High prevalence of muscle weakness and probable sarcopenia in patients with inflammatory bowel disease.

BACKGROUND: This study aimed to determine the prevalence of probable sarcopenia and sarcopenia in patients with inflammatory bowel disease (IBD) by using the European Working Group on Sarcopenia in Older People (EWGSOP2) diagnostic criteria. METHODS: Sarcopenia was assessed by using the sequential four-step algorithm. (1) Find: Sarcopenia risk by simple clinical symptom index (strength, assistance walking, rise from a chair, climb stairs, and falls [SARC-F questionnaire]). (2) Assess: Probable sarcopenia by low muscle strength on handgrip. (3) Confirm: Confirmed sarcopenia by low appendicular skeletal muscle mass on bioimpedance analysis. (4) Severity: Severe sarcopenia by low 4-m gait speed test. RESULTS: A total of 129 adult patients with IBD younger than 65 years and 50 age- and sex-matched healthy control (HC) participants were included to the study. Handgrip strength, gait speed, and SARC-F scores were significantly lower in patients with IBD than in the HCs (P = 0.032, <0.0001, and <0.0001, respectively). Based on the EWGSOP2 definition, 17.8% of patients with IBD had probable sarcopenia, and six patients had confirmed sarcopenia. According to the ethnicity-based population thresholds, 34.9% of patients with IBD had probable sarcopenia, and two patients had confirmed sarcopenia. Corticosteroid use within the past year was identified as an independent risk factor for low muscle strength (P = 0.012; odds ratio, 4.133), along with advanced age and disease activity. CONCLUSION: One-third of the patients younger than 65 years with IBD had probable sarcopenia, defined as low muscle strength, whereas the incidence of confirmed sarcopenia remained relatively low.

The risk of development of primary biliary cholangitis among incidental antimitochondrial M2 antibody-positive patients.

Background and Aim: This study investigated the risk of the development of primary biliary cholangitis (PBC) in individuals who were incidentally identified as having positive antimitochondrial antibodies (AMA)-M2. Materials and Methods: We retrospectively reviewed extractable nuclear antibody (ENA) panel test results to identify the incidental AMA-M2-positive patients. Patients who filled the diagnostic criteria for PBC were excluded. AMA-M2-positive patients were further evaluated by physical examination, liver biochemistry, liver ultrasonography, and transient elastography (TE) and were also closely followed. Results: We included 48 (n=45, 93% female) individuals with a median age of 49 (range: 20-69) years. The median follow-up duration was 27 months (range: 9-42) after the detection of AMA-M2. Thirty-three (69%) patients had concomitant autoimmune/inflammatory disorders. Twenty-eight (58%) individuals showed seropositivity for ANA, and 21 had (43%) positive AMA. Fifteen (31%) patients developed typical PBC according to the international PBC diagnostic criteria during the follow-up, and five of them (18%) had significant fibrosis (≥8.2 kPA) by TE at the time of PBC diagnosis. Conclusion: Two-thirds of the incidental AMA-M2-positive patients developed typical features of PBC after a median 27-month follow-up. Our results suggest that AMA-M2 patients should be closely followed up to detect the late development of PBC.

Radiological Quantification of Sarcopenic Obesity and its Role in Chronic Liver Disease Severity.

RATIONALE AND OBJECTIVES: To define sarcopenic obesity (SaO) among chronic liver disease (CLD) patients via CT and MRI, and assess its impact on liver disease severity. MATERIALS AND METHODS: CLD patients referred from the Gastroenterology and Hepatology Department diagnosed as chronic hepatitis B (N:101), cirrhosis (N:110), and hepatocellular carcinoma (N:169) with available information on body height, weight, Child-Pugh and MELD scores within 2 weeks of CT or MRI scanning were included in the study. Cross-sectional examinations were retrospectively evaluated for skeletal muscle index (SMI) and visceral adipose tissue area (VATA). The disease severity was assessed by Child-Pugh and MELD scoring. RESULTS: The rate of sarcopenia and SaO in the cirrhotic patients was higher than that in the chronic hepatitis B patients (p <0.033 and p < 0.004, respectively). The rate of sarcopenia and SaO in HCC patients was higher than that in the chronic hepatitis B patients (p <0.001 and p <0.001, respectively). Sarcopenic patients in Chronic hepatitis B, cirrhotic, and HCC groups had higher MELD scores than nonsarcopenic patients (p <0.035, p <0.023, and p <0.024, respectively). Despite finding a similar increase in Child-Pugh scores in cirrhotic and HCC sarcopenic patients, results were statistically insignificant (p <0.597 and p <0.688). HCC patients with SaO had higher MELD scores than patients with other body composition catagories (p <0.006). Cirrhotic patients with SaO had higher MELD scores than nonsarcopenic obese patients (p <0.049). Chronic hepatitis B patients with obesity had low MELD scores (p <0.035). Cirrhotic and HCC patients with obesity had higher MELD scores (p <0.01 and p <0.024, respectively). Cirrhotic and HCC patients with obesity had higher Child-Pugh scores than nonobese patients but only HCC patients showed statistically significance (p <0.480 and p <0.001). CONCLUSION: Radiologic evaluation of SaO and harmonizing body composition with MELD scoring is critical in CLD management.

Diagnostic performance of lactate dehydrogenase (LDH) isoenzymes levels for the severity of COVID-19.

Background: Lactate dehydrogenase (LDH) levels predict coronavirus disease 2019 (COVID-19) severity. We investigated LDH isoenzyme levels to identify the tissue responsible for serum LDH elevation in patients with COVID-19. Methods: Hospitalised COVID-19 patients with serum LDH levels exceeding the upper reference limit included. LDH isoenzymes were detected quantitatively on agarose gels. The radiological severity of lung involvement on computed tomography was scored as 0-5 for each lobe (total possible score, 0-25). Disease severity was determined using the World Health Organization (WHO) clinical progression scale. Results: In total, 111 patients (mean age, 59.96 ± 16.14), including 43 females (38.7%), were enrolled. The serum levels of total LDH and all five LDH isoenzymes were significantly higher in the severe group. The levels of all LDH isoenzymes excluding LDH5 positively correlated with the WHO score. LDH3 levels correlated with chest computed tomography findings (r2 = 0.267, p = 0.005). On multivariate analysis, LDH3 was an independent risk factor for the deterioration of COVID-19. Conclusions: LDH3 appears to be an independent risk factor for deterioration in patients with COVID-19. LDH elevation in patients with COVID-19 predominantly resulted from lung, liver and muscle damage.

Biologic Therapy Carries a Very Low Risk of Reactivation in Hepatitis B Surface Antigen-Negative Phase of Hepatitis B.

BACKGROUND: The risk of hepatitis B reactivation in hepatitis B surface antigen-negative phase of hepatitis B virus-infected patients exposed to biologic agents is not clear. We aimed to investigate the reactivation rate in hepatitis B surface antigen-negative phase of hepatitis B virus-infected patients after biologic therapy. METHODS: Patients followed at gastroenterology, rheumatology, and dermatology clinics with a diagnosis of immune-mediated inflam matory diseases were screened. Immune-mediated inflammatory diseases patients exposed to biologic agents with a negative hepatitis B surface antigen and positive hepatitis B core immunoglobulin G antibody were included in the study. RESULTS: We screened 8266 immune-mediated inflammatory disease patients, and 2484 patients were identified as exposed to biologic agents. Two hundred twenty-one patients were included in the study. The mean age was 54.08 ± 11.69 years, and 115 (52.0%) patients were female. The median number of different biologic subtype use was 1 (range: 1-6). The mean biologic agent exposure time was 55 (range: 2-179) months. One hundred and fifty-two (68.8%) patients used a concomitant immunomodulatory agent, and 84 (38.0%) patients were exposed to corticosteroids during biologic use. No hepatitis B reactivation with a reverse seroconversion of hepatitis B surface antigen positivity was seen. Antiviral prophylaxis for hepatitis B was applied to 48 (21.7%) patients. Hepatitis B virus-DNA was screened in 56 (25.3%) patients prior to the biologic exposure. Two patients without antiviral prophylaxis had hepatitis B virus-DNA reactivation with a negative hepatitis B surface antigen during exposure to the biologic agent. CONCLUSION: We found 2 reactivations and no hepatitis B surface antigen seroconversion in our cohort. Antiviral prophylaxis for patients exposed to biologic agents may need to be discussed in more detail.

Improving the Computer-Aided Estimation of Ulcerative Colitis Severity According to Mayo Endoscopic Score by Using Regression-Based Deep Learning.

BACKGROUND: Assessment of endoscopic activity in ulcerative colitis (UC) is important for treatment decisions and monitoring disease progress. However, substantial inter- and intraobserver variability in grading impairs the assessment. Our aim was to develop a computer-aided diagnosis system using deep learning to reduce subjectivity and improve the reliability of the assessment. METHODS: The cohort comprises 11 276 images from 564 patients who underwent colonoscopy for UC. We propose a regression-based deep learning approach for the endoscopic evaluation of UC according to the Mayo endoscopic score (MES). Five state-of-the-art convolutional neural network (CNN) architectures were used for the performance measurements and comparisons. Ten-fold cross-validation was used to train the models and objectively benchmark them. Model performances were assessed using quadratic weighted kappa and macro F1 scores for full Mayo score classification and kappa statistics and F1 score for remission classification. RESULTS: Five classification-based CNNs used in the study were in excellent agreement with the expert annotations for all Mayo subscores and remission classification according to the kappa statistics. When the proposed regression-based approach was used, (1) the performance of most of the models statistically significantly increased and (2) the same model trained on different cross-validation folds produced more robust results on the test set in terms of deviation between different folds. CONCLUSIONS: Comprehensive experimental evaluations show that commonly used classification-based CNN architectures have successful performance in evaluating endoscopic disease activity of UC. Integration of domain knowledge into these architectures further increases performance and robustness, accelerating their translation into clinical use.

Presence of axial spondyloarthritis associated sacroiliitis and structural changes on MR enterography: A direct comparison with sacroiliac joint MRI.

INTRODUCTION: To investigate the acute inflammatory and structural changes of sacroiliitis as auxiliary findings on magnetic resonance enterography (MRE) and their presence on closely timed conventional magnetic resonance imaging of the sacroiliac joint (SI joint MRI). MATERIALS AND METHODS: We screened axial spondyloarthritis patients for the simultaneous presence of MREs and SI joint MRIs. Two blinded radiologists evaluated SI joint MRIs and MREs on two separate occasions. We used the Assessment of SpondyloArthritis International Society (ASAS)/Outcome Measures in Rheumatology Network (OMERACT) definitions for SI joint MRI. We implemented previously published standard definitions for osteitis, erosion, sclerosis, and fatty infiltration of SI joint in MREs that contain T1w and T1w post-gadolinium sequences. RESULTS: SI joint MRI and MRE images were present in 43 patients. The median time between the two modalities was 14 (0-89) days. Twelve patients had ASAS-defined positive SI joint MRI. Radiologist-1 and radiologist-2 detected osteitis on MRE in nine and eight out of these 12 patients, respectively. The two radiologists detected ankylosis and fatty metaplasia with a complete agreement and sclerosis with an almost perfect agreement. Both radiologists agreed on erosions on SI joint MRI in the same 10 cases. Radiologists did not identify acute inflammatory or structural changes on MRE in patients with a negative SI joint MRI for these lesions. CONCLUSION: Along with intestinal findings, additional reporting of acute inflammatory and structural changes of the SI joint on a MRE is valuable and may alert physicians to the presence of previously not diagnosed axial spondyloarthritis.

Staphylococcus aureus costochondritis and chest wall abscess in a COVID-19 patient treated with tocilizumab.

Coronavirus disease 2019 (COVID-19) is a worldwide pandemic, causing a global health threat. Up to 15% of the confirmed cases develop severe disease, requiring hospitalization or intensive care unit (ICU) admission. Tocilizumab, an IL-6 receptor antagonist, is a promising treatment of severe pneumonia with acute respiratory distress syndrome (ARDS) or cytokine release syndrome (CRS) in the course of COVID-19. We report a suppurative costochondritis and chest wall abscess in a severe COVID-19 patient treated with tocilizumab.

Evaluation of the Impact of Metabolic Syndrome on Fibrosis in Metabolic Dysfunction-Associated Fatty Liver Disease.

BACKGROUND: Metabolic syndrome (MS) is a condition that consists of several disorders, and the individual impact of these disorders on metabolic dysfunction-associated fatty liver disease (MAFLD) is still not clear in a combined diagnosis of MS. In this study, we aimed to investigate the effect of MS on advanced fibrosis in patients with MAFLD. METHODS: We recruited the patients from our gastroenterology out-patient clinic who were being followed up for MAFLD. MAFLD was diagnosed with liver biopsy in all patients. The frequency of MS and other metabolic parameters were also compared between groups with advanced fibrosis and groups in which fibrosis was not as advanced. RESULTS: In total, we enrolled 424 biopsy-proven MAFLD patients to the study. In univariate analysis, individuals with greater age, body mass index (BMI), higher aspartate transaminase (AST), MS, impaired fasting glucose, hypertension, enlarged waist circumference (WC), diabetes mellitus (DM), and women had significantly increased risk for fibrosis. In multivariate analysis, it was found that DM, greater age, higher BMI, and increased AST were seen more commonly in MAFLD patients with advanced fibrosis. CONCLUSION: Greater age, a higher BMI, higher AST and a diagnosis of diabetes were more commonly associated with advanced fibrosis. However, DM was found to be the strongest predictive factor of advanced fibrosis in our cohort (OR: 2.495). Multivariate analyses did not indicate a significantly common occurrence of MS in the advanced fibrosis group, despite its important role in MAFLD pathophysiology.

Monocyte transcriptomes from patients with axial spondyloarthritis reveal dysregulated monocytopoiesis and a distinct inflammatory imprint.

BACKGROUND: In patients with axial spondyloarthritis (axSpA), monocytes show a pre-activated phenotype. Gut inflammation is a trigger of monocyte activation and may also affect their development in the bone marrow (BM). As gut inflammation is commonly observed in axSpA patients, we performed a detailed analysis of monocyte transcriptomes of axSpA patients in two cohorts and searched for signs of activation and developmental adaptations as putative imprints of gut inflammation. METHODS: Transcriptomes of blood CD14+ monocytes of HLA-B27+ axSpA patients and healthy controls (HC) were generated by microarrays from cohort 1 and by RNA-sequencing from cohort 2. Differentially expressed genes from both analyses were subjected to gene set enrichment analysis (GSEA) and to co-expression analysis in reference transcriptomes from BM cells, blood cells and activated monocytes. As serological markers of translocation, 1,3 beta-glycan, intestinal fatty acid binding protein, and lipopolysaccharide binding protein (LBP) were determined by LAL and ELISA. RESULTS: Transcriptome analysis identified axSpA-specific monocyte signatures showing an imprint of LPS/cytokine-activated monocytes, late granulopoietic BM cells, blood neutrophils, and G-CSF-mobilized blood cells, which suggests LPS/TNF activation and more prominent BM adaptation promoting a neutrophil-like phenotype. GSEA mapped axSpA upregulated genes to inflammatory responses and TNFα signaling and downregulated probe-sets to metabolic pathways. Among translocation markers, LBP levels were significantly increased in axSpA patients vs. HC (p < 0.001). Stratified analysis by disease activity and stage identified an "active disease signature" (BASDAI ≥ 4) with an imprint of LPS/cytokine-activated monocytes and CD16+ monocyte subsets. The "AS signature" (vs. non-radiographic axSpA) showed a reinforced neutrophil-like phenotype due to deprivation of dendritic cell transcripts. CONCLUSIONS: The neutrophil-like phenotype of axSpA monocytes points towards a biased monocytopoiesis from granulocyte-monocyte progenitors. This shift in monocytopoiesis and the LPS/cytokine imprint as well as the elevated LBP levels are indicators of systemic inflammation, which may result from bacterial translocation. The BM adaptation is most prominent in AS patients while disease activity appears to be linked to activation and trafficking of monocytes.

Liver stiffness is associated with disease severity and worse clinical scenarios in coronavirus disease 2019: A prospective transient elastography study.

BACKGROUND: Pre-existing chronic liver disease is currently considered a poor prognostic factor for coronavirus disease 2019 (COVID-19). The present study aimed to investigate the association of liver stiffness measurement (LSM) with disease severity and clinical course of COVID-19. METHODS: We prospectively recruited consecutive hospitalised adult patients with COVID-19 in a 3-month period. Demographic, laboratory, clinical and vibration-controlled transient elastography (VCTE) features were recorded at entry, and all patients were prospectively followed-up. Severe liver fibrosis was defined as an LSM value higher than 9.6 kPA. Multivariate logistic regression analysis was performed to reveal factors associated with disease severity and outcomes. RESULTS: Out of 98 eligible patients with COVID-19, 12 (12.2%) had severe liver fibrosis. Patients with severe liver fibrosis had higher baseline disease severity (P = .022), more commonly required oxygen treatment at entry (P = .010), and had intensive-care unit (ICU) requirements during the 6 (1-39)-day median follow-up time (P = .017). The presence of severe liver fibrosis was independently associated with disease severity (odds ratio (OR): 7.685, 95% confidence interval (CI): 1.435-41.162, P = .017) and ICU requirement (OR: 46.656, 95% CI: 2.144-1015.090, P = .014). LSM was correlated with alanine aminotransferase levels (P = .005, r: 0.283), but not with other markers of acute hepatic injury or inflammation. CONCLUSION: Initial VCTE application might help physicians identify patients who are more likely to have severe illness or worse clinical outcomes, in addition to other well-established clinical and laboratory factors. Further multicentre prospective studies are warranted to validate our results.

Recommendations for Reopening Endoscopy Units in Turkey: A Set-up Plan from a Tertiary Center in Istanbul.

In the midst of Coronavirus-19 (COVID-19) pandemic, endoscopic procedures have been separated for only urgent and semi-urgent cases for the last few months to prevent transmission in endoscopy units. This approach will perhaps resolve the burden of elective procedures in the months ahead of us. As we observe a downtrend in new cases of COVID-19 in Turkey, a strategy for reopening endoscopy units is required. We are stepping into a time period where we should not only re-provide the essential services to our patients but also maintain the safety of healthcare workers and preserve the valuable personal protective equipment as well. Herein, we aim to share the available knowledge in performing endoscopy during the pandemic and the set-up plan of a tertiary center in Istanbul for reopening the endoscopy unit in the era of the COVID-19 pandemic.

Femoral Vein Wall Thickness Measurement May Be a Distinctive Diagnostic Tool to Differentiate Behçet's Disease with Intestinal Involvement and Crohn's Disease.

BACKGROUNDS: Behçet's disease (BD) and Crohn's disease (CD) cannot be easily differentiated in young adults presenting with nonspecific gastrointestinal (GI) manifestations due to similar extraintestinal manifestations. We recently showed that increased common femoral vein (CFV) thickness is a distinctive feature of BD, rarely present in other inflammatory or vascular diseases with a specificity higher than 80% for the cutoff value of ≥ 0.5 mm. We suggest that CFV thickness measurement with ultrasonography (US) can be a diagnostic tool for BD. AIMS: To assess the diagnostic performance of CFV thickness measurement in the differential diagnosis of BD and CD. METHODS: Patients with BD (n = 69), CD (n = 38), and healthy controls (HC) (n = 38) were included in the study. Bilateral CFV thickness was measured with Doppler US. RESULTS: Both right and left CFV thicknesses were significantly higher in BD compared to HC and CD (for right: 0.76 mm vs 0.33 mm, for left: 0.78 mm vs 0.35 mm, p < 0.001 for both). CFV thicknesses in CD were similar to HC (p > 0.05 for both). CFV thickness was also similar between BD patients with and without GI involvement (p = 0.367). The diagnostic cutoff values of ≥ 0.5 mm for CFV thickness performed well against to both CD and HCs for discrimination of BD. The sensitivity and specificity rates were > 85% for both HC and CD. Positive and negative predictive values in our tertiary clinical setting were > 90%. CONCLUSION: We found significantly lower CFV thickness in CD compared to BD. Our results suggest that CFV wall thickness measurement is a distinctive diagnostic tool for the differentiation of BD and CD and can be helpful in daily practice for the differentiation of two diseases.

High incidence of hepatitis B core antibody positivity in metabolic-associated fatty liver disease-related cirrhosis.

Background and Aim: The coexistence of metabolic-associated fatty liver disease (MAFLD) in the course of chronic hepatitis B virus infection increases liver-related morbidity. A positive correlation was found between positive hepatitis B core antibody (anti-HBc) and the risk of cirrhosis and hepatocellular carcinoma (HCC) in MAFLD. The relationship between anti-HBc positivity and MAFLD progression to fibrosis, cirrhosis, and liver-related outcomes was determined. Materials and Methods: This is a retrospective study including 242 patients with biopsy-proven MAFLD, 130 patients with clinically diagnosed MAFLD-related cirrhosis, and 62 patients with MAFLD-related or cryptogenic HCC. Anti-HBc antibody results were compared with clinical outcomes. Results: Anti-HBc positivity was associated with fibrosis severity (p=0.005). Anti-HBc was positive in 19 (20.2%), 33 (25.8%), 53 (35.3%), and 27 (43.5%) patients with F0-F1 fibrosis, F2-F3 fibrosis, cirrhosis (F4), and HCC, respectively. Median steatosis score was grade 3 in anti-HBc positive patients and grade 2 in negative patients (p=0.07). Anti-HBc positivity was not associated with significant fibrosis (≥F2), cirrhosis, and any liver related complications including HCC. Conclusion: Higher anti-HBc positivity was found in MAFLD patients with advanced fibrosis and cirrhosis compared to patients with early stage fibrosis. No relation was found between anti-HBc positivity and development of cirrhosis, HCC or other liver related complications.

Causes of erectile dysfunction in non-alcoholic fatty liver disease.

Background and Aim: Erectile dysfunction (ED) is an important and commonly seen disorder in patients with non-alcoholic fatty liver disease (NAFLD). The objective of this study was to assess the rate of ED and its causes in a group of NAFLD patients. Materials and Methods: The International Index of Erectile Function questionnaire (IIEF-5) was used to evaluate the presence, causes, and severity of ED. Participants with an IIEF-5 score of <22 who agreed to undergo a urological evaluation were referred to a urologist for further assessment. Results: A total of 136 NAFLD patients were enrolled in the study. According to the IIEF-5, 68 (50.0%) patients had ED. Multivariate analysis indicated that older age, obesity, and hypertension were associated with ED. Seventeen patients had multiple etiological factors for ED. Psychogenic ED was identified in 19 patients (39.6%), vasculogenic ED in 35 patients (72.9%), drug-related ED in 3 patients (6.3%), and neurogenic ED in 6 patients (12.5%). Conclusion: ED is frequently seen in NAFLD patients, which may, at least in part, be due to common risk factors. Vasculogenic dysfunction is the most common single source of ED in NAFLD patients. Nonetheless, all potential etiologies should be carefully investigated, with special attention given to psychogenic factors, since they may be more frequent and relevant than expected.

Validation and reliability of the Turkish version of the inflammatory bowel disease questionnaire for ulcerative colitis and Crohn's disease.

BACKGROUND/AIMS: Inflammatory bowel diseases (IBD) impairs patients' quality of life (QoL). Inflammatory bowel disease questionnaire (IBDQ) is created to measure the health-related QoL specific for IBD. We planned to investigate the validation and reliability of the Turkish translation of IBDQ. MATERIALS AND METHODS: Patients filled self-report questionnaires (Turkish Inflammatory bowel disease questionnaire (TrIBDQ) and Short Form-36 (SF-36)) themselves under a physician's supervision, and they were free to ask questions about the questionnaires. The participants then filled the same questionnaire after at least two weeks. Construct validity, discriminant ability, reliability, and susceptibility to change were analyzed separately for the IBD patients. Intra-class correlation coefficient (ICC) was used to assess test-retest reliability. Cronbach's alpha values were used to assess internal consistency. RESULTS: A hundred patients enrolled in the study, 53 with Crohn's disease (CD), 47 with ulcerative colitis (UC). We found a moderate to high positive correlation between the TrIBDQ domains and the SF-36 dimensions. In UC and CD, TrIBDQ was able to differentiate active disease and remission. We found Cronbach's alpha for TrIBDQ domains ranged from 0.76-0.94 in CD and from 0.79-0.92 in UC. The total Cronbach's alpha for TrIBDQ was 0.96 in CD and 0.95 in UC. Sensitivity-to-change analyses of the bowel, systemic, and emotional scores showed statistically significant differences between their baseline and follow-up values. CONCLUSION: TrIBDQ is a valid and reliable tool for assessing the quality of life in Turkish speaking IBD patients. Thus it can be used in clinical research and practice.