Background: After critical illness, new or worsening impairments in physical, cognitive, and/or mental health function are common among patients who have survived. Who should be screened for long-term impairments, what tools to use, and when, remain unclear. Objectives: Provide pragmatic recommendations to clinicians caring for adult survivors of critical illness related to screening for post-discharge impairments. Participants: 31 international experts in risk-stratification and assessment of survivors of critical illness, including practitioners involved in the Society of Critical Care Medicine's (SCCM) Thrive Post-ICU Collaboratives, survivors of critical illness, and clinical researchers. Design: SCCM consensus conference on post-intensive care syndrome (PICS) prediction and assessment, held in Dallas, in May, 2019.Meeting Outcomes: We concluded that existing tools are insufficient to reliably predict PICS. We identified factors before (e.g., frailty, pre-existing functional impairments), during (e.g., duration of delirium, sepsis, acute respiratory distress syndrome), and after (e.g., early symptoms of anxiety, depression, or post-traumatic stress disorder (PTSD)) critical illness that can be used to identify patients at high-risk for cognitive, mental health, and physical impairments after critical illness in whom screening is recommended. We recommend serial assessments, beginning within 2-4 weeks of hospital discharge, using the following screening tools: Montreal Cognitive Assessment

An ICU-RC identified a high prevalence of cognitive impairment, anxiety, depression, physical debility, lifestyle changes, and medication-related problems warranting intervention. Whether an ICU-RC can improve ICU recovery in the US should be investigated in a systematic way.

Rationale: Effective therapeutic interventions for chronic, idiopathic lung diseases remain elusive. Normalized T-cell function is an important contributor to spontaneous resolution of pulmonary sarcoidosis. Up-regulation of inhibitor receptors, such as programmed death-1 (PD-1) and its ligand, PD-L1, are important inhibitors of T-cell function.Objectives: To determine the effects of PD-1 pathway blockade on sarcoidosis CD41 T-cell proliferative capacity.Methods: Gene expression profiles of sarcoidosis and healthy control peripheral blood mononuclear cells were analyzed at baseline and follow-up. Flow cytometry was used to measure ex vivo expression of PD-1 and PD-L1 on systemic and bronchoalveolar lavage-derived cells of subjects with sarcoidosis and control subjects, as well as the effects of PD-1 pathway blockade on cellular proliferation after T-cell receptor stimulation. Immunohistochemistry analysis for PD-1/PD-L1 expression was conducted on sarcoidosis, malignant, and healthy control lung specimens.

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Background Women have an increased prevalence of severe asthma compared to men. IL-17A is associated with severe asthma and requires IL-23 receptor (IL-23R) signaling, which is negatively regulated by Let-7f miRNA. Objective Determine the mechanism by which 17β-estradiol (E2) and progesterone (P4) increase IL-17A production. Methods IL-17A production was determined by flow cytometry in Th17 cells from women (n=14) and men (n=15) with severe asthma. Cytokine levels were measured by ELISA and IL-23R and Let-7f expression by qPCR in Th17 differentiated cells from healthy women (n=13) and men (n=14). In sham-operated or ovariectomized female mice, 17β-E2, P4, 17β-E2+P4, or vehicle pellets were administered for 3 weeks prior to ex vivo Th17 cell differentiation. Airway neutrophil infiltration and KC expression was also determined in OVA-challenged WT female recipient mice with an adoptive transfer of OVA-specific Th17 cells from female and male mice. Results In severe asthma patients and healthy controls, IL-17A production was increased in Th17 cells from women compared to men. IL-23R expression was increased and Let-7f expression was decreased in Th17 differentiated cells from women compared to men. In ovariectomized mice, IL-17A and IL-23R expression was increased and Let-7f expression was decreased in the Th17 cells from mice administered 17β-E2+P4 compared to vehicle. Further, transfer of female OVA-specific Th17 cells increased acute neutrophil infiltration in the lungs of OVA-challenged recipient mice compared to transfer of male OVA-specific Th17 cells. Conclusions 17β-E2+P4 increased IL-17A production from Th17 cells, providing a potential mechanism for the increased prevalence of severe asthma in women compared to men.

Background IL-13 is a central mediator of airway responsiveness and mucus expression in allergic airway inflammation and IL-13 is currently a therapeutic target for asthma. However, little is known about how IL-13 regulates human CD4+ T cell lineages because the IL-13 receptor α1 (IL-13Rα1), a subunit of the IL-13 receptor, has not previously been reported to exist on human T cells. Objective To determine if human CD4+ Th17 cells express IL-13Rα1 and if IL-13 regulates Th17 cytokine production. Methods Naïve human CD4+ cells were isolated from whole blood, activated with anti-CD3 and anti-CD28, and polarized to Th1, Th2, Th17, or induced T regulatory cells in the presence of IL-13 (0–10ng/ml). Cell supernatants, total RNA, or total protein was examined four days after Th17 polarization. Results Th17 cells, but not Th0, Th1, Th2 or induced T regulatory cells, expressed IL-13Rα1. IL-13 attenuated IL-17A production as well as expression of RORC2, Runx1, and IRF-4 in Th17 polarized cells. IL-13 neither inhibited IFN-γ production from Th1 cells nor inhibited IL-4 production from Th2 cells. Furthermore, attenuation of IL-17A production only occurred when IL-13 was present within 24 hours of T cell activation or at the time of restimulation. Conclusions IL-13Rα1 is expressed on human CD4+ Th17 cells, and IL-13 attenuates IL-17A production at polarization and restimulation. While IL-13 is an attractive therapeutic target for decreasing symptoms associated with asthma, these results suggest that therapies inhibiting IL-13 production could have adverse side effects by increasing IL-17A production.

Background Many patients experience complications following critical illness; these are now widely referred to as post–intensive care syndrome (PICS). An interprofessional intensive care unit (ICU) recovery center (ICU-RC), also known as a PICS clinic, is one potential approach to promoting patient and family recovery following critical illness. Objectives To describe the role of an ICU-RC critical care pharmacist in identifying and treating medication-related problems among ICU survivors. Methods A prospective, observational cohort study was conducted of all outpatient appointments of a tertiary care hospital’s ICU-RC between July 2012 and December 2015. The pharmacist completed a full medication review, including medication reconciliation, interview, counseling, and resultant interventions, during the ICU-RC appointment. Results Data from all completed ICU-RC visits were analyzed (n = 62). A full medication review was performed in 56 (90%) of these patients by the pharmacist. The median number of pharmacy interventions per patient was 4 (interquartile range = 2, 5). All 56 patients had at least 1 pharmacy intervention; 22 (39%) patients had medication(s) stopped at the clinic appointment, and 18 (32%) patients had new medication(s) started. The pharmacist identified 9 (16%) patients who had an adverse drug event (ADE); 18 (32%) patients had ADE preventive measures instituted. An influenza vaccination was administered to 13 (23%) patients despite an inpatient protocol to ensure influenza vaccination prior to discharge. A pneumococcal vaccination was administered to 2 (4%) patients. Conclusions Use of a critical care pharmacist resulted in the identification and treatment of multiple medication-related problems in an ICU-RC as well as implementation of preventive measures.