Goals of medical students participating in scholarly concentration programmes.

OBJECTIVES: Scholarly concentration (SC) programmes are increasingly common in medical school curricula, fostering student participation in mentored research. Endpoints including publication rates and impact on career path have been reported, but student goals have not been described. We describe how career plans and gender impact the importance of students' SC-related goals. Understanding student goals may enhance mentorship of professional development and self-directed learning skills. METHODS: First-year students at two US medical schools were surveyed. Students reported intentions regarding career-long research and specialty interests. Using a 5-point scale, students assigned importance to 13 goals (eight skill-related goals, four accomplishment-related goals and mentorship), Composite scores for skills-related and accomplishment-related goals were used for analysis. Regression analyses, controlling for school, were used to determine whether intentions regarding career-long research, interest in highly competitive residency or gender were associated with increased importance of different goals. RESULTS: We surveyed 288 first-year medical students and received 186 responses (64.6% response rate). Compared with their peers, students interested in career-long research placed more importance on both skill-related goals (beta coefficient, 1.87; 95% confidence interval [CI], 1.03-2.71; p < 0.001) and accomplishment-related goals (odds ratio [OR], 1.71; 95% CI, 1.09-2.69; p = 0.02). By contrast, compared with their peers, students interested in highly competitive specialties placed more importance only on accomplishment-related goals (OR, 2.18; 95% CI, 1.15-4.11; p = 0.02). Compared with men, women placed more importance on mentorship (OR, 2.47; 95% CI, 1.23-4.97; p = 0.01) and were less likely to be interested in highly competitive residencies (39.4% versus 54.9%, p = 0.04). CONCLUSIONS: Gender and career plans are associated with importance of SC-related goals in the first year of medical school. This knowledge enables faculty to promote students' appreciation of important learning goals in the setting of student research, which may help students engage in self-directed learning across their medical education.

Excessive mechanical stress increases HMGB1 expression in human lung microvascular endothelial cells via STAT3.

Ventilator-induced lung injury (VILI) occurs when the lung parenchyma and vasculature are exposed to repetitive and excessive mechanical stress via mechanical ventilation utilized as supportive care for the adult respiratory distress syndrome (ARDS). VILI induces gene expression and systemic release of inflammatory mediators that contribute to the multi-organ dysfunction and morbidity and mortality of ARDS. HMGB1, an intracellular transcription factor with cytokine properties, is a late mediator in sepsis and ARDS pathobiology, however, the role of HMGB1 in VILI remains poorly described. We now report HMGB1 expression in human lung microvessel endothelial cells (ECs) exposed to excessive, equibiaxial mechanical stress, an in vitro correlate of VILI. We determined that high amplitude cyclic stretch (18% CS) increased HMGB1 expression (2-4-fold) via a signaling pathway with critical involvement of the transcription factor, STAT3. Concomitant exposure to 18% CS and oxidative stress (H2O2) augmented HMGB1 expression (~13 fold increase) whereas lipopolysaccharide (LPS) challenge increased HMGB1 expression in static EC, but not in 18% CS-challenged EC. In contrast, physiologic, low amplitude cyclic stretch (5% CS) attenuated both oxidative H2O2- and LPS-induced increases in HMGB1 expression, suggesting that physiologic mechanical stress is protective. These results indicate that HMGB1 gene expression is markedly responsive to VILI-mediated mechanical stress, an effect that is augmented by oxidative stress. We speculate that VILI-induced HMGB1 expression acts locally to increase vascular permeability and alveolar flooding, thereby exacerbating systemic inflammatory responses and increasing the likelihood of multi-organ dysfunction.

Residency Program Directors' Views on Research Conducted During Medical School: A National Survey.

PURPOSE: With the United States Medical Licensing Examination Step 1 transition to pass/fail in 2022, uncertainty exists regarding how other residency application components, including research conducted during medical school, will inform interview and ranking decisions. The authors explore program director (PD) views on medical student research, the importance of disseminating that work, and the translatable skill set of research participation. METHOD: Surveys were distributed to all U.S. residency PDs and remained open from August to November 2021 to query the importance of research participation in assessing applicants, whether certain types of research were more valued, productivity measures that reflect meaningful research participation, and traits for which research serves as a proxy. The survey also queried whether research would be more important without a numeric Step 1 score and the importance of research vs other application components. RESULTS: A total of 885 responses from 393 institutions were received. Ten PDs indicated that research is not considered when reviewing applicants, leaving 875 responses for analysis. Among 873 PDs (2 nonrespondents), 358 (41.0%) replied that meaningful research participation will be more important in offering interviews. A total of 164 of 304 most competitive specialties (53.9%) reported increased research importance compared with 99 of 282 competitive (35.1%) and 95 of 287 least competitive (33.1%) specialties. PDs reported that meaningful research participation demonstrated intellectual curiosity (545 [62.3%]), critical and analytical thinking skills (482 [55.1%]), and self-directed learning skills (455 [52.0%]). PDs from the most competitive specialties were significantly more likely to indicate that they value basic science research vs PDs from the least competitive specialties. CONCLUSIONS: This study demonstrates how PDs value research in their review of applicants, what they perceive research represents in an applicant, and how these views are shifting as the Step 1 exam transitions to pass/fail.

HMGB1 induces human lung endothelial cell cytoskeletal rearrangement and barrier disruption.

Acute lung injury (ALI) results from loss of alveolar-capillary barrier integrity and the evolution of high-permeability pulmonary edema resulting in alveolar flooding and significant morbidity and mortality. HMGB1 is a late mediator of sepsis which uniquely participates in the evolution of sepsis and sepsis-induced ALI. The molecular events by which HMGB1 contributes to ALI remain poorly characterized. We characterized the role of HMGB1 in endothelial cell (EC) cytoskeletal rearrangement and vascular permeability, events essential to paracellular gap formation and barrier dysfunction characteristic of ALI. Initial experiments demonstrated HMGB1-mediated dose-dependent (5-20 µg/ml) decreases in transendothelial cell electrical resistance (TER) in the human pulmonary artery EC, a reflection of loss of barrier integrity. Furthermore, HMGB1 produced dose-dependent increases in paracellular gap formation in concert with loss of peripheral organized actin fibers, dissociation of cell-cell junctional cadherins, and the development of central stress fibers, a phenotypic change associated with increased contractile activity and increased EC permeability. Using siRNA strategies directed against known HMGB1 receptors (RAGE, TLR2, TLR4), we systematically determined that the receptor for advanced glycation end products (RAGE) is the primary receptor signaling HMGB1-induced TER decreases and paracellular gap formation via p38 MAP kinase activation and phosphorylation of the actin-binding protein, Hsp27. These studies add to the understanding of HMGB1-induced inflammatory events and vascular barrier disruption and offer the potential for clinical intervention in sepsis-induced ALI.

The Physician-Investigator Workforce: Looking Ahead.

Support of the U.S. health professions investigator workforce is critically important to the continued advancement of health care nationally. Physician-investigators comprise one segment of this health professions investigator workforce, which also includes investigators in the nursing, pharmacy, and dentistry professions, and others. Among physician health professionals in particular, the term "physician-investigator" has been described as encompassing physicians engaged in research in various ways including "clinical researchers" (physicians with clinical duties who do clinical, patient-centered research), "clinician-scientists" (physicians with clinical roles who perform research in laboratories or using computational tools), and "physician-scientists" (physicians focused on research with little or no clinical activity). Broadly defined, physician-investigators are included in various groups of researchers described in several articles recently published in Academic Medicine; these articles provide details on a range of approaches, with supporting outcomes data, being taken to train, support, and retain physicians in the health professions investigator workforce. The authors of this commentary examine selected literature, including several articles in this issue among others, along with Association of American Medical Colleges data, to offer observations about programs that train physician-investigators. Evidence-informed single-program approaches for early-career researchers can sustain continued research interest and foster the career development of the emerging physician-investigator workforce. Collaborative multi-institutional approaches offer the benefit of multisite work to power outcomes studies and to increase generalizability beyond a specific institutional program. System-wide institutional approaches may be particularly critical in supporting physician-investigators across all career stages. Although the articles discussed in this commentary are largely (although not exclusively) focused on various initiatives and programs designed to develop and sustain the physician-investigator workforce, such initiatives and programs may have value in addressing shared challenges of developing, supporting, and retaining the broader investigator workforce across all health professions.

The Impact of a Scholarly Concentration Program on Student Interest in Career-Long Research: A Longitudinal Study.

PURPOSE: Concerns remain regarding the future of the physician-scientist workforce. One goal of scholarly concentration (SC) programs is to give students skills and motivation to pursue research careers. The authors describe SC and student variables that affect students' career plans. METHOD: Medical students graduating from the University of Chicago SC program in 2014 and 2015 were studied. The authors measured change in interest in career-long research from matriculation to graduation, and used ordinal logistic regression to determine whether program satisfaction, dissemination of scholarship, publication, and gender were associated with increased interest in a research career. RESULTS: Among students with low baseline interest in career-long research, a one-point-higher program satisfaction was associated with 2.49 (95% CI 1.36-4.57, P = .003) odds of a one-point-increased interest in a research career from matriculation to graduation. Among students with high baseline interest in career-long research, both publication (OR 5.46, 95% CI 1.40-21.32, P = .02) and female gender (OR 4.83, 95% CI 1.11-21.04, P = .04) were associated with increased odds of a one-point-increased interest in career-long research. CONCLUSIONS: The impact of an SC program on change in career plans during medical school was analyzed. Program satisfaction, publication, and female gender were associated with increased intent to participate in career-long research depending on baseline interest in career-long research. Two ways to bolster the physician-scientist workforce are to improve satisfaction with existing SC programs and to formally support student publication. Future work to track outcomes of SC program graduates is warranted.

Extracorporeal membrane oxygenation after stem cell transplant: clinical decision-making in the absence of evidence.

OBJECTIVE: To discuss the ethical dilemmas that arise in considering innovative therapies for critically ill children when there is little data to support their use. DESIGN: Case report of a 13-yr-old patient after autologous peripheral blood stem cell transplant for stage III neuroblastoma with sepsis and hemodynamic instability who survived to discharge after a 6-day course of extracorporeal membrane oxygenation (ECMO) support. The case serves as a source of discussion of the following: the use of available data in deciding to proceed with an unproved therapy, the approach to conversations to obtain informed consent, and the need for institutional oversight and hypothesis-driven data collection to advance pediatric critical care. SETTING: Pediatric intensive care unit at a university hospital. PATIENT: One adolescent with stage III neuroblastoma. RESULTS: Despite a lack of data to support the use of ECMO in a neutropenic oncology patient after autologous peripheral blood stem cell transplant, our patient had clinical features that suggested he was a reasonable ECMO candidate. His family gave informed consent to use ECMO and he survived. It is ethical to consider and use innovative therapies when patient characteristics are suggestive that the therapy may be successful even in the absence of evidence. This requires physicians' attention to the best interest of the patient and should occur in the setting of informed consent and rigorous data collection. CONCLUSIONS: The boundaries among standard therapy, innovative therapy, and research can be quite fluid. This case illustrates the ethical imperative to consider therapies that may be appropriate for a critically ill child even without evidence predictive of success, to have entry criteria and treatment protocols for such therapies, and to collect data from such experiences to advance the standard of care.