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A B S T R A C T The effect of increased capillary perilmealility on1 glomerular immultine comiiplex localizationi was studied in rats immiluniized with proximial tul)ular anitigeni (Fx1A) to induce autologouis imnmunie complex nephropathy (AICN). AICN rats were made proteinuric 1)V-injection or uniilateral renal perfusion with amiiinoinucleoside of puromycin (PA) before developing sul)epithelial conmplex deposits. Control AICN kidneys developed diffuse granular deposits of IgG and Fx1A oIn the subepithelial surf'ace of the glomerular b)asement membrane (GBM) at 3 wk by immuiinofluiorescence and electron microscopy, and dep(isits increased in sul)-se(quienit weekly biopsies. In conitrast, PA-nephrotic AICN kidneys developed few or no GBM deposits and a significant increase in mesangial localization of IgG and FxlA during the period of PA-induced proteinuria. These alterationis in complex localizationi were documenited 1)oth in rats with PA nephrosis andl in unilaterally PA-inephrotic kidneys compared with conitralateral controls in the sanme animiials, thus excluidinig any effect of PA on the imnililiiopatlhogenetic mlechaniisnm in AICN as ani explaniation for these finidings. The absence of GBMi deposits closely correlated with reducedl stainiing for polyanionic glomierilar sialoproteini in proteinutiric kidneys, siniee PA-perfuised kidneys studied 2 wk after resdoltutioin of proteinutria demiion strated retuirni of niormlial staininig for sialoprotein Portionis of this work were presented at the 8th Ainutal

Background E-cigarette, or Vaping, Product Use-Associated Lung Injury (EVALI) is a disease entity related to the use of battery-operated or superheating devices that create an aerosolized form of nicotine and tetrahydrocannabinol (THC) and/or other substances for inhalation. Methods We performed a literature review to document epidemiology, pathogenesis and risk factors, diagnosis, clinical presentation, evaluation and management of EVALI. Results In the summer of 2019, an outbreak of EVALI cases brought this disease entity into the national spotlight. Since being recognized as a serious pulmonary disease with public health implications, more than 2600 cases have been reported to CDC with 68 deaths as of February 2020. The pathophysiology of EVALI remains unknown. Substances such as Vitamin E acetate have been implicated as a possible causes of lung injury. The CDC has established case definitions of “confirmed EVALI” cases to help guide identification of the disease and assist in surveillance. While clinical judgement by healthcare providers is imperative in the identification of EVALI cases, the heterogeneous presentations of EVALI make this difficult as well. Ultimately most investigative studies should be aimed at ruling out other disease processes that can present similarly. Treatment is centered around removing the offending substance and providing supportive care. Conclusions EVALI is a serious pulmonary disease with public health implications. Diagnosis requires a high degree of suspicion to diagnose and exclusion of other possible causes of lung disease. It may be beneficial to involve a pulmonary specialist early in the management of this disease which is generally supportive care.

Background Although both leukocytosis and leukopenia have been considered Systemic Inflammatory Response Syndrome criteria, leukopenia is not generally considered a normal response to infection. We sought to evaluate the prognostic validity of leukopenia as a sign of sepsis-defining hematological organ dysfunction within the Sepsis-3 framework. We hypothesized that leukopenia is associated with higher risk of mortality than leukocytosis among patients with suspected infection. Methods We performed a retrospective cohort study using the Medical Information Mart v1.4 in Intensive Care-III database. Multivariable regression models were used to evaluate the association between leukopenia and mortality in patients with suspected infection defined by Sepsis-3. Results We identified 5,909 ICU patients with suspected infection; 250 (4.2%) had leukopenia. Leukopenia was associated with increased in-hospital mortality compared with leukocytosis (OR, 1.5; 95% CI 1.1–1.9). After adjusting for demographics and comorbidities in the Sepsis-3 consensus model, leukopenia remained associated with increased risk of mortality compared with leukocytosis (OR 1.6, 95% CI 1.2–2.2). Further adjustment for the platelet component of the SOFA attenuated the association between leukopenia and mortality (OR decreased from 1.5 to 1.1). However, 83 (1.4%) of patients had leukopenia without thrombocytopenia and 14 had leukopenia prior to thrombocytopenia. Conclusions Among ICU patients with suspected infection, leukopenia was associated with increased risk of death compared with leukocytosis. Due to correlation with thrombocytopenia, leukopenia did not independently improve the prognostic validity of SOFA; however, leukopenia may present as a sign of sepsis prior to thrombocytopenia in a small subset of patients.

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