Activating mutations in CD8+ T-cells correlate to serological positivity in rheumatoid arthritis.

Objectives: Large granular lymphocyte (LGL) leukemia is a rare hematologic malignancy characterized by clonal expansion of cytotoxic T-cells frequent somatic activating mutations. Based on the disease overlap between LGL leukemia rheumatoid arthritis (RA)a putative role for CD8+ T-cells in RA we hypothesized that mutations may be detected in RA patient CD8+ T-cells correlate with clinical characteristics.

Methods: Blood samples, clinical parameters, and demographics were collected from 98 RA patients and 9 healthy controls (HCs).

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.

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.

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.

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.

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.

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 CD16/CD56 NK cells.

Frequent somatic TET2 mutations in chronic NK-LGL leukemia with distinct patterns of cytopenias.

Chronic natural killer large granular lymphocyte (NK-LGL) leukemia, also referred to as chronic lymphoproliferative disorder of NK cells, is a rare disorder defined by prolonged expansion of clonal NK cells. Similar prevalence of STAT3 mutations in chronic T-LGL and NK-LGL leukemia is suggestive of common pathogenesis. We undertook whole-genome sequencing to identify mutations unique to NK-LGL leukemia.

Mobilizing an institutional supportive response for healthcare workers and other staff in the context of COVID-19: The Yale experience.

The burden of the COVID-19 pandemic upon healthcare workers necessitates a systematic effort to support their resilience. This article describes the Yale University and Yale New Haven Health System effort to unite several independent initiatives into a coherent integrated model for institutional support for healthcare workers. Here, we highlight both opportunities and challenges faced in attempting to support healthcare workers during this pandemic.

Large granular lymphocyte leukemia serum and corresponding hematological parameters reveal unique cytokine and sphingolipid biomarkers and associations with STAT3 mutations.

Large granular lymphocyte (LGL) leukemia is a rare hematological disorder with expansion of the T-cell or natural killer (NK) cell lineage. Signal transducer and activator of transcription 3 (STAT3) exhibits somatic activating mutations in 30%-40% of LGL leukemia cases. Transcriptional targets of STAT3 include inflammatory cytokines, thus previous studies have measured cytokine levels of LGL leukemia patients compared to normal donors.

Advances in the Diagnosis and Treatment of Large Granular Lymphocytic Leukemia.

Purpose Of Review: The past decade in LGL leukemia research has seen increased pairing of clinical data with molecular markers, shedding new insights on LGL leukemia pathogenesis and heterogeneity. This review summarizes the current standard of care of LGL leukemia, updates from clinical trials, and our congruent improved understanding of LGL pathogenesis.

Recent Findings: Various clinical reports have identified associations between stem, bone marrow, and solid organ transplants and incidence of LGL leukemia.

Organizational strategies to reduce physician burnout and improve professional fulfillment.

Burnout is highly prevalent among physicians and has been associated with negative outcomes for physicians, patients, staff, and health-care organizations. Reducing physician burnout and increasing physician well-being is a priority. Systematic reviews suggest that organization-based interventions are more effective in reducing physician burnout than interventions targeted at individual physicians.

Genomics of LGL leukemia and select other rare leukemia/lymphomas.

Genomic analysis of cancer offers the hope of identifying new treatments or aiding in the selection of existing treatments. Rare leukemias pose additional challenges in this regard as samples may be hard to acquire and when found the underlying pathway may not be attractive to drug development since so few individuals are affected. In this case, it can be useful to identify common mutational overlap among subsets of rare leukemias to increase the number of individuals that may benefit from a targeted therapy.

Cross-sectional survey of workplace stressors associated with physician burnout measured by the Mini-Z and the Maslach Burnout Inventory.

Rising physician burnout has adverse effects on healthcare. This study aimed to identify remediable stressors associated with burnout using the 10-item Mini-Z and the Maslach Burnout Inventory (MBI), and to compare performance of the Mini-Z's single-item burnout metric against the 22-item MBI. Surveys were emailed to 4,118 clinicians affiliated with an academic health system; 1,252 clicked the link, and 557 responded (completion rate 44%).

Vitamin D pathway activation selectively deactivates signal transducer and activator of transcription (STAT) proteins and inflammatory cytokine production in natural killer leukemic large granular lymphocytes.

Calcitriol, the active form of vitamin D, has been well documented to act directly on immune cells and malignant cells. Activated T cells are one of the best characterized targets of calcitriol, with effects including decreasing inflammatory cytokine output and promoting anti-inflammatory cytokine production. However, the effects of calcitriol on natural killer (NK) cells are less clear.

Dysregulation of the IFN-γ-STAT1 signaling pathway in a cell line model of large granular lymphocyte leukemia.

T cell large granular lymphocyte leukemia (T-LGLL) is a rare incurable disease that is characterized by defective apoptosis of cytotoxic CD8+ T cells. Chronic activation of the Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) pathway is a hallmark of T-LGLL. One manifestation is the constitutive phosphorylation of tyrosine 701 of STAT1 (p-STAT1).