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Context.--The data on status of apoptosis in patients with celiac disease are conflicting. Furthermore, complex interaction between intrinsic and common apoptotic pathways, apoptotic inhibitors, and epithelial cell proliferation is largely unclear for patients with celiac disease. Objectives.--To determine the role of apoptosis and epithelial cell regeneration in celiac disease. Design.--Twenty five treatment naive patients with celiac disease and 6 patients with functional dyspepsia, as controls, were included and duodenal biopsy specimens from all were subjected to immunohistochemistry with markers of intrinsic apoptotic pathway (AIF, H2AX, p53), common pathway (CC3, M30), apoptotic inhibitors (XlAP, Bcl2), and epithelial proliferation (Ki-67). Apoptotic and proliferation indices were calculated. Results.--Expression of end apoptotic products, that is, H2AX in the cell nuclei (P = .01) and M30 in the cell cytoplasm (P < .01), was significantly upregulated in celiac disease in comparison to controls. Cleaved caspase3 was also upregulated in villous cytoplasm in celiac disease. Apoptotic inhibitor Bcl2 was significantly down-regulated in celiac disease in comparison to controls. In addition, Ki-67 proliferation index was upregulated both in the crypts and villous mucosal epithelium in comparison to the crypts of the controls. Conclusions.--Treatment naive patients with celiac disease have significantly higher level of apoptosis that involves both the common and intrinsic apoptotic pathways. Increased apoptosis and unequaled cell regeneration in crypts probably results in villous atrophy. Down-regulation of apoptotic inhibitors in treatment naive celiac disease imparts an additional pro apoptotic effect. (Arch Pathol Lab Med. 2013;137:1262-1269; doi: 10.5858/arpa.2012-0354-OA), Villous atrophy is the histomorphologic hallmark of celiac disease, which possibly occurs owing to increased cell destruction/enhanced apoptosis and/or a defect in epithelial cell regeneration. (1-5) While a few studies [...]

Background and Aim: While the prevalence of celiac disease (CD) is increasing globally, the prevalence of tropical sprue (TS) is declining. Still, there are certain regions in the world where both patients with CD and TS exist and differentiation between them is a challenging task. We conducted a systematic review of the literature to find out differentiating clinical, endoscopic, and histological characteristics between CD and TS. Methods: Medline, PubMed, and EMBASE databases were searched for keywords: celiac disease, coeliac, celiac, tropical sprue, sprue, clinical presentation, endoscopy, and histology. Studies published between August 1960 and January 2018 were reviewed. Out of 1063 articles available, 12 articles were included in the final analysis. Results: Between the patients with CD and TS, there was no difference in the prevalence and duration of chronic diarrhea, abdominal distension, weight loss, extent of abnormal fecal fat content, and density of intestinal inflammation. The following features were more common in CD: short stature, vomiting/dyspepsia, endoscopic scalloping/attenuation of duodenal folds, histological high modified Marsh changes, crescendo type of IELosis, surface epithelial denudation, surface mucosal flattening, thickening of subepithelial basement membrane and celiac seropositivity; while those in TS include anemia, abnormal urinary D‐xylose test, endoscopic either normal duodenal folds or mild attenuation, histologically decrescendo type of IELosis, low modified Marsh changes, patchy mucosal changes, and mucosal eosinophilia. Conclusions: Both patients with CD and TS have overlapping clinical, endoscopic, and histological characteristics, and there is no single diagnostic feature for differentiating CD from TS except for celiac specific serological tests. [ABSTRACT FROM AUTHOR]

Thyroid carcinoma is the most common neoplasm of endocrine malignancies. Differentiated thyroid carcinoma (DTC) constitutes 90% of the thyroid carcinomas, rest being medullary thyroid carcinoma (MTC), and anaplastic thyroid carcinoma (ATC). Distant metastases occur in up to 10% of patients with DTC. Metastases to axillary lymph nodes (ALN) are very rare. As per literature, only 25 cases have been reported. We report an unusual case of 47-year-old male with Hürthle cell carcinoma of the thyroid presenting with a solitary axillary lymph node metastasis 17 years after thyroidectomy, along with review of literature. [ABSTRACT FROM AUTHOR]

Background/Aims: Classical M1 macrophage activation exhibits an inflammatory phenotype while alternative M2 macrophage activation exhibits an anti-inflammatory phenotype. We aimed to determine whether there are discriminant patterns of macrophage polarization in Crohn's disease (CD) and intestinal tuberculosis (iTB). Methods: Colonic mucosal biopsies from 29 patients with iTB, 50 with CD, and 19 controls were examined. Dual colored immunohistochemistry was performed for iNOS/CD68 (an M1ϕ marker) and CD163/CD68 (an M2ϕ marker), and the ratio of M1ϕ to M2ϕ was assessed. To establish the innate nature of macrophage polarization, we analyzed the extent of mitochondrial depolarization, a key marker of inflammatory responses, in monocyte-derived macrophages obtained from CD and iTB patients, following interferon-γ treatment. Results: M1ϕ polarization was more prominent in CD biopsies (P =0.002) than in iTB (P =0.2) and control biopsies. In granuloma-positive biopsies, including those in CD, M1ϕ predominance was significant (P =0.001). In iTB, the densities of M1ϕ did not differ between granuloma-positive and granuloma-negative biopsies (P =0.1). Interestingly, higher M1ϕ polarization in CD biopsies correlated with high inflammatory response exhibited by peripheral blood-derived monocytes from these patients. Conclusions: Proinflammatory M1ϕ polarization was more common in colonic mucosa of CD patients, especially in the presence of mucosal granulomas. Further characterization of the innate immune system could help in clarifying the pathology of iTB and CD. [ABSTRACT FROM AUTHOR]

Background: Risk calculators have traditionally utilized serum prostate-specific antigen (PSA) values in addition to clinical variables to predict the likelihood of prostate cancer (PCa).Purpose: To develop a prebiopsy multiparametric MRI (mpMRI)-based risk score (RS) and a statistical equation for predicting the risk of PCa in biopsy-naive men with serum PSA between 4-10 ng/mL that may help reduce unnecessary biopsies.Study Type: Prospective cross-sectional study.Subjects: In all, 137 consecutive men with PSA between 4-10 ng/mL underwent prebiopsy mpMRI (diffusion-weighted [DW]-MRI and MR spectroscopic imaging [MRSI]) during 2009-2015 were recruited for this study.Field Strength/sequence: 1.5T (Avanto, Siemens Health Care, Erlangen, Germany); T1 -weighted, T2 -weighted, DW-MRI, and MRSI sequences were used.Assessment: All eligible patients underwent mpMRI-directed, cognitive-fusion transrectal ultrasound (TRUS)-guided biopsies.Statistical Tests: An equation model and an RS were developed using receiver operating characteristic (ROC) curve analysis and a multivariable logistic regression approach. A 10-fold crossvalidation and simulation analyses were performed to assess diagnostic performance of various combinations of mpMRI parameters.Results: Of 137 patients, 32 were diagnosed with PCa on biopsy. Multivariable analysis, adjusted with positive pathology, showed apparent diffusion coefficient (ADC), metabolite ratio, and PSA as significant predictors of PCa (P < 0.05). A statistical equation was derived using these predictors. A simple 6-point mpMRI-based RS was derived for calculating the risk of PCa and it showed that it is highly predictive for PCa (odds ratio = 3.74, 95% confidence interval [CI]: 2.24-6.27, area under the curve [AUC] = 0.87). Both models (equation and RS) yielded high predictive performance (AUC ≥0.85) on validation analysis.Data Conclusion: A statistical equation and a simple 6-point mpMRI-based RS can be used as a point-of-care tool to potentially help limit the number of negative biopsies in men with PSA between 4 and 10 ng/mL.Level Of Evidence: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1227-1236. [ABSTRACT FROM AUTHOR]

Aim: This study investigates the fall in total serum bilirubin levels within 1 week after surgery, as a marker to predict early outcome in biliary atresia (BA) patients post-Kasai portoenterostomy (KP). Methods: The ratio of total serum bilirubin levels at the 7th postoperative day to the preoperative level (TB7/TB0) in patients undergoing KP was calculated (January 2011-July 2015). Patients were stratified after 3-months follow-up into outcome groups depending on the clinical clearance of jaundice and TB7/TB0 ratio was correlated to outcome and liver histopathological changes in these groups. Results: Sixty-one patients (M:F = 44:17), median age 75 days were included. At the end of 3 months, 27 (44.39%) were anicteric while 26 (42.6%) were still clinically jaundiced. Patients with a higher median value of TB7/TB0, that is, 0.856 were more likely to have jaundice at the end of 3 months as compared to patients with a lower median value of 0.615 (P < 0.0001). A cutoff TB7/TB0 ratio >0.723 predicted the KP outcome with 84.6% sensitivity and 81.5% specificity. The difference in TB7/TB0 ratio between patients with varying severity of liver histopathological changes was also significant, namely, cholestasis (P = 0.01), hepatocellular damage (P = 0.03), portal inflammation (P = 0.04), and portal fibrosis (P = 0.02). Conclusions: The rapidity of fall in the total serum bilirubin levels within 1 week post-KP was able to predict the likely outcome in BA patients. [ABSTRACT FROM AUTHOR]

Study design: Prospective observational cohort. Objective: To investigate the difference in plasma levels of syndecan-1 (due to glycocalyx degradation) and soluble thrombomodulin (due to endothelial damage) in isolated severe traumatic brain injury (TBI) patients with/without early coagulopathy. A secondary objective was to compare the effects of the degree of TBI endotheliopathy on hospital mortality among patients with TBI-associated coagulopathy (TBI-AC). Methods: Data was prospectively collected on isolated severe TBI (sTBI) patients with Glasgow Coma Scale (GCS) ≤8 less than 12 h after injury admitted to a level I trauma centre. Isolated sTBI patients with samples withdrawn prior to blood transfusion were stratified by conventional coagulation tests as coagulopathic (prothrombin time (PT) ≥ 16.7 s, international normalized ratio (INR) ≥ 1.27, and activated partial thromboplastin time (aPTT) ≥ 28.8 s) and non-coagulopathic. Twenty healthy controls were also included. Plasma levels of thrombomodulin and syndecan-1 were estimated by ELISA. With receiver operating characteristic curve (ROC) analysis, we defined endotheliopathy as a syndecan-1 cut-off level that maximized the sum of sensitivity and specificity for predicting TBI-AC. Results: Inclusion criteria were met in 120 cases, with subjects aged 35.5 ± 12.6 years (88.3% males). TBI-AC was identified in 50 (41.6%) patients, independent of age, gender, and GCS, but there was an association with acidosis (60%; p = 0.01). Following isolated sTBI, we found insignificant changes in soluble thrombomodulin (sTM) levels between patients with isolated TBI and controls, and sTM levels were lower in coagulopathic compared to non-coagulopathic patients. Elevations in plasma syndecan-1 (ng/mL) levels were seen compared to control (31.1(21.5-30.6) vs. 24.8(18.5-30.6); p = 0.08). Syndecan-1(ng/mL) levels were significantly elevated in coagulopathic compared to non-coagulopathic patients (33.7(21.6-109.5) vs. 29.9(19.239.5); p = 0.03). Using ROC analysis (area under the curve = 0.61; 95% Confidence Interval (CI) 0.50 to 0.72), we established a plasma syndecan-1 level cutoff of ≥30.5 ng/mL (sensitivity % = 55.3, specificity % = 52.3), with a significant association with TBI-associated coagulopathy. Conclusion: Subsequent to brain injury, elevated syndecan-1 shedding and endotheliopathy may be associated with early coagulation abnormalities. A syndecan-1 level ≥30.5 ng/mL identified patients with TBI-AC, and may be of importance in guiding management and clinical decision-making. [ABSTRACT FROM AUTHOR]