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Context.--The histologic features in patients with acute-on-chronic liver failure (ACLF) are evolving, and histologic indicators of patients' poor prognosis are not yet fully established. Objective.--To evaluate the independent histologic predictors of 28-day mortality in ACLF patients on core-needle liver biopsies. Design.--Core-needle biopsies from patients with a diagnosis of ACLF (n = 152) as per the European Association for the Study of the Liver criteria were included during 8 years. Liver biopsies from 98 patients with compensated chronic liver disease were included as disease controls for histologic comparison. Features of ongoing changes, such as hepatic necrosis, hepatic apoptosis, cholestasis, hepatocyte degeneration, bile ductular proliferation, Mallory-Denk bodies, steatosis, and extent of liver fibrosis, were analyzed for predicting short-term mortality (28 days). A P value of Results.--In our cohort of ACLF patients, the following etiologies for acute decompensation were identified: alcohol, 47 of 152 (30.9%); sepsis, 24 of 152 (15.7%); hepatotropic viruses, 20 of 152 (13.1%); drug-induced liver injury, 11 of 152 (7.2%); autoimmune flare, 9 of 152 (5.9%); mixed etiologies, 5 of 152 (3.2%); and cryptogenic, 36 of 152 (23.6%). On histologic examination, hepatic necrosis (P Conclusions.--Dense lobular necroinflammatory activity is a clinically independent histologic predictor of 28-day short-term mortality in patients with ACLF., Acute-on-chronic liver failure (ACLF) syndrome is characterized by abrupt hepatic decompensation secondary to acute insult in patients with chronic liver disease (CLD), having high short-term mortality. (1-3) The diagnosis and [...]

Objective Independent assessment of SARS-CoV-2 antigen (COV2Ag) tests remains important as varying performance between assays is common. We assessed the performance of a new high-throughput COV2Ag test compared to SARS-CoV-2 nucleic acid amplification tests (NAAT). Methods A total of 347 nasopharyngeal samples collected from January to October 2021 were assessed by NAAT as part of standard-of-care testing (CDC LDT or GeneXpert System, Cepheid) and COV2Ag using the ADVIA Centaur CoV2Ag assay (Siemens Healthineers). Results Among NAAT positive specimens we found 82.4% agreement and in NAAT negative specimens we found 97.3% agreement (overall agreement 85.6%). In symptomatic persons, COV2Ag agreed with NAAT 90.0% (n = 291), and in asymptomatic persons, 62.5% (n = 56). Agreement between positive NAAT and COV2Ag increased at lower cycle threshold (Ct) values. Conclusion The COV2Ag assay exceeded the World Health Organization minimum performance requirements of ≥ 80% sensitivity and ≥ 97% specificity. The COV2Ag assay is helpful for large scale screening efforts due to high-throughput and reduced wait times. [ABSTRACT FROM AUTHOR]

Objectives: There is concern that the anti-severe acute respiratory syndrome coronavirus 2 therapeutic monoclonal antibodies, used as preexposure prophylaxis in patients with multiple myeloma, may appear as a detectable monoclonal protein by electrophoretic methods, resulting in misinterpretation or inability to measure therapeutic responses in some patients. In this pilot study, we characterize the effect of tixagevimab plus cilgavimab (Evusheld; T + C) on interpretation of serum protein electrophoresis (SPE), immunofixation electrophoresis (IFE), and serum free light chain (sFLC) assays.Methods: We performed spiking experiments with T + C at serum maximum concentration following a 300-mg dose (1× Cmax) and at 10 times the concentration of Cmax (10× Cmax) with pooled serum samples. SPE and IFE technical procedures were performed on the SPIFE 3000, and sFLC and immunoglobulin G1 (IgG1) subtype quantitation was performed on the Optilite.Results: T + C-associated interference was not visible as an M-spike in normogammaglobulinemic pooled samples. Hypogammaglobulemic pooled samples at 10× Cmax demonstrated an M-spike in SPE and immunoglobulin Gκ pattern in IFE. No increases were noted in the results of sFLC or IgG1 levels.Conclusions: This study indicates that T + C at pharmacologic Cmax is unlikely to interfere with SPE, IFE, sFLC, or IgG1 analyses when spiked into patient serum samples, but further evaluation of recently injected patients may be warranted. [ABSTRACT FROM AUTHOR]

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]

Objective: Independent assessment of SARS-CoV-2 antigen (COV2Ag) tests remains important as varying performance between assays is common. We assessed the performance of a new high-throughput COV2Ag test compared to SARS-CoV-2 nucleic acid amplification tests (NAAT)., Methods: A total of 347 nasopharyngeal samples collected from January to October 2021 were assessed by NAAT as part of standard-of-care testing (CDC LDT or GeneXpert System, Cepheid) and COV2Ag using the ADVIA Centaur CoV2Ag assay (Siemens Healthineers)., Results: Among NAAT positive specimens we found 82.4% agreement and in NAAT negative specimens we found 97.3% agreement (overall agreement 85.6%). In symptomatic persons, COV2Ag agreed with NAAT 90.0% (n = 291), and in asymptomatic persons, 62.5% (n = 56). Agreement between positive NAAT and COV2Ag increased at lower cycle threshold (Ct) values., Conclusion: The COV2Ag assay exceeded the World Health Organization minimum performance requirements of ≥ 80% sensitivity and ≥ 97% specificity. The COV2Ag assay is helpful for large scale screening efforts due to high-throughput and reduced wait times., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The pancreatobiliary carcinomas are characterized by presence of desmoplastic stroma. Overexpression of secreted protein acid and rich in cysteine (SPARC), a matrix producing agent has been documented in pancreatic ductal adenocarcinomas, with survival benefits. This study was targeted to see if SPARC expression in pancreatobiliary carcinomas is responsible for stromal desmoplasia and its prognostic significance., Methods: In this retrospective study 48 cases of pancreatic cancer and 27 cases of cholangiocarcinoma were analyzed. The expression pattern of SPARC and vascular endothelial growth factor (VEGF) (angiogenic factors) was evaluated by immunohistochemistry on formalin fixed paraffin embedded tissues. Immunoreactivity was scored semi quantitatively based on stain intensity and stain distribution. SPARC expression was correlated with tumor histology, stromal desmoplasia, VEGF expression, various histological parameters and overall survival in patients. Real time polymerase chain reaction was performed in few cases to validate the immunohistochemistry expression pattern., Results: SPARC expression was high in peritumoral stroma in pancreatic carcinoma than in pancreatic controls; however, SPARC expression pattern was not grossly different in desmoplastic and non-desmoplastic pancreatobiliary carcinomas and in cholangiocarcinomas. No definite correlation was noted between SPARC expression and histological markers of severity and overall survival data., Conclusions: The relevance of SPARC expression in pancreato-biliary carcinomas though may still be important for therapeutic decision making, it is not responsible for peritumoral stromal desmoplasia in these tumors and it does not have any significant prognostic implication., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

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., (© 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Histological assessment of dysplasia in Barrett's esophagus (BE) has high inter-observer variability. Hence, use of ancillary markers for early detection of dysplasia in BE is an important clinical question., Methods: In this retrospective study consecutive cases of BE (n = 59), over a period of 4 years were included. Hematoxylin and eosin stained sections were reviewed independently by 3 senior qualified pathologists, who graded the dysplasia according to the Vienna Classification system and inter-observer agreement was analysed using the Kappa statistics. Subsequently Alpha-Methyl Acyl-CoA Racemase (AMACR), p53, CyclinD1, β-catenin, H2AX and M30 immunohistochemical (IHC) stains were examined on the following disease categories: BE with no dysplasia [NFD] (45), BE with indefinite for dysplasia (IFD) (4), low grade dysplasia (LGD) (3), high grade dysplasia (HGD) (2) and in adenocarcinomas (5). H score was calculated by adding up products of different grades of stain distribution and stain intensities (range of scores 0-300)., Results: Among the 3 pathologists, overall agreement was poor (k 0.06; 95% CI -0.089 to 0.145), with highest disagreement noted for differentiating the LGD and IFDs (k = 0.21). After revising the histological criteria, the kappa improved to 0.53. Among the IHC stains performed, p53, β-catenin, H2AX and M30 stains were significantly useful to differentiate between IFD and LGD (P values: 0.04, 0.004, 0.05 & 0.04, respectively). AMACR and β-catenin stains though were up-regulated in HGD/adenocarcinomas than in other categories, their expression were not statistically different between the IFD and LGDs., Conclusions: A detail histological scoring system may bring uniformity in histological interpretation of dysplasia in BE. Using a combined panel of IHC stains seems helpful in detection of dysplasia in BE, especially to differentiate the IFD and LGD changes in BE., (Copyright © 2018 Elsevier GmbH. All rights reserved.)