Serum metabolomic signatures of fatty acid oxidation defects differentiate host-response subphenotypes of acute respiratory distress syndrome

BACKGROUND: Fatty acid oxidation (FAO) defects have been implicated in experimental models of acute lung injury and associated with poor outcomes in critical illness. In this study, we examined acylcarnitine profiles and 3-methylhistidine as markers of FAO defects and skeletal muscle catabolism, respectively, in patients with acute respiratory failure. We determined whether these metabolites were associated with host-response ARDS subphenotypes, inflammatory biomarkers, and clinical outcomes in acute respiratory failure. METHODS: In a nested case-control cohort study, we performed targeted analysis of serum metabolites of patients intubated for airway protection (airway controls), Class 1 (hypoinflammatory), and Class 2 (hyperinflammatory) ARDS patients (N = 50 per group) during early initiation of mechanical ventilation. Relative amounts were quantified by liquid chromatography high resolution mass spectrometry using isotope-labeled standards and analyzed with plasma biomarkers and clinical data. RESULTS: Of the acylcarnitines analyzed, octanoylcarnitine levels were twofold increased in Class 2 ARDS relative to Class 1 ARDS or airway controls (P = 0.0004 and \u3c 0.0001, respectively) and was positively associated with Class 2 by quantile g-computation analysis (P = 0.004). In addition, acetylcarnitine and 3-methylhistidine were increased in Class 2 relative to Class 1 and positively correlated with inflammatory biomarkers. In all patients within the study with acute respiratory failure, increased 3-methylhistidine was observed in non-survivors at 30 days (P = 0.0018), while octanoylcarnitine was increased in patients requiring vasopressor support but not in non-survivors (P = 0.0001 and P = 0.28, respectively). CONCLUSIONS: This study demonstrates that increased levels of acetylcarnitine, octanoylcarnitine, and 3-methylhistidine distinguish Class 2 from Class 1 ARDS patients and airway controls. Octanoylcarnitine and 3-methylhistidine were associated with poor outcomes in patients with acute respiratory failure across the cohort independent of etiology or host-response subphenotype. These findings suggest a role for serum metabolites as biomarkers in ARDS and poor outcomes in critically ill patients early in the clinical course

Sexual Health as Part of Gynecologic Cancer Care: What Do Patients Want?

Objective Sexual health is important to quality of life; however, the sexual health of gynecologic cancer patients is infrequently and inadequately addressed. We sought to understand patient experiences and preferences for sexual health care to help inform strategies for improvement. Methods/Materials An anonymous, cross-sectional survey of outpatient gynecologic cancer patients at a large academic medical center was performed as part of a larger study examining patient and caregiver needs. The survey explored patient-provider discussions about sexuality across 3 domains (experiences, preferences, barriers) and 4 phases of cancer care (diagnosis, treatment, treatment completion, follow-up). Age, relationship status, sexual activity, and cancer type were recorded. Results Mean age was 63 years. Most patients had ovarian cancer (38%) or endometrial cancer (32%). Thirty-seven percent received treatment within the last month, 55% were in a relationship, and 35% were sexuality active. Thirty-four percent reported sexuality as somewhat or very important, whereas 27% felt that it was somewhat or very important to discuss. Importance of sexuality was associated with age, relationship status, and sexual activity but not cancer type. Fifty-seven percent reported never discussing sexuality. Age was associated with sexuality discussions, whereas relationship status, sexual activity, and cancer type were not. The most common barrier to discussion was patient discomfort. Follow-up was identified as the best time for discussion. Sexuality was most often discussed with a physician or advanced practice provider and usually brought up by the provider. Conclusions Demographic predictors of importance of sexuality to the patient are age, relationship status, and sexual activity. Providers primarily use age as a proxy for importance of sexuality; however, relationship status and sexual activity may represent additional ways to screen for patients interested in discussing sexual health. Patient discomfort with discussing sexuality is the primary barrier to sexual health discussions, and awareness of this is key to developing effective approaches to providing sexual health care

Brief Report: Hydroxychloroquine does not induce hemolytic anemia or organ damage in a "humanized" G6PD A- mouse model.

BackgroundHydroxychloroquine (HCQ) is widely used in the treatment of malaria, rheumatologic disease such as lupus, and most recently, COVID-19. These uses raise concerns about its safe use in the setting of glucose-6-phosphate dehydrogenase (G6PD) deficiency, especially as 11% of African American men carry the G6PD A- variant. However, limited data exist regarding the safety of HCQ in this population.Study design and methodsRecently, we created a novel "humanized" mouse model containing the G6PD deficiency A- variant (Val68Met) using CRISPR technology. We tested the effects of high-dose HCQ administration over 5 days on hemolysis in our novel G6PD A- mice. In addition to standard hematologic parameters including plasma hemoglobin, erythrocyte methemoglobin, and reticulocytes, hepatic and renal function were assessed after HCQ.ResultsResidual erythrocyte G6PD activity in G6PD A- mice was ~6% compared to wild-type (WT) littermates. Importantly, we found no evidence of clinically significant intravascular hemolysis, methemoglobinemia, or organ damage in response to high-dose HCQ.ConclusionsThough the effects of high doses over prolonged periods was not assessed, this study provides early, novel safety data of the use of HCQ in the setting of G6PD deficiency secondary to G6PD A-. In addition to novel safety data for HCQ, to our knowledge, we are the first to present the creation of a "humanized" murine model of G6PD deficiency