Significant Histological Abnormalities Research Articles

HISTOPATHOLOGIC FINDINGS IN 10 CASES OF MORTALITY IN CAPTIVE MALAYSIAN FIRE SNAILS (PLATYMMA TWEEDIEI).

Malaysian fire snails (Platymma tweediei), face threats to their environment, including habitat destruction and the illegal wildlife trade. Captive breeding projects are likely to play a role in the survival of this species; however, mortality in captive populations potentially presents a significant challenge. This paper presents the results of histopathologic examination of tissues from 10 P. tweediei casualties in a captive population at Chester Zoo. In October 2022, a captive breeding program was established with 20 wild-born P. tweediei. All adult founder animals died by July 2023, of which 10 were submitted for necropsy and histopathology of organs. Significant histologic abnormalities were present in all cases, primarily affecting the lung, integument, and heart. Histological analyses indicated a pneumonia-like condition was prevalent in all cases, suggesting potential environmental factors contributed to respiratory infections. A variety of possible etiologic or secondary infectious agents were present in sections including bacteria, fungi, and trematodes. There were some challenges in interpreting the histologic changes, emphasizing the need for more reference material and studies on the normal histologic anatomy of terrestrial gastropods. The findings underline the importance of understanding mortality events in captive populations to improve husbandry and environmental management. Additionally, the study recommends the submission of fresh specimens for necropsy to enhance diagnostic capabilities, such as bacterial culture, and suggests targeted sampling strategies for future research on captive snail species.

Lectin histochemistry in the small intestines of piglets naturally infected with porcine epidemic diarrhea virus.

Porcine epidemic diarrhea virus (PEDV) binds to particular cell surface receptors to penetrate cells. The virus specifically identifies certain carbohydrate structures present on the surface of the cell to facilitate the binding process. Nevertheless, the influence of viral infections on specific alterations of glycoconjugates in the small intestines remains unexplored. This work aimed to examine the alterations in glycoconjugates in the small intestines of piglets naturally infected with PEDV using lectin histochemistry. Six piglets including three PEDV-infected and three non-infected piglets were evaluated. Small intestinal samples were histopathologically examined, and lectin histochemistry was performed. Piglets infected with PEDV had significant histological abnormalities in their small intestines, such as pronounced villous atrophy, varying degrees of villous fusion, and diverse mucosal alterations. Specific regions of the duodenum, jejunum, and ileum showed discernible variations in glycoconjugate distribution, as determined by lectin histochemistry. Compared with the controls, the PEDV-infected piglets showed significant changes in N-acetylglucosamine- and galactose-binding lectins (particularly wheat germ agglutinin and Arachis hypogaea (peanut) agglutinin) in multiple intestinal regions. These findings can enhance understanding of how viruses such as PEDV impact the glycoconjugate composition of the small intestines and emphasize the potential connection between the pathogenesis of PEDV and glycoconjugate.

Predictors of Significant Histological Hepatic Abnormality in Treatment-Naive Patients Infected with HBeAg-Negative Chronic Hepatitis B.

This study aimed to determine the predictors for significant hepatic abnormality (SHA), a treatment indication, by assessing demographic, laboratory, and radiological results of chronic hepatitis B (CHB) patients who underwent liver biopsy. In this retrospective study, individuals with untreated hepatitis B e-antigen (HBeAg)-negative CHB infection were enrolled. Multivariate analysis modeling was conducted with parameters identified as predictors for SHA in univariate analysis. Optimal threshold levels for variables to predict SHA in patients with chronic hepatitis B were determined based on receiver operating characteristic (ROC) curve analysis. A total of 566 patients with untreated chronic hepatitis B were included in the cohort; 61% (345/566) were male, and the median age was 41 years (interquartile range [IQR]=34-50). Notably, 36.9% (209/566) had SHA. In the multivariate analysis, utilizing different models, age, gender, HBV-DNA, LDL, ALT, and platelet count were identified as the most reliable predictors for SHA in CHB patients. For predicting SHA, the area under the ROC curve values of HBV-DNA, AST, and ALT were 0.704 (sensitivity=62.8%, specificity=76.2%; p<0.0001), 0.747 (sensitivity=51.9%, specificity=88.9%; p<0.0001), and 0.737 (sensitivity=68.6%, specificity=68.4%; p<0.0001), respectively. In our study, age, male gender, ALT, AST, HBV-DNA, LDL cholesterol, platelet count, and FIB-4 score were independent predictors of SHA in HBeAg-negative chronic hepatitis B. The most sensitive parameters for SHA were LDL and ALT. The most specific parameters were age, AST, and APRI score. SHA may occur in patients with high HBV-DNA levels, even if ALT values are normal in HBeAg-negative patients.

Determination of the median lethal dose of zinc gluconate in mice and safety evaluation.

Zinc Gluconate (ZG) is a safe and effective supplement for zinc. However, there is limited research on the optimal dosage for intravenous injection and the safety evaluation of animal models for ZG. This study aims to determine the safe dose range of ZG for intravenous injection in C57BL/6J mice. A Dose titration experiment was conducted to determine the LD50 and 95% confidence interval (95%CI) of ZG in mice. Based on the LD50, four sub-lethal doses (SLD) of ZG were evaluated. Following three injections of each SLD and monitoring for seven days, serum zinc levels were measured, and pathological changes in the liver, kidney, and spleen tissues of mice were determined by histological staining. The dose titration experiment determined the LD50 of ZG in mice to be 39.6mg/kg, with a 95%CI of 31.8-49.3mg/kg. There was a statistically significant difference in the overall serum zinc levels (H = 36.912, P < 0.001) following SLD administration. Pairwise comparisons showed that the serum zinc levels of the 1/2 LD50 and 3/4 LD50 groups were significantly higher than those of the control group (P < 0.001); the serum zinc level of the 3/4 LD50 group was significantly higher than those of the 1/8 LD50 and 1/4 LD50 groups (P < 0.05). There was a positive correlation between the different SLDs of ZG and the serum zinc levels in mice (rs = 0.973, P < 0.001). H&E staining showed no significant histological abnormalities or lesions in the liver, kidney, and spleen tissues of mice in all experimental groups. The appropriate dose range of ZG for intravenous injection in C57BL/6J mice was clarified, providing a reference for future experimental research.

Are biopsies from endoscopically normal terminal ileum necessary?

The terminal ileum is typically examined during colonoscopies, especially in patients with inflammatory bowel disease (IBD) and diarrhea. The yield from performing biopsies of endoscopically normal appearing terminal ileum is less clear, and may be associated with greater costs, healthcare utilization and risk. We aimed to determine whether the biopsy results from endoscopically normal terminal ileum affect clinical management. This was a retrospective chart review of patients who underwent an ileocolonoscopy with terminal ileum biopsy at a multisite tertiary healthcare system. Patients with a diagnosis of IBD, prior ileocecal resection, or endoscopically abnormal appearing terminal ileum were excluded. Clinical and laboratory data were obtained from the electronic medical record. Comparison between patients was performed using Pearson's chi-square test. A total of 1018 consecutive patients were identified. Of the 299 who met the inclusion criteria, the majority were female (62.0%) and white (94.7%). Nearly 40% of the patients had a body mass index of 30 kg/m2 or above (38.1%). Terminal ileum biopsies were abnormal in 13 patients (4.3%): 5 patients had chronic ileitis, 6 had acute ileitis, 1 had acute and chronic ileitis, and 1 had amyloid deposition. All patients with either chronic or acute ileitis had chronic diarrhea listed as an indication for their colonoscopy. In patients with a normal appearing terminal ileum, clinically significant histologic abnormalities on biopsies were found in a very small percentage. Based on our findings, the routine biopsy of endoscopically normal appearing terminal ileum has limited diagnostic and therapeutic utility.

Clinical and histological features of patients with chronic hepatitis B virus infection in the grey zone.

Chronic HBV infection patients who do not conform to any of the usual immune states are regarded as 'grey zone' patients. We aimed to investigate the proportion of chronic HBV infection patients in the grey zone, and evaluate the clinical characteristics and liver pathological changes in grey zone patients. Clinical data of 1391 treatment-naive chronic HBV infection patients with liver biopsy were collected. Natural history of HBV infection was determined based on European Association for the Study of the Liver (EASL) 2017, American Association for the Study of Liver Diseases (AASLD) 2018 and Chinese 2019 guidelines for the prevention and treatment of chronic HBV infection. Significant liver histological changes and associated risk factors of normal ALT grey zone patients were analysed. According to EASL, AASLD and Chinese criteria, there were 50.0%, 28% and 37.4% chronic HBV infection patients in the grey zone. Among the 353 grey zone patients with normal ALT, 72.4% had significant liver histological changes. ALT (optimal cut-off value 25 IU/L) and HBV DNA (optimal cut-off value 18,000 IU/mL) were independent risk factors of significant liver histological abnormalities. In conclusion, a substantial proportion of grey zone patients with normal ALT have significant liver histological changes that can be predicted by levels of serum ALT and HBV DNA. These results provide guidance of antiviral treatment in grey zone patients.

Evaluating the in-vivo effects of olive oil, soya bean oil, and vitamins against oxidized ghee toxicity.

The aim of this study was to examine the protective role of various lipids (olive and soya oil) and vitamin (E and C) against the toxicity of thermally oxidized ghee in rabbits. Vanaspati ghee was thermally oxidized on a hot plate at 100°C for ten consecutive hours, and the oxidized ghee was stored in a refrigerator at -20°C until administration. Thirty male rabbits were purchased as experimental animals at a local market and were divided into ten corresponding groups of three based on their body weight. The blood samples of 5 ml were collected on day 0, 7, and 14 of the experiment for the analysis of hematological and biochemical serum parameters. We observed that oxidized ghee significantly elevated ALT level by affecting liver hepatocytes. Furthermore, vitamin E rapidly decreased the ALT levels compared to vitamin C and other oils. The oxidized ghee caused a significant increase in cholesterol compared to the other groups. Vitamin E and C showed the best antioxidant activity and decreased cholesterol levels to normal. Histopathological examinations of the normal rabbits' liver sections revealed no significant histological abnormality. The liver of the rabbits fed with oxidized ghee had an intact lobular architecture but the portal tracts showed inflammation and mild fibrosis, the bile ducts showed proliferation, and the hepatocytes showed feathery degeneration. In the liver sections from the groups fed with oxidized ghee and different doses of olive oil inflammation in portal tracts and large vacuoles in the hepatocytes were observed. The group fed with oxidized ghee and vitamin E had intact lobular architecture with no significant histological abnormality in portal tracts but fatty changes were present in the hepatocytes. These findings support the antioxidant activity of vitamins C and E as they reduced liver infection caused by oxidized ghee. It was concluded that oxidized ghee was highly toxic and not safe for consumption. The present study indicated that soya bean oil and vitamin E were more effective in protecting against the toxicity of thermally oxidized ghee than olive oil and vitamin C.

THE UTILITY OF BIOPSYING ENDOSCOPICALLY NORMAL APPEARING TERMINAL ILEUM

Abstract INTRODUCTION The terminal ileum is often evaluated during colonoscopy procedures. A common indication for endoscopic examination and biopsy of an endoscopically normal appearing terminal ileum is in patients with inflammatory bowel disease (IBD). 1 In patients without IBD, indications for biopsying an endoscopically normal appearing terminal ileum are less clear and may be associated with increased cost and healthcare utilization, as well as increased levels of anxiety for patients. In this study, we aim to determine the indications for examining and biopsying an endoscopically normal appearing terminal ileum in patients without IBD and if, upon review of these biopsies, there is change in management. METHODS This was a retrospective chart review of patients who underwent colonoscopy with terminal ileum biopsy at Mayo Clinic between 1/1/2021 and 6/30/21. Patients were excluded if they had a history of IBD, prior ileocecal resection, or an endoscopically abnormal terminal ileum. Clinical and laboratory data, as well as outcomes of interest, were obtained from the electronic medical record. Comparisons between patients were performed using Pearson’s chi-square, Student’s and Mann-Whitney tests. RESULTS A total of two hundred consecutive patients were identified as having had biopsies from their endoscopically normal appearing terminal ileum. After reviewing the charts, 69 met inclusion criteria. Of the 69 patients, the majority were female (68.1%) and white (89.9%). Nearly half the patients had a BMI of 30 or above (49.3%). The most common indication for colonoscopy among these patients was chronic diarrhea followed by abdominal pain and hematochezia. Terminal ileum mucosa was histologically abnormal in 6 patients (8.7%): four patients had chronic ileitis, one had acute ileitis, and one had acute and chronic ileitis. All patients with either chronic or acute ileitis had chronic diarrhea listed as an indication for their colonoscopy. The patient with acute and chronic ileitis underwent colonoscopy for suspected Crohn’s disease due to incidental asymptomatic findings of small bowel inflammation on CT enterography. CONCLUSIONS In patients with a normal appearing terminal ileum, clinically significant histologic abnormalities on biopsies were found in a small percentage of patients. Although our sample size is small, there may not be diagnostic and therapeutic utility to routinely biopsy endoscopically normal appearing terminal ileum in patients, even in those with chronic diarrhea. Large prospective studies are needed to further support this observation. REFERENCES 1McHugh, Jonathan B et al. “The diagnostic value of endoscopic terminal ileum biopsies.” The American journal of gastroenterology vol. 102,5 (2007): 1084-9.

Number and distribution of eosinophils and lymphocytes in the Japanese pediatric gastrointestinal tract: in search of a definition for "abnormally increased eosinophils".

Primary eosinophilic gastrointestinal disorders (EGIDs) constitute chronic allergic inflammation. The number of eosinophils is one of the diagnostic criteria; more than 20 eosinophils per high-power field (HPF) in the gastrointestinal (GI) tract are considered abnormal in Japan. However, the quantity of eosinophils considered normal varies according to anatomical location and geographical region; such values have not been reported in Japanese pediatric patients, nor have the numbers of lymphocytes in the normal pediatric stomach. To establish a reference for defining diagnostic criteria for EGIDs, we evaluated the number of eosinophils in the normal Japanese pediatric GI tract. We examined 131 biopsy cases without significant clinical history, endoscopic abnormality, or histological abnormality. Immunohistochemical analysis of CD3 and CD20 was performed. The mean eosinophil density was highest in the cecum (49.5 ± 22.4 per HPF). Counts of more than 20 eosinophils per HPF were observed in the duodenum [bulb (20.0 ± 9.6) and second portion (30.0 ± 15.8)], terminal ileum (38.3 ± 22.7), cecum (49.5 ± 22.4), ascending colon (42.3 ± 25.3), transverse colon (29.4 ± 17.0), and descending colon (32.2 ± 17.9). Counts of fewer than 10 eosinophils per HPF were observed in the stomach and rectum; a count of fewer than one eosinophil per HPF was observed in the esophagus. More than 100 CD3-positive T cells per HPF were observed in the stomach. The mean numbers of eosinophils in the bowel were greater than 20 per HPF. For Japanese pediatrics, the current threshold eosinophil count should be revised.

Histology Altering Effect of Smoking in Rodents' Trachea

Aim: The purpose of this study was to investigate the effects of the cigarette smoke. Duration &amp; Place of Study: Jan 2018 to may 2021 Rashid Latif medical college Lahore Material and Method: Two different groups of male albino rats were exposed to cigarette smoke using a specially developed smoking machine for duration of three months on a daily basis over the course of the experiment. Both populations of rats were made up entirely of albinos. Result: Significant histological abnormalities occurred in the tracheal epithelium of albino rats that were exposed to cigarette smoke for a period of three months. The rats were given the smoke. The multiplication of epithelial cells, the disruption of the cilia, and the formation of inclusion bodies were some of the alterations that occurred as a result of this. In addition to alveoli that had collapsed and blood extravasations, a considerable thickening of the alveolar wall of the lung alveoli was seen. Conclusion: These modifications show that nicotine may generate changes in tissue that are comparable to those induced by chronic irritation of tissue. This may result in a reduction in the efficiency of gaseous exchange in alveoli and may predispose to the development of neoplastic abnormalities.

QHBsAg for the Identification of Liver Histological Abnormalities in HBeAg-Negative Chronic Hepatitis B Patients with Normal and Mildly Elevated ALT Levels.

Backgrounds Noninvasive detection of histological abnormalities remains challenging in patients with HBeAg-negative chronic HBV infection with normal or mildly elevated levels of alanine aminotransferase (ALT). This study aimed to assess the utility of serum quantitative hepatitis B surface antigen (qHBsAg) in identifying significant histological lesions in this population. Methods This is a single-center study with retrospective analysis of 392 treatment-naive patients of HBeAg-negative chronic HBV infection with normal or mildly elevated levels of ALT. Results In this cohort, significant necroinflammation and fibrosis were found in 69.4% and 61.5% of patients, respectively. Patients with qHBsAg >1000 IU/mL (N = 236) had more hepatic inflammation of ≥G2 (75.4% vs. 60.9%, P < 0.01) or fibrosis ≥ S2 (66.1% vs. 54.5%, P < 0.05) compared to those without (N = 156). Serum HBsAg (cutoff point = 1000 IU/mL), aspartate aminotransferase (AST) level (cutoff point = 25 IU/L), age (cutoff point = 40 years), and HBV family history were identified as independent predictors of significant histological abnormalities in multivariate logistic analysis. Conclusions A significantly higher proportion of patients with histological abnormalities were found in patients with qHBsAg >1000 IU/mL than those without. The qHBsAg level together with age, AST, and family history of HBV infection could be used as an algorithm to help noninvasive patient selection for antiviral therapy.

Hypoglycemic Activity of Aqueous Extract of Latex from Hancornia speciosa Gomes: A Study in Zebrafish and In Silico

Hancornia speciosa Gomes is a tree native to Brazil and has therapeutic potential for several diseases. Ethnopharmacological surveys have reported that the plant is used as a hypoglycemic agent and to lose weight. This study aimed to evaluate the effects of the aqueous extract from H. speciosa latex (LxHs) in a zebrafish model of diabetes. The extract was evaluated through high-performance thin-layer chromatography (HTPLC), nuclear magnetic resonance (NMR), and Fourier-transform infrared spectroscopy (FT-IR). We then tested treatments with LxHs (500, 1000, and 1500 mg/kg) by assessing blood glucose levels in alloxan-induced diabetic animals, and metformin was used as a control. The toxicity was evaluated through histopathology of the pancreas and biochemical assessment of serum levels of AST, ALT, creatinine, and urea. The extract was also assessed for acute toxicity through several parameters in embryos and adult animals. Finally, we performed in silico analysis through the SEA server and docking using the software GOLD. The phytochemical study showed the compounds cornoside, dihydrocornoide, and 1-O-methyl-myoinositol (bornesitol). The treatment with all doses of LxHs significantly decreased alloxan-induced hyperglycemia without any significant histological or biochemical abnormalities. No significant frequency of teratogenesis was observed in the embryos exposed to the extract, and no significant behavioral changes or deaths were observed in adult animals. In silico, the results showed a potential interaction between inositol and enzymes involved in carbohydrates’ metabolism. Overall, the results show a hypoglycemic activity of the extract in vivo, with no apparent toxicity. The computational studies suggest this could be at least partially due to the presence of bornesitol, since inositols can interact with carbohydrates’ enzymes.

Abstract B23: The mammary tissue microbiome in breast cancer development

Abstract Introduction: Breast cancer is the most prevalent type of cancer among women (other than some nonmelanoma skin cancers), with approximately one in eight women diagnosed with breast cancer during their lifetime. The mammary tissue microbiome has recently been characterized, and shifts in the abundance of mammary tissue bacterial taxa have been associated with benign and malignant breast tumors. This suggests particular bacterial taxa as oncogenic and key in driving breast cancer development. However, these studies utilized mammary tissue obtained from breast reduction or enhancement surgery as healthy control tissue, which has significant histologic abnormalities compared to tissue from normal healthy donors. The Susan G. Komen Tissue Bank (KTB) at the Indiana University Simon Cancer Center (IUSCC) is a unique and precious repository of normal breast tissue, ideal for compositional and functional analyses of the mammary tissue microbiome. We have also identified a subset of women who donated healthy tissue to the KTB and later developed breast cancer. This provides us with a rare opportunity to study shifts in the mammary microbiome composition that may preclude breast cancer development. Our research objective is to compare the composition of the mammary microbiome in healthy and prediagnostic tissue to that of cancerous tissue. Methods: Our cohort comprises four tissue subsets: healthy (n = 50), prediagnostic (n = 15), adjacent normal (n = 50), and tumor (n = 50) selected from the KTB and IUSCC Tissue Banks. DNA was isolated from all 165 tissue samples. DNA from three of these samples, two positive controls, and two negative controls was submitted for Illumina Miseq paired-end sequencing of the V4 region of the 16S gene at the University of California, Davis Host Microbe Systems Core Lab. Results/Conclusions: The breast tissue samples display microbiome compositions dominated by three phyla: Proteobacteria, Firmicutes, and Bacteroidetes. Negative controls displayed fewer than 10 reads and positive controls yielded accurate percentages of several difficult-to-lyse bacteria. In January 2020, all 165 DNA samples will be submitted for 16S rRNA metagenomic sequencing for analysis of the microbiome composition among the four tissue subsets. We will use multivariate linear modeling to adjust for clinical factors such as age, BMI, and menopausal status and to determine if microbiome composition is modified by cancer status. This work will be fundamental in characterizing the composition of the healthy mammary tissue microbiome and identifying microbial determinants of breast cancer. Citation Format: Jaelyn Gabel, Courtney Hoskinson, Annie Kump, Karin B. Michels, Natascia Marino, Leah T. Stiemsma. The mammary tissue microbiome in breast cancer development [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr B23.

High-Output (HO) Ostomy With Histopathologic Abnormality: Examination of 78 Stoma Specimens

Abstract Background HO (&gt;2,000 mL output/day) is a serious complication following ostomy procedure. HO may be associated with variable underlying conditions or idiopathic. We encountered an ileostomy case with diffuse subepithelial collagen deposits resembling collagenous colitis from a patient with history of HO without underlying cause. A subset of idiopathic HO may be associated with histopathologic abnormalities of the bowel. Methods Resected stomas from ostomy malfunction were searched using ICD-9 and CPT codes (2003-2018). Archived pathology materials were reviewed and activity, villous blunting, pyloric metaplasia (PM), and subepithelial collagen deposits were assessed. Trichrome stain was performed when necessary. Clinical history was obtained from medical records. Results Sixty-one ileostomies and 17 colostomies were retrieved from 69 patients. Types of ostomy malfunction were stricture/obstruction (n = 21), hernia (n = 10), ischemia/necrosis (n = 4), leak (n = 4), abscess/adhesion (n = 3), skin breakdown (n = 3), prolapse (n = 3), retraction (n = 2), reepithelialization (n = 1), and unclear/not specified (n = 15). Thirty-two patients had inflammatory bowel disease (IBD; 19 Crohn disease [CD], 13 ulcerative colitis [UC]). All HOs were from ileostomy, and 16 had risk factors for HO, including IBD (n = 9 [56%]; 7 CD, 2 UC), short bowel (n = 6, 3 with CD), pelvic/intra-abdominal abscess (n = 2), sepsis (n = 2), and prokinetic (n = 1). Five ileostomies from CD showed PM, while 11 lacked significant histologic abnormalities. Among 5 (24%) idiopathic HOs, 1 was the index case with diffuse subepithelial collagen deposits with subtotal villous blunting, 1 showed PM, and 1 had focal activity. Remaining 2 ileostomies from idiopathic HO were unremarkable. Stomas from patients with other types of ostomy malfunction showed compatible histologic changes. Fifteen cases without ostomy malfunction did not show histologic abnormality. Conclusion Most HO represents functional abnormality without histopathologic abnormality except in IBD. However, idiopathic HO may be associated with histopathologic abnormalities in the stoma suggestive of acute/chronic enteritis and scarring, which may be underrecognized and treatable.

Recours au test virologique HPV dans la prise en charge des atypies glandulaires en Alsace entre 2014 et 2016

The new recommendations by the National Institute of Cancer (January 2017) recommend the use of a complementary human papillomavirus (HPV) virologic test during the diagnosis of atypical glandular cells in pap smear. The aim of this study was the performance analysis of the HPV virologic test for the detection of significant histological cervical abnormalities (CIN2 or more) in case of atypical glandular cells before the new recommendations were published. We performed a descriptive and retrospective cohort study in Alsace between January 2014 and December 2016. We have included, from the EVE-association database, the patients with atypical glandular cells in pap smear. In total, 1074 patients had a pap smear with atypical glandular cells ; 0.18% of total pap smears. This study included 152 patients who had a HPV test. We observed 6 cases of CIN2 (3.9%) and 12 cases of CIN3 (7.9%). No in situ adenocarcinoma nor invasive carcinoma were detected. The sensitivity of the HPV test was 88.9% (95% CI: [0.65; 0.99]), the specificity was 65.9% (95% CI: [0.55; 0.76]), the positive predictive value was 34% (95% CI: [0.21; 0.49]) and the negative predictive value was 96.8% (95% CI: [0.89; 0.99]). The detection of HPV in atypical glandular cells seems to be powerful with an excellent negative predictive value but, because of moderate sensitivity and due to the risk of histologic lesion progression, the current recommendations should to be applied with care.

Role of Nerve and Muscle Biopsies in Pediatric Patients in the Era of Genetic Testing

An operative biopsy is an important component in the diagnosis and treatment of neuromuscular disorders (NMDs). However, recent advances in molecular genetics suggest less invasive genetic testing should be the initial approach. The purpose of our study was to demonstrate the diagnostic value of muscle or nerve biopsy within the pediatric population at a pediatric academic center and offer recommendations for genetic testing in relation to biopsy to achieve the highest diagnostic yield. Following institutional review board approval, we retrospectively reviewed the electronic medical record of 221 pediatric patients who underwent muscle and/or nerve biopsy for suspicion of NMD from January 2007 to March 2018. Demographics, family history, clinical presentations, genetic testing results, pathology results, anesthesia complications, clinical diagnoses, and clinic follow-up data were collected. Chi-square analysis was done for statistical significance. A total of 220 underwent muscle biopsy, and 15 underwent nerve biopsy. Not all patients received genetic testing. The average age at biopsy was 7.7y. Biopsy revealed significant histologic abnormalities in 62.9% (139), directly leading to a specific clinical diagnosis in 33.9% (75). When genetic testing was done before biopsy, definite pathogenic variants were found in 7.6% (9). When genetic testing was done after biopsy, definite pathogenic variants were found in 45.0% (27). Genetic testing yield for pathogenic variants was higher when done after biopsy (P value < 0.00001). Muscle and nerve biopsies may provide significant diagnostic value. Biopsy helped to rule in or out NMD and guide genetic testing. Our data suggest NMD genetic testing yield was higher when done after biopsy.

Diacerein protects against glycerol-induced acute kidney injury: Modulating oxidative stress, inflammation, apoptosis and necroptosis

Necroptosis is suggested to have an important role in the pathogenesis of rhabdomyolysis induced acute kidney injury (AKI). In this study, the renoprotective effect of diacerein on glycerol-induced AKI was investigated. Twenty four male albino rats were included in this study and divided into four groups: (group I) saline control group, (group II) glycerol-treated group, (groups III&IV) diacerein+glycerol -treated groups (25 and 50mg/kg/day) respectively. Renal malondialdehyde (MDA) level in addition to catalase and heme oxygenase (HO) activities were estimated. Comet assay and histopathological changes were evaluated. The levels of pro-apoptotic Bcl-2-associated X (Bax) protein, tumor necrosis factor alpha (TNF-α) and receptor-interacting serine/threonine-protein kinases 3 (RIPK3) were measured by ELISA. RIPK3 and mixed lineage kinase domain-like pseudokinase (MLKL) mRNA expression were assessed by real time PCR. Glycerol treatment caused significant renal histological abnormalities and functional impairment (increased urea and creatinine). Increased levels of renal MDA with concomitant decrease in renal catalase activity and significant DNA damage in comet assay were observed. High expression of RIPK3 and MLKL in the glycerol-treated group with marked elevation of Bax, TNF-α and RIPK3 levels and HO-1 activity were also documented. Diacerein treatment dependently attenuated glycerol induced structural and functional changes in kidney and significantly elicit reduction of renal tissue oxidative damage whereas it decreased renal expression of RIPK3 and MLKL, and decreased Bax, TNF-α and RIPK3 levels and HO-1 activity. CONCLUSION: These results demonstrated that diacerein might have potential application in the amelioration of AKI via its anti-oxidant, anti-inflammatory, anti-apoptotic and anti-necroptotic effects.

Diagnostic Dilemma for Low Viremia with Significant Fibrosis; is Hepatitis B Virus DNA Threshold Level a Good Indicator for Predicting Liver Damage?

Background:The most important difficulties about management of hepatitis B are still determining the liver damage and the right time to start antiviral therapy.Aims:To reveal the role of hepatitis B virus DNA threshold level for prediction of liver fibrosis and inflammation in young-aged hepatitis B e-antigen negative chronic hepatitis B patients.Study Design:Diagnostic accuracy study.Methods:A total of 273 hepatitis B e-antigen negative young chronic hepatitis B patients with any hepatitis B virus DNA levels between 2008 and 2016, who had liver biopsy after at least 6 months follow up period, enrolled in this retrospective study. We created two groups as case and control, cases with hepatitis B virus DNA levels below 2000 IU/mL and controls with hepatitis B virus DNA levels over 2000 IU/mL. Having histological activity index ≥4 or/and fibrosis scores ≥2 were defined as significant histological abnormality. Then, we analyzed the relationship between these groups.Results:We showed that significant fibrosis may occur in one third of young chronic hepatitis B patients with low viremia (30.2%, n=42/139 in cases, 55.2%, n=74/134 in controls). Among the 42 cases with low viremia and significant fibrosis, 21.4% had alanine aminotransferase level between 40-59 U/L, 42.8% had alanine aminotransferase level between 60-79 U/L, and 35.7% had alanine aminotransferase level over 80 U/L. There was weak correlation between hepatitis B virus DNA threshold level and fibrosis score (p<0.001, rho=0.253). The optimum serum hepatitis B virus DNA threshold level in our study for predicting significant fibrosis was 1293 IU/mL (p<0.001, AUC: 0.657±0.034). The optimum alanine aminotransferase threshold level for predicting significant histological activity index and fibrosis was 64.5 and 59.5 U/L, respectively. The sensitivity and the specificity of 1293 vs 2000 IU/mL hepatitis B virus DNA threshold with 60 U/L alanine aminotransferase threshold level for predicting F≥2 fibrosis score were similar (sensitivity: 0.43 and 0.38, specificity: 0.76 and 0.77, respectively).Conclusion:Significant fibrosis may occur even in young cases with low viremia. It is not possible to define a single threshold hepatitis B virus DNA level for differentiating inactive carriers from patients with hepatitis B e-antigen-negative chronic hepatitis. Diagnostic accuracy of hepatitis B virus DNA with alanine aminotransferase thresholds for the prediction of significant fibrosis is weak.

Pediatric medicolegal autopsy in France: A forensic histopathological approach

The aim of postmortem medicolegal examination in pediatric death is primarily to establish the circumstances and causes of death and to exclude child abuse. In France, pediatric death is systematically documented by medicolegal or medical autopsy. In case of medicolegal autopsy, the complementary examinations, requested and financed by justice, are rarely limited to a histopathological examination. However in medical autopsies other tools are available to the pathologist as toxicology, biochemistry and molecular biology. The purpose of this article is to evaluate the efficacy of forensic histopathology in pediatric forensic autopsies. We analyze the main causes of pediatric death in a forensic context. Between 2004 and 2015, 157 infant deaths were identified in Marseille university hospital. The forensic histopathology and autopsy reports of all 157 cases were available for systematic review. Medical or surgical causes represented 41,3% of deaths in our center, accidental causes 8.1% and child abuse 28,8%. The definitive diagnosis was made at autopsy in 30% of cases and at histopathological examination in 70% highlighting that forensic histopathology is an indispensable tool in pediatric medicolegal autopsies. Significant histological abnormalities may be detected in selected organs such as the brain, lungs, heart, liver, adrenal glands and kidneys in spite of macroscopically normal appearances. This justifies systematic sampling of all organs. Despite the implementation of the French sudden infant death protocol which recommends medical autopsies, too many pediatric autopsies are carried out in a medicolegal context. 30% of the cases remain without diagnosis at the end of the autopsy and histological examination. This number could be reduced by the contribution of others laboratory investigation.

Gelofusine Ameliorates Colistin-Induced Nephrotoxicity.

Colistin therapy is used as the last line of defense against life-threatening Gram-negative infections. Nephrotoxicity is the major dose-limiting side effect that impedes optimal dosing of patients. This study aims to examine the nephroprotective effect of the plasma volume expander gelofusine against colistin-induced nephrotoxicity. Renal protection was assessed in mice that were subcutaneously injected with colistin sulfate (14 mg/kg of body weight × 6 doses every 2 h; accumulated dose, 84 mg/kg) and simultaneously injected in the intraperitoneal region with gelofusine (75, 150, 300, or 600 mg/kg × 6). At 2 and 20 h after the last colistin dose, mice were euthanized, and the severity of renal alteration was examined histologically. Histological findings in mice revealed that colistin-induced nephrotoxicity was ameliorated by gelofusine in a dose-dependent manner, whereas significant histological abnormalities were detected in the kidneys of mice in the colistin-only group. The impact of coadministered gelofusine on colistin pharmacokinetics was investigated in rats. Rats were administered a single intravenous dose of gelofusine at 400 mg/kg 15 min prior to the intravenous administration of colistin (1 mg/kg). Gelofusine codosing did not alter the pharmacokinetics of colistin in rats; however, gelofusine did significantly lower the accumulation of colistin in the kidney tissue of mice. This is the first study demonstrating the protective effect of gelofusine against colistin-induced nephrotoxicity. These findings highlight the clinical potential of gelofusine as a safe adjunct for ameliorating the nephrotoxicity and increasing the therapeutic index of polymyxins.