tbuckley/cabot-search huggingface dataset:
Complication Rates After Ultrasonography-Guided Nerve Blocks Performed in the Emergency Department
Authors: Andrew Goldsmith, Lachlan Driver, Nicole M. Duggan, Matthew Riscinti, David Martin, Michael Heffler, Hamid Shokoohi, Andrea Dreyfuss, Jordan Sell, Calvin Brown, Christopher Fung, Leland Perice, Daniel Bennett, Natalie Truong, S. Zan Jafry, Michael Macias, Joseph Brown, Arun Nagdev
Journal: JAMA Network Open (2024)

Importance Ultrasonography-guided nerve blocks (UGNBs) have become a core component of multimodal analgesia for acute pain management in the emergency department (ED). Despite their growing use, national adoption of UGNBs has been slow due to a lack of procedural safety in the ED. Objective To assess the complication rates and patient pain scores of UGNBs performed in the ED. Design, Setting, and Participants This cohort study included data from the National Ultrasound-Guided Nerve Block Registry, a retrospective multicenter observational registry encompassing procedures performed in 11 EDs in the US from January 1, 2022, to December 31, 2023, of adult patients who underwent a UGNB. Exposure UGNB encounters. Main Outcomes and Measures The primary outcome of this study was complication rates associated with ED-performed UGNBs recorded in the National Ultrasound-Guided Nerve Block Registry from January 1, 2022, to December 31, 2023. The secondary outcome was patient pain scores of ED-based UGNBs. Data for all adult patients who underwent an ED-based UGNB at each site were recorded. The volume of UGNB at each site, as well as procedural outcomes (including complications), were recorded. Data were analyzed using descriptive statistics of all variables. Results In total, 2735 UGNB encounters among adult patients (median age, 62 years [IQR, 41-77 years]; 51.6% male) across 11 EDs nationwide were analyzed. Fascia iliaca blocks were the most commonly performed UGNBs (975 of 2742 blocks [35.6%]). Complications occurred at a rate of 0.4% (10 of 2735 blocks). One episode of local anesthetic systemic toxicity requiring an intralipid was reported. Overall, 1320 of 1864 patients (70.8%) experienced 51% to 100% pain relief following UGNBs. Operator training level varied, although 1953 of 2733 procedures (71.5%) were performed by resident physicians. Conclusions and Relevance The findings of this cohort study of 2735 UGNB encounters support the safety of UGNBs in ED settings and suggest an association with improvement in patient pain scores. Broader implementation of UGNBs in ED settings may have important implications as key elements of multimodal analgesia strategies to reduce opioid use and improve patient care.
Bidirectional Risk Modulator and Modifier Variant of Dilated and Hypertrophic Cardiomyopathy in <i>BAG3</i>
Authors: Joseph Park, Michael G. Levin, David Zhang, Nosheen Reza, Jonathan O. Mead, Eric D. Carruth, Melissa A. Kelly, Alex Winters, Colleen M. Kripke, Renae L. Judy, Scott M. Damrauer, Anjali T. Owens, Lisa Bastarache, Anurag Verma, Daniel D. Kinnamon, Ray E. Hershberger, Marylyn D. Ritchie, Daniel J. Rader
Journal: JAMA Cardiology (2024)

Importance The genetic factors that modulate the reduced penetrance and variable expressivity of heritable dilated cardiomyopathy (DCM) are largely unknown. BAG3 genetic variants have been implicated in both DCM and hypertrophic cardiomyopathy (HCM), nominating BAG3 as a gene that harbors potential modifier variants in DCM. Objective To interrogate the clinical traits and diseases associated with BAG3 coding variation. Design, Setting, and Participants This was a cross-sectional study in the Penn Medicine BioBank (PMBB) enrolling patients of the University of Pennsylvania Health System’s clinical practice sites from 2014 to 2023. Whole-exome sequencing (WES) was linked to electronic health record (EHR) data to associate BAG3 coding variants with EHR phenotypes. This was a health care population-based study including individuals of European and African genetic ancestry in the PMBB with WES linked to EHR phenotypes, with replication studies in BioVU, UK Biobank, MyCode, and DCM Precision Medicine Study. Exposures Carrier status for BAG3 coding variants. Main Outcomes and Measures Association of BAG3 coding variation with clinical diagnoses, echocardiographic traits, and longitudinal outcomes. Results In PMBB (n = 43 731; median [IQR] age, 65 [50-76] years; 21 907 female [50.1%]), among 30 324 European and 11 198 African individuals, the common C151R variant was associated with decreased risk for DCM (odds ratio [OR], 0.85; 95% CI, 0.78-0.92) and simultaneous increased risk for HCM (OR, 1.59; 95% CI, 1.25-2.02), which was confirmed in the replication cohorts. C151R carriers exhibited improved longitudinal outcomes compared with noncarriers as assessed by age at death (hazard ratio [HR], 0.85; 95% CI, 0.74-0.96; median [IQR] age, 71.8 [63.1-80.7] in carriers and 70.3 [61.6-79.2] in noncarriers) and heart transplant (HR, 0.81; 95% CI, 0.66-0.99; median [IQR] age, 56.7 [46.1-63.1] in carriers and 55.6 [45.2-62.9] in noncarriers). C151R was associated with reduced risk of DCM (OR, 0.42; 95% CI, 0.24-0.74) and heart failure (OR, 0.27; 95% CI, 0.14-0.50) among individuals harboring truncating TTN variants in exons with high cardiac expression (n = 358). Conclusions and Relevance BAG3 C151R was identified as a bidirectional modulator of risk along the DCM-HCM spectrum, as well as an important genetic modifier variant in TTN -mediated DCM. This work expands on the understanding of the etiology and penetrance of DCM, suggesting that BAG3 C151R is an important genetic modifier variant contributing to the variable expressivity of DCM, warranting further exploration of its mechanisms and of genetic modifiers in DCM more broadly.
Supply and Geographic Distribution of Geriatric Physicians and Geriatric Nurse Practitioners
Authors: Ying Xue, Lusine Poghosyan, Qinyun Lin
Journal: JAMA Network Open (2024)

The rapidly growing population of older adults and their concomitant high prevalence of chronic health conditions require an increased supply in the specialized geriatric workforce to meet increasing health care demands. Understanding trends and geographic disparities in the supply of the geriatric workforce is essential for developing effective policies.
Treatments and Patient Outcomes Following Stroke Center Expansion
Authors: Yu-Chu Shen, Anthony S. Kim, Renee Y. Hsia
Journal: JAMA Network Open (2024)

Importance It is unclear how certified stroke center expansion contributes to improved access to stroke treatment and patient outcomes, and whether these outcomes differ by baseline stroke center access. Objective To examine changes in rates of admission to stroke centers, receipt of thrombolysis and mechanical thrombectomy, and mortality when a community gains a newly certified stroke center within a 30-minute drive. Design, Setting, and Participants This cohort study compared changes in patient outcomes when a community (defined by area zip code) experienced a stroke center expansion relative to the same community type that did not experience a change in access. Medicare fee-for-service beneficiaries with a primary diagnosis of acute ischemic stroke who were admitted to hospitals between January 1, 2009, and December 31, 2019, were included. The data analysis was performed between October 1, 2023, and September 9, 2024. Exposure New certification of a stroke center within a 30-minute driving time of a community. Main Outcomes and Measures The main outcomes were rates of admission to a certified stroke center, receipt of thrombolytics (delivered using drip-and-ship and drip-and-stay methods), mechanical thrombectomy, and 30-day and 1-year mortality estimated using a linear probability model with community fixed effects. Results Among the 2 853 508 patients studied (mean [SD] age, 79.5 [8.5] years; 56% female), 66% lived in communities that had a stroke center nearby at baseline in 2009, and 34% lived in communities with no baseline access. For patients without baseline access, after stroke center expansion, the likelihood of admission to a stroke center increased by 38.98 percentage points (95% CI, 37.74-40.21 percentage points), and receipt of thrombolytics increased by 0.48 percentage points (95% CI, 0.24-0.73 percentage points). Thirty-day and 1-year mortality decreased by 0.28 percentage points (95% CI, −0.56 to −0.01) and 0.50 percentage points (95% CI, −0.84 to −0.15 percentage points), respectively, after expansion. For patients in communities with baseline stroke center access, expansion was associated with an increase of 9.37 percentage points (95% CI, 8.63-10.10 percentage points) in admission to a stroke center but no significant changes in other outcomes. Conclusions and Relevance In this cohort study, patients living in communities without baseline stroke center access experienced significant increases in stroke center admission and thrombolysis and a significant decrease in mortality after a stroke center expansion. Improvements were smaller in communities with preexisting stroke center access. These findings suggest that newly certified stroke centers may provide greater benefits to underserved areas and are an important consideration when deciding when and where to expand health care services.
Emergency Medical Service Agency Cardiac Arrest Practices
Authors: Henry E. Wang
Journal: JAMA Cardiology (2024)

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Discontinuation of Glucagon-Like Peptide-1 Receptor Agonists
Authors: Sadiya S. Khan, Chiadi E. Ndumele, Dhruv S. Kazi
Journal: JAMA (2024)

This Viewpoint discusses the health benefits of glucagon-like peptide-1 receptor agonists (GLP-1 RAs); summarizes the clinical, policy, and equity implications of GLP-1 RA discontinuation; and calls for the identification and implementation of strategies to improve long-term adherence to GLP-1 RA therapy.
Academic Physician and Trainee Occupational Well-Being by Sexual and Gender Minority Status
Authors: Carl G. Streed, May Navarra, Jessica Halem, Miriam T. Stewart, Susannah G. Rowe
Journal: JAMA Network Open (2024)

Importance Few studies have explored the association between sexual and gender minority (SGM) status and occupational well-being among health care workers. Objectives To assess the prevalence of burnout, professional fulfillment, intent to leave, anxiety, and depression by self-reported SGM status. Design, Setting, and Participants This cross-sectional survey study collected data from October 2019 to July 2021, from 8 academic medical institutions participating in the Healthcare Professional Well-Being Academic Consortium. The survey, including questions on SGM status, was administered to attending physicians and trainees. Statistical analyses were performed from June 1, 2023, to February 29, 2024. Exposure SGM status was determined via self-reported sexual orientation and gender identity. Main Outcomes and Measures Primary outcomes measured were the Professional Fulfillment Index (burnout and professional fulfillment), intent to leave, and self-reported anxiety and depression using the Patient-Reported Outcomes Measurement Information System short-form 4-item measure. Results Of 20 541 attendings and 6900 trainees, 8376 attendings and 2564 trainees responded and provided SGM status. Of these respondents, 386 attendings (4.6%) and 212 trainees (8.3%) identified as SGM. Compared with their non-SGM peers, SGM attendings had a lower prevalence of professional fulfillment (133 of 386 [34.5%] vs 3200 of 7922 [40.4%]) and a higher prevalence of burnout (181 of 382 [47.4%] vs 2791 of 7883 [35.4%]) and intent to leave (125 of 376 [33.2%] vs 2433 of 7873 [30.9%]) (all P &amp;amp;lt; .001). Compared with their non-SGM peers, SGM trainees had a lower prevalence of professional fulfillment (63 of 211 [29.9%] vs 833 of 2333 [35.7%]) and a higher prevalence of burnout (108 of 211 [51.2%] vs 954 of 2332 [40.9%]) (both P &amp;amp;lt; .001). After adjusting for age and race and ethnicity, SGM attendings had higher odds of burnout than their non-SGM peers (adjusted odds ratio, 1.57 [95% CI, 1.27-1.94]; P &amp;amp;lt; .001). Results for burnout were similar among the SGM trainees compared with their non-SGM peers (adjusted odds ratio, 1.47 [1.10-1.96]; P = .01). Conclusions and Relevance In this cross-sectional survey study of academic physicians and trainees, SGM attendings and trainees had higher levels of burnout and lower levels of professional fulfillment. SGM attendings had greater intent to leave than their non-SGM peers, but trainees did not. These disparities represent an opportunity for further exploration to retain SGM health care workers.
Transcranial Direct Current Stimulation Combined With Repetitive Transcranial Magnetic Stimulation for Depression
Authors: Dongsheng Zhou, Xingxing Li, Shuochi Wei, Chang Yu, Dongmei Wang, Yuchen Li, Jiaxin Li, Junyao Liu, Shen Li, Wenhao Zhuang, Yanli Li, Ruichenxi Luo, Zhiwang Liu, Jimeng Liu, Yongming Xu, Jialin Fan, Guidong Zhu, Weiqian Xu, Yiping Tang, Raymond Y. Cho, Thomas R. Kosten, Xiang-Yang Zhang
Journal: JAMA Network Open (2024)

Importance Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are both recognized as effective treatments for depression when applied individually. However, it is unknown whether rTMS combined with tDCS has better efficacy in the treatment of major depressive disorder (MDD). Objective To investigate the clinical effectiveness and safety of rTMS, tDCS, tDCS + rTMS, and sham tDCS + sham rTMS after 2 weeks of treatment in patients with MDD. Design, Setting, and Participants This double-blind, sham-controlled randomized clinical trial was conducted from November 2021 to April 2023 at 3 hospitals in China (Kangning Hospital affiliated with Ningbo University, Lishui Second People’s Hospital, and Taizhou Second People’s Hospital). Adult patients (aged 18-65 years) who were diagnosed with major depressive disorder were recruited. Participants were randomly assigned to 1 of 4 interventions: active tDCS + active rTMS, sham tDCS + active rTMS, active tDCS + sham rTMS, and sham tDCS + sham rTMS. Data analysis followed an intention-to-treat approach. Intervention Patients received a 2-week course of treatment. The tDCS was administered using a 2-mA direct current stimulator with electrodes placed on the left and right dorsolateral prefrontal cortex (DLPFC). Each tDCS session lasted 20 minutes and was conducted 30 to 60 minutes prior to the rTMS session for a total of 10 sessions. The rTMS was delivered at a frequency of 10 Hz using a figure-8 coil placed on the left DLPFC, with each session consisting of 1600 pulses. Treatments were administered 5 times per week for 2 weeks. Sham treatments were performed with a pseudostimulation coil and emitted only sound. Main Outcomes and Measures The primary outcome was the change in total score from baseline to week 2 on the 24-item Hamilton Depression Rating Scale (HDRS-24; score range: 0-52, with the highest score indicating more severe symptoms). Results A total of 240 participants (139 females [57.9%]; mean [SD] age, 32.50 [15.18] years) were included. As a primary outcome, patients who received active tDCS + active rTMS showed a significantly greater reduction in mean (SD) HDRS-24 total scores compared with patients in the other 3 groups (active tDCS + active rTMS: 18.33 [5.39], sham tDCS + active rTMS: 14.86 [5.59], active tDCS + sham rTMS: 9.21 [4.61], and sham tDCS + sham rTMS: 10.77 [5.67]; F 3,236 = 35.79; η 2 = 0.31 [95% CI, 0.21-0.39]; P &amp;amp;lt; .001). Conclusions and Relevance This trial found that tDCS + rTMS was a more effective and safe treatment option than either the tDCS or rTMS intervention alone for patients with MDD. Trial Registration China Clinical Trial Registry Identifier ChiCTR2100052122 .
College Course About Flourishing and Students’ Mental Health During SARS-CoV-2
Authors: Matthew J. Hirshberg, Blake A. Colaianne, Mark T. Greenberg, Karen Kurotsuchi Inkelas, Richard J. Davidson, David Germano, John D. Dunne, Robert W. Roeser
Journal: JAMA Network Open (2024)

This cohort study examines the association of a college course designed to strengthen skills for mental health taken in 2018 or 2019 with measures of anxiety, depression, and flourishing during the early months of the SARS-CoV-2 pandemic in 2020.
The UBA1-STUB1 axis mediates cancer immune escape and resistance to checkpoint blockade
Authors: Yi Bao, Gabriel Cruz, Yuping Zhang, Yuanyuan Qiao, Rahul Mannan, Jing Hu, Fan Yang, Mahnoor Gondal, Miriam Shahine, Sarah Kang, Somnath Mahapatra, Alec Chu, Jae Eun Choi, Jiali Yu, Heng Lin, Stephanie J. Miner, Dan R. Robinson, Yi-Mi Wu, Yang Zheng, Xuhong Cao, Fengyun Su, Rui Wang, Noshad Hosseini, Marcin Cieslik, Ilona Kryczek, Ulka Vaishampayan, Weiping Zou, Arul M. Chinnaiyan
Journal: Cancer Discovery (2024)

Our study reveals UBA1 as a predictive biomarker for clinical outcomes in ICB cohorts, mediating cancer immune evasion and ICB resistance. We further highlight JAK1 stabilization as a key mechanism of UBA1 inhibition and nominate the UBA1-STUB1 axis as an immuno-oncology therapeutic target to improve the efficacy of ICB.
Aberrant activation of wound healing programs within the metastatic niche facilitates lung colonization by osteosarcoma cells
Authors: James B. Reinecke, Leyre Jimenez Garcia, Amy C. Gross, Maren Cam, Matthew V. Cannon, Matthew J. Gust, Jeffrey P. Sheridan, Berkley E. Gryder, Ruben Dries, Ryan D. Roberts
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Lung metastasis is responsible for most deaths caused by osteosarcoma. How malignant bone cells coerce the lung microenvironment to support metastatic growth remains unclear. We sought to identify metastasis-specific therapeutic vulnerabilities by delineating the cellular and molecular mechanisms essential to metastatic niche formation in the lung. Experimental design: We used single-cell transcriptomics (scRNA-seq) to characterize molecular changes induced within lung tissues by disseminated osteosarcoma cells. We then evaluated the ability of nintedanib to reverse metastasis-specific changes in both immunocompetent mouse and immunodeficient xenograft models. Molecular pharmacodynamic studies used single-nucleus and spatial transcriptomics to define the tumor-intrinsic and -extrinsic changes induced by the drug. Results: Osteosarcoma cells induced acute alveolar epithelial injury upon lung dissemination. scRNA-seq demonstrated that the surrounding lung stroma adopts a chronic, non-resolving wound-healing phenotype similar to diseases associated with lung injury. Accordingly, metastasis-associated lung demonstrated marked fibrosis, likely due to the accumulation of pathogenic, pro-fibrotic, partially differentiated epithelial intermediates and macrophages. Our data suggested that nintedanib prevented metastatic progression in multiple murine and human xenograft models by inhibiting osteosarcoma-induced fibrosis. Conclusions: Fibrosis is essential to osteosarcoma lung metastasis and represents a targetable vulnerability. Our data support a model where interactions between osteosarcoma and epithelial cells induce the deposition of extracellular matrix proteins—a reaction disrupted by the anti-fibrotic TKI nintedanib. Our data shed light on the non-cell autonomous effects of TKIs on metastasis and provide a roadmap for using single-cell and spatial transcriptomics to define the mechanism of action of TKIs on metastases in animal models.
“Effectiveness and safety of negative pressure wound therapy in patients with deep sternal wound infection: a systematic review and meta-analysis”
Authors: Yen-Ting Liu, Shih-Han Lin, Chi Peng, Ren-Wen Huang, Cheng-Hung Lin, Chung-Chen Hsu, Shih-Heng Chen, Yu-Te Lin, Che-Hsiung Lee
Journal: International Journal of Surgery (2024)

Background: Deep sternal wound infection (DSWI) is a severe and life-threatening complication following cardiovascular surgery. Negative pressure wound therapy (NPWT) has emerged as a promising therapeutic bridging option for DSWI. In this systematic review and meta-analysis, the authors aimed to evaluate the impact of NPWT on clinical outcomes in patients with DSWI. Material and Methods: A comprehensive literature search was conducted according to the PRISMA guideline in electronic databases, including PubMed, Embase, and Cochrane Library. Data extraction was performed independently by two reviewers, and risk of bias was assessed by ROBINS-I tool. The primary outcomes assessed were mortality rate and reinfection rate. The secondary outcomes assessed were length of hospital stay and ICU stay. Results: In this systematic review identified a total of 36 studies, comprising 3681 patients with DSWI who received treatment. The meta-analysis revealed that NPWT was associated with a significant reduction in mortality rate (RR 0.46, 95% CI: 0.35–0.61, P &lt;0.000001) and reinfection rate (RR 0.43, 95% CI: 0.25–0.74, P =0.002) compared to conventional wound management. Furthermore, pooling of these studies showed significant difference between the NPWT and conventional treatment groups in length of hospital stay (mean difference: −4.49, 95% CI: −8.14 to −0.83; P =0.02) and length of ICU stay (mean difference: −1.11, 95% CI: −2.18 to −0.04; P =0.04). Conclusion: This systematic review and meta-analysis provide evidence that NPWT is superior to conventional treatment for patients with DSWI following cardiovascular surgery.