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Objective: The aim of this study was to evaluate the diagnostic utility of calretinin immunostaining in colonic biopsy specimens in patients having a clinical suspicion of Hirschsprung's disease. Study Design: This study was a Cross sectional validation study. Place and Duration of Study: The study was conducted at Pakistan institute of medical sciences, Shaheed Zulfiqar Ali Bhutto Medical University (SZABMU), Islamabad, for a period of 11 months (December 2018 to November 2019). Materials and Methods: Sixty specimens from patients including multiple colonic biopsies and biopsies from rectum for doubted Hirschsprung's disease were evaluated. The biopsies were processed in Histopathology lab and Hematoxylin and eosin slides were examined. 30 ganglionic segments and 30 aganglionic segments along with control specimens were further stained with calretinin immunohistochemical marker and evaluated. Results: On Hematoxylin and eosin staining, 30 biopsies showed ganglion cells and 30 biopsies showed absence of ganglion cells. Calretinin immunohistochemistry was then evaluated on these ganglionic and aganglionic segments. In this study, sensitivity was found to be 91.4 % and a 100% of specificity was established. The positive predictive value and negative predictive value was found to be 100% and 89.2% respectively. Conclusion: Calretinin immunohistochemical marker can be applied on colonic and rectal biopsy specimens as a dependable and adjunctive tool for diagnosing Hirschsprung's disease, as it is easy and reliable to be used in daily practice.

Context: Neurotensin is associated with cardiometabolic diseases but its role with mortality risk in humans is unknown. Objective: This work aims to examine the prediction of proneurotensin (Pro-NT) with respect to total and cause-specific mortality in a middle-aged cohort. Methods: In the population-based middle-aged cohort (n = 4632; mean age, 57 years) of the Malmö Diet and Cancer Study, Pro-NT was assessed and total as well as causespecific mortality was studied. Main cause of death was based on the International Classification of Diseases. Results: During a mean follow-up of 20 ± 3 years, 950 men and 956 women died. There was significantly increased mortality risk in individuals belonging to the highest quartile (Q) of Pro-NT (Q4, Pro-NT = 149 pmol/L) compared with Qs 1 to 3 (Pro-NT < 149 pmol/L), hazard ratio (HR), 95% CI of 1.29 (1.17-1.42; P < .001). Data were adjusted for sex and age. No significant interaction was observed between Pro-NT and sex on mortality risk. Individuals within Q4 vs Qs 1 to 3 had an HR of 1.41 (95% CI, 1.18-1.68; P < .001) for death due to cardiovascular disease (n = 595/4632); 2.53 (95% CI, 1.37-4.67; P = .003), due to digestive tract disease (n = 42/4632), 1.62 (95% CI, 1.04-2.52; P = .032) due to mental and behavioral disease (n = 90/4632); and 1.91 (95% CI, 1.15-3.19; P = .013) due to unspecific causes (n = 64/4632). There was no significant relationship between Pro-NT and deaths due to cancer, infections, neurological, or other causes. Adjustment for cardiovascular risk factors only marginally changed these results. Conclusion: The relationship between Pro-NT and total mortality risk was mainly driven by cardiovascular mortality, but high Pro-NT also predicts death from digestive, mental, and behavioral disease and deaths attributed to unspecific causes. [ABSTRACT FROM AUTHOR]