Association of COVID-19 Visitor Limitations and Goals of Care Discussions in the Intensive Care Unit.

INTRODUCTION: The COVID-19 pandemic led to visitor restrictions in many hospitals. Since care in the surgical intensive care unit (SICU) often engages visitors as surrogate decision-makers, we investigated whether there was an association between COVID-19-related visitor restrictions, goals of care discussions (GOCD), and patient outcomes in SICU patients. METHODS: We conducted a retrospective review of trauma and emergency general surgery (EGS) patients admitted to a rural tertiary SICU between July 2019 and April 2021, dividing patients into those admitted during COVID-19 visitor restrictions and those admitted at other times. Using univariate and multivariate logistic regression analyses, we compared the primary outcome, incidence of GOCD, and incidence of prolonged hospital (> 14 d) and intensive care unit length of stay (LOS, > 7 d) between the two groups. RESULTS: One hundred seventy nine of 368 study patients (48.6%) presented during restricted visitation. The proportion of GOCD was 38.0% and 36.5% in the restricted and nonrestricted visitation cohorts, respectively (P = 0.769). GOCD timing and outcomes were similar in both groups. The use of telecommunication increased during restricted visitation, as did the proportion of trauma patients admitted to the SICU. On multivariable logistic regression, age and patient category were independent predictors of GOCD. On outcomes analysis, visitor restriction was associated with prolonged hospital LOS for EGS patients (odds ratio 2.44, 95% confidence interval 1.01-5.91, P value 0.048). CONCLUSIONS: Restricted visitation was not associated with changes in frequency or outcome of GOCD, but was associated with prolonged hospital LOS among EGS patients who had SICU admissions. Further investigation of patient/surrogate satisfaction with virtual GOCD in the SICU setting is needed.

Fine epitope signature of antibody neutralization breadth at the HIV-1 envelope CD4-binding site.

Major advances in donor identification, antigen probe design, and experimental methods to clone pathogen-specific antibodies have led to an exponential growth in the number of newly characterized broadly neutralizing antibodies (bnAbs) that recognize the HIV-1 envelope glycoprotein. Characterization of these bnAbs has defined new epitopes and novel modes of recognition that can result in potent neutralization of HIV-1. However, the translation of envelope recognition profiles in biophysical assays into an understanding of in vivo activity has lagged behind, and identification of subjects and mAbs with potent antiviral activity has remained reliant on empirical evaluation of neutralization potency and breadth. To begin to address this discrepancy between recombinant protein recognition and virus neutralization, we studied the fine epitope specificity of a panel of CD4-binding site (CD4bs) antibodies to define the molecular recognition features of functionally potent humoral responses targeting the HIV-1 envelope site bound by CD4. Whereas previous studies have used neutralization data and machine-learning methods to provide epitope maps, here, this approach was reversed, demonstrating that simple binding assays of fine epitope specificity can prospectively identify broadly neutralizing CD4bs-specific mAbs. Building on this result, we show that epitope mapping and prediction of neutralization breadth can also be accomplished in the assessment of polyclonal serum responses. Thus, this study identifies a set of CD4bs bnAb signature amino acid residues and demonstrates that sensitivity to mutations at signature positions is sufficient to predict neutralization breadth of polyclonal sera with a high degree of accuracy across cohorts and across clades.

An ethical framework for global psychiatry.

Existing literature addresses the ethical considerations of global health work and how medical school curricula can help prepare students for them, but little has been written regarding an ethical approach to global psychiatry. In this paper we summarize prominent ethical issues that arise in global health psychiatry in order to provide a foundation for a framework in global health psychiatry. These issues include obtaining informed consent in the face of language barriers, diagnosing and treating for mental illnesses while navigating communities where such conditions are heavily stigmatized, and justifying the cessation of proving care to current patients for the sake of providing care to new patients abroad. To help prepare psychiatrists and students for work that engages these issues, we propose a multi-step process to assist the practicing global psychiatrist in recognizing ethical dilemmas and evaluating potential courses of action based on their respective ethical merits.

Glucocorticoid-induced tumor necrosis factor receptor family-related protein triggering enhances HIV-specific CD4+ T cell cytokine secretion and protects HIV-specific CD4+ T cells from apoptosis.

Human immunodeficiency virus (HIV)-specific CD4(+) T cell cytokine secretion is characteristically weak during HIV infection, in part because HIV-specific CD4(+) T cells undergo massive apoptotic deletion. Glucocorticoid-induced tumor necrosis factor (TNF) receptor family-related (GITR) protein triggering enhances murine antigen-specific T cell cytokine secretion by protecting T cells from apoptosis. Therefore, we investigated the impact of GITR triggering on HIV-specific CD4(+) T cell cytokine secretion and on apoptosis of HIV-specific CD4(+) T cells. In HIV-infected subjects, CD4(+) T cell surface expression of GITR was greater than that in uninfected control subjects, and phytohemagglutinin induction of additional GITR expression was impaired. However, antibody triggering of GITR significantly increased HIV-specific CD4(+) T cell expression of TNF- alpha and interferon (IFN)- gamma . The percentage increase in HIV-specific CD4(+) T cell expression of TNF- alpha correlated directly with the absolute peripheral CD4(+) T cell count. Furthermore, GITR triggering reduced the expression of intracellular activated caspase-3 in HIV-specific CD4(+) T cells. Taken together, these data suggest that, despite abnormal GITR expression during HIV infection, GITR triggering enhances HIV-specific CD4(+) T cell cytokine expression and protects HIV-specific CD4(+) T cells from apoptosis.