A Standardized Protocol for the Safe Retrieval of Infectious Postmortem Human Brain for Studying Whole-Brain Pathology.

ABSTRACT: We describe a safe and standardized perfusion protocol for studying brain pathology in high-risk autopsies using a custom-designed low-cost infection containment chamber and high-resolution histology. The output quality was studied using the histological data from the whole cerebellum and brain stem processed using a high-resolution cryohistology pipeline at 0.5 µm per pixel, in-plane resolution with serial sections at 20-µm thickness. To understand the pathophysiology of highly infectious diseases, it is necessary to have a safe and cost-effective method of performing high-risk autopsies and a standardized perfusion protocol for preparing high-quality tissues. Using the low-cost infection containment chamber, we detail the cranial autopsy protocol and ex situ perfusion-fixation of 4 highly infectious adult human brains. The digitized high-resolution histology images of the Nissl-stained series reveal that most of the sections were free of processing artifacts, such as fixation damage, freezing artifacts, and osmotic shock, at the macrocellular and microcellular level. The quality of our protocol was also tested with the highly sensitive immunohistochemistry staining for specific protein markers. Our protocol provides a safe and effective method in high-risk autopsies that allows for the evaluation of pathogen-host interaction, the underlying pathophysiology, and the extent of the infection across the whole brain at microscopic resolutions.

Rodenticide ingestion is an important cause of acute hepatotoxicity in Tamil Nadu, southern India.

BACKGROUND AND AIM: Though rodenticidal hepatotoxicity is reported from India, there is no systematic study to assess its magnitude. This study aimed to assess exposure to rodenticide as a risk factor for acute hepatotoxicity in Tamil Nadu, India. METHODS: We retrospectively analyzed acute hepatotoxicity caused by ingestion of hepatotoxin or potentially hepatotoxic drug overdose across 15 hospitals in 6 districts of Tamil Nadu from 1 January 2019 to 30 June 2019. Study exclusion criteria were idiosyncratic drug-induced liver injury and chronic liver diseases. RESULTS: Of the 702 patients, 685 gave history of consuming rodenticide; hepatotoxicity in the other patients resulted from paracetamol overdose (n=10) and due to other drugs (n=7); 97% patients had a suicidal intent. Of 671 patients with complete data, ratio of number of patients with hepatotoxicity due to rodenticide to paracetamol overdose was 450:6 (i.e. 75:1). The 451 rodenticidal hepatotoxicity patients (255 males, 75% were 15-34 years old) underwent conservative management (n=396), plasma exchange (n=54) and plasma exchange followed by liver transplant (n=1); 159 patients (35%) had poor outcome (131 died, 28 discharged in moribund state). Based on our observations, we estimate a case burden of 1584 rodenticidal hepatotoxicity patients (95% CI: 265-6119) with poor outcome in 554 patients in Tamil Nadu from January 2019 to June 2019. Population attributable risk for rodenticide as cause of hepatotoxicity was 22.7%. CONCLUSION: Rodenticide ingestion was an important cause of acute hepatotoxicity in Tamil Nadu. Most patients were young and one-third had poor outcome. Public health interventions are needed to address this.

Rodenticidal hepatotoxicity: Raised plasma Von Willebrand factor levels predict in-hospital survival and preliminary report of the outcome of Von Willebrand factor reducing management protocol.

BACKGROUND: High Von Willebrand factor (VWF) levels may predispose to multi-organ failure in acute liver failure (ALF). In rodenticide-induced hepatotoxicity patients, we analyzed if plasma VWF levels predicted survival and also the outcome of VWF lowering by N-acetyl cysteine (NAC), fresh frozen plasma (FFP) infusions, and plasma exchange (PLEX). METHODS: We retrospectively analyzed prospectively collected data. Hepatotoxicity was classified as uncomplicated acute hepatitis (UAH), acute liver injury (ALI), and ALF. ALF patients, if not opting for liver transplantation, had PLEX and NAC; ALI patients received NAC ± FFP (PLEX, if worsening); UAH patients had NAC. Plasma VWF antigen was measured (normal, 50% to 150%). In-hospital survival was analyzed as discharged alive or died/discharged in a terminal condition (poor outcome). RESULTS: Twenty-four consecutive rodenticide-induced hepatotoxicity patients (UAH in 1, ALI in 20, ALF in 3) from December 2017 to January 2019 were studied. Baseline VWF levels were 153%, 423 (146-890)% median (range), and 448 (414-555)% in UAH, ALI, ALF patients; model for end-stage liver disease (MELD) scores were 11, 24 (12-38), 36 (32-37) and in-hospital survival rates were 100%, 85%, 67%, respectively. VWF levels were higher in patients with poor outcome (555 [512-890]%) than in those discharged alive (414 [146-617]%) (p-value = 0.04). The area under the receiver operating curve of the VWF level, MELD score, and sequential organ failure assessment score to predict survival was 0.92, 0.84, and 0.66, respectively. Of 4 patients meeting criteria for liver transplantation (none had transplantation), 3 (75%) survived. CONCLUSIONS: High VWF levels predict poor outcome in rodenticide-induced hepatotoxicity. VWF reduction may be useful in such patients.

Analysis of risk factors of dowry death--a south Indian study.

Dowry deaths in the newly married brides are a burning problem of southern India. The objective of the current study was to identify the risk groups. This prospective study was carried out on 140 cases. Results revealed that majority of the victims (83%) were young aged between 18 and 26 years, childless (65.7%) and mostly died within 4 years of marriage (77.2%). About 80% of the victims were illiterates (53%), house wives of rural background (62.9%) and from middle socio-economic group (81%). Husband alone or along with in laws (75%) and joint family (85%) were mainly responsible for death. The common causes of death implicated are hanging, burning and poisoning. Mostly the place of occurrence was in-laws house. Suicidal deaths accounted in 57% and the rest being homicide. At the end some potential risk factors and their remedial measures suggested.