Translational research : the journal of laboratory and clinical medicine
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Clostridioides difficile infection (CDI) is an urgent threat to global public health. Patient susceptibility to C. difficile is highly dependent on host immune status and gut dysbiosis resulting in loss of protective microbiota consortia that prevent spore germination, pathogen colonization, and disease pathogenesis. Recent clinical studies highlight the problems of differentiating symptomatic CDI from asymptomatic C. difficile carriage in patients with diarrhea. In this review, we consider how integration of microbiome and host immune systems biology data may aid in the clinical diagnosis of CDI when validated against gold standard testing and combined with standard microbiology laboratory assays.
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Acute respiratory failure and a systemic coagulopathy are critical aspects of the morbidity and mortality characterizing infection with severe acute respiratory distress syndrome-associated coronavirus-2, the etiologic agent of Coronavirus disease 2019 (COVID-19). We examined skin and lung tissues from 5 patients with severe COVID-19 characterized by respiratory failure (n= 5) and purpuric skin rash (n = 3). COVID-19 pneumonitis was predominantly a pauci-inflammatory septal capillary injury with significant septal capillary mural and luminal fibrin deposition and permeation of the interalveolar septa by neutrophils. ⋯ In addition, there was co-localization of COVID-19 spike glycoproteins with C4d and C5b-9 in the interalveolar septa and the cutaneous microvasculature of 2 cases examined. In conclusion, at least a subset of sustained, severe COVID-19 may define a type of catastrophic microvascular injury syndrome mediated by activation of complement pathways and an associated procoagulant state. It provides a foundation for further exploration of the pathophysiologic importance of complement in COVID-19, and could suggest targets for specific intervention.
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Despite advances in antimicrobial treatments, infection remains a common complication of intensive chemotherapy in patients with acute leukemia. It has become progressively apparent that the current antimicrobial focus has shortcomings that result from disruption of the commensal microbial communities of the gut. ⋯ Several innovative concepts have been proposed and tested in animal models and humans, with the overarching goal of preventing damage to the microbiota and facilitating its recovery. In this review, we discuss these approaches, examine critical knowledge gaps, and explore how they may be filled in future research.