tbuckley/cabot-search huggingface dataset:
Demographic trends and outcome measures found in randomized controlled trials of wellness interventions among medical trainees: A systematic review.
Authors: Andrew Irving Hearn, Daniella Chrabuszcz, James Bao, Kristen Elizabeth Hearn, Lauren H Yaeger, Carolyn RT Stoll, Graham A. Colditz
Journal: Journal of Clinical Oncology (2024)

9014 Background: To our knowledge, there is no systematic review that identifies and characterizes the wellness interventions with high-quality evidence in the form of randomized controlled trials (RCTs) among medical education trainees (medical students, residents, and fellows). Methods: A medical librarian (YL) searched Embase, MEDLINE, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), APA PsycINFO, and Clinicaltrials.gov from the earliest timepoint to March 2022. We included full text/ published studies that were prospective RCTs that included quantifiable measures related to mental health, wellness, or other measures of wellbeing. Medical students, residents, and/or fellows must be included in the intervention that is intended to improve wellbeing. We excluded studies that included only qualitative outcome measures, had no control group, or took place outside the USA. Results: Our search strategy resulted in 3,806 unique articles. 161 articles passed initial screening of titles and abstracts, and 46 studies met eligibility criteria with dates ranging from 1980 to 2022. A total of 8,016 participants were studied with the majority of studies (26) focusing on medical students, a minority of studies (20) focusing on residents, and no studies that included fellows. A minority (10) of studies were multi-institutional with the vast majority (36) being single-institutional. Outcome measures shared among two or more studies include variants of the Maslach Burnout Inventory (MBI) (5), Perceived Stress Scale (PSS) (5), PHQ-9 (5), Five-Facet Mindfulness Questionnaire (FFMQ) (5), State Trait Anxiety Inventory (STAI) (3), step count (3), Epworth Sleepiness Scale (ESS) (2), General Anxiety Disorder-7 (GAD-7) (2), Global Severity Index (GSI) (2), and Brief Symptom Index (BSI) (2). Interventions included in two or more studies center around mindfulness and/or meditation practices (15), cognitive behavioral therapy (CTB) (3), hypnosis (3), activity trackers (2), flexible work hours (2), and massage and/or manipulation (2). Conclusions: We conducted a systematic review to identify evidence-based wellness interventions and in the process potentially inform future research in regards to standardized outcome measures and highlighting the need for interventions targeting fellows, particularly in fields with a majority of physicians reporting burnout such as hematology/oncology. 1 1. McKenna J. Medscape Physician Burnout &amp; Depression Report 2024: “We Have Much Work to Do". Medscape. Published 2024. https://www.medscape.com/slideshow/2024-lifestyle-burnout-6016865.
Global interest in podcasts designed for medical oncology trainees.
Authors: Ryan Holstead, Ryann Quinn
Journal: Journal of Clinical Oncology (2024)

9019 Background: Audio podcasts allow for medical education to be disseminated in an on-demand format and are globally accessible. There are currently a limited number of trainee-directed medical oncology podcasts and their global impact has not been shown. “Talking about Tumors with Ryann and Ryan” is an English language, evidence-based, free-to-use podcast that was initiated in April 2022 with a focus on education of trainees new to the field. Methods: Geographic statistics were collected for podcast episodes with greater than 30 days of availability. The proportion of listeners from different regions was compared between episodes. Trends in listeners from North America and global audiences were descriptively analyzed. Results: 34 episodes were included in this analysis, with content in gastrointestinal, breast, thoracic and cutaneous malignancies. Episodes had a median of 115 downloads, with consistently &gt;30% from outside of Canada and the United States (median 37.3 +/- 6.4%). Twenty-four countries had greater than 10 downloads. The largest audience beyond North America was Australia (13%), Israel (4%), United Kingdom (3%), Pakistan (3%), Sweden (2%), India (1%), and Hong Kong (1%). A review of individual cities within countries was relatively constant, suggestive of persistent listenership. Conclusions: There is a global interest for introductory medical oncology education. Presentation in an evidence-based format and awareness of variation in regional approaches to systemic therapy can increase the impact of podcasts, which by their design can reach a global audience. The development of an index for early education oncology podcasts may improve visibility and access to those interested in this medium.
Observing attending physician teaching behaviors during inpatient hematology/oncology consultation.
Authors: Michael Trainer, Patricia O'Sullivan, Sam Brondfield
Journal: Journal of Clinical Oncology (2024)

9017 Background: Inpatient consultation is a primary responsibility of fellows and residents. Consults are complex tasks that impose significant cognitive load (CL) on trainees, potentially jeopardizing patient safety. We previously published strategies for attendings to optimize trainee CL during consults, and we also demonstrated that distractions are a prominent source of trainee CL during consults. Strategies to optimize CL have not been studied during inpatient consultation. Therefore, we aimed to observe and categorize attending behaviors that might affect trainee CL during consults using hematology/oncology as a model. Methods: After discussion with author SB (an oncologist who frequently performs and teaches inpatient oncology consultation), one author (MT, a neurology resident with experience performing consults outside of hematology/oncology) observed 10 new inpatient hematology and oncology consult discussions between attendings and fellows or residents at the University of California, San Francisco in 2023. The observer used our published set of strategies, divided into the three CL types (intrinsic load [IL] strategies to optimize the consult for the trainee, extraneous load [EL] strategies to reduce distractions, and germane load [GL] strategies to promote learning), as a checklist of attending behaviors and noted whether each behavior occurred during the discussions. Results: Discussions between four attendings and five trainees (three fellows and two residents) on inpatient hematology and oncology consult services were observed. Two attendings identified as female (one hematologist and one oncologist) and two male (one hematologist and one oncologist). Out of 18 attending behaviors on the checklist (six each of IL, EL, and GL), 13 (72%) were observed at least once. The median number of behaviors observed during one consult discussion was 3.5 (range 1-5, interquartile range 2-4.75). GL behaviors occurred most often (14 times across the 10 discussions), IL behaviors next most often (11 times), and EL behaviors least often (seven times). All four attendings exhibited at least one behavior from each CL type. The most commonly observed behavior was “teaching by sharing clinical reasoning” (GL). Conclusions: Hematology/oncology attendings exhibited observable behaviors related to optimizing trainee CL during inpatient consults and demonstrated behaviors intended to promote learning (GL) more frequently than behaviors intended to reduce trainee distractions (EL). Based on these data, hematology/oncology consult attendings may wish to augment their use of behaviors intended to reduce distractions, which are prominent during inpatient consults, to avoid trainee cognitive overload. Future research might correlate measured trainee CL with attending teaching behaviors to demonstrate the impact of these behaviors and optimize consult teaching interactions.
Eosinophil Depletion with Benralizumab for Eosinophilic Esophagitis
Authors: Marc E. Rothenberg, Evan S. Dellon, Margaret H. Collins, Albert J. Bredenoord, Ikuo Hirano, Kathryn A. Peterson, Laura Brooks, Julie M. Caldwell, Harald Fjällbrant, Hanna Grindebacke, Calvin N. Ho, Matthew Keith, Christopher McCrae, Dominic Sinibaldi, Wendy I. White, Catherine J. Datto
Journal: New England Journal of Medicine (2024)

Benralizumab is an eosinophil-depleting anti-interleukin-5 receptor α monoclonal antibody. The efficacy and safety of benralizumab in patients with eosinophilic esophagitis are unclear.
In situ engineered magnesium alloy implant for preventing postsurgical tumor recurrence
Authors: Wanying Li, Yinghui Wang, Chaojie Che, Xinyu Fu, Yang Liu, Dongzhi Xue, Shuai Zhang, Rui Niu, Hao Zhang, Yue Cao, Shuyan Song, Liren Cheng, Hongjie Zhang
Journal: Bioactive Materials (2024)

Invasive tumors are difficult to be completely resected in clinical surgery due to the lack of clear resection margins, which greatly increases the risk of postoperative recurrence. However, chemotherapy and radiotherapy as the traditional means of postoperative adjuvant therapy, are limited in postoperative applications, such as multi-drug resistance and low sensitivity, etc. Therefore, an engineered magnesium alloy rod is designed as a postoperative implant to completely remove postoperative residual tumor tissue and inhibit tumor recurrence by gas and mild magnetic hyperthermia therapy (MMHT). As a reactive metal, magnesium alloy responds to the acidic tumor microenvironment by continuously generating hydrogen. The in-situ generation of hydrogen not only protects the surrounding normal tissue, but also enables the magnesium alloy to achieve MMHT under low-intensity alternating magnetic field (AMF). Furthermore, the numerous reactive oxygen species (ROS) produced by heat stress will combine with nitric oxide (NO) generated in situ, to produce more toxic reactive nitrogen species (RNS) storm. In summary, engineered magnesium alloy can completely remove residual tumor tissue and inhibit tumor recurrence by MMHT and RNS storm under low-intensity AMF, and the biodegradability of magnesium alloy makes great potential for clinical application.
Fc–Fc interactions and immune inhibitory effects of IgG4: implications for anti-PD-1 immunotherapies
Authors: Weifeng Zhang, Xueling Chen, Xingxing Chen, Jirui Li, Hui Wang, Xiaomiao Yan, Han Zha, Xiaonan Ma, Chanyuan Zhao, Meng Su, Liangli Hong, Penghao Li, Yanyu Ling, Wenhui Zhao, Yu Xia, Baiyong Li, Tianjing Zheng, Jiang Gu
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background The majority of anti-programmed cell-death 1 (PD-1) monoclonal antibodies (mAbs) use S 228 P mutation IgG4 as the structural basis to avoid the activation of immune cells or complement. However, little attention has been paid to the Fc–Fc interactions between IgG4 and other IgG Fc fragments that could result in adverse effects. Fc-null IgG1 framework is a potential safer alternative to avoid the undesirable Fc–Fc interactions and Fc receptor binding derived effects observed with IgG4. This study provides a comprehensive evaluation of anti-PD-1 mAbs of these two frameworks. Methods Trastuzumab and rituximab (both IgG1), wildtype IgG1 and IgG4 were immobilized on nitrocellulose membranes, coated to microplates and biosensor chips, and bound to tumor cells as targets for Fc–Fc interactions. Wildtype IgG1 and IgG4, anti-PD-1 mAb nivolumab (IgG4 S 228 P), penpulimab (Fc-null IgG1), and tislelizumab (Fc-null IgG4 S 228 P-R 409 K) were assessed for their binding reactions to the immobilized IgG proteins and quantitative kinetic data were obtained. To evaluate the effects of the two anti-PD-1 mAbs on immune responses mediated by trastuzumab and rituximab in the context of combination therapy, we employed classic immune models for antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and complement dependent cytotoxicity. Tumor-bearing mouse models, both wildtype and humanized, were used for in vivo investigation. Furthermore, we also examined the effects of IgG1 and IgG4 on diverse immune cell populations Results Experiments demonstrated that wildtype IgG4 and nivolumab bound to immobilized IgG through Fc–Fc interactions, diminishing antibody-dependent cell-mediated cytotoxicity and phagocytosis reactions. Quantitative analysis of kinetic parameters suggests that nivolumab and wildtype IgG4 exhibit comparable binding affinities to immobilized IgG1 in both non-denatured and denatured states. IgG4 exerted inhibitory effects on various immune cell types. Wildtype IgG4 and nivolumab both promoted tumor growth in wildtype mouse models. Conversely, wildtype IgG1, penpulimab, and tislelizumab did not show similar adverse effects. Conclusions Fc-null IgG1 represents a safer choice for anti-PD-1 immunotherapies by avoiding both the adverse Fc–Fc interactions and Fc-related immune inhibitory effects of IgG4. Fc-null IgG4 S 228 P-R 409 K and Fc-null IgG1 displayed similar structural properties and benefits. This study contributes to the understanding of immunotherapy resistance and the advancement of safer immune therapies for cancer.
Phase 3 randomized COMMODORE 1 trial: Crovalimab versus eculizumab in complement inhibitor‐experienced patients with paroxysmal nocturnal hemoglobinuria
Authors: Phillip Scheinberg, Diego Villa Clé, Jin Seok Kim, Erfan Nur, Mustafa N. Yenerel, Wilma Barcellini, Debora Bonito, Valentina Giai, Marek Hus, YooJin Lee, Cristina Barrenetxea Lekue, Jens Panse, Yasutaka Ueda, Simon Buatois, Brittany Gentile, Anna Kiialainen, Himika Patel, Sasha Sreckovic, Marianne Uguen, John Edwards, Zsolt Nagy, Austin G. Kulasekararaj
Journal: American Journal of Hematology (2024)

Abstract Crovalimab, a novel C5 inhibitor, allows for low‐volume, every‐4‐ week, subcutaneous self‐administration. COMMODORE 1 (NCT04432584) is a phase 3, global, randomized trial evaluating crovalimab versus eculizumab in C5 inhibitor‐experienced patients with paroxysmal nocturnal hemoglobinuria (PNH). Adults with lactate dehydrogenase ≤1.5 × upper limit of normal and receiving approved eculizumab doses for ≥24 weeks were randomized 1:1 to receive crovalimab (weight‐based tiered dosing) or continue eculizumab. The original primary study objective was efficacy; however, given the evolving treatment landscape, target recruitment was not met, and all efficacy endpoints became exploratory, with safety as the new primary objective. Exploratory efficacy endpoints included transfusion avoidance, hemolysis control, breakthrough hemolysis, hemoglobin stabilization, FACIT‐Fatigue score, and patient preference (crovalimab vs. eculizumab). Eighty‐nine patients were randomized (45 to crovalimab; 44 to eculizumab). During the 24‐week primary treatment period, adverse events (AEs) occurred in 77% of patients receiving crovalimab and 67% receiving eculizumab. No AEs led to treatment withdrawal or death, and no meningococcal infections occurred. 16% of crovalimab‐treated patients had transient immune complex reactions (also known as Type III hypersensitivity events), an expected risk when switching between C5 inhibitors that bind to different C5 epitopes; most were mild/moderate and all resolved without treatment modification. Crovalimab‐treated patients had sustained terminal complement activity inhibition, maintained disease control, and 85% preferred crovalimab over eculizumab. Together with phase 3 COMMODORE 2 results in complement inhibitor‐naive patients, these data support crovalimab's favorable benefit–risk profile. Crovalimab is a new C5 inhibitor for PNH that is potentially less burdensome than existing therapies for this lifelong disease.
Understanding fellow hematology curriculums: Characterizing perspectives and defining opportunities for improvement.
Authors: Richard Godby, Prasanth Lingamaneni, Naseema Gangat, Jonas Paludo
Journal: Journal of Clinical Oncology (2024)

9018 Background: Comprehensive hematology education during fellowship is paramount for providing high-quality care, especially in busy practices. Variability in fellow educational experiences is expected. However, fellowship programs must ensure a well-rounded, equitable educational experience for all fellows to prepare them for practice and board exams in the increasingly dynamic field of hematology. Methods: We administered an e-mail survey to hematology/oncology fellows (n=30) at Mayo (Rochester) to explore inpatient hematology education experiences and the Fellow Hematology Curriculum (FHC) during 2021-2022. Based on results, we designed a fellow-led, consultant-supervised quality improvement (QI) initiative to improve FHC. Responses were in a five-point Likert scale and open-ended format. Results: Twenty fellows completed the survey (66% response rate). Respondents were well distributed (35% PGY4, 25% PGY5, 40% PGY6). Resources most used for self-education were ASH SAP (85%), UpToDate (80%), and NCCN guidelines (50%). 100% of respondents agreed/strongly agreed that the FHC could be improved. 95% agreed/strongly agreed that there is a high degree of variability among consultants regarding engagement in fellows’ education. 45% agreed that education is adequately paired with relevant clinical duties to reinforce key concepts. 25% agreed that FHC had well-defined structure and objectives. In the open-ended responses, a structured curriculum covering a set list of topics paired with the relevant rotation was the most common recommendation by the fellows for improving the FHC and the inpatient hematology educational experience. This prompted a QI initiative to implement a structured, evidence-based curriculum covering essential topics required for hematology practice. Each week of a four-week rotation has a relevant theme (eg, “Marrow Failure week” during the inpatient leukemia service). Fellows selected a topic of interest and created a lecture to be used by all faculty and learners during the relevant rotation (eg, “Aplastic Anemia” during the Marrow Failure). Consultants and pharmacists in respective disease groups reviewed the topics and presentations. These lectures are now provided to fellows and faculty via e-mail prior to relevant rotations. Conclusions: Our survey demonstrated that trainees’ individual educational experiences on inpatient hematology services are widely variable and largely unsatisfying without some form of structured, relevant learning. We identified the need for deliberate, coordinated education as a gap to bridge toward achieving the goal of equitable, comprehensive learning. We intend to perform a post-implementation survey after one year of practicing a structured, relevantly paired FHC. This assessment will be used to make improvements in subsequent iterations of the FHC using the Plan-Do-Study-Act methodology.
NKG2A genetic deletion promotes human primary NK cell anti-tumor responses better than an anti-NKG2A monoclonal antibody
Authors: Ying Gong, Wilfred T.V. Germeraad, Xulin Zhang, Nisha Wu, Bo Li, Lynn Janssen, Zongzhong He, Marion J.J. Gijbels, Bodeng Wu, Birgit L.M.G. Gijsbers, Timo I. Olieslagers, Gerard M.J. Bos, Lei Zheng, Roel G.J. Klein Wolterink
Journal: Molecular Therapy (2024)

Natural killer (NK) cells eliminate infected or cancer cells via their cytotoxic capacity. NKG2A is an inhibitory receptor on NK cells and cancer cells often overexpress its ligand HLA-E to evade NK cell surveillance. Given the successes of immune checkpoint blockade in cancer therapy, NKG2A is an interesting novel target. However, anti-NKG2A antibodies have shown limited clinical response. In the pursuit of enhancing NK cell-mediated anti-tumor responses, we devised a Cas9-based strategy to delete KLRC1, encoding NKG2A, in human primary NK cells. Our approach involved electroporation of KLRC1-targeting Cas9 ribonucleoprotein resulting in effective ablation of NKG2A expression. Compared with anti-NKG2A antibody blockade, NKG2A
Vaginal anaerobes are associated with cervicitis: A case-control study
Authors: Erica L. Plummer, Lenka A. Vodstrcil, Jennifer A. Danielewski, Gerald L. Murray, Michelle L. Doyle, Rosie L. Latimer, Christopher K. Fairley, Eric P.F. Chow, Suzanne M. Garland, Catriona S. Bradshaw
Journal: Journal of Infection (2024)

Cervicitis is associated with important reproductive sequelae. Primary causes include chlamydia and gonorrhoea, but a known sexually transmitted infection (STI) is not identified in >50% of cases (i.e. STI-negative cervicitis). Bacterial vaginosis (BV) and specific BV-associated bacteria have also been associated with cervicitis, but data are limited. We investigated the association between STI-negative cervicitis and vaginal microbiota composition.
Targeted RNAseq from patients’ urinary cells to validate pathogenic noncoding variants in autosomal dominant polycystic kidney disease genes: a proof of concept
Authors: Guillaume Dorval, Gérald Le Gac, Vincent Morinière, Chandran Ka, Claire Goursaud, Bertrand Knebelmann, Pierre Marijon, Sophie Nambot, Nicolas Cagnard, Patrick Nitschké, Laurence Michel-Calemard, Marie-Pierre Audrézet, Laurence Heidet
Journal: Kidney International (2024)
Phase 1/2 trials of human bone marrow–derived clonal mesenchymal stem cells for treatment of adults with moderate to severe atopic dermatitis
Authors: Hyun-Min Seo, Bark-Lynn Lew, Yang Won Lee, Sang Wook Son, Chang Ook Park, Young Lip Park, Jin-Ok Baek, Min Kyung Shin, Dong Hyun Kim, Dong Hun Lee, Yong Hyun Jang, Hyun-Chang Ko, Chan-Ho Na, Young-Joon Seo, Dong-Sik Ham, Dong-Jun Kim, Gwang Seong Choi
Journal: Journal of Allergy and Clinical Immunology (2024)

Mesenchymal stem cells (MSCs) play important roles in therapeutic applications by regulating immune responses.
Polyp size is associated with colorectal cancer death across histologic polyp subtypes: a retrospective study of a screening colonoscopy registry
Authors: Jasmin Zessner-Spitzenberg, Elisabeth Waldmann, Lisa-Maria Rockenbauer, Alexandra Demschik, Daniela Penz, Michael Trauner, Monika Ferlitsch
Journal: Endoscopy (2024)

Abstract Background Surveillance colonoscopy after polyps have been detected at screening aims to reduce the risk for subsequent colorectal cancer, so-called post-colonoscopy colorectal cancer (PCCRC). Inconsistencies exist as to whether the risk should be stratified by histologic subtype. We aimed to compare the risk for PCCRC mortality in screening participants with sessile serrated lesions (SSLs)/traditional serrated adenomas (TSAs), hyperplastic polyps (HPPs), or conventional adenomas. Methods Screening colonoscopy registry data were linked to death registry data between 2010 and 2022. We assessed the association of PCCRC death after a diagnosis of SSL/TSA, conventional adenoma, or HPP by Cox regression, and stratified by polyp size ≥10 and &lt;10 mm. Results 383,801 participants were included in the analysis. There were 1490 HPPs ≥10 mm (2.6%), compared with 1853 SSL/TSAs (19.6%) and 10,960 conventional adenomas (12.9%). When adjusted for polyp location, the association of polyp size ≥10 mm with PCCRC death was of similar magnitude in participants with conventional adenomas (hazard ratio [HR] 3.68, 95%CI 2.49–5.44), SSL/TSAs (HR 2.55, 95%CI 1.13–5.72), and HPPs (HR 5.01, 95%CI 2.45–10.22). Participants with HPPs mostly died of tumors in the distal colon (54.1%; n = 20), while participants with SSL/TSAs more frequently died of proximal tumors (33.3%; n = 3). Conclusions Across all histologic types, participants with polyps ≥10 mm had at least a two-fold increase in the likelihood of PCCRC death compared with those with polyps &lt;10 mm. These data suggest that size, rather than histologic subtype, should be a determinant for risk stratification after screening colonoscopy.