Mortality in Patients with Obesity and Acute Respiratory Distress Syndrome Receiving Extracorporeal Membrane Oxygenation: The Multicenter ECMObesity Study.

Rationale: Patients with obesity are at increased risk for developing acute respiratory distress syndrome (ARDS). Some centers consider obesity a relative contraindication to receiving extracorporeal membrane oxygenation (ECMO) support, despite growing implementation of ECMO for ARDS in the general population. Objectives: To investigate the association between obesity and mortality in patients with ARDS receiving ECMO. Methods: In this large, international, multicenter, retrospective cohort study, we evaluated the association of obesity, defined as body mass index ⩾ 30 kg/m2, with ICU mortality in patients receiving ECMO for ARDS by performing adjusted multivariable logistic regression and propensity score matching. Measurements and Main Results: Of 790 patients with ARDS receiving ECMO in our study, 320 had obesity. Of those, 24.1% died in the ICU, compared with 35.3% of patients without obesity (P < 0.001). In adjusted models, obesity was associated with lower ICU mortality (odds ratio, 0.63 [95% confidence interval, 0.43-0.93]; P = 0.018). Examined as a continuous variable, higher body mass index was associated with decreased ICU mortality in multivariable regression (odds ratio, 0.97 [95% confidence interval, 0.95-1.00]; P = 0.023). In propensity score matching of 199 patients with obesity to 199 patients without, patients with obesity had a lower probability of ICU death than those without (22.6% vs. 35.2%; P = 0.007). Conclusions: Among patients receiving ECMO for ARDS, those with obesity had lower ICU mortality than patients without obesity in multivariable and propensity score matching analyses. Our findings support the notion that obesity should not be considered a general contraindication to ECMO.

A 24-Year-Old Woman Presenting With Altered Mental Status and Multiorgan Failure.

CASE PRESENTATION: A 24-year-old previously healthy woman was brought to the hospital for acute altered mental status. One week prior to presentation, she had developed a sore throat, nausea, and vomiting. At that time, SARS-CoV-2 polymerase chain reaction and rapid streptococcal pharyngitis test results were both negative. On the day prior to presentation, the patient had developed an erythematous painful rash on her left arm. The following day she was noted to be agitated, combative, and having trouble communicating, prompting ED evaluation. In the ED, the patient was tachycardic to 108 beats/min and tachypneic to 30 breaths/min but normotensive and afebrile. Her initial workup was notable for leukocytosis with bandemia, acute liver injury with coagulopathy, and acute renal failure. She was intubated, transferred to our hospital, and admitted to the MICU. The patient's medical history was notable for obesity and oral contraceptive use. She had no family history of autoimmune, rheumatologic, or hematologic disorders. She was a student and worked part time in retail. She had no recent travel or outdoor exposure. The patient's family was unaware of any tobacco or drug use but did report that she drank socially.

Obesity-associated Breast Inflammation among Hispanic/Latina Breast Cancer Patients.

Breast white adipose tissue inflammation (BWATi) is associated with obesity and higher breast cancer risk among non-Hispanic white women. Obesity is prevalent in Hispanic/Latina patients with breast cancer, and the occurrence of BWATi in this population is not well-characterized. The association between BWATi and body mass index (BMI) was evaluated in Hispanic/Latina patients with breast cancer who underwent mastectomy. BWATi was defined as the presence of crown-like structures of the breast (CLS-B), detected by CD68 IHC in nontumor breast tissue. BWATi severity was quantified as number of CLS-B/cm2 Adipocyte diameter was measured using hematoxylin and eosin-stained breast tissue sections. Preoperative BMI (within 1 week prior to mastectomy) was categorized as normal (18.5-<25.0 kg/m2), overweight (25.0-<30.0 kg/m2), class I obesity (30.0-<35.0 kg/m2), and class II-III obesity (35.0 kg/m2 or above). Patient charts were abstracted to record clinicopathologic features and liver function tests <90 days before mastectomy. The study included 91 women (mean age 69 years; range 36-96 years). Prevalence of BWATi increased with BMI (24% in normal weight, 34% in overweight, 57% in class I obesity, and 65% in class II-III obesity; P trend <0.01). Severe BWATi (>0.27 CLS-B/cm2) was associated with higher BMI (P trend = 0.046) and greater adipocyte diameter (P = 0.04). Adjusting for BMI, neoadjuvant chemotherapy, and elevated alanine aminotransferase were associated with severe BWATi, and current smoking was associated with mild BWATi (all P < 0.05). BWATi was associated with higher BMI in Hispanic/Latina patients with breast cancer, consistent with previously described associations in other populations.

Adiposity, Inflammation, and Breast Cancer Pathogenesis in Asian Women.

Obesity is associated with white adipose tissue (WAT) inflammation in the breast, elevated levels of the estrogen biosynthetic enzyme, aromatase, and systemic changes that predispose to breast cancer development. We examined whether WAT inflammation and its associated systemic effects correlate with body fat levels in an Asian population where body mass index (BMI) is not an accurate assessment of obesity and cancer risk. We also investigated whether biologic differences could account for the greater proportion of premenopausal estrogen receptor (ER)-positive breast cancer in Asian versus Western countries. Breast WAT and fasting blood were prospectively collected from Taiwanese women undergoing mastectomy for breast cancer treatment. Body composition was measured in a subgroup using bioelectrical impedance analysis. WAT inflammation was defined by the presence of crown-like structures of the breast, which are composed of dead or dying adipocytes surrounded by macrophages. Findings were compared with U.S. Caucasian women. In the Taiwanese cohort (n = 72), breast WAT inflammation was present in 31 (43%) women and was associated with elevated BMI (P < 0.01) and increased levels of body fat (P < 0.01), C-reactive protein (P = 0.02), triglycerides (P < 0.01), insulin resistance scores (P = 0.04), and lower HDL cholesterol (P < 0.01). ER+ tumors were associated with greater body fat versus other subtypes (P = 0.03). Compared with U.S. Caucasians (n = 267), Taiwanese women had larger breast adipocytes despite lower BMI after adjusting for BMI and menopausal status (P = 0.01). A subclinical inflammatory state associated with increased adiposity and metabolic dysfunction could contribute to breast cancer pathogenesis in Asian women. Cancer Prev Res; 11(4); 227-36. ©2017 AACR.

Menopause Is a Determinant of Breast Aromatase Expression and Its Associations With BMI, Inflammation, and Systemic Markers.

Context: Most estrogen-dependent breast cancers occur after menopause, despite low levels of circulating estrogens. Breast expression of the estrogen-biosynthetic enzyme, aromatase, is proposed to drive breast cancer development after menopause. However, the effects of menopause on breast aromatase expression are unknown. Objective: To determine the effect of menopause on breast aromatase expression in relation to body mass index (BMI), white adipose tissue inflammation (WATi), and systemic markers of metabolic dysfunction. Design, Setting, and Participants: Cross-sectional study of 102 premenopausal (age 27 to 56) and 59 postmenopausal (age 45 to 74) women who underwent mastectomy for breast cancer treatment/prevention. Outcome: Breast tissue was assessed for the presence of crown-like structures and the expression and activity of aromatase. Systemic markers examined include interleukin (IL)-6, insulin, glucose, leptin, adiponectin, high-sensitivity C-reactive protein (hsCRP), cholesterol, and triglycerides. Multivariable analysis was performed for aromatase messenger RNA (mRNA) in relation to BMI, WATi, and blood markers. Results: Postmenopausal women had higher BMI and more breast WATi than premenopausal women. Fasting levels of IL-6, glucose, leptin, hsCRP, and homeostatic model assessment 2 insulin resistance score were higher in the postmenopausal group. BMI was positively correlated with aromatase mRNA in both pre- and postmenopausal women. Aromatase levels were higher in breast tissue of postmenopausal women, with levels being higher in inflamed vs noninflamed, independent of BMI. Adipocyte diameter and levels of leptin, hsCRP, adiponectin, and high-density lipoprotein cholesterol were more strongly correlated with aromatase in postmenopausal than premenopausal women. Conclusions: Elevated aromatase in the setting of adipose dysfunction provides a possible mechanism for the higher incidence of hormone-dependent breast cancer in obese women after menopause.