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Structured Interdisciplinary Bedside Rounds (SIBR) is a standardized, team-based intervention for hospitals to deliver high quality interprofessional care. Despite its potential for improving IPC and the workplace environment, relatively little is known about SIBR's effect on these outcomes. Our study aimed to assess the fidelity of SIBR implementation on an inpatient medicine teaching unit and its effects on perceived IPC and workplace efficiency. We conducted a quasi-experimental study with 88 residents and 44 nurses at a large academic medical center and observed 1308 SIBR encounters over 24 weeks. Of these 1308 encounters, the bedside nurse was present for 96.7%, physician for 97.6%, and care manager for 94.7, and 64.7% occurred at the bedside. Following SIBR implementation, perceived IPC improved significantly among residents (93.3% versus 67.9%, p <.024) and nurses (73.7% versus 36.0%, p <.008) compared to before implementation. Moreover, residents perceived greater workplace efficiency operationalized as being paged less frequently with questions by nurses (20.0% versus 49.1%, p =.01). No statistically significant improvements were reported regarding burnout, meaning at work, and workplace satisfaction. Our implementation of SIBR significantly improved perceived IPC and workplace efficiency, which are two important domains of healthcare quality. Future work should examine the impact of SIBR on patient-centered outcomes such as patient experience. [ABSTRACT FROM AUTHOR]

We identified 2 genes, histone deacetylase 1 (HDAC1) and HDAC2, contributing to the pathogenesis of proteinuric kidney diseases, the leading cause of end-stage kidney disease. mRNA expression profiling from proteinuric mouse glomeruli was linked to Connectivity Map databases, identifying HDAC1 and HDAC2 with the differentially expressed gene set reversible by HDAC inhibitors. In numerous progressive glomerular disease models, treatment with valproic acid (a class I HDAC inhibitor) or SAHA (a pan-HDAC inhibitor) mitigated the degree of proteinuria and glomerulosclerosis, leading to a striking increase in survival. Podocyte HDAC1 and HDAC2 activities were increased in mice podocytopathy models, and podocyte-associated Hdacl and [Hdac2.sup.fl/fl] genetic ablation improved proteinuria and glomerulosclerosis. Podocyte early growth response 1 (EGR1) was increased in proteinuric patients and mice in an HDAC1- and HDAC2-dependent manner. Loss of EGR1 in mice reduced proteinuria and glomerulosclerosis. Longitudinal analysis of the multicenter Veterans Aging Cohort Study demonstrated a 30% reduction in mean annual loss of estimated glomerular filtration rate, and this effect was more pronounced in proteinuric patients receiving valproic acid. These results strongly suggest that inhibition of HDAC1 and HDAC2 activities may suppress the progression of human proteinuric kidney diseases through the regulation of EGR1., Introduction The kidney filtration barrier is composed of fenestrated endothelial cells, the glomerular basement membrane, and the podocytes. The podocyte is a terminally differentiated epithelial cell, which in concert with [...]

De novo autoimmune hepatitis (DAIH) is an important cause of late allograft dysfunction following liver transplantation, but its cause and underlying pathogenesis remains unclear. We sought to identify specific innate and adaptive immune mechanisms driving the pro-inflammatory cytokine secreting regulatory T cell (Treg) phenotype in DAIH and determine if modulation of these pathways could resolve the inflammatory milieu observed in the livers of patients with DAIH. Here, we demonstrate toll-like receptors (TLRs) 2- and 4-mediated inflammasome activation in CD14++ monocytes, a finding that is key to maintaining dysfunctional Tregs in patients with DAIH. Furthermore, silencing of TLR 2 and 4 in CD14++ monocytes prevented activation of the inflammasome and significantly decreased IFN-γ production by FOXP3+ Tregs. We also observed significantly increase in expression of tumor necrosis factor α-induced protein 3 (TNFAIP3), a negative regulator of the NLRP3 Inflammasome, in monocytes/macrophages of liver transplant subjects who have normal allograft function and do not have DAIH. TNFAIP3 expression was virtually absent in monocytes/macrophages of patients with DAIH. Our findings suggest that autoimmunity in DAIH is promoted by CD14++ monocytes predominantly through activation of inflammatory signaling pathways.

Background Head and neck squamous cell cancer (HNSCC) occurs at higher rates among persons with HIV (PWH). This study compares the impact of sociodemographic and clinicopathologic characteristics on outcomes among PWH-HNSCC compared with HNSCC patients without HIV. Methods Patient data from HNSCC individuals were collected at a single academic hospital center between 2002 and 2018. Forty-eight patients with HIV (HIV-HNSCC) and 2894 HNSCC patients without HIV were included. Multivariate analysis determined predictors of survival using Cox proportional hazards regression model. HIV-positive and -negative tumors were analyzed by quantitative immunofluorescence for expression of CD4, CD8, CD20 and PD-L1. Results HIV-HNSCC patients had a lower median overall survival than HNSCC patients without HIV (34 [18–84] vs 94 [86–103] months; P <.001). In multivariate analysis that included age, sex, race/ethnicity, stage, site, tobacco use, time to treatment initiation, and insurance status, HIV was an independent predictor of poorer survival, with a hazard ratio of 1.98 (95% CI: 1.32–2.97; P <.001). PWH with human papillomavirus (HPV)–positive oropharyngeal tumors also had worse prognosis than HPV-positive oropharyngeal tumors in the population without HIV (P <.001). The tumor microenvironment among HIV-HNSCC patients revealed lower intratumoral CD8 infiltration among HIV+ HPV+ tumors compared with HIV– HPV+ tumors (P =.04). Conclusions HIV-HNSCC patients had worse prognosis than the non-HIV population, with HIV being an independent predictor of poor clinical outcomes when accounting for important sociodemographic and clinicopathologic factors. Our findings highlight differences in tumor biology that require further detailed characterization in large cohorts and increased inclusion of PWH in immunotherapy trials. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Background: We sought to characterize readiness, barriers to, and facilitators of providing medications for addiction treatment (MAT) in HIV clinics. Setting: Four HIV clinics in the northeastern United States. Methods: Mixed-methods formative evaluation conducted June 2017–February 2019. Surveys assessed readiness [visual analog scale, less ready (0–<7) vs. more ready (≥7–10)]; evidence and context ratings for MAT provision; and preferred addiction treatment model. A subset (n = 37) participated in focus groups. Results: Among 71 survey respondents (48% prescribers), the proportion more ready to provide addiction treatment medications varied across substances [tobacco (76%), opioid (61%), and alcohol (49%) treatment medications (P values < 0.05)]. Evidence subscale scores were higher for those more ready to provide tobacco [median (interquartile range) = 4.0 (4.0, 5.0) vs. 4.0 (3.0, 4.0), P = 0.008] treatment medications, but not significantly different for opioid [5.0 (4.0, 5.0) vs. 4.0 (4.0, 5.0), P = 0.11] and alcohol [4.0 (3.0, 5.0) vs. 4.0 (3.0, 4.0), P = 0.42] treatment medications. Median context subscale scores ranged from 3.3 to 4.0 and generally did not vary by readiness status (P values > 0.05). Most favored integrating MAT into HIV care but preferred models differed across substances. Barriers to MAT included identification of treatment-eligible patients, variable experiences with MAT and perceived medication complexity, perceived need for robust behavioral services, and inconsistent availability of on-site specialists. Facilitators included knowledge of adverse health consequences of opioid and tobacco use, local champions, focus on quality improvement, and multidisciplinary teamwork. Conclusions: Efforts to implement MAT in HIV clinics should address both gaps in perspectives regarding the evidence for MAT and contextual factors and may require substance-specific models. [ABSTRACT FROM AUTHOR]

Background Pneumocystis jirovecii is an opportunistic fungus that causes Pneumocystis pneumonia (PCP) in immunocompromised hosts. Over an 11-month period, we observed a rise in cases of PCP among kidney-transplant recipients (KTR), prompting an outbreak investigation. Methods Clinical and epidemiologic data were collected for KTR diagnosed with PCP between July 2019 and May 2020. Pneumocystis strain typing was performed using restriction fragment length polymorphism analyses and multilocus sequence typing in combination with next-generation sequencing. A transmission map was drawn, and a case-control analysis was performed to determine risk factors associated with PCP. Results Nineteen cases of PCP in KTR were diagnosed at a median of 79 months post-transplantation; 8 received monthly belatacept infusions. Baseline characteristics were similar for KTR on belatacept versus other regimens; the number of clinic visits was numerically higher for the belatacept group during the study period (median 7.5 vs 3). Molecular typing of respiratory specimens from 9 patients revealed coinfection with up to 7 P. jirovecii strains per patient. A transmission map suggested multiple clusters of interhuman transmission. In a case-control univariate analysis, belatacept, lower absolute lymphocyte count, non-White race, and more transplant clinic visits were associated with an increased risk of PCP. In multivariate and prediction power estimate analyses, frequent clinic visits was the strongest risk factor for PCP. Conclusions Increased clinic exposure appeared to facilitate multiple clusters of nosocomial PCP transmission among KTR. Belatacept was a risk factor for PCP, possibly by increasing clinic exposure through the need for frequent visits for monthly infusions. [ABSTRACT FROM AUTHOR]