Absence of Case of Mucormycosis (March 2020–May 2021) under strict protocol driven management care in a COVID-19 specific tertiary care intensive care unit

AimsWith a sudden increase in cases of mucormycosis seen in Covid ?19 patients, we conducted a retrospective analysis of all admitted patients in a tertiary care covid-19 hospital looking at incidence of mucormycosis.MethodsIntensive care unit daily rounds data stored in an electronic format was retrieved by one of the consultants, looking for incidence of mucormycosis, diabetes mellitus, adherence to protocol for steroid use, glycemic control and use of monoclonal antibodies. Also, patients follow up data base of post covid Outpatients Department was searched for cases of mucormycosis.ResultsA total of 5248 patients were admitted between March 2020 to May 2021, of which 1027 were in ICU and 4221 in wards. Of the 1027 patients admitted in Intensive care unit, 915 received steroids and 417 had diabetes as existing co-morbidity. No case of mucormycosis was reported during the stay in the hospital and during immediate outpatient department follow up. The low dose steroids were administered as per state government protocol for treating COVID 19, a nurse driven strict glycemic control regime (blood glucose level was maintained between 140 and 180 mg/dl through the admission in ICU and was achieved consistently in 842 (82%) patients, followed along with minimal use of other immunomodulatory like monoclonal antibodies.ConclusionA strict adherence to protocol of low dose steroids coupled with strict glycemic control helped in eliminating the risk and incidence of mucormycosis in a tertiary care dedicated covid-19 hospital.     

Exosomes secreted by prostate cancer cells under hypoxia promote matrix metalloproteinases activity at pre-metastatic niches

Approximately, 30 000 men die from prostate cancer (PCa) every year in the United States, mainly due to the metastasis. Thus, the key events associated with PCa metastasis are under rigorous investigation, with recent studies showing that preparation of pre-metastatic niches (PMN) in distant organs is an important step. However, the molecular basis for PMN preparation is still unclear. Hypoxia in primary tumors promotes aggressiveness; however, its precise role in metastasis is not clear. We recently reported that exosomes secreted by PCa cells under hypoxia promote stemness and invasiveness in naïve PCa cells; however, whether these extracellular vesicles also influence PMN remains unknown. In the present study, we isolated exosomes from human PCa PC3 cells under normoxic (21% O₂, exosomes secreted under normoxic condition [Exo^Normoxic]) and hypoxic (1% O₂, exosomes secreted under hypoxic condition [Exo^Hypoxic]) conditions, and characterized their effect (10 µg exosomes, intraperitoneal (IP) treatment every 48 hours for 4 weeks) on key biomarkers associated with PMN in nude mice. Whole animal fluorescence imaging showed that Exo^Hypoxic treatment promotes matrix metalloproteinases (MMPs) activity in several putative metastatic sites. Histological studies confirmed that Exo^Hypoxic treatment enhanced the level of MMP2, MMP9, and extracellular matrix proteins (fibronectin and collagen) as well as increased the number of CD11b+ cells at selective PMN sites. Furthermore, proteomic profiling of exosomes by liquid chromatography/mass spectrometry identified cargo proteins in Exo^Normoxic and Exo^Hypoxic as well as distinct canonical pathways targeted by them. These results suggest that exosomes secreted by PCa cells under hypoxia plausibly remodel distant PMN, and thus, could be a potential target to control metastatic PCa.     

Kratom induced severe cholestatic liver injury histologically mimicking primary biliary cholangitis: A case report

BACKGROUND Kratom is a psychoactive substance that is isolated from the plant Mitragyna speciosa. The leaves can be chewed fresh or dried, smoked, or infused similar to herbal teas. The plant leaves have been used by natives of Southeast Asia for centuries. The substance has been used for its stimulant activity at low doses, and as an opium substitute at higher doses due to a morphine like effect.CASE SUMMARY A 37-year-old female with a history of depression and obesity(body mass index: 32) presented to emergency room with a week-long history of nausea, decreased appetite, fatigue, and two days of jaundice. On admission bilirubin was markedly elevated. Her condition was thought to be due to consumption of Kratom 2 wk before onset of symptoms. Liver biopsy showed changes mimicking primary biliary cholangitis. Patient's symptoms and jaundice improved quickly.CONCLUSION The use of Kratom has been on the rise in recent years across the United States and Europe. Several case reports have associated adverse health impact ofKratom-containing products including death due to its ability to alter levels of consciousness. Only a few case reports have highlighted the hepatotoxic effects of Kratom. Even fewer reports exist describing the detailed histopathological changes.     

Computational pathology definitions,best practices,and recommendations for regulatory guidance: a white paper from the Digital Pathology Association

In this white paper, experts from the Digital Pathology Association (DPA) define terminology and concepts in the emerging field of computational pathology, with a focus on its application to histology images analyzed together with their associated patient data to extract information. This review offers a historical perspective and describes the potential clinical benefits from research and applications in this field, as well as significant obstacles to adoption. Best practices for implementing computational pathology workflows are presented. These include infrastructure considerations, acquisition of training data, quality assessments, as well as regulatory, ethical, and cyber-security concerns. Recommendations are provided for regulators, vendors, and computational pathology practitioners in order to facilitate progress in the field. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Detection of Individual Prostate Cancer Foci via Multiparametric Magnetic Resonance Imaging

Background

Multiparametric magnetic resonance imaging (mpMRI) undoubtedly affects the diagnosis and treatment of localized prostate cancer (CaP). However, clinicians need a better understanding of its accuracy and limitations in detecting individual CaP foci to optimize management.