The relationship between body composition and left ventricular performance in women with breast, lymphoma, or sarcoma cancer.

BACKGROUND: To understand how body composition in those with elevated body mass index impacts left ventricular function decline during cancer treatment, we determined the association between baseline body mass index (BMI), intra-abdominal adipose tissue (IAT) and subcutaneous adipose tissue (SAT) with baseline to 3-month left ventricular ejection fraction (LVEF) change among women receiving potentially cardiotoxic chemotherapy for breast cancer, lymphoma, or sarcoma. METHODS: Women underwent potentially cardiotoxic chemotherapy, such as doxorubicin, cyclophosphamide, paclitaxel, and trastuzumab, for treatment of breast cancer, lymphoma, or sarcoma. We obtained magnetic resonance images (MRIs) of body composition and cardiac function prior to treatment, and then a repeat MRI for cardiac function assessment at three months into treatment. Analyses and assessment of abdominal adipose tissue volumes and LVEF outcomes were conducted by independent reviewers blinded to all patient identifiers. A general linear model was created to examine associations between adipose tissue depots, BMI, and 3-month LVEF change. RESULTS: Women (n = 210) aged 56 ± 11 years with breast cancer, lymphoma, and sarcoma were enrolled (n = 195, 14, 1 respectively). Baseline BMI, IAT, and SAT fat were independently associated with 3-month LVEF declines (p = 0.001 to 0.025 for all). After adjusting for baseline cardiovascular disease risk factors, BMI, IAT, and SAT, BMI remained the only variable associated with 3-month LVEF decline (p = 0.047). CONCLUSIONS: These results suggest that factors other than abdominal adipose tissue or traditional cardiovascular risk factors may contribute to 3-month declines in LVEF among women with elevated BMI receiving potentially cardiotoxic chemotherapy. Further investigation should be conducted on psychosocial stress, physical activity, sleep, or diet. TRIAL REGISTRATION: DETECTIV_NCT01719562, WF99112, & WF97415-NCT02791581.

Hypertension Severity and Declines in Left Ventricular Ejection Fraction Among Women Receiving Adjuvant Chemotherapy for Breast Cancer (WF-97415 UPBEAT).

BACKGROUND: Hypertension is a risk factor for experiencing left ventricular ejection fraction (LVEF) declines during receipt of potentially cardiotoxic breast cancer (BC) treatment. We sought to determine whether the hypertension stage is associated with LVEF decline during BC treatment. METHODS: Across 24 centers, cardiac magnetic resonance measures of LVEF and brachial arterial blood pressure (BP) measurements were performed in women with stages I to III BC before and 3 months after initiating potentially cardiotoxic chemotherapy. Using multivariable analysis, we assessed in a blinded fashion the association between 3-month ΔLVEF and precancer treatment American Heart Association/American College of Cardiology stages of hypertension. RESULTS: Among 204 women, age averaged 56±1 years with 75% being White and 20% of Black race. Participants received anthracycline (45.6%), trastuzumab (22.5%), cyclophosphamide (52.9%), or paclitaxel (50%). After accounting for pretreatment LVEF, diabetes status, tobacco use, age, the number of antihypertensive medications, and body mass index, those with stage II hypertension experienced an LVEF decline of -2.89% ([95% CI, -0.69% to -5.19%]; P=0.01) relative to individuals with normal BP. Other stages saw nonsignificant declines relative to normal BP to elevated BP (-1.63% [95% CI, -0.62% to 3.88%]; P=0.16) and stage I hypertension (-0.94% [95% CI, -0.90% to 2.78%]; P=0.32). CONCLUSIONS: Compared with women receiving treatment for BC with normal BP, there is a stronger association of decline in LVEF in women with stage II hypertension relative to women with other hypertension stages. This raises the possibility that stage along with hypertension presence may be associated with an increased risk for the LVEF decline among women receiving potentially cardiotoxic chemotherapy for BC. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02791581 and NCT01719562.

Impact of COVID-19 on American Family Physicians' Intent to Retreat from Clinical Care.

PURPOSE: This survey evaluated whether the COVID-19 pandemic was a traumatic stress event for family physicians associated with burnout, changes in life priorities, and intentions to retreat from clinical practice. METHODS: We report on 683 clinically active family physicians surveyed through the Council of Academic Family Medicine's Educational Research Alliance (CERA) in the fall of 2021. RESULTS: Overall, 35.2% of family physicians experienced the pandemic as a traumatic stress like event. This was associated with changing life priorities (OR 2.6, CI 1.8-3.9), burnout (OR 1.6, CI 1.1 to 2.4), and withdrawal from clinical practice in various ways. Those who changed their priorities in life were more likely to restrict scope of practice (OR 3.9, CI 2.6-5.9), reduce clinical work effort (OR 3.4, 2.3 to 5.1), relocate (OR 3.1, CI 2.0 to 4.8), retire (OR 2.7, CI 1.4-4.9), reroute their career away from patient care (OR 2.1, CI 1.4-3.1) and less likely to avoid redesigning the practice to improve well-being (OR 0.3, CI 0.2-0.7). Those who experienced burnout were more likely to retire (OR 5.5, CI 2.8 to 10.5), reduce clinical work effort (OR 4.2, CI 2.9-6.1), reroute their career away from patient care (OR 3.9, CI 2.6-5.8), relocate (OR 3.8, CI 2.4 to 5.9), and restrict scope of practice (OR 3.3, CI 2.3 to 4.9). Overall, 48.5% of family physicians expressed some intention to retreat from clinical practice. CONCLUSION: The COVID-19 pandemic impacted family physician's career plans. Remedying burnout is a high-yield opportunity for retaining clinically active family physicians. Physicians retreating from clinical medicine related to changing life's priorities needs further exploration.

Burnout and Disengagement in Pathology: A Prepandemic Survey of Pathologists and Laboratory Professionals.

CONTEXT.­: Despite widely prevalent burnout and attendant disengagement in medicine, the specific patterns and drivers within pathology and laboratory medicine are uncommonly studied. OBJECTIVE.­: To assess the prevalence and drivers of burnout among pathology and laboratory medicine professionals, retrospectively, prior to the COVID-19 pandemic. DESIGN.­: This was a cross-sectional, mixed-methods study engaging pathology and laboratory medicine professionals as subjects. RESULTS.­: Of 2363 respondents, 438 identified as pathologists, 111 as pathology assistants, and 911 as pathology and laboratory professionals. The burnout rate was 58.4% (1380 of 2363) across all respondents in pathology and laboratory medicine. Burnout varied by job role (P < .01) and was highest among pathology and laboratory professionals. Disparities in burnout rate were observed by race. Fifty-six percent (1323 of 2363) of respondents felt that they had at least 1 symptom of burnout and were advancing toward a breaking point. Underlying factors ranked highly among all groups included control over workload and loss of meaning in work. CONCLUSIONS.­: Data provided from this cohort may help departments create successful strategies to reduce disengagement and burnout in the laboratory, especially during periods of increased stress as experienced during the COVID-19 pandemic. Further, these data may serve as a baseline comparison for future studies.

COVID-19 Traumatic Disaster Appraisal and Stress Symptoms Among Health Care Workers: Insights From the Yale Stress Self-assessment.

OBJECTIVE: To determine to what extent did health care workers experience the pandemic as a severe stress event. METHODS: This cross-sectional evaluation of 8299 health care workers, representing a 22% response rate, utilized machine learning to predict high levels of escalating stress based on demographics and known predictors for adverse psychological outcomes after trauma. RESULTS: A third of health care workers experienced the pandemic as a potentially traumatic stress event; a greater proportion of health care workers experienced high levels of escalating stress. Predictive factors included sense of control, ability to manage work-life demands, guilt or shame, age, and level of education. Gender was no longer predictive after controlling for other factors. Escalating stress was especially high among nonclinical academics and clinical private practitioners. CONCLUSION: Findings suggest adverse effects on total worker health, care quality, professionalism, retention, and acute and chronic mental health.

CCL22 mutations drive natural killer cell lymphoproliferative disease by deregulating microenvironmental crosstalk.

Chronic lymphoproliferative disorder of natural killer cells (CLPD-NK) is characterized by clonal expansion of natural killer (NK) cells where the underlying genetic mechanisms are incompletely understood. In the present study, we report somatic mutations in the chemokine gene CCL22 as the hallmark of a distinct subset of CLPD-NK. CCL22 mutations were enriched at highly conserved residues, mutually exclusive of STAT3 mutations and associated with gene expression programs that resembled normal CD16dim/CD56bright NK cells. Mechanistically, the mutations resulted in ligand-biased chemokine receptor signaling, with decreased internalization of the G-protein-coupled receptor (GPCR) for CCL22, CCR4, via impaired ß-arrestin recruitment. This resulted in increased cell chemotaxis in vitro, bidirectional crosstalk with the hematopoietic microenvironment and enhanced NK cell proliferation in vivo in transgenic human IL-15 mice. Somatic CCL22 mutations illustrate a unique mechanism of tumor formation in which gain-of-function chemokine mutations promote tumorigenesis by biased GPCR signaling and dysregulation of microenvironmental crosstalk.