc interval on the ECG. However, clinical heterogeneity and non-diagnostic QTc intervals may cause a delay in the diagnosis. In such cases, genetic tests such as NGS panel analysis enable a definitive diagnosis. We present the first study that aimed to expand the LQTS's mutational spectrum by NGS panel analysis from Turkey. METHODS Fifty-seven unrelated patients with clinically diagnosed LQTS were investigated using an NGS panel that includes six LQTS-related genes. Clinical aspects, outcome, and molecular analysis results were reviewed. RESULTS Pathogenic(53%)/likely pathogenic(23%)/VUS(4%) variants were detected in any of the genes examined in 79% of the patients. Among all detected variants, KCNQ1(71%) was the most common gene, followed by SCN5A(11%), KCNH2(10%), CALM1(5%), and CACNA1C(3%). Twelve novel variants were detected. Among the variants in KCNQ1, the c.1097G>A variant was present in 42% of patients. This variant also composed 31% of the variants detected in all of the genes. CONCLUSION Our study expands the spectrum of the variations associated with LQTS with twelve novel variants in five genes. And also it draws attention to the frequency of the KCNQ1 c.1097G>A variant and forms the basis for new studies to determine the possible founder effect in the Turkish population. Furthermore, identifying new variants and clinical findings has importance in elaborating the roles of related genes in pathophysiology and determining the variable expression and incomplete penetration rates in this syndrome. This article is protected by copyright. All rights reserved.

SUMMARY OBJECTIVE: The objectives of this study were to describe lung computed tomography findings of patients with COVID-19 diagnosed by real-time reverse transcription polymerase chain reaction test, investigate whether the findings differ regarding age and gender, and evaluate the diagnostic performance of chest computed tomography based on the duration of symptoms at the time of presentation to the hospital. METHODS: From March 11 to May 11, 2020, 1271 consecutive patients (733 males and 538 females) were included in this retrospective, cross-sectional study. Based on age, patients were divided into five separate subgroups. Then based on the duration of symptoms, patients were divided into five separate phases. The presence of lung lesion(s) and their characteristics, distribution patterns, and the presence of concomitant pleural thickening/effusion and other findings (malignancy, metastasis, chronic obstructive pulmonary disease, interstitial lung disease, bronchiectasis, bronchiectasis, cardiomegaly, pericardial effusion) were evaluated by five radiologists independently. RESULTS: The “normal lung computed tomography finding” was the most common chest CT finding (37%), followed by ground-glass opacity (31%). Regardless of the shape of the lesion, the distribution features were significant (peripheral, subpleural, and lower lobe distribution) (p

© 2022 by the authors.We present the interim results of the efficacy, immunogenicity, and safety of the two-dose schedules of TURKOVAC versus CoronaVac. This was a randomized, observer-blinded, non-inferiority trial (NCT04942405). Volunteers were 18–55 years old and randomized at a 1:1 ratio to receive either TURKOVAC or CoronaVac at Day 0 and Day 28, both of which are 3 μg/0.5 mL of inactivated severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) adsorbed to aluminum hydroxide. The primary efficacy outcome was the prevention of polymerase chain reaction (PCR)-confirmed symptomatic coronavirus disease 2019 (COVID-19) at least 14 days after the second dose in the modified per-protocol (mPP) group. Safety analyses were performed in the modified intention-to-treat (mITT) group. Between 22 June 2021 and 7 January 2022, 1290 participants were randomized. The mITT group consisted of 915 participants, and the mPP group consisted of 732 participants. During a median follow-up of 90 (IQR 86–90) days, the relative risk reduction with TURKOVAC compared to CoronaVac was 41.03% (95% CI 12.95–60.06) for preventing PCR-confirmed symptomatic COVID-19. The incidences of adverse events (AEs) overall were 58.8% in TURKOVAC and 49.7% in CoronaVac arms (p = 0.006), with no fatalities or grade four AEs. TURKOVAC was non-inferior to CoronaVac in terms of efficacy and demonstrated a good safety and tolerability profile.

Objective: The majority of the liver function tests are not specific to the liver. The histological liver damage begins before patients are diagnosed with cirrhosis and continues afterwards. Therefore, there is an increasing demand for early and specific markers that are correlated with liver damage. This study aims to investigate if serum and urinary liver fatty acid-binding protein (L-FABP) levels could be used as an early diagnostic marker of liver cirrhosis. Material and Methods: This cross-sectional study included 30 patients with compensated liver cirrhosis, 27 patients with decompensated liver cirrhosis, and 30 healthy controls. The patients and healthy controls were tested for serum and urinary L-FABP levels. Results: The serum and urinary L-FABP levels were higher in patients with cirrhosis than the healthy controls (both p

Background The aim of this study was to evaluate the prevalence of osteopenia and osteoporosis in adult patients with celiac disease (CD) at diagnosis and/or in the follow-up after a gluten-free diet (GFD). Methods Adult patients diagnosed with CD were retrospectively screened through follow-up records and computer databases. Patients assessed by dual-energy X-ray absorptiometry (DEXA) at diagnosis and/or in the follow-up after a GFD were included in the study. Results One hundred patients who underwent a DEXA scan at least once after diagnosis or after being on a GFD were included in the study. The mean age of the patients at diagnosis was 34.61 ± 10.3 years, and 84% of the patients (n = 84) were female. At the time of diagnosis (n = 46), the prevalence of osteopenia and osteoporosis was 67.3% and 15.2%, respectively, at the lumbar spine, and 43.4% and 10.8%, respectively, at the femur. After a GFD (n = 78), the prevalence of osteopenia and osteoporosis was 61.5% and 8.9%, respectively, at the lumbar spine, and 37.1% and 2.5%, respectively, at the femur. Conclusion The prevalence of CD patients with low bone mineral density (BMD) is high after diagnosis and in the follow-up after a GFD. It is important for all patients with CD to undergo a DEXA scan to determine the follow-up and/or treatment characteristics.

The HCC-RESCUE score was developed to predict hepatocellular carcinoma (HCC) risk in Korean chronic hepatitis B (CHB) patients under entecavir therapy. We aimed to validate the HCC-RESCUE score to predict HCC risk in Caucasian CHB patients under entecavir or tenofovir therapy and to compare the predictive performance of the HCC-RESCUE score with those of the CAMD, PAGE-B and modified PAGE-B (mPAGE-B) scores. The study included 647 nucleos(t)ide analogue-naive noncirrhotic and compensated/decompensated cirrhotic patients who had received entecavir or tenofovir for ≥6 months and did not develop HCC during the first 6 months of therapy. Patients with HCC-RESCUE scores ≤64, 65-84 and ≥85 points were classified into low-, intermediate- and high-risk groups, respectively. The AUROCs of the HCC-RESCUE, CAMD, PAGE-B and mPAGE-B scores to predict HCC risk at 5 years were 0.875, 0.870, 0.866 and 0.880, and those at 10 years were 0.862, 0.845, 0.841 and 0.862, respectively (both p .05). Cumulative HCC incidences at 5 years were 0.0%, 10.5% and 15.8%, and those at 10 years were 1.4%, 15.5% and 24.9%, respectively, in the low-, intermediate- and high-risk groups based on the HCC-RESCUE score (both log rank p .001). In the entecavir versus tenofovir cohorts, the AUROCs of the HCC-RESCUE score to predict HCC risk at 5 and 10 years were 0.831 versus 0.898 and 0.803 versus 0.910, respectively (both p .05). The HCC-RESCUE score accurately predicted HCC risk in Caucasian CHB patients under entecavir or tenofovir therapy. A substantial proportion of patients can be dropped from HCC surveillance by using the HCC-RESCUE score.

Inherited pathogenic variants account for 5% to 10% of all breast cancer (BC) and colorectal cancer (CRC) cases. Here, we sought to profile the pathogenic variants in 25 cancer susceptibility genes in Turkish population. Germline pathogenic variants were screened in 732 BC patients, 189 CRC patients and 490 cancer-free elderly controls, using next-generation sequencing-based multigene panel testing and multiplex ligation-dependent probe amplification testing. Pathogenic variants were detected in 17.2% of high-risk BC patients and 26.4% of high-risk CRC patients. More than 95% of these variants were clinically actionable. BRCA1/2 and mismatch repair genes (MLH1, MSH2 and MSH6) accounted for two-thirds of all pathogenic variants detected in high-risk BC and CRC patients, respectively. Pathogenic variants in PALB2, CHEK2, ATM and TP53 were also prevalent in high-risk BC patients (4.5%). BRCA1 exons 17-18 deletion and CHEK2 c.592+3A>T were the most common variants predisposing to BC, and they are likely to be founder variants. Three frequent MUTYH pathogenic variants (c.884C>T, c.1437_1439delGGA and c.1187G>A) were responsible for all MUTYH biallelic cases (4.4% of high-risk CRC patients). The total pathogenic variant frequency was very low in controls (2.4%) and in low-risk BC (3.9%) and CRC (6.1%) patients. Our study depicts the pathogenic variant spectrum and prevalence in Turkish BC and CRC patients, guiding clinicians and health authorities for genetic testing applications and variant classification in Turkish population.

Systemic autoinflammatory diseases (SAIDs) may not always present with typical clinical findings of a monogenic disease. We aimed to genetically screen and diagnose these clinically unclassified patients by next-generation sequencing (NGS) analysis.A total of 64 patients who had clinical findings of a periodic fever syndrome but did not meet the clinical diagnostic criteria for any SAID or had clinical findings for more than one monogenic SAID were identified as "clinically unclassified SAIDs." NGS panel analysis, including 16 genes, was performed in these patients. Patients, who could not be classified as one of the defined SAID after the result of the NGS gene analysis, were identified as "undefined SAID."The most common autoinflammatory symptoms in unclassified SAID patients were abdominal pain (60.9%), arthralgia (48.4%), urticarial rash (43.8%), myalgia (40.6%), oral aphthae (28.1%), and conjunctivitis (20.3%), respectively. In the result of the NGS gene panel screening, pathogenic, likely pathogenic variants, or VUS (variants of uncertain significance) were detected in 36 of 64 patients in at least one gene in the NGS panel. A total of 15 patients were diagnosed with a monogenic SAID according to both phenotypic and genotypic data; 12 patients as FMF, two patients as FCAS, and one patient as TRAPS, respectively. A total of 49 patients who did not meet the classification criteria including genetic results for a monogenic SAID were followed as undefined SAID.The classification criteria described for SAIDs so far unfortunately do not cover all patients with signs of periodic fevers. The NGS gene panel appears to be a useful diagnostic tool for some of the patients with clinically unclassified SAID findings. Key Points • The classification criteria described for SAIDs do not cover all patients with signs of periodic fevers • The use of the undefined SAID nomenclature will benefit clinicians for diagnosis and initiating early treatment • The NGS panel appears to be a useful diagnostic tool in patients with clinically unclassified SAIDs.

OBJECTIVE: Turkey is one of the latest countries that COVID-19 disease was reported, with the first case on March 11, 2020, and since then, Istanbul became the epicenter of the pandemic in Turkey. Here, we reveal sequences of the virus isolated from three different patients with various clinical presentations. METHODS: Nasopharyngeal swab specimens of the patients were tested positive for the COVID-19 by qRT-PCR. Viral RNA extraction was performed from the same swab samples. Amplicon based libraries were prepared and sequenced using the Illumina NextSeq platform. Raw sequencing data were processed for variant calling and generating near-complete genome sequences. All three genomes were evaluated and compared with other worldwide isolates. RESULTS: The patients showed various clinics (an asymptomatic patient, patient with mild disease, and with severe pulmonary infiltration). Amplicon-based next-generation sequencing approach successfully applied to generate near-complete genomes with an average depth of 2.616. All three viral genomes carried the D614G variant (G clade according to GISAID classification) with implications for the origin of a spread first through China to Europe then to Istanbul. CONCLUSION: Here, we report the viral genomes circulating in Istanbul for the first time. Further sequencing of the virus isolates may enable us to understand variations in disease presentation and association with viral factors if there is any. In addition, the sequencing of more viral genomes will delineate the spread of disease and will guide and ease the necessary measures taken to stem the spread of the novel coronavirus.

Concurrent pathogenic variants (PVs) in cancer predisposition genes have been reported in 0.1-2% of hereditary cancer (HC) patients. Determining concurrent PVs is crucial for the diagnosis, treatment, and risk assessment of unaffected family members. Next generation sequencing based diagnostic tests, which are widely used in HCs, enable the evaluation of multiple genes in parallel. We have screened the family members of a patient with bilateral breast cancer who was found to have concurrent PVs in BRCA1 (NM_007294.3;c.5102_5103del, p.Leu1701Glnfs*14) and MUTYH (NM_001128425.1;c.884CT, p.Pro295Leu). Further analysis revealed concurrent PVs in CHEK2 (NM_007194.4;c.1427CT, p.Thr476Met) and MUTYH (NM_001128425.1;c.884CT, p.Pro295Leu) in the maternal uncle of the index case. Eight additional family members were found to have PVs in BRCA1 and MUTYH among 26 tested relatives. The sister and the brother of the index case who were diagnosed with breast and colon cancers, respectively, presented with the same genotype as the index case. Each family member was evaluated individually for clinical care and surveillance. This is the first report describing a family with BRCA1, MUTYH and CHEK2 concurrent PVs. Our findings provide valuable information for the assessment and management considerations for families with concurrent PVs.

OBJECTIVE: There are many instruments to measure disease activity in ulcerative colitis. While determining clinical activity according to these instruments, many clinical and laboratory parameters are needed to be followed. Determination of disease activity with non-invasive and objective inflammatory indicators may be a practical and objective way. CRP/Albumin ratio (CAR) is an inflammatory marker that is considered to have prognostic value in various cancers, sepsis and acute pancreatitis. In this study, we aim to investigate diagnostic performance CAR in determining the clinical severity of ulcerative colitis. METHODS: Between November 2011 and February 2017, hospital records and follow-up cards of patients with ulcerative colitis were reviewed retrospectively. One hundred forty-nine patients were included in this study. Patient's demographic data, laboratory values, clinical disease activity, according to Truelove & Witts criteria and endoscopic activity according to the Mayo sub-score and treatments, were recorded. Diagnostic performance of CAR analyzed to determine the clinical severity. RESULTS: Of the patients included in this study, 99 (62%) were male, and 50 (38%) were female. Mean age was 45.22+-14 years. When patients were grouped into remission, mild, moderate and severe disease according to disease activity, there was a statistically significant difference between CRP, CAR, erythrocyte sedimentation rate (ESR) and albumin levels (p=0.001; p

INTRODUCTION[|]Aim: In this study we aimed to investigate presence of subclinical atherosclerosis with measuring epicardial fat thickness (EFT) and carotid intima media thickness (c-IMT), to evaluate low level inflammation with hsCRP and to evaluate whether there is a relationship between lipid profile, atherogenic indices and hsCRP with these subclinical atherosclerosis markers in patients with celiac disease (CD). [¤]METHODS[|]After exclusion and inclusion criteria were applied, 31 patients with CD (24 female, mean age: 39.4+-12.3 years) and 32 healthy controls (21 female, mean age: 39.5+-4.4 years), totally 63 cases, were recruited. Subclinical atherosclerosis was evaluated with EFT by transthoracic echocardiography and cIMT by ultrasonography. Inflammatory markers including erythrocyte sedimentation rate (ESR), hsCRP, and lipid profile were recorded. Also, atherogenic indices were calculated: Castelli risk index I and II (TG/HDL-c and LDL-c/HDL-c, respectively), atherogenic index of plasma (AIP; logarithm TG/HDL-c), non-HDL-c (TG-HDL-c), and atherogenic coefficient (AC; non-HDL-c/HDL-c).[¤]RESULTS[|]EFT was significantly higher in the CD group (0.49+-0.10 vs. 0.49+-0.09; p-value: 0.02). Although cIMT was higher in the patient group, it did not reach statistical significance (0.51+-0.08, 0.47+-0.08; p-value: 0.10). HDL cholesterol level was found to be significantly lower (42.0+-8.8 vs. 50.0+-13.7; p-value: 0.01), and the plasma atherogenic index was found to be significantly higher in the patient group (0.98+-0.50 vs. 0.62+-0.64; p-value: 0.02). hsCRP (3.51+-3.18 vs. 1.92+-1.40; p-value: 0.02) and ESR (17.2+-12.8 with 9.7+-3.1; p-value: 0.01) were found to be significantly higher in the CD group. Although there was a significant positive correlation between EFT and hsCRP (r: 0.453; p-value: 0.01), there was a significant negative correlation between cIMT and HDL-cholesterol (−0.339; p-value: 0.05), and a significant positive correlation with the other components of the atherogenic index was found.[¤]DISCUSSION AND CONCLUSION[|]The risk of atherosclerosis has been increased in patients with CD. Chronic inflammation may be responsible for this increase along with atherogenic indices.[¤]

Background: It is controversial whether entecavir or tenofovir differs in reducing hepatocellular carcinoma (HCC) risk. We aimed to compare the efficacy of entecavir and tenofovir in reducing HCC risk in chronic hepatitis B (CHB) patients. Methods: This retrospective study included 607 nucleos(t)ide naive CHB patients who had received entecavir or tenofovir. Patients who developed HCC during the first 12 months of therapy were excluded. Cumulative HCC incidences at years 2, 3, 4, 5 and 10 were compared between entecavir and tenofovir groups. Factors associated with HCC were determined by univariate and multivariate analyses. Results: Nineteen (3.1%) patients developed HCC, 12 (4.8%) in entecavir group and 7 (1.9%) in tenofovir group (P = .045). In the entire cohort, cumulative HCC incidences at years Z 3, 4, 5 and 10 were 1.8%, 2.9%, 4.4%, 5.2% and 9.9% in entecavir group, and 0.6%, 2.4%, 2.4%, 2.4% and 3.7% in tenofovir group, respectively (log-rank P = .130). In multivariate analysis, age >= 50 years, cirrhosis, decompensated cirrhosis, high GGT and low platelet levels were associated with HCC in the entire cohort. In advanced fibrosis/cirrhosis cohort, cumulative HCC incidences at years 2, 3, 4, 5 and 10 were 4.6%, 7.1%, 8.6%,12.1% and 15.5% in entecavir group, and 1.8%, 5.6%, 5.6%, 5.6% and 8.5% in tenofovir group, respectively (log-rank P = .267). In multivariate analysis, age >= 50 years, decompensated cirrhosis, high GOT and low platelet levels were associated with HCC in the advanced fibrosis/cirrhosis cohort. Conclusion: Entecavir and tenofovir are similarly effective in reducing HCC risk in CHB patients. WOS:000670759200009 Q4

The impact of chronic hepatitis B virus (HBV) infection and nucleos(t)ide analogue (NUC) treatment on disease severity and clinical outcomes in patients with coronavirus 2019 (COVID-19) is unknown. The objective of this study was to determine whether HBV infection and the use of NUCs impacts mortality in patients with COVID-19.A total of 231 adult patients (77 with COVID-19 and HBV coinfection) with a laboratory-confirmed diagnosis of COVID-19 were enrolled in this retrospective study. Univariate and binary logistic regression analysis were performed to evaluate the risk factors for mortality from COVID-19.Patients with COVID-19 and HBV coinfection had a similar rate of mortality to those without HBV coinfection (7.8% vs 9.7%; p=0.627). Cardiovascular disease (odds ratio [OR]: 8.22, 95% confidence interval [CI]: 1.52-44.2; p=0.014) and a high basal aspartate transaminase level (OR: 7.94, 95% CI: 1.81-34.8; p=0.006) were independent predictors of mortality due to COVID-19. In the COVID-19 and HBV coinfection group, the patients who died had a significantly higher median level of HBV DNA than patients who survived (378 IU/mL vs 0 IU/mL; p=0.048). Thirty (39%) patients with HBV coinfection received NUC treatment, and none of these patients died.HBV infection was not associated with mortality in patients with COVID-19, and it seems that NUC treatment for HBV infection might have an antiviral effect on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Next-generation sequencing (NGS) is used increasingly in hereditary cancer patients' (HCP) management. While enabling evaluation of multiple genes simultaneously, the technology brings to light the dilemma of variant interpretation. Here, we aimed to reveal the underlying reasons for the discrepancy in the evidence titles used during variant classification according to ACMG guidelines by two different bioinformatic specialists (BIs) and two different clinical geneticists (CGs). We evaluated final reports of 1920 cancer patients and 189 different variants from 285 HCP were enrolled to the study. A total of 173 of these variants were classified as pathogenic (n = 132) and likely pathogenic (n = 41) by the BI and an additional 16 variants, that were classified as VUS by at least one interpreter and their classification would change the clinical management, were compared for their evidence titles between different specialists. The attributed evidence titles and the final classification of the variants among BIs and CGs were compared. The discrepancy between P/LP final reports was 22.5%. The discordance between CGs was 30% whereas the discordance between two BIs was almost 75%. The use of PVS1, PS3, PP3, PP5, PM1, PM2, BP1, BP4 criteria markedly varied from one expert to another. This difference was particularly noticeable in PP3, PP5, and PM1 evidence and mostly in the variants affecting splice sites like BRCA1(NM_007294.4) c.4096 + 1 G > A and CHEK2(NM_007194.4) c.592 + 3 A > T. With recent advancements in precision medicine, the importance of variant interpretations is emerging. Our study shows that variant interpretation is subjective process that is in need of concrete definitions for accurate and standard interpretation.

Bag-1 protein is a crucial target in cancer to increase the survival and proliferation of cells. The Bag-1 expression is significantly upregulated in primary and metastatic cancer patients compared to normal breast tissue. Overexpression of Bag-1 decreases the efficiency of conventional chemotherapeutic drugs, whereas Bag-1 silencing enhances the apoptotic efficiency of therapeutics, mostly in hormone-positive breast cancer subtypes. In this study, we generated stable Bag-1 knockout (KO) MCF-7 breast cancer cells to monitor stress-mediated cellular alterations in comparison to wild type (wt) and Bag-1 overexpressing (Bag-1 OE) MCF-7 cells. Validation and characterization studies of Bag-1 KO cells showed different cellular morphology with hyperactive Akt signaling, which caused stress-mediated actin reorganization, focal adhesion decrease and led to mesenchymal characteristics in MCF-7 cells. A potent Akt inhibitor, MK-2206, suppressed mesenchymal transition in Bag-1 KO cells. Similar results were obtained following the recovery of Bag-1 isoforms (Bag-1S, M, or L) in Bag-1 KO cells. The findings of this study emphasized that Bag-1 is a mediator of actin-mediated cytoskeleton organization through regulating Akt activation. © 2022 Kilbas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

BackgroundThe central role in the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), called as coronavirus disease 2019 (COVID-19), infection is attributed to angiotensin-converting enzyme 2 (ACE-2). ACE-2 expressing respiratory system involvement is the main clinical manifestation of the infection. However, literature about the association between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and higher ACE-2 expressing kidney is very limited. In this study, we primarily aimed to investigate whether there is a kidney injury during the course of SARS-CoV-2 infection. The predictive value of kidney injury for survival was also determined.MethodsA total of 47 participants who met the inclusion criteria were included in the study. The participants were classified as ‘‘COVID-19 patients before treatment’’ ‘‘COVID-19 patients after treatment’’, ‘‘COVID-19 patients under treatment in ICU’’ and ‘‘controls’’. The parameters comorbidity, serum creatinine and cystatin C levels, CKD-EPI eGFR levels, KIM-1 and NGAL levels, urine KIM-1/creatinine and NGAL/creatinine ratios were statistically compared between the groups. The associations between covariates including kidney disease indicators and death from COVID-19 were examined using Cox proportional hazard regression analysis.ResultsSerum creatinine and cystatin C levels, urine KIM-1/creatinine levels, and CKD-EPI, CKD-EPI cystatin C and CKD-EPI creatinine-cystatin C eGFR levels exhibited significant difference in the groups. The causes of the difference were more altered kidney function and increased acute kidney damage in COVID-19 patients before treatment and under treatment in ICU. Additionally, incidences of comorbidity and proteinuria in the urine analysis were higher in the COVID-19 patients under treatment in ICU group. Urine KIM-1/creatinine ratio and proteinuria were associated with COVID-19 specific death.ConclusionsWe found that COVID-19 patients under treatment in ICU exhibited extremely higher levels of serum cystatin C, and urine KIM-1/creatinine and urine NGAL/creatinine ratios. These results clearly described the acute kidney damage by COVID-19 using molecular kidney damage markers for the first time in the literature. Lowered CKD-EPI, CKD-EPI cystatin C and CKD-EPI creatinine-cystatin C eGFR levels were determined in them, as well. Urine KIM-1/creatinine ratio and proteinuria were associated with COVID-19 specific death. In this regard, considering kidney function and kidney damage markers must not be ignored in the COVID-19 patients, and serial monitoring of them should be considered.

Background. The gut-liver axis is one of the most emphasized topics in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Intestinal microbiota dysbiosis has been shown to be a predictor of disease severity and progression to fatty liver disease. Therefore, research addressing gut-based therapies has become popular. Objectives. To investigate the effect of lactulose and polyethylene glycol 3350 (PEG 3350) in mice with induced obesity and NAFLD at a non-diarrheal dose. Materials and methods. Thirty-six C57BL/6J male mice were divided into 6 groups. The first 2 groups (n = 6 each) were used as an induced obesity model (group A) and NAFLD model (group B) for 8 weeks. The remaining 24 animals were categorized into control diet group, high-fat diet (HFD) group, HFD + lactulose group, and HFD + PEG 3350 group. Serum and liver tissue samples were obtained for biochemical and histopathological analyses, respectively. Results. The HFD + lactulose treatment group displayed a significant decrease in liver weight (1.3 (1.3- 1.4) kg compared to 1.8 (1.6-1.9) kg) and NAFLD activity score (NAS) (1.5 (1.0-3.0) compared to 5.0 (4.0-5.0), respectively; p = 0.0043, p = 0.0021) when compared with the HFD group. However, a decrease in body weight (35.0 (34.6-36.0) kg compared to 40.9 (34.7-41.9) kg) and hepatosteatosis (HS) rate (33.3% compared to 100.0%) were not statistically significant (p = 0.1796, p = 0.0606, respectively). The HFD + PEG 3350 treatment group showed a statistically significant decrease in body weight (32.4 (30.2-33.9) kg compared to 40.9 (34.7-41.9) kg), liver weight (1.5 (1.3-1.5) kg compared to 1.8 (1.6-1.9) kg), HS rate (16.7% compared to 100.0%) and NAS (0.5 (0.0-1.0) compared to 5.0 (4.0-5.0); p = 0.0086, p = 0.0086, p = 0.0151, and p = 0.0021, respectively) when compared with the HFD group. Conclusions. We demonstrated that non-diarrheal dose of lactulose and PEG 3350 reduced hepatic inflammation in mice with induced NAFLD. It was also observed that PEG 3350 decreased HS and body weight. We believe these mechanisms can be utilized as novel therapeutic approaches in NAFLD in prospective human studies.

Objective: The fibrosis stage during diagnosis and the response to ursodeoxycholic acid in the 1st year of treatment are considered to be prognostic indicators in primary biliary cholangitis (PBC). Determining these indicators with non-invasive models can enable the risk of liver failure to be monitored with continuous variables from the moment of diagnosis. The aim of this study was to evaluate the diagnostic performance of non-invasive models for determining the prognostic indicators in patients with PBC. Materials and Methods: Data from patients with PBC were screened retrospectively. Patients were divided into early (≤2) and advanced (≥3) fibrosis groups. In addition, treatment response status according to the Paris-II criteria and liver failure risk (LFR) according to the UK-PBC score were determined. The S-Index consisting of gamma-glutamyltransferase (GGT), platelets (PLT), and albumin, (S-index: 1000×GGT÷[PLT×Albumın2]), other non-invasive models were calculated. The diagnostic effectiveness of non-invasive indicators to determine the fibrosis stage, response to treatment, and low LFR was analyzed. Results: Fifty-three patients were included in the study. The overall mean age at diagnosis was 49.6±13.6 years and 86.8% of the patients (n=46) were female. The S-Index was able to determine fibrosis stage, treatment responded, and patients with low LFR (AUC: 0.747, 0.823, and 0.752; p=0.006

SummaryCOVID-19 is a viral respiratory disease caused by SARS-CoV-2 infection. Global efforts of genomic surveillance of the virus give chance to track the spread of the pandemic. Global emergence of some viral mutations called attention and various studies have been suggested about increased infectivity of the virus. Herein, we sequenced viral genomes isolated from 184 patients in Istanbul and analyzed clinical metadata for the investigation of any viral mutation which affects the disease course of the host. We did not detect any viral mutations affecting the disease outcome in our cohort. Besides, we observed intra-host mutations in 76% of the isolates. Insertion/deletion and stop-gain mutations are also significantly less common among intra-host variants compared to consensus viral genome mutations. Longitudinal genomic surveillance is essential for timely detection of any lineages that might affect clinical outcome, the performance of diagnostic assays, or even the immunological escape of the virus.

The study investigated whether there is a male reproductive system coronavirus disease‐2019 (COVID‐19) phenomenon. Thirty participants who met the inclusion criteria were enrolled in the study between April and May 2020. The participants were assigned in one of the three groups including COVID‐19 patients before and after treatment, and controls. Presence of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) within the semen samples was investigated. Additionally, participant's demographics, semen parameters and serum sex hormone levels were compared between the groups. SARS‐CoV‐2 was not detected within the semen samples. Sperm morphology and serum sex hormone levels were significantly different between the groups. In the post hoc analysis, sperm morphology was significantly lower in the COVID‐19 patients. Patients before treatment had significantly lower serum FSH, LH and T levels than controls. However, patients after treatment had similar serum FSH, LH and T levels with controls and patients before treatment. In our opinion, COVID‐19 and its treatment had no specific deteriorative effect on male sexual health at a short‐time period. In the patients before treatment, decreased serum of T, FSH and LH levels was consistent with acute patient stress due to COVID‐19. Similarly, it seems that decreased sperm morphology was associated with the acute fever.

There is a need to treat COVID-19 patients suffering from respiratory problems, resulting in decreased oxygen levels and thus leading to mitochondrial dysfunction and metabolic abnormalities. Here, we investigated if a high oral dose of a mixture of Combined Metabolic Activators (CMA) can restore metabolic function and thus aid the recovery of COVID-19 patients. We conducted a placebo-controlled, open-label phase 2 study and a double-blinded phase 3 clinical trials to investigate the time of symptom-free recovery on ambulatory patients using a mixture of CMA consisting of NAD+ and glutathione precursors. The results of both studies showed that the time to complete recovery was significantly shorter in the CMA group (6.6 vs 9.3 days) in phase 2 and (5.7 vs 9.2 days) in phase 3 trials. A comprehensive analysis of the blood metabolome and proteome showed that the plasma levels of proteins and metabolites associated with inflammation and antioxidant metabolism are significantly improved in patients treated with the metabolic activators as compared to placebo. The results show that treating patients infected with COVID-19 with a high dose of CMAs leads to a more rapid symptom-free recovery, suggesting a role for such a therapeutic regime in the treatment of infections leading to respiratory problems.

The clinicians initially prefer to define patients with the systemic autoinflammatory disease (SAID)'s based on recommended clinical classification criteria; then, they confirm the diagnosis with genetic testing. We aimed to compare the initial phenotypic diagnoses of the patients who were followed up with the preliminary diagnosis of a monogenic SAID, and the genotypic results obtained from the next-generation sequence (NGS) panel.Seventy-one patients with the preliminary diagnosis of cryopyrin-associated periodic fever syndrome (CAPS), mevalonate kinase deficiency (MKD), or tumor necrosis factor-alpha receptor-associated periodic fever syndrome (TRAPS) were included in the study. The demographic data, clinical findings, laboratory results, and treatments were recorded. All patients were examined by NGS panel analysis including 16 genes. The genetic results were compared with the initial Federici score to determine whether they were compatible with each other.Thirty patients were initially classified as MKD, 22 as CAPS, and 19 as TRAPS. The frequency of clinical manifestations was urticarial rash 57.7%, diarrhea 49.2%, abdominal pain 47.8%, arthralgia 45%, oral aphthae 43.6%, myalgia 32.3%, tonsillitis 28.1%, and conjunctivitis 25.3%, respectively. After NGS gene panel screening, 13 patients were diagnosed with CAPS, 8 with MKD, 7 with familial Mediterranean fever, 5 with TRAPS, and 2 with NLRP12-associated periodic syndrome. The remaining 36 patients were genetically identified as undefined SAID since they were not classified as one of the defined SAIDs after the result of the NGS panel.We have demonstrated that clinical diagnostic criteria may not always be sufficient to establish the correct diagnosis. There is still low accordance between clinical diagnoses and molecular analyses. In the case of a patient with a preliminary diagnosis of a monogenic SAID with the negative result of target gene analysis, other autoinflammatory diseases should also be kept in mind in the differential diagnosis. Key Points • Monogenic autoinflammatory diseases can present with different clinical manifestations. • The clinical diagnostic criteria may not always be sufficient to reach the correct diagnosis in autoinflammatory diseases. • In the case of a patient with a preliminary diagnosis of a monogenic SAID with the negative result of target gene analysis, other autoinflammatory diseases should be kept in mind in the differential diagnosis.

SUMMARYCOVID-19 is a global threat with an increasing number of infections. Research on IgG seroprevalence among health care workers (HCWs) is needed to re-evaluate health policies. This study was performed in three pandemic hospitals in Istanbul and Kocaeli. Different clusters of HCWs were screened for SARS-CoV-2 infection. Seropositivity rate among participants was evaluated by chemiluminescent microparticle immunoassay. We recruited 813 non-infected and 119 PCR-confirmed infected HCWs. Of the previously undiagnosed HCWs, 22 (2.7%) were seropositive. Seropositivity rates were highest for cleaning staff (6%), physicians (4%), nurses (2.2%) and radiology technicians (1%). Non-pandemic clinic (6.4%) and ICU (4.3%) had the highest prevalence. HCWs in “high risk group” had similar seropositivity rate with “no risk” group (2.9 vs 3.6p=0.7), indicating the efficient implementation of protection measures in the hospitals in Turkey. These findings might lead to the re-evaluation of infection control and transmission dynamics in hospitals.

OBJECTIVE An association of gastric cancer and precursor lesions with gastric xanthelasma has frequently been reported. However, the incidence of both gastric xanthelasma and gastric cancer precursor lesions increases with age. The aim of this study was to evaluate the frequency and characteristics of atrophic gastritis, intestinal metaplasia and dysplasia in patients with gastric xanthelasma compared to controls. MATERIAL AND METHODS Cases with gastric xanthelasma endoscopically and histopathologically were included in this prospective study. The patients included in the study were compared with age- and sex-matched controls in terms of the frequency and characteristics of atrophic gastritis, intestinal metaplasia, dysplasia and cancer. RESULTS In a series of 1892 upper endoscopies, 108 patients (5.7%) were found to have gastric xanthelasma. The average age of the patients was 61.41 ± 11.43 years. Among the patients, 58 (53.7%) were male. The frequencies of atrophic gastritis, intestinal metaplasia, dysplasia and gastric cancer in the xanthelasma group (n = 108) were 31.5, 68.5, 3.7 and 2.8%, respectively. The frequencies of atrophic gastritis, intestinal metaplasia, dysplasia and gastric cancer in the control group (n = 183) were 11.5, 31.7, 0.5 and 0.5%, respectively. Compared to the control group, the frequency of these cancer precursor lesions and the prevalence of advanced stage based on operative link on gastritis intestinal metaplasia assessment were found to be higher in the xanthelasma group (P < 0.05). CONCLUSION Gastric xanthelasma is associated with an increased frequency of gastric precancerous lesions and should be considered an important marker.

The gold standard method in the diagnosis of SARS-CoV-2 infection is the detection of viral RNA in nasopharyngeal sample by RT-PCR. Recently, saliva samples has been suggested as an alternative due to being fast, reliable and non-invasive, rather than nasopharyngeal samples. We compared RT-PCR results in nasopharyngeal, oro-nasopharyngeal and saliva samples of COVID-19 patients. 98 of 200 patients were positive in RT-PCR analysis performed before the hospitalization. In day 0, at least one sample was positive in 67% of 98 patients. Positivity rate was 83% for both oro-nasopharyngeal and nasopharyngeal samples, while it was 63% for saliva samples (p

BACKGROUND/AIMS: Hepatitis B reactivation (HBVR) is an important risk of treatment with tumor necrosis factor inhibitors (anti-TNF). While antiviral prophylaxis is recommended before treatment in hepatitis B surface antigen (HBsAg) positive patients, there is no clear approach for the follow-up or prophylactic treatment of patients with past hepatitis B virus (HBV) infection. This study aimed to evaluate patients with past HBV infection treated with anti-TNF for HBVR and/or HBVR-associated biochemical breakthrough. MATERIALS AND METHODS: Patients who received anti-TNF therapy and had past HBV infection (HBsAg negative, anti-HBc IgG positive, anti-HBs negative or positive) were screened and evaluated at 3-month intervals for viral and biochemical breakthrough according to a liver function test (ALT) and HBV DNA level. RESULTS: A total of 653 patients who received anti-TNF therapy were screened. Ninety of these patients had past HBV infection and had not received antiviral prophylaxis. Anti-HBs positivity and isolated anti-HBc IgG positivity were seen in 87.7% (n: 79) and 12.2% (n: 11) of these patients, respectively. No HBVR was seen in 20% (n: 18) of patients who were followed up regularly, and no HBVR-associated biochemical breakthrough was found in patients who were not followed up regularly in terms of HBV DNA level (80%, n: 72) during the follow-up period (26±16 months). CONCLUSION: The use of anti-TNF in patients with past HBV infection has a low risk for HBVR. A follow-up for the ALT and HBV DNA levels at 3-month intervals may be more reasonable than administering antiviral prophylaxis to all patients.

BackgroundThe new type of Coronavirus infection had become a pandemic in a very short period since it was first seen in Wuhan. The outbreak had a negative impact on all health care systems throughout the world and overwhelmed the diagnostic laboratories as well. During the pandemic, handling patient specimens in accordance with the universal guidelines was troublesome as WHO, CDC and ECDC required cold chain compliance during transporting and storing the swap samples.Materials and methodsIn this study, we tested diagnostic performance of RT-PCR on 30 swab samples stored at ambient temperature and compared them with the samples stored at +4°C.ResultsOur results revealed that all the samples stored at ambient temperature remain PCR positive for at least five days. We did not see any false negativity.ConclusionIn conclusion, we report that transferring and storing of nasopharyngeal/oropharyngeal samples at ambient temperature could be possible in the resource-limited conditions like pandemic.

The WHO-named Coronavirus Disease 2019 (COVID-19) infection had become a pandemic within a short time period since it was detected in Wuhan. The outbreak required the screening of millions of samples daily and overwhelmed diagnostic laboratories worldwide. During this pandemic, the handling of patient specimens according to the universal guidelines was extremely difficult as the WHO, CDC and ECDC required cold chain compliance during transport and storage of the swab samples. The aim of this study was to compare the effects of two different storage conditions on the COVID-19 real-time PCR assay on 30 positive nasopharyngeal and/or oropharyngeal samples stored at both ambient temperature (22 ± 2 °C) and +4 °C. The results revealed that all the samples stored at ambient temperature remain PCR positive for at least six days without any false-negative result. In conclusion, transporting and storing these types of swab samples at ambient temperature for six days under resource-limited conditions during the COVID-19 pandemics are acceptable.

The clinical outcome of hepatitis B virus (HBV) infection depends on the success or failure of the immune responses to HBV, and varies widely among individuals, ranging from asymptomatic self-limited infection, inactive carrier state, chronic hepatitis, cirrhosis, hepatocellular carcinoma, to liver failure, depending on the success or failure of immune response to HBV. Genome-wide association studies (GWAS) identified key genetic factors influencing the pathogenesis of HBV-related traits. In this review, we discuss GWAS for persistence of HBV infection, antibody response to hepatitis B vaccine, and HBV-related advanced liver diseases. HBV persistence is associated with multiple genes with diverse roles in immune mechanisms. The strongest associations are found within the classical human leukocyte antigen (HLA) genes, highlighting the central role of antigen presentation in the immune response to HBV. Associated variants affect both epitope binding specificities and expression levels of HLA molecules. Several other susceptibility genes regulate the magnitude of adaptive immune responses, determining immunity vs tolerance. HBV persistence and nonresponse to vaccine share the same risk variants, implying overlapping genetic bases. On the other hand, the risk variants for HBV-related advanced liver diseases are largely different, suggesting different host-virus dynamics in acute vs chronic HBV infections. The findings of these GWAS are likely to pave the way for developing more effective preventive and therapeutic interventions by personalizing the management of HBV infection.

Key Clinical Message We used a multi‐gene panel testing to identify the germline variants in a mother‐daughter pair with early‐onset breast cancer, and detected one pathogenic protein‐truncating variant in BRCA2. Our results highlight the importance of genetic testing in identifying the pathogenic mutation running in cancer families.

Cancer is a multifactorial disorder; however, 5–10% of all cancers show hereditary background. In recent years many targeted next generation sequencing panels comprising cancer predisposition genes have been developed and used for diagnostic purposes in patients with increased cancer risk. Screening multiple genes at a time allows multiple variants in different genes to be detected as well. This study aims to determine the cases with concurrent mutations in different hereditary cancer predisposition genes and how they are clinically affected. Here, we screened 1090 index cases by next generation sequencing based hereditary cancer panels and evaluated the reflection of multiple variations on the phenotype. We detected 11 (1%) cases with pathogenic variants in more than one gene. These concurrent variations occurred mostly in BRCA1/2 (7/11) accompanied with MUTYH, ATM, CHECK2, NBN, and RAD50. In addition, MUTYH&ATM, NBN&MSH6, MUTYH&CHEK2 double heterozygous cases were detected. Moreover, we identified a case with three heterozygous variations in CDH1, MUTYH, and CHEK2. These patients presented malignancies that were mostly related to pathogenic variations they carried. Although they are rare, defining double heterozygous cases is important for managing appropriate therapy and accurate genetic consulting for the patients and family members.

Background COVID-19 has caused millions of deaths globally, yet the cellular mechanisms underlying the various effects of the disease remain poorly understood. Recently, a new analytical platform for comprehensive analysis of plasma protein profiles using proximity extension assays combined with next generation sequencing has been developed, which allows for multiple proteins to be analyzed simultaneously without sacrifice on accuracy or sensitivity. Methods We analyzed the plasma protein profiles of COVID-19 patients (n = 50) with mild and moderate symptoms by comparing the protein levels in newly diagnosed patients with the protein levels in the same individuals after 14 days. Findings The study has identified more than 200 proteins that are significantly elevated during infection and many of these are related to cytokine response and other immune-related functions. In addition, several other proteins are shown to be elevated, including SCARB2, a host cell receptor protein involved in virus entry. A comparison with the plasma protein response in patients with severe symptoms shows a highly similar pattern, but with some interesting differences. Interpretation The study presented here demonstrates the usefulness of "next generation plasma protein profiling" to identify molecular signatures of importance for disease progression and to allow monitoring of disease during recovery from the infection. The results will facilitate further studies to understand the molecular mechanism of the immune-related response of the SARS-CoV-2 virus. Funding This work was financially supported by Knut and Alice Wallenberg Foundation.

Background and study aims The success rate of Helicobacter pylori (H. pylori) eradication with the classical triple therapy is gradually declining. In this study, we aimed to compare and assess the efficacies of six different eradication regimens including sequential protocols. Patients and methods Endoscopically confirmed nonulcer dyspepsia patients were enrolled. H. pylori presence was determined either histologically or by a rapid urease test. Treatment-naive patients were randomly assigned to an either one of three 10-day (OAC, OTMB, and OACB) or one of three sequential protocols (OA + OCM, OA + OCMB, and OA + OMDB) (O = omeprazole, A = amoxicillin, C = clarithromycin, T = tetracycline, M = metronidazole, B = bismuth, D = doxycycline). The eradication was assessed 6–8 weeks after the completion of the treatment by a 14C-urea breath test. Results In total, 301 patients were included. Fifty-two percent of the participants (n = 157) were female, and the mean age was 44.9 years (range = 18–70). The intention to treat (ITT) and per protocol (PP) eradication rate for each regimen is as follows: OAC (ITT = 61.2%, PP = 75%), OTMB (83.3%, 87%), OACB (76.5%, 79.6%), OA + OCM (72.3%, 73.9%), OA + OCMB (82.7%, 89.6%), and OA + OMDB (59.3%, 65.3%). Smoking significantly affected the eradication rate (P = 0.04). Conclusion In this study, OTMB and OA + OCMB were significantly superior to the triple therapy and succeeded to reach the eradication rate proposed by the Maastricht consensus (over 80%). These two bismuth-containing regimens could be considered for first-line therapy in the regions with high clarithromycin resistance.

NCI-2020-0130

Objective In our study, we aimed to evaluate the endoscopic features such as prevalence and localization of polypoid lesions determined by us using esophagogastroduodenoscopy and histopathological characteristics of biopsy specimens taken in detail. Methods The data of 19,560 patients undergoing upper gastrointestinal endoscopy for any reason between 2009 and 2015 in our endoscopy unit were screened retrospectively and endoscopic and histopathological findings were analyzed in detail. Results In our study, the polypoid lesion was detected in 1.60% (n=313) of 19,560 patients. The most common localization of the polypoid lesions was determined to be gastric localization (n=301, 96.2%) and antrum with a rate of 33.5% (n=105). When 272 patients in whom biopsy specimen could be taken was investigated, the most frequently seen lesion was polyp (n=115, 43.4%). Hyperplastic polyps (n=81, 29.8%) were the most frequently seen type among all polyps. In histopathological evaluation of the lesions, the prevalence rates of intestinal metaplasia (IM), surrounding tissue IM, atrophy, dysplasia, and neoplasia (adenocarcinoma, squamous cell carcinoma, gastrointestinal stromal tumor, neuroendocrine tumor, and metastatic tumor) among premalignant lesions were determined to be 16.9%, 11.2%, 4.1%, 1.1%, and 3.7%, respectively. Conclusion Polypoid lesions can be seen in endoscopic investigations. In histopathological investigations, while the vast majority of these lesions are benign polyps, some of them are diagnosed as premalignant or malignant lesions. In our study, we determined malignant lesions higher than the similar studies in the literature. This condition shows how effective endoscopic procedure and histopathological evaluation are of vital importance.