HISTOMORPHOLOGICAL FINDINGS AND CLINICO-RADIOLOGICAL CORRELATION OF INTESTINAL ATRESIA AT A TERTIARY CARE CENTRE

Background: An atresia is a congenital defect of a hollow viscus that results in complete obstruction of the lumen. Intestinal atresia is one of the most frequent causes of bowel obstruction in the newborn and can occur at any point in the gastrointestinal tract. This study was undertaken to study the histomorphological findings of intestinal atresia and to correlate it with different subtypes and clinico-radiological feature. Material and methods: This was a prospective observational study conducted in 24 months on the resected gastrointestinal tract of 40 neonatal intestinal obstruction cases admitted in Pediatric surgery ward received in the Department of Pathology, Indira Gandhi Institute of Medical Sciences, Patna. Control Group- A total of 5 cases of vitello-intestinal duct patency were taken as control and compared with the study group. Results: With respect to total 40 cases, there were six, i.e. 15.0% female babies and 34, i.e. 85.0% male babies studied. Out of that, 15 i.e. 37.50% were full term and 25, i.e. 62.5% were premature. Mucosa showed oedema, ulceration and flattening in 9 cases. Apart from flattening and oedema, mucosa was denuded at some places and also showed congestion and extravasated blood in 6 cases each. Abnormal villus configuration, calcium deposition in 4 cases each and hypertrophied mucosa were found in 3 cases. Luminal narrowing, loss of mucosa, duplication of mucosa and gangrenewere found in one case each. Sub mucosal changes showed congestion in 33 cases, oedema in 15, Fibrosis in 4, thickened submucosa in 2 cases and dilated irregular branching blood vessels, extravasted blood, calcification in 1 case each. Muscularispropria having changes i.e. thinning in 16 cases, congestion, hypertrophy in 4 cases each, focal loss in 3 cases, calcification in 2 cases and thinning in 2 cases. Similarly, histopathological changes in serosa shows serositis in 16 cases, congestion in 11 cases and thinning in 3 cases. Oedema and congestion were present in 2 cases, hypertrophy and calcification in 1 case each. Conclusion:In this study spectrum of histomorphological changes in the atretic segment has been described. Histomorphological changes at atretic segment can be valuable to surgeons in deciding the type of surgery and minimizing the postoperative intestinal dysmotility, which remains the most common complication of intestinal atresia.

Hepatocytes Protection by Vitamin E in Alcoholic Liver Injury: A Light Microscopic Study

Background: Alcohol induces histomorphological changes in the liver and vitamin E has a protective role against these changes. Objective: To observe changes in hepatocytes of rabbits exposed to intragastric administration of alcohol and the protective role of vitamin E against these changes. Study Design: Analytical experimental study Place and Duration of Study: Department of Anatomy, Pathology and Pharmacology of Peshawar Medical College, Peshawar, Pakistan from 1st January 2016 to 30th June 2016. Methodology: Eighteen male rabbits domestic type (Oryctolaguscuniculus) were included. Experimental duration for category E8 animals was 8 weeks while for category E4 animals it was 4 weeks. The groups were, control group A in which animals were given proper food and normal saline as drinking water, experimental group B in which animals were fed on proper diet and 30% ethanol solution (30 ml/kg/day) orally daily with normal saline and experimental group C in which animals were treated with proper diet, 30% ethanol solution (30 ml/kg/day), vitamin E (50 mg/kg/day) orally daily and normal saline as drinking water. Results: The difference in the ALT, hepatocyte count and size and hepatocyte nuclear count and size of control and experimental groups and experimental group B-II and C-II from both category E4 and E8 showed a highly significant P values. Conclusion: Alcohol causes histomorphological changes in the liver even in the short period of 4-8 weeks and these changes can be minimized by the antioxidant action of vitamin E. Keywords: Alcohol, Liver, Histomorphology, Vitamin E, Hepatocyte, ALT

An Albumin-Binding Domain Peptide Confers Enhanced Immunoprotection Against Viral Myocarditis by CVB3 VP1 Vaccine

Coxsackievirus B3 (CVB3)-induced viral myocarditis is a common clinical cardiovascular disease without effective available vaccine. In this study, we tried to potentiate the immunoprotection efficacy of our previous CVB3-specific VP1 protein vaccine by introducing a streptococcal protein G-derived, draining lymph nodes (dLNs)-targeting albumin-binding domain (ABD) peptide. We found that compared with the original VP1 vaccine, ABD-fused VP1 (ABD-VP1) vaccine gained the new ability to efficiently bind murine albumin both in vitro and in vivo, possessed a much longer serum half-life in serum and exhibited more abundance in the dLNs after immunization. Accordingly, ABD-VP1 immunization not only significantly facilitated the enrichment and maturation of dendritic cells (DCs), induced higher percentages of IFN-γ+ CD8+ cells in the dLNs, but also robustly promoted VP1-induced T cell proliferation and cytotoxic T lymphocyte (CTL) responses in the spleens. More importantly, ABD-VP1 also elicited higher percentages of protective CD44hi CD62Lhi memory T cells in dLNs and spleens. Consequently, obvious protective effect against viral myocarditis was conferred by ABD-VP1 vaccine compared to the VP1 vaccine, reflected by the less body weight loss, improved cardiac function, alleviated cardiac histomorphological changes and an increased 28-day survival rate. Our results indicated that the ABD might be a promising immune-enhancing regime for vaccine design and development.

SARS-CoV-2 infection and pancreatic disease

SARS-CoV-2 is an etiological factor in several diseases that the WHO designated covid-19. Covid-19 infection may affect the digestive tract, including the pancreas. The main/most common symptoms of covid-19 include fever (71.6%), cough (68.9%) subjective feeling of shortness of breath (71.2%). The gastrointestinal symptoms include abdominal pain, nausea and vomiting and/or diarrhea. The relationship of covid-19 and pancreas affection is not clearly described. A common finding is hyperlipasemia, eventually hyperamylasemia. Both conditions are usually associated with either no or minimal histomorphological changes, i.e. changes referred to as edematous glandular infiltration. Rarely, a necrotic form was reported. Nevertheless, the mortality of patients with acute pancreatitis who were covid-19 positive was higher than in covid-19 negative individuals. The available data indicate there is a link between covid-19 infection and the pancreas presenting as an acute disorder of the gland. SARS-CoV-2 impairment of both exocrine and endocrine function of the pancreas is multifactorial. It is debatable whether the involvement of the gland is directly related to the presence of the virus or whether it is an epiphenomenon. Angiotensin-converting enzyme 2 (ACE-2) receptors, inflammatory changes (especially in pancreatic beta cells), together with high IL-18 levels, virus-induced lipotoxicity and immunological dysregulation play an important role in the induction of pancreatic damage. During the covid-19 pandemic, pancreatopathies represent a very lively topic and are being studied intensively. Keywords SARS-CoV-2, COVID-19, chronic pancreatitis, pancreas, endoscopy

Human small intestinal infection by SARS-CoV-2 is characterized by a mucosal infiltration with activated CD8+ T cells

The SARS-CoV-2 pandemic has so far claimed over three and a half million lives worldwide. Though the SARS-CoV-2 mediated disease COVID-19 has first been characterized by an infection of the upper airways and the lung, recent evidence suggests a complex disease including gastrointestinal symptoms. Even if a direct viral tropism of intestinal cells has recently been demonstrated, it remains unclear, whether gastrointestinal symptoms are caused by direct infection of the gastrointestinal tract by SARS-CoV-2 or whether they are a consequence of a systemic immune activation and subsequent modulation of the mucosal immune system. To better understand the cause of intestinal symptoms we analyzed biopsies of the small intestine from SARS-CoV-2 infected individuals. Applying qRT-PCR and immunohistochemistry, we detected SARS-CoV-2 RNA and nucleocapsid protein in duodenal mucosa. In addition, applying imaging mass cytometry and immunohistochemistry, we identified histomorphological changes of the epithelium, which were characterized by an accumulation of activated intraepithelial CD8+ T cells as well as epithelial apoptosis and subsequent regenerative proliferation in the small intestine of COVID-19 patients. In summary, our findings indicate that intraepithelial CD8+ T cells are activated upon infection of intestinal epithelial cells with SARS-CoV-2, providing one possible explanation for gastrointestinal symptoms associated with COVID-19.

Effect of orthodontic force on dental pulp histomorphology and tissue factor expression:

ABSTRACT Objectives To evaluate the effects of orthodontic force on histomorphology and tissue factor expression in the dental pulp. Materials and Methods Two reviewers comprehensively and systematically searched the literature in the following databases: Latin American and Caribbean Health Sciences, Embase, Cochrane, PubMed, Scopus, Web of Science, and Grey literature (Google Scholar, OpenGrey, and ProQuest) up to September 2020. According to the Population, Intervention, Comparison, Outcomes, Studies criteria, randomized clinical trials (RCTs) and observational studies that evaluated the effects of orthodontic force on dental pulp were included. Case series/reports, laboratory-based or animal studies, reviews, and studies that did not investigate the association between orthodontic force and pulpal changes were excluded. Newcastle-Ottawa Scale and Cochrane risk-of-bias tool were used to assess the risk of bias. The overall certainty level was evaluated with the Grading of Recommendations Assessment, Development and Evaluation tool. Results 26 observational studies and five RCTs were included. A detailed qualitative analysis of articles showed a wide range of samples and applied methodologies concerning impact of orthodontic force on the dental pulp. The application of orthodontic force seems to promote several pulpal histomorphological changes, including tissue architecture, cell pattern, angiogenesis, hard tissue deposition, inflammation, and alteration of the expression levels of 14 tissue factors. Conclusions Although the included articles suggest that orthodontic forces may promote histomorphological changes in the dental pulp, due to the very low-level of evidence obtained, there could be no well-supported conclusion that these effects are actually due to orthodontic movement. Further studies with larger samples and improved methods are needed to support more robust conclusions.

Correlation of placental histomorphology with doppler velocimetry in preeclampsia and IUGR and their perinatal outcome

Background: Though numerous placental ischemic changes are described in relation to placental insufficiency, universally accepted criteria are unavailable till date leading to under or over reporting. Present study is an attempt to define standardized grading system for placental dysmorphology and correlate it with Doppler changes. The objective was to study placental histomorphology in preeclampsia and IUGR (Intrauterine Growth Restriction), to correlate the placental histomorphology with multivessel Doppler findings and their perinatal outcome in preeclampsia and IUGR.Methods: Prospective study was done over 2 years, 64 antenatal women with preeclampsia and/or IUGR were recruited, their multivessel Doppler measurements were recorded and placental histomorphological changes were studied post-delivery which were graded as either low or high grade placentas considering degree and number of ischemic changes observed.Results: Out of 64 cases, 33 (51.5%) cases had low grade changes and 31 (48.5%) had high grade changes. Out of 33 patients with low grade placentas 24 (73%) had normal Doppler, 20 (65%) out of 31 high grade placenta had abnormal Doppler. Placental histomorphology correlated well with Doppler abnormality (Coefficient of Kappa test). Syncytial knots>50%, presence of hypermature villi, infarcts, fibrin deposits were significantly associated with abnormal Doppler. High grade placenta group had significantly poor perinatal outcome (Chi square test).Conclusions: We formulated a grading system of placental dysmorphology in preeclampsia and IUGR which correlated well with clinical Doppler abnormality and perinatal outcome. Further studies are warranted to develop preventive strategies aimed at specific high grade placental changes seen in pregnancies with abnormal Doppler and develop strategies to improve perinatal outcome.

Maternal underweight and obesity are associated with placental pathologies in human pregnancy

Introduction: Maternal underweight and obesity are prevalent conditions, associated with chronic, low-grade inflammation, poor fetal development, and long-term adverse outcomes for the child. The placenta senses and adapts to the pregnancy environment in an effort to support optimal fetal development. However, the mechanisms driving these adaptations, and the resulting placental phenotypes, are poorly understood. We hypothesised that maternal underweight and obesity would be associated with increased prevalence of placental pathologies in term and preterm pregnancies. Methods: Data from 12,154 pregnancies were obtained from the Collaborative Perinatal Project, a prospective cohort study conducted from 1959 to 1974. Macro and microscopic placental pathologies were analysed across maternal prepregnancy body mass index (BMI) to assess differences in the presence of pathologies among underweight, overweight, and obese BMI groups compared to normal weight reference BMI at term and preterm. Placental pathologies were also assessed across fetal sex. Results: Pregnancies complicated by obesity had placentae with increased fetal inflammation at preterm and increased maternal inflammation at term. In term pregnancies, increasing maternal BMI associated with increased maternal vascular malperfusion (MVM), odds of an appropriate mature placenta for gestational age, and placental weight, and decreased placental efficiency. Male placentae, independent of maternal BMI, had increased inflammation, MVM, and placental efficiency than female placentae, particularly at term. Discussion: Maternal underweight and obesity are not inert conditions for the placenta, and the histomorphological changes driven by suboptimal maternal BMI may serve as indicators of adversities experienced in utero and potential predictors of future health trajectories.