Search

Interprofessional education has been promoted as a strategy to dismantle professional silos and promote collaborative patient care. Citing this, medical educators have emphasized the widespread integration of interprofessional education into undergraduate medical education curricula. However, in the current residency training environment, little reinforcement exists for principles gleaned from interprofessional education, and little is known about the role that interprofessional providers have in resident education. In this perspective, we offer the concept and practice of interprofessional teaching to bolster the benefits of interprofessional education during residency training. Interprofessional teaching, relatively unexplored and potentially underutilized, may offer many of the same benefits of interprofessional education but is more readily adapted for the graduate medical education setting. The intensive care unit, characterized by a culture of multidisciplinary teamwork and complex patient care, is an ideal setting in which to use interprofessional teaching. Prior to enthusiastically implementing interprofessional teaching interventions, careful consideration should be paid to the setting, strategies, and impact on all key stakeholders.

Approximately 12 million adults in the United States receive a diagnosis of chronic obstructive pulmonary disease (COPD) each year, and it is the fourth leading cause of death. Chronic obstructive pulmonary disease refers to a group of diseases that cause airflow obstruction and a constellation of symptoms, including cough, sputum production, and shortness of breath. The main risk factor for COPD is tobacco smoke, but other environmental exposures also may contribute. The GOLD (Global Initiative for Chronic Obstructive Lung Disease) 2020 Report aims to provide a nonbiased review of the current evidence for the assessment, diagnosis, and treatment of patients with COPD. To date, no conclusive evidence exists that any existing medications for COPD modify mortality. The mainstay of treatment for COPD is inhaled bronchodilators, whereas the role of inhaled corticosteroids is less clear. Inhaled corticosteroids have substantial risks, including an increased risk for pneumonia. Here, 2 experts, both pulmonologists, reflect on the care of a woman with severe COPD, a 50-pack-year smoking history, frequent COPD exacerbations, and recurrent pneumonia. They consider the indications for inhaled corticosteroids in COPD, when inhaled corticosteroids should be withdrawn, and what other treatments are available.

Objectives A bundled consent process, where patients or surrogates provide consent for all commonly performed procedures on a single form at the time of ICU admission, has been advocated as a method for improving both rates of documented consent and patient/family satisfaction, but there has been little published literature about the use of bundled consent. We sought to determine how residents in an academic medical center with a required bundled consent process actually obtain consent and how they perceive the overall value, efficacy, and effects on families of this approach. Design Single-center survey study. Setting Medical ICUs in an urban academic medical center. Subjects Internal medicine residents. Interventions We administered an online survey about bundled consent use to all residents. Quantitative and qualitative data were analyzed. Measurements and main results One-hundred two of 164 internal medicine residents (62%) completed the survey. A majority of residents (55%) reported grouping procedures and discussing general risks and benefits; 11% reported conducting a complete informed consent discussion for each procedure. Respondents were divided in their perception of the value of bundled consent, but most (78%) felt it scared or stressed families. A minority (26%) felt confident that they obtained valid informed consent for critical care procedures with the use of bundled consent. An additional theme that emerged from qualitative data was concern regarding the validity of anticipatory consent. Conclusions Resident physicians experienced with the use of bundled consent in the ICU held variable perceptions of its value but raised concerns about the effect on families and the validity of consent obtained with this strategy. Further studies are necessary to further explore what constitutes best practice for informed consent in critical care.

Leukocyte telomere length (LTL), MUC5B rs35705950, and TOLLIP rs5743890 have been associated with idiopathic pulmonary fibrosis (IPF). In this observational cohort study, we assessed the associations between these genomic markers and outcomes of survival and rate of disease progression in patients with interstitial pneumonia with autoimmune features (IPAF, n=250) and connective tissue disease-associated interstitial lung disease (CTD-ILD, n=248). IPF (n=499) was used as a comparator. LTL of IPAF and CTD-ILD patients (mean age-adjusted log-transformed T/S of −0.05, [SD 0.29] and −0.04 [0.25], respectively) are longer than IPF (−0.17 [0.32]). For IPAF, LTL

Objectives: We present a pilot study exploring the effects of a brief, 30-minute educational intervention targeting resident communication surrounding dying in the intensive care unit (ICU). We sought to determine whether simulation or didactic educational interventions improved resident-reported comfort, preparation, and skill acquisition. We also sought to identify resident barriers to using the word “dying.” Methods: In this mixed-methods prospective study, second- and third-year medical residents were randomized to participate in a simulation-based communication training or a didactic session. Residents completed a pre–post survey after the sessions evaluating the sessions and reflecting on their use of the word “dying” in family meetings. Results: Forty-five residents participated in the study. Residents reported increases in comfort (Mean [M]-pre = 3.3 [standard deviation: 0.6], M-post = 3.7 [0.7]; P < .01, Cohen d = 0.75) and preparation (M-pre = 3.4 [0.7], M-post = 3.9 [0.6]; P < .01, d = 1.07) using the word “dying” after both the simulation and didactic versions. Residents randomized to the simulation reported they were more likely to have learned new skills as compared to residents in the didactic (M-simulation = 2.2 [0.4], M-didactic = 1.9 [0.3]; P = .015, d = 0.80). They estimated that they used the word “dying” in 50% of their end-of-life (EOL) conversations and identified uncertain prognosis as the main barrier to explicitly stating the word “dying.” Conclusion: A 30-minute educational intervention improves internal medicine residents’ self-reported comfort and preparation in talking about death and dying in the ICU. Residents in simulation-based training were more likely to report they learned new skills as compared to the didactic session. Residents report multiple barriers to using the word “dying” EOL conversations.

Obtaining informed consent has been traditionally viewed as a mundane task, learned on the job and often relegated to an inexperienced member of the healthcare team. In reality, the process of obtaining informed consent is complex, challenging, and warrants focused teaching, observation and feedback. There are few published standards for what should be included in a high-quality informed consent conversation, and little or no guidance regarding how to best teach the process of conducting this type of shared decision-making conversation. The following twelve tips provide a roadmap for teaching the essential components of how to obtain informed consent, including both content and communication skills, with a focus on common pitfalls for trainees, and strategies to address them.

IAV pneumonia remains a serious global health problem, and preventative and therapeutic strategies remain limited. AM are critical effector cells in the control of influenza, impairing IAV replication, promoting IAV clearance, and promoting efferocytosis and resolution of lung inflammation. MBL, an innate immune pattern recognition molecule, present in the lungs, binds IAV, and plasma MBL deficiency is associated with increased susceptibility to IAV, although the mechanism remains incompletely understood, and the influence of MBL on the IAV-AM interaction has not been established. In the current study, focusing on human macrophages (U937 cell line and clinically relevant human AM), data demonstrated that unopsonized IAV is readily internalized, induced release of TNF and ROS, and promoted macrophage apoptosis. In contrast, IAV, opsonized with rhMBL, reduced IAV uptake and macrophage apoptosis and dramatically reduced TNF release and ROS. Macrophage host-defense responses were reduced further in the presence of MASPs. Taken together, these data support the concept that rhMBL may serve a protective innate host response and a critical biological response modifier function by limiting AM inflammation, oxidative injury, and AM apoptosis, which may allow effective IAV clearance while limiting collateral damage to vital organs, such as the lungs.

TLR-4–mediated signaling is significantly impaired in macrophages from HIV+ persons, predominantly owing to altered MyD88-dependent pathway signaling caused in part by constitutive activation of PI3K. In this study we assessed in these macrophages if the blunted increase in TLR-4–mediated TNF-α release induced by lipid A (LA) is associated with PI3K-induced upregulation of mammalian target of rapamycin (mTOR) activity. mTOR inhibition with rapamycin enhanced TLR-4–mediated TNF-α release, but suppressed anti-inflammatory IL-10 release. Targeted gene silencing of mTOR in macrophages resulted in LA-induced TNF-α and IL-10 release patterns similar to those induced by rapamycin. Rapamycin restored MyD88/IL-1R–associated kinase interaction in a dose-dependent manner. Targeted gene silencing of MyD88 (short hairpin RNA) and mTOR (RNA interference) inhibition resulted in TLR-4–mediated 70-kDa ribosomal protein S6 kinase activation and enhanced TNF-α release, whereas IL-10 release was inhibited in both silenced and nonsilenced HIV+ macrophages. Furthermore, mTOR inhibition augmented LA-induced TNF-α release through enhanced and prolonged phosphorylation of ERK1/2 and JNK1/2 MAPK, which was associated with time-dependent MKP-1 destabilization. Taken together, impaired TLR-4–mediated TNF-α release in HIV+ macrophages is attributable in part to mTOR activation by constitutive PI3K expression in a MyD88-dependent signaling pathway. These changes result in MAPK phosphatase 1 stabilization, which shortens and blunts MAPK activation. mTOR inhibition may serve as a potential therapeutic target to upregulate macrophage innate immune host defense responsiveness in HIV+ persons.

Tuberculosis (TB) disease remains one of the highest causes of mortality in HIV-infected individuals, and HIV–TB coinfection continues to grow at alarming rates, especially in sub-Saharan Africa. Surprisingly, a number of important areas regarding coinfection remain unclear. For example, increased risk of TB disease begins early in the course of HIV infection; however, the mechanism by which HIV increases this risk is not well understood. In addition, there is lack of consensus on the optimal way to diagnose latent TB infection and to manage active disease in those who are HIV infected. Furthermore, effective point-of-care testing for TB disease remains elusive. This review discusses key areas in the epidemiology, pathogenesis, diagnosis, and management of active and latent TB in those infected with HIV, focusing attention on issues related to high- and low-burden areas. Particular emphasis is placed on controversial areas where there are gaps in knowledge and on future directions of study.

Mycobacterium tuberculosis disease represents an enormous global health problem, with exceptionally high morbidity and mortality in HIV-seropositive (HIV + ) persons. Alveolar macrophages from HIV + persons demonstrate specific and targeted impairment of critical host cell responses, including impaired M. tuberculosis -mediated tumor necrosis factor (TNF) release and macrophage apoptosis. Vitamin D may promote anti- M. tuberculosis responses through upregulation of macrophage NO, NADPH oxidase, cathelicidin, and autophagy mechanisms, but whether vitamin D promotes anti- M. tuberculosis mechanisms in HIV + macrophages is not known. In the current study, human macrophages exposed to M. tuberculosis demonstrated robust release of TNF, IκB degradation, and NF-κB nuclear translocation, and these responses were independent of vitamin D pretreatment. In marked contrast, HIV + U1 human macrophages exposed to M. tuberculosis demonstrated very low TNF release and no significant IκB degradation or NF-κB nuclear translocation, whereas vitamin D pretreatment restored these critical responses. The vitamin D-mediated restored responses were dependent in part on macrophage CD14 expression. Importantly, similar response patterns were observed with clinically relevant human alveolar macrophages from healthy individuals and asymptomatic HIV + persons at high clinical risk of M. tuberculosis infection. Taken together with the observation that local bronchoalveolar lavage fluid (BALF) levels of vitamin D are severely deficient in HIV + persons, the data from this study demonstrate that exogenous vitamin D can selectively rescue impaired critical innate immune responses in vitro in alveolar macrophages from HIV + persons at risk for M. tuberculosis disease, supporting a potential role for exogenous vitamin D as a therapeutic adjuvant in M. tuberculosis infection in HIV + persons.

Human macrophages at mucosal sites are essential targets for acute HIV infection. During the chronic phase of infection, they are persistent reservoirs for the AIDS virus. HIV virions gain entry into macrophages following ligation of surface CD4-CCR5 co-receptors, which leads to the release of two copies of HIV ssRNA. These events lead to reverse transcription and viral replication initiation. Toll-like receptors TLR7 and TLR8 recognize specific intracellular viral ssRNA sequences, but in human alveolar macrophages, their individual roles in TLR-mediated HIV ssRNA recognition are unclear. In the current study, HIV-1 ssRNA induced TNFα release in a dose-dependent manner in adherent human macrophages expressing both intracellular TLR7 and TLR8. This response was reduced by inhibiting either endocytosis (50 μm dynasore) or endosomal acidification (1 μg/ml chloroquine). Either MYD88 or TLR8 gene knockdown with relevant siRNA reduced HIV-1 ssRNA-mediated TNFα release, but silencing TLR7 had no effect on this response. Furthermore, HIV-1 ssRNA induced histone 4 acetylation at the TNFα promoter as well as trimethylation of histone 3 at lysine 4, whereas TLR8 gene knockdown reduced these effects. Taken together in human macrophages, TLR8 binds and internalizes HIV ssRNA, leading to endosomal acidification, chromatin remodeling, and increases in TNFα release. Drugs targeting macrophage TLR8-linked signaling pathways may modulate the innate immune response to acute HIV infection by reducing viral replication.

Lung endothelium is believed to be a quiescent tissue with the potential to exhibit rapid and effective repair after injury. Endothelial progenitor cells derived from the bone marrow have been proposed as one source of new endothelial cells that may directly contribute to pulmonary endothelial cell homeostasis and repair. Here we use bone marrow transplantation models, using purified hematopoietic stem cells (HSCs) or unfractionated whole marrow, to assess engraftment of cells in the endothelium of a variety of tissues. We find scant evidence for any contribution of bone marrow-derived cells to the pulmonary endothelium in the steady state or after recovery from hyperoxia-induced endothelial injury. Although a rare population of CD45-/CD31+/VECadherin+ bone marrow-derived cells, originating from HSCs, can be found in lung tissue after transplantation, these cells are not readily found in anatomic locations that define the pulmonary endothelium. Moreover, by tracking transplanted bone marrow cells obtained from donor transgenic mice containing endothelial lineage-selective reporters (Tie2-GFP), no contribution of bone marrow-derived cells to the adult lung, liver, pancreas, heart, and kidney endothelium can be detected, even after prolonged follow-up periods of 11 months or after recovery from hyperoxic pulmonary endothelial injury. Our findings argue against any significant engraftment of bone marrow-derived cells in the pulmonary vascular endothelium.

Alveolar macrophages (AMs) are the predominant effector cell in the lungs and contribute to a critical first line of defense against bacterial pathogens through recognition by pattern recognition receptors such as Toll-like receptor 4 (TLR4). TLR4-mediated tumor necrosis factor α (TNFα) release is significantly impaired in HIV+ macrophages, but whether HIV impairs myeloid differentiation factor 88 (MyD88)–dependent and/or MyD-independent TLR4 signaling pathways in human macrophages is not known. Comparing human U937 macrophages with HIV+ U1 macrophages (HIV-infected U937 subclone), the current study shows that HIV infection is associated with impaired macrophage TLR4-mediated signaling, specifically targeting the MyD88-dependent TLR4-mediated signaling pathway (reduced MyD88–interleukin-1 receptor–associated kinase [IRAK] interaction, IRAK phosphorylation, nuclear factor [NF]–κB nuclear translocation, and TNFα release) while preserving the MyD88-independent TLR4-mediated signaling pathway (preserved STAT1 phosphorylation, interferon regulatory factor [IRF] nuclear translocation, and interleukin-10 [IL-10] and RANTES release). Extracellular TLR4 signaling complex was intact (similar levels of CD14 and MD2), and similar patterns of response were observed in clinically relevant AMs from healthy and asymptomatic HIV+ persons at high clinical risk of pneumonia. Taken together, these data support the concept that chronic HIV infection is associated with specific and targeted disruption of critical macrophage TLR4 signaling, which in turn may contribute to disease pathogenesis of bacterial pneumonia.