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GDF-15 in Pulmonary and Critical Care Medicine.

ABSTRACT: GDF-15 (growth differentiation factor 15) acts both as a stress-induced cytokine with diverse actions at different body sites and as a cell-autonomous regulator linked to cellular senescence and apoptosis. For multiple reasons, this divergent transforming growth factor-β molecular superfamily member should be better known to pulmonary researchers and clinicians. In ambulatory individuals, GDF-15 concentrations in peripheral blood are an established predictive biomarker of all-cause mortality and of adverse cardiovascular events. Concentrations upon admission of critically ill patients (without or with sepsis) correlate with organ dysfunction and independently predict short- and long-term mortality risk. GDF-15 is a major downstream mediator of p53 activation, but it can also be induced independently of p53, notably by nonsteroidal antiinflammatory agents. GDF-15 blood concentrations are markedly elevated in adults and children with pulmonary hypertension. Concentrations are also increased in chronic obstructive pulmonary disease, in which they contribute to mucus hypersecretion, airway epithelial cell senescence, and impaired antiviral defenses, which together with murine data support a role for GDF-15 in chronic obstructive pulmonary disease pathogenesis and progression. This review summarizes biological and clinical data on GDF-15 relevant to pulmonary and critical care medicine. We highlight the recent discovery of a central nervous system receptor for GDF-15, GFRAL (glial cell line-derived neurotrophic factor family receptor-α-like), an important advance with potential for novel treatments for obesity and cachexia. We also describe limitations and controversies in the existing literature, and we delineate research questions that must be addressed to determine whether GDF-15 can be therapeutically manipulated in other clinical settings.

SUBMITTER: Verhamme FM

PROVIDER: S-EPMC6543753 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe prevalence of burnout and depressive symptoms is high among physician trainees.Research questionWhat is the burden of burnout and depressive symptoms among fellows training in pulmonary and critical care medicine (PCCM) and what are associated individual fellow, program, and institutional characteristics?Study design and methodsWe conducted a cross-sectional electronic survey of fellows enrolled in pulmonary, PCCM, and critical care medicine training programs in the United States to assess burnout and depressive symptoms. Burnout symptoms were measured using the Maslach Burnout Index two-item measure. The two-item Primary Care Evaluation of Mental Disorders Procedure was used to screen for depressive symptoms. For each of the two outcomes (burnout and depressive symptoms), we constructed three multivariate logistic regression models to assess individual fellow characteristics, program structure, and institutional polices associated with either burnout or depressive symptoms.ResultsFive hundred two of the 976 fellows who received the survey completed it-including both outcome measures-giving a response rate of 51%. Fifty percent of fellows showed positive results for either burnout or depressive symptoms, with 41% showing positive results for depressive symptoms, 32% showing positive results for burnout, and 23% showing positive results for both. Reporting a coverage system in the case of personal illness or emergency (adjusted OR [aOR], 0.44; 95% CI, 0.26-0.73) and access to mental health services (aOR, 0.14; 95% CI, 0.04-0.47) were associated with lower odds of burnout. Financial concern was associated with higher odds of depressive symptoms (aOR, 1.13; 95% CI, 1.05-1.22). Working more than 70 hours in an average clinical week and the burdens of electronic health record (EHR) documentation were associated with a higher odds of both burnout and depressive symptoms.InterpretationGiven the high prevalence of burnout and depressive symptoms among fellows training in PCCM, an urgent need exists to identify solutions that address this public health crisis. Strategies such as providing an easily accessible coverage system, access to mental health resources, reducing EHR burden, addressing work hours, and addressing financial concerns among trainees may help to reduce burnout or depressive symptoms and should be studied further by the graduate medical education community.

Project description:Background: Burnout is common among physicians who care for critically ill patients and is known to contribute to worse patient outcomes. Fellows training in pulmonary and critical care medicine (PCCM) have risk factors that make them susceptible to burnout; for example, clinical environments that require increased intellectual and emotional demands with long hours. The Accreditation Council for Graduate Medical Education has recognized the increasing importance of trainee burnout and encourages training programs to address burnout. Objective: To assess factors related to training and practice that posed a threat to the well-being among fellows training in PCCM and to obtain suggestions regarding how programs can improve fellow well-being. Methods: We conducted a qualitative content analysis of data collected from a prior cross-sectional electronic survey with free-response questions of fellows enrolled in pulmonary, PCCM, and critical care medicine training programs in the United States. Fellows were asked what factors posed a threat to their well-being and what changes their training program could implement. Responses were qualitatively coded and categorized into themes using thematic analysis. Results: A total of 427 fellows (44% of survey respondents) completed at least one free-response question. The majority of respondents (60%) identified as male and white/non-Hispanic (59%). The threats to well-being and burnout were grouped into five themes: clinical burden, individual factors, team culture, limited autonomy, and program resources. Clinical burden was the most common threat discussed by fellows. Fellows highlighted factors contributing to burnout that specifically pertained to trainees including challenging interpersonal relationships with attending physicians and limited protected educational time. Fellows proposed solutions addressing clinical care, changes at the program or institution level, and organizational culture changes to improve well-being. Conclusion: This study provides insight into factors fellows report as contributors to burnout and decreased well-being in addition to investigating fellow-driven solutions toward improving well-being. These solutions may help pulmonary, PCCM, and critical care medicine program directors better address fellow well-being in the future.

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GDF-15 in Pulmonary and Critical Care Medicine.

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