Genomic disparity impacts variant classification of cancer susceptibility genes in Turkish breast cancer patients.

OBJECTIVE: Turkish genome is underrepresented in large genomic databases. This study aims to evaluate the effect of allele frequency in the Turkish population in determining the clinical utility of germline findings in breast cancer, including invasive lobular carcinoma (ILC), mixed invasive ductal and lobular carcinoma (IDC-L), and ductal carcinoma (DC). METHODS: Two clinic-based cohorts from the Umraniye Research and Training Hospital (URTH) were used in this study: a cohort consisting of 132 women with breast cancer and a non-cancer cohort consisting of 492 participants. The evaluation of the germline landscape was performed by analysis of 27 cancer genes. The frequency and type of variants in the breast cancer cohort were compared to those in the non-cancer cohort to investigate the effect of population genetics. The variant allele frequencies in Turkish Variome and gnomAD were statistically evaluated. RESULTS: The genetic analysis identified 121 variants in the breast cancer cohort (actionable = 32, VUS = 89) and 223 variants in the non-cancer cohort (actionable = 25, VUS = 188). The occurrence of 21 variants in both suggested a possible genetic population effect. Evaluation of allele frequency of 121 variants from the breast cancer cohort showed 22% had a significantly higher value in Turkish Variome compared to gnomAD (p < 0.0001, 95% CI) with a mean difference of 60 times (ranging from 1.37-354.4). After adjusting for variant allele frequency using the ancestry-appropriate database, 6.7% (5/75) of VUS was reclassified to likely benign. CONCLUSION: To our knowledge, this is the first study of population genetic effects in breast cancer subtypes in Turkish women. Our findings underscore the need for a large genomic database representing Turkish population-specific variants. It further highlights the significance of the ancestry-appropriate population database for accurate variant assessment in clinical settings.

Concurrent Pathogenic Variants of BRCA1, MUTYH and CHEK2 in a Hereditary Cancer Family.

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.884C>T, p.Pro295Leu). Further analysis revealed concurrent PVs in CHEK2 (NM_007194.4;c.1427C>T, p.Thr476Met) and MUTYH (NM_001128425.1;c.884C>T, 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.

Does Hepatic Steatosis Influence the Virological Response with Chronic Hepatitis B Patients Treated with Entecavir or Tenofovir Disoproxil Fumarate?

BACKGROUND: The effect of hepatic steatosis on the response to antiviral therapy administered in chronic hepatitis B patients is yet to be clarified. In this study, our aim was to determine the effect of hepatic steatosis on the virological response in chronic hepatitis B patients who were treated with entecavir or tenofovir disoproxil fumarate. METHODS: This retrospective cohort study was performed using the data of liver biopsy-proven chronic hepatitis B patients with or without hepatic steatosis, who received entecavir or tenofovir disoproxil fumarate treatment between 2012 and 2017. The undetectable serum hepatitis B virus deoxyribonucleic acid level under treatment was defined as the complete virological response. The predictors of virological response were determined, and it was checked whether the virological response was affected by hepatic steatosis in chronic hepatitis B patients who have undergone entecavir or tenofovir disoproxil fumarate treatment. RESULTS: A total of 324 chronic hepatitis B patients, of which 203 (63%) were males, were included in the study. The median age of the patients was 42 years (range: 35-51 years). Hepatic steatosis was observed in 25% of the patients, and steatohepatitis in 4%. The median time to complete virological response was found to be 6 months (range: 3-9 months). In the full analysis model, the log hepatitis B virus deoxyribonucleic acid was determined as the factor most associated with virological response (P < .001). No statistically signifi- cant relationship was detected between hepatic steatosis and virological response (P = .409). CONCLUSION: Concomitant hepatic steatosis has no significant impact on the virological response in chronic hepatitis B patients who have undergone entecavir or tenofovir disoproxil fumarate treatment.

A New Risk-Scoring System for Colorectal Cancer and Polyp Screening by Turkish Colorectal Cancer and Polyp Study Group.

BACKGROUND: Colorectal cancer is one of the most commonly diagnosed types of cancer worldwide. An early diagnosis and detection of colon cancer and polyp can reduce mortality and morbidity from colorectal cancer. Even though there are a variety of options in screen- ing tests, the question remains on which test is the most effective for the early detection of colorectal cancer. In this prospective study, we aimed to develop a simple, useful, effective, and reliable scoring system to detect colon polyp and colorectal cancer. METHODS: We enrolled 6508 subjects over the age of 18 from 16 centers, with colonoscopy screening. The age, smoking status, alcohol consumption, body mass index, polyp incidence, polyp size, number and localization, and pathologic findings were recorded. RESULTS: The age, male gender, obesity, smoking, and family history were found as independent risk factors for adenomatous polyp. We have developed a new scoring system which can be used for these factors. With a score of 4 or above, we found the following: sensitivity 81%, specificity 40%, positive predictive value 25.68%, and negative predictive value 89.84%, for adenomatous polyp detection; and sensitivity 96%, specificity 39%, positive predictive value 3.35%, negative predictive value 99.29%, for colorectal cancer detection. CONCLUSION: Even though the first colorectal cancer screening worldwide is generally performed for individuals over 50 years of age, we recommend that screening for colorectal cancer might begin for those under 50 years of age as well. Individuals with a score ≥ 4 must be included in the screening tests for colorectal cancer.

Determining the accuracy of next generation sequencing based copy number variation analysis in Hereditary Breast and Ovarian Cancer.

BACKGROUND: 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). RESEARCH DESIGN AND METHODS: 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. RESULTS: 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 in BRCA1/2. The results of this study showed that despite the high false positive call rate of the NGS-CNV algorithm, there were no false negative calls. The cases that were determined to be negative by the NGS and positive by the MLPA were actually carrying SNVs that were located on the MLPA probe binding sites. CONCLUSION: The diagnostic performance of NGS-CNV analysis is promising; however, the need for confirmation by different methods remains.

Consistency of variant interpretations among bioinformaticians and clinical geneticists in hereditary cancer panels.

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.

Altered kidney function induced by SARS-CoV-2 infection and acute kidney damage markers predict survival outcomes of COVID-19 patients: a prospective pilot study.

BACKGROUND: Literature with regard to coronavirus disease 2019 (COVID-19) associated morbidities and the risk factors for death are still emerging. In this study, we investigated the presence of kidney damage markers and their predictive value for survival among hospitalized subjects with COVID-19. METHODS: Forty-seven participants was included and grouped as: 'COVID-19 patients before treatment', 'COVID-19 patients after treatment', 'COVID-19 patients under treatment in intensive care unit (ICU)', and 'controls'. Kidney function tests and several kidney injury biomarkers were compared between the groups. Cumulative rates of death from COVID-19 were determined using the Kaplan-Meier method. The associations between covariates including kidney injury markers and death from COVID-19 were examined, as well. RESULTS: Serum creatinine and cystatin C levels, urine Kidney Injury Molecule-1 (KIM-1)/creatinine ratio, and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), CKD-EPI cystatin C, and CKD-EPI creatinine-cystatin C levels demonstrated significant difference among the groups. The most significant difference was noted between the groups 'COVID-19 patients before treatment' and 'COVID-19 patients under treatment in ICU'. Advancing age, proteinuria, elevated serum cystatin C, and urine KIM-1/creatinine ratio were all significant univariate correlates of death (p < 0.05, for all). However, only elevated urine KIM-1/creatinine ratio retained significance in an age, sex, and comorbidities adjusted multivariable Cox regression (OR 6.11; 95% CI: 1.22-30.53; p = 0.02), whereas serum cystatin C showing only a statistically non-significant trend (OR 1.42; 95% CI: 0.00-2.52; p = 0.09). CONCLUSIONS: Our findings clearly demonstrated the acute kidney injury related to COVID-19. Moreover, urine KIM-1/creatinine ratio was associated with COVID-19 specific death.

Effects of Long-Term Tenofovir and Entecavir Treatment on Bone Mineral Density in Patients with Chronic Hepatitis B.

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.

Mutational spectrum of congenital long QT syndrome in Turkey; identification of 12 novel mutations across KCNQ1, KCNH2, SCN5A, KCNJ2, CACNA1C, and CALM1.

INTRODUCTION: Long QT syndrome (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 electrocardiography. However, clinical heterogeneity and nondiagnostic QTc intervals may cause a delay in the diagnosis. In such cases, genetic tests such as next-generation sequencing (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%)/variant of unknown significance (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.

COVID-19 PCR test performance on samples stored at ambient temperature.

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.

Chest computed tomography findings of 1271 patients with COVID-19 pneumonia and classifications with different age groups: a descriptive study from Istanbul, Turkey.

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<0.05). The presence of pleural thickening posteriorly and adjacent to the lesion was statistically different in groups 1-3 (p<0.05). Other concomitant pathologies, except pulmonary congestion, did not suppress the typical findings of COVID-19. CONCLUSION: Chest computed tomography findings were mostly normal in the early phase (P1). Therefore, it may be appropriate to perform the first computed tomography screening of COVID-19 after 6 days to decrease the radiation exposure.

Next generation plasma proteome profiling of COVID-19 patients with mild to moderate symptoms.

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.

Chest computed tomography findings of 1271 patients with COVID-19 pneumonia and classifications with different age groups: a descriptive study from Istanbul, Turkey

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<0.05). The presence of pleural thickening posteriorly and adjacent to the lesion was statistically different in groups 1-3 (p<0.05). Other concomitant pathologies, except pulmonary congestion, did not suppress the typical findings of COVID-19. CONCLUSION: Chest computed tomography findings were mostly normal in the early phase (P1). Therefore, it may be appropriate to perform the first computed tomography screening of COVID-19 after 6 days to decrease the radiation exposure.

Concurrent pathogenic variations in patients with hereditary cancer syndromes.

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.

Bone Mineral Density Screening and the Frequency of Osteopenia/Osteoporosis in Turkish Adult Patients With Celiac Disease.

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.

Combined Metabolic Activators Accelerates Recovery in Mild-to-Moderate COVID-19.

COVID-19 is associated with mitochondrial dysfunction and metabolic abnormalities, including the deficiencies in nicotinamide adenine dinucleotide (NAD+ ) and glutathione metabolism. Here it is investigated if administration of a mixture of combined metabolic activators (CMAs) consisting of glutathione and NAD+ precursors can restore metabolic function and thus aid the recovery of COVID-19 patients. CMAs include l-serine, N-acetyl-l-cysteine, nicotinamide riboside, and l-carnitine tartrate, salt form of l-carnitine. Placebo-controlled, open-label phase 2 study and double-blinded phase 3 clinical trials are conducted to investigate the time of symptom-free recovery on ambulatory patients using CMAs. The results of both studies show that the time to complete recovery is significantly shorter in the CMA group (6.6 vs 9.3 d) in phase 2 and (5.7 vs 9.2 d) in phase 3 trials compared to placebo group. A comprehensive analysis of the plasma metabolome and proteome reveals major metabolic changes. Plasma levels of proteins and metabolites associated with inflammation and antioxidant metabolism are significantly improved in patients treated with CMAs as compared to placebo. The results show that treating patients infected with COVID-19 with CMAs lead to a more rapid symptom-free recovery, suggesting a role for such a therapeutic regime in the treatment of infections leading to respiratory problems.

Polypoid lesions detected in the upper gastrointestinal endoscopy: A retrospective analysis in 19560 patients, a single-center study of a 5-year experience in Turkey.

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.

Does sampling saliva increase detection of SARS-CoV-2 by RT-PCR? Comparing saliva with oro-nasopharyngeal swabs.

The gold standard method in the diagnosis of SARS-CoV-2 infection is the detection of viral RNA in the nasopharyngeal sample by RT-PCR. Recently, saliva samples have been suggested as an alternative sample. In the present study, we aimed to compare 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. On day 0, at least one sample was positive in 67 % of 98 patients. The positivity rate was 83 % for both oro-nasopharyngeal and nasopharyngeal samples, while it was 63 % for saliva samples (p < 0.001). On day 5, RT-PCR was performed in 59 patients, 34 % had at least one positive result. The positivity rate was 55 % for both saliva and nasopharyngeal samples, while it was 60 % for oro-nasopharyngeal samples. Our study shows that the sampling saliva does not increase the sensitivity of RT-PCR tests at the early stages of infection. However, on the 5th day, viral RNA detection rates in saliva were similar to nasopharyngeal and oro-nasopharyngeal samples. In conclusion, we suggest that, in patients receiving treatment, RT-PCR in saliva, in addition to the standard samples, is important to determine the isolation period and control transmission.

Are nucleos(t)ide analogues effective against severe outcomes in COVID-19 and hepatitis B virus coinfection?

Background and Aim: 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. Materials and Methods: 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. Results: 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. Conclusion: 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.

The same mutation in a family with adenosine deaminase 2 deficiency.

The deficiency of adenosine deaminase 2 (DADA2) has recently been defined as a monogenetic autosomal recessive autoinflammatory disease. DADA2 is mainly characterized by high fever, livedo racemose, early-onset stroke, mild immunodeficiency and clinically polyarteritis nodosa (PAN)-like symptoms. Mutations in CECR1 (cat eye syndrome chromosome region, candidate 1) are responsible for DADA2. Livedoid racemose, lacunar infarct due to involvement in small vessel of the central nervous system, peripheral neuropathy, digital ulcers and loss of fingers are predominantly seen in the disease which could progress to end-stage organ failure and death in some patients. A wide spectrum of severity in phenotype as well as in the age of onset has been reported in the literature. This phenotypic variability is also found in our clinical practice even in patients with the same mutation. Here, we present a family diagnosed with DADA2, with the previously reported p.Gly47Arg mutation in CECR1.