Karen Herbst

Obesity and associated complications including diabetes, cardiometabolic dysfunction, disability, malignancy and premature mortality are considered epidemic. Research on obesity is therefore of worldwide importance. The development of obesity is a multifactorial phenomenon with contributions from biological, behavioral, genetic and environmental factors. Obesity and its associated issues require various lifestyle modifications and treatment options such medication, exercise, diet, surgery, pharmacological therapy and dietary supplements...

Somatic structural variants (SVs) are widespread in cancer, but their impact on disease evolution is understudied due to a lack of methods to directly characterize their functional consequences. We present a computational method, scNOVA, which uses Strand-seq to perform haplotype-aware integration of SV discovery and molecular phenotyping in single cells by using nucleosome occupancy to infer gene expression as a readout. Application to leukemias and cell lines identifies local effects of copy-balanced rearrangements on gene deregulation, and consequences of SVs on aberrant signaling pathways in subclones...

Lipedema is a common disorder characterized by excessive deposition of subcutaneous adipose tissue (SAT) in the legs, hips, and buttocks, mainly occurring in adult women. Although it appears to be heritable, no specific genes have yet been identified. To identify potential genetic risk factors for lipedema, we used bioelectrical impedance analysis and anthropometric data from the UK Biobank to identify women with and without a lipedema phenotype. Specifically, we identified women with both a high percentage of fat in the lower limbs and a relatively small waist, adjusting for hip circumference...

Lipedema is a disease with abnormally increased adipose tissue deposition and distribution. Pain sensations have been described in the clinical evaluation of lipedema, but its etiology remains poorly understood. We hypothesized that pain sensitivity measurements and ex vivo quantitation of neuronal cell body distribution in the skin would be lipedema stage-dependent, and could, thus, serve to objectively characterize neuropathic pain in lipedema. The pain was assessed by questionnaire and peripheral cutaneous mechanical sensitization (von-Frey) in lipedema ( n = 27) and control ( n = 23) consenting female volunteers...

The arrival and establishment of adventive, invasive forest insects are a threat to the health, diversity, and productivity of forests in Canada and the world at large, and their early detection is essential for successful eradication and management. For that reason, the Canadian Food Inspection Agency (CFIA) conducts annual surveys at high risk sites such as international ports and freight terminals, industrial zones, and disposal sites for solid wood packaging material using two methods: (1) semiochemical-baited traps deployed in a total of about 63-80 sites per year in British Columbia (BC), Ontario (ON), Quebec (QC), New Brunswick (NB), Nova Scotia (NS), and Newfoundland and Labrador (NL); and (2) rearing of insects from bolts collected from stressed trees and incubated in modified shipping containers in four cities (Vancouver, Toronto, Montreal, and Halifax)...

BACKGROUND Lipedema is a loose connective tissue disease characterized by disproportionate subcutaneous adipose tissue hypertrophy in the extremities. There is evidence of impaired lymphatic function in women with lipedema at all stages without signs of trophic skin changes associated with hereditary or acquired lymphedema. A modification of suction lipectomy is used to treat lipedema tissue and can reduce pain, limb size, and limb swelling and reduce the need for compression in women with lipedema. Studies have shown that modified liposuction can improve quality of life and mobility...

INTRODUCTION: A risk of amphetamine use is amphetamine-induced psychosis (AIP). Symptoms of AIP include hallucinations, delusions, and agitation. While AIP may resolve with abstinence from amphetamines, antipsychotics are commonly used despite not being FDA approved. The primary objective of this study was to compare length of stay (LOS) for patients with AIP treated with antipsychotics vs untreated. Secondary aims were to determine antipsychotic prescribed, proportion of patients utilizing as needed doses, time to initiation, and readmissions...

PURPOSE: Dynamic changes in circulating tumor DNA (ctDNA) are under investigation as an early indicator of treatment outcome. EXPERIMENTAL DESIGN: Serial plasma ctDNA (baseline, 8 weeks, and at progression) was prospectively incorporated into the SWOG S1403 clinical trial of afatinib ± cetuximab in tyrosine kinase inhibitor-naïve, EGFR mutation tissue-positive non-small cell lung cancer. RESULTS: EGFR mutations were detected in baseline ctDNA in 77% (82/106) of patients, associated with the presence of brain and/or liver metastases and M1B stage...

OBJECTIVE: Lipedema is an inflammatory subcutaneous adipose tissue disease that develops in women and may progress to lipolymphedema, a condition similar to lymphedema, in which lymphatic dysfunction results in irresolvable edema. Because it has been shown that dilated lymphatic vessels, impaired pumping, and dermal backflow are associated with presymptomatic, cancer-acquired lymphedema, this study sought to understand whether these abnormal lymphatic characteristics also characterize early stages of lipedema prior to lipolymphedema development...

PURPOSE: Resistance to immune checkpoint inhibition (ICI) in advanced non-small-cell lung cancer (NSCLC) represents a major unmet need. Combining ICI with vascular endothelial growth factor (VEGF)/VEGF receptor inhibition has yielded promising results in multiple tumor types. METHODS: In this randomized phase II Lung-MAP nonmatch substudy (S1800A), patients ineligible for a biomarker-matched substudy with NSCLC previously treated with ICI and platinum-based chemotherapy and progressive disease at least 84 days after initiation of ICI were randomly assigned to receive ramucirumab plus pembrolizumab (RP) or investigator's choice standard of care (SOC: docetaxel/ramucirumab, docetaxel, gemcitabine, and pemetrexed)...

BACKGROUND: Lipedema exhibits excessive lower-extremity subcutaneous adipose tissue (SAT) deposition, which is frequently misidentified as obesity until lymphedema presents. MR lymphangiography may have relevance to distinguish lipedema from obesity or lymphedema. HYPOTHESIS: Hyperintensity profiles on 3T MR lymphangiography can identify distinct features consistent with SAT edema in participants with lipedema. STUDY TYPE: Prospective cross-sectional study...

Crisis standards of care have been widely developed by healthcare systems and states in the United States during the COVID-19 pandemic, and in some rare cases have actually been used to allocate medical resources. All publicly available U.S. crisis standards of care with a mechanism for allocating scarce resources make use of the Sequential Organ Failure Assessment (SOFA) score in hopes of assigning scarce resources to those patients who are more likely to survive. We reflect on the growing body of evidence suggesting that the SOFA score has limited accuracy in predicting mortality among patients hospitalized with COVID-19 and that the SOFA score systematically disfavors Black patients...

BACKGROUND: The phase III S0819 trial investigated addition of cetuximab to first-line chemotherapy (CT) in NSCLC. Subgroup analyses suggested an OS benefit among patients with EGFR copy number gain in squamous cell carcinomas (SCC), (HR = 0.58 [0.39-0.86], P = .0071). A more detailed model based on EGFR FISH, EGFR IHC and KRAS mutation status was evaluated to yield a more precise predictive paradigm of cetuximab-based therapy in advanced NSCLC. METHODS: FISH was performed using the Colorado Scoring Criteria; H-Score was used to quantify EGFR IHC expression (cut-off ≥ 200)...

In Alzheimer disease, Tau pathology is thought to propagate from cell to cell throughout interconnected brain areas. However, the forms of Tau released into the brain interstitial fluid (ISF) in vivo during the development of Tauopathy and their pathological relevance remain unclear. Combining in vivo microdialysis and biochemical analysis, we find that in Tau transgenic mice, human Tau (hTau) present in brain ISF is truncated and comprises at least 10 distinct fragments spanning the entire Tau protein. The fragmentation pattern is similar across different Tau transgenic models, pathological stages and brain areas...

BACKGROUND: Sequential Organ Failure Assessment (SOFA) score predicts probability of in-hospital mortality. Many crisis standards of care suggest the use of SOFA scores to allocate medical resources during the COVID-19 pandemic. RESEARCH QUESTION: Are SOFA scores elevated among Non-Hispanic Black and Hispanic patients hospitalized with COVID-19, compared to Non-Hispanic White patients? STUDY DESIGN AND METHODS: Retrospective cohort study conducted in Yale New Haven Health System, including 5 hospitals with total of 2681 beds...

BACKGROUND: The COVID-19 pandemic has had a devastating impact in the United States, particularly for Black populations, and has heavily burdened the healthcare system. Hospitals have created protocols to allocate limited resources, but there is concern that these protocols will exacerbate disparities. The sequential organ failure assessment (SOFA) score is a tool often used in triage protocols. In these protocols, patients with higher SOFA scores are denied resources based on the assumption that they have worse clinical outcomes...

INTRODUCTION: S1400F is a non-match substudy of Lung Cancer Master Protocol (Lung-MAP) evaluating the immunotherapy combination of durvalumab and tremelimumab to overcome resistance to anti-programmed death ligand 1 (PD-(L)1) therapy in patients with advanced squamous lung carcinoma (sq non-small-cell lung cancer (NSCLC)). METHODS: Patients with previously treated sqNSCLC with disease progression after anti-PD-(L)1 monotherapy, who did not qualify for any active molecularly targeted Lung-MAP substudies, were eligible...

IMPORTANCE: Nivolumab plus ipilimumab is superior to platinum-based chemotherapy in treatment-naive advanced non-small cell lung cancer (NSCLC). Nivolumab is superior to docetaxel in advanced pretreated NSCLC. OBJECTIVE: To determine whether the addition of ipilimumab to nivolumab improves survival in patients with advanced, pretreated, immunotherapy-naive squamous (Sq) NSCLC. DESIGN, SETTING, AND PARTICIPANTS: The Lung Cancer Master Protocol (Lung-MAP) S1400I phase 3, open-label randomized clinical trial was conducted from December 18, 2015, to April 23, 2018, randomizing patients in a 1:1 ratio to nivolumab alone or combined with ipilimumab...

BACKGROUND Lipedema is a loose connective tissue disease that causes disproportionate subcutaneous fat accumulation on the extremities. As a result of the increased subcutaneous tissue accumulation, lipedema is often confused with obesity by both physicians and patients. Poor awareness and limited diagnosis of lipedema contribute to the confusion of lipedema with obesity and can lead to decreased body image acceptance. Patients with lipedema may have anorexia nervosa, an eating disorder characterized by a distortion of body image, incorrect self-identification of being overweight, restricted eating behavior, and a relentless pursuit of weight loss...

BACKGROUND: Lipedema is a loose connective tissue disease predominantly in women identified by increased nodular and fibrotic adipose tissue on the buttocks, hips and limbs that develops at times of hormone, weight and shape change including puberty, pregnancy, and menopause. Lipedema tissue may be very painful and can severely impair mobility. Non-lipedema obesity, lymphedema, venous disease, and hypermobile joints are comorbidities. Lipedema tissue is difficult to reduce by diet, exercise, or bariatric surgery...