Translational research : the journal of laboratory and clinical medicine
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Community acquired pneumonia is a leading cause of mortality in the United States. Along with predisposing comorbid health status, age is an independent risk factor for determining the outcome of pneumonia. Research over the last few decades has contributed to better understanding the underlying immunodysregulation and imbalanced redox homeostasis tied to this aged population group that increases susceptibility to a wide range of pathologies. ⋯ Mitochondria-targeted antioxidants have a number of molecular strategies that include targeting the biophysical properties of mitochondria, mitochondrial localization of catalytic enzymes, and mitigating mitochondrial membrane potential. Results of several antioxidant studies both in vitro and in vivo have demonstrated promising potential as a therapeutic in the treatment of pneumonia in the elderly. More human studies will need to be conducted to evaluate its efficacy in this clinical setting.
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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.