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The American medical profession participated extensively in preparedness and mobilization for the First World War, with more than one in five doctors voluntarily enlisting in various branches of the Army and Navy Medical Corps. Medical officers were widely valorized for suspending their civilian careers and for sacrificing their professional income while in service. Because of the meager commissions that medical officers received by comparison with fees many doctors earned in established private medical practices, scores of county medical societies implemented organizational solutions to this business problem, with the hopes of removing a significant disincentive to enlistment. In these "practice protection plans," a civilian doctor promised to take care of the patients of a military doctor, to forward a portion of the fees collected thereby to the family of the military doctor, and to refer these patients to the military doctor upon his return. Despite initial enthusiasm and promotion, these plans ultimately tailed to achieve their objectives, leading some medical officers to accuse civilian doctors of being opportunistic, unpatriotic "slackers." This episode reveals the limits of professional cooperation in American medicine at the time and the need to explain organizational failures in the grand narrative of professionalization during the "Golden Age" of American medicine. [ABSTRACT FROM AUTHOR]

Teaching the history of epidemics remains a critical mission of our profession, both inside and outside of the classroom. Charles E. Rosenberg's "dramaturgical model" of epidemic response endures as a useful and flexible heuristic. Through guided discussion of the dramaturgical model, students can develop a shared vocabulary and a working theory of epidemic responses through time. Students can apply the model, then revise and refine it for themselves through writing assignments and careful comparisons of epidemics in different times, places, and populations. Special consideration must be given to teaching the history of epidemics during the present SARS-CoV-2 pandemic. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cell-based immunotherapy is being explored for treating infectious diseases, including viral infections. Here, we discuss evidence of NK cell responses to different viruses, ongoing clinical efforts to treat such infections with NK cell products, and review platforms to generate NK cell products.

Background: The mechanism by which natural killer (NK) cell education results in licensed NK cells with heightened effector function against missing self-targets is not known., Objective: We sought to identify potential mechanisms of enhanced function in licensed human NK cells., Methods: We used expanded human NK cells from killer immunoglobulin-like receptor (KIR)/HLA-genotyped donors sorted for single-KIR + cells to generate pure populations of licensed and unlicensed NK cells. We performed proteomic and gene expression analysis of these cells before and after receptor cross-linking and performed functional and metabolic analysis before and after interference with selected metabolic pathways. We verified key findings using freshly isolated and sorted NK cells from peripheral blood., Results: We confirmed that licensed human NK cells are greater in number in peripheral blood and proliferate more in vitro than unlicensed NK cells. Using high-throughput protein analysis, we found that unstimulated licensed NK cells have increased expression of the glycolytic enzyme pyruvate kinase muscle isozyme M2 and after KIR cross-linking have increased phosphorylation of the metabolic modulators p38-α and 5' adenosine monophosphate-activated protein kinase α. After cytokine expansion and activation, unlicensed NK cells depended solely on mitochondrial respiration for cytolytic function, whereas licensed NK cells demonstrated metabolic reprogramming toward glycolysis and mitochondrial-dependent glutaminolysis, leading to accumulation of glycolytic metabolites and depletion of glutamate. As such, blocking both glycolysis and mitochondrial-dependent respiration was required to suppress the cytotoxicity of licensed NK cells., Conclusions: Collectively, our data support an arming model of education in which enhanced glycolysis in licensed NK cells supports proliferative and cytotoxic capacity., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Relapse has emerged as the most important cause of treatment failure after allogeneic hematopoietic stem cell transplantation (HSCT). To test the hypothesis that natural killer (NK) cells can decrease the risk of leukemia relapse, we initiated a phase 1 dose-escalation study of membrane-bound interleukin 21 (mbIL21) expanded donor NK cells infused before and after haploidentical HSCT for high-risk myeloid malignancies. The goals were to determine the safety, feasibility, and maximum tolerated dose. Patients received a melphalan-based reduced-intensity conditioning regimen and posttransplant cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis. NK cells were infused on days -2, +7, and +28 posttransplant. All NK expansions achieved the required cell number, and 11 of 13 patients enrolled received all 3 planned NK-cell doses (1 × 10 5 /kg to 1 × 10 8 /kg per dose). No infusional reactions or dose-limiting toxicities occurred. All patients engrafted with donor cells. Seven patients (54%) developed grade 1-2 acute GVHD (aGVHD), none developed grade 3-4 aGVHD or chronic GVHD, and a low incidence of viral complications was observed. One patient died of nonrelapse mortality; 1 patient relapsed. All others were alive and in remission at last follow-up (median, 14.7 months). NK-cell reconstitution was quantitatively, phenotypically, and functionally superior compared with a similar group of patients not receiving NK cells. In conclusion, this trial demonstrated production feasibility and safety of infusing high doses of ex vivo-expanded NK cells after haploidentical HSCT without adverse effects, increased GVHD, or higher mortality, and was associated with significantly improved NK-cell number and function, lower viral infections, and low relapse rate posttransplant., (© 2017 by The American Society of Hematology.)

Purpose: This study was conducted to evaluate the radiology resources utilized by patients infected with novel influenza A (H1N1) during the 2009 summer outbreak to aid in pandemic planning for the 2010 influenza season., Materials and Methods: Of the 222 patients diagnosed or presumed to have H1N1 infection in the authors' health system from May 1 to July 18, 2009, 66 received imaging, including at least one chest imaging study directly related to the infection. Fourteen of these patients required advanced mechanical ventilation and were admitted to the intensive care unit (ICU; group 1); the remainder were managed as outpatients (27 of 52) or required brief hospitalizations (25 of 52) without mechanical ventilation (group 2; n = 52). The imaging histories of all 66 patients were reviewed for the period of hospitalization for group 1 patients and from 10 days before to 30 days after the diagnosis of influenza infection for group 2 patients to determine the number, types, and temporal distribution of radiology procedures performed during the flu outbreak., Results: Thirty percent of all patients with known or presumed influenza (H1N1) underwent radiologic imaging. The 14 patients in the ICU received a total of 469 chest radiographic studies (mean, 33.5), 15 thoracic CT examinations, and 170 additional imaging studies, the most common of which were 72 abdominal radiographic studies and 16 abdominal CT examinations. Seventy-one percent (334 of 469) of all the radiographic examinations in ICU patients were obtained during a single month. In contrast, group 2 patients received a total of 71 chest radiographic studies (mean, 1.4), 6 thoracic CT examinations, and 28 additional imaging studies, spread roughly evenly over the study period, with a subtle peak in early June., Conclusions: The majority of patients with H1N1 infection (70%) received no imaging studies. Patients sufficiently ill to require some level of imaging had, on average, just over one chest radiographic study. The 6% of patients who required ICU stays received an average of 33.5 chest radiographic studies and one thoracic CT examination. This information should be useful for health care organizations in planning their radiology resource needs during an H1N1 flu pandemic., (Copyright 2010 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Respiratory tract bacterial strains are becoming increasingly resistant to currently marketed macrolide antibiotics. The current alternative telithromycin (1) from the newer ketolide class of macrolides addresses resistance but is hampered by serious safety concerns, hepatotoxicity in particular. We have discovered a novel series of azetidinyl ketolides that focus on mitigation of hepatotoxicity by minimizing hepatic turnover and time-dependent inactivation of CYP3A isoforms in the liver without compromising the potency and efficacy of 1.