Estradiol and Dihydrotestosterone Levels in COVID-19 Patients.

OBJECTIVE: To determine differences in plasma sex hormone levels in male and female coronavirus disease 2019 (COVID-19) patients and healthy volunteers (HVs) because cell entry of severe acute respiratory syndrome coronavirus 2 occurs via the angiotensin-converting enzyme 2 receptor which is downregulated by 17ß-estradiol. PATIENTS AND METHODS: Citrated plasma samples were collected from 101 patients with COVID-19 upon presentation to the emergency department and from 40 HVs between November 1, 2020, and May 30, 2021. Plasma 17ß-estradiol and 5α-dihydrotestosterone (DHT) levels were measured using enzyme-linked immunosorbent assay (pg/mL). Data are presented as median and quartiles (IQR). Wilcoxon rank sum test with a P value less than .05 was considered significant. RESULTS: Patients with COVID-19 (median age, 49 years) included 51 males and 50 females (25 postmenopausal). Hospital admission was required for 58.8% of male patients (n = 30) and 48.0% of female patients (n = 24) (66.7% postmenopausal, n = 16) Healthy volunteers (median age, 41 years) included 20 males and 20 females (9 postmenopausal). Female patients with COVID-19 were found to have decreased 17ß-estradiol levels (18.5 [IQR, 10.5-32.3] pg/mL; 41.4 [IQR, 15.5-111.0] pg/mL, P=.025), and lower 17ß-estradiol to DHT ratios (0.073 [IQR, 0.052-0.159] pg/mL; 0.207 [IQR, 0.104-0.538] pg/mL, P=.015) than female HVs. Male patients with COVID-19 were found to have decreased DHT levels (302.8 [IQR, 249.9-470.8] pg/mL; 457.2 [IQR, 368.7-844.3] pg/mL, P=.005), compared with male HVs. Levels of DHT did not differ between female patients with COVID-19 and female HVs, whereas 17ß-estradiol levels did not differ between male patients with COVID-19 and male HVs. CONCLUSION: Sex hormone levels differ between patients with COVID-19 and HVs, with sex-specific patterns of hypogonadism in males and females. These alterations may be associated with disease development and severity.

Effects of Sugammadex on Time of First Postoperative Bowel Movement: A Retrospective Analysis.

OBJECTIVE: To determine whether time to first postoperative bowel movement after intraperitoneal surgery differs among neuromuscular blockade reversal with either anticholinesterase/anticholinergic combination vs sugammadex. PATIENTS AND METHODS: Sugammadex was introduced to our practice in October 2016. Patients were identified who underwent intraperitoneal surgery between January 1, through June 30, 2016, and January 1 through June 30, 2017, and received aminosteroid neuromuscular blockade for paralysis. Reversal was initiated with neostigmine, coadministered with glycopyrrolate (neostigmine/glycopyrrolate) for control participants and sugammadex for patients. Time to first bowel movement was determined from nursing documentation for study cohorts (2016 and 2017). We compared times to first bowel movement between cases and controls using raw and inverse probability of treatment weighting (IPTW) analyses. RESULTS: In the 2016 cohort, 2583 received neostigmine/glycopyrrolate. Of 2750 patients in 2017, sugammadex reversal technique was administered to 1500 patients and neostigmine/glycopyrrolate to 1250 participants. Without weighting, the groups were relatively balanced for most baseline characteristics, and after IPTW, all standardized differences were <0.035. In comparison with the 2016 and 2017 controls, sugammadex treatment was associated with faster occurrence of first bowel movement. For 2016, unweighted hazard ratio (HR) (95% confidence interval [CI]) was 1.35 (1.21-1.51) (P<.001). After IPTW, HR (95% CI) was 1.27 (1.12-1.43) (P<.001). For 2017, unweighted HR (95% CI) was 1.51 (1.31-1.72) (P<.001); after IPTW, it was 1.25 (1.08-1.45) (P =.003). CONCLUSION: Patients undergoing intraperitoneal surgery who had aminosteroid neuromuscular blockade reversal with sugammadex had earlier first postoperative bowel movement than patients with reversal through neostigmine/glycopyrrolate.

A "Fundamentals" Train-the-Trainer Approach to Building Pediatric Critical Care Expertise in the Developing World.

Pediatric Fundamental Critical Care Support (PFCCS) is an educational tool for training non-intensivists, nurses, and critical care practitioners in diverse health-care settings to deal with the acute deterioration of pediatric patients. Our objective was to evaluate the PFCCS course as a tool for developing a uniform, reproducible, and sustainable model for educating local health-care workers in the optimal management of critically ill children in the Republic of Georgia. Over a period of 18 months and four visits to the country, we worked with Georgian pediatric critical care leadership to complete the following tasks: (1) survey health-care needs within the Republic of Georgia, (2) present representative PFCCS lectures and simulation scenarios to evaluate interest and obtain "buy-in" from key stakeholders throughout the Georgian educational infrastructure, and (3) identify PFCCS instructor candidates. Georgian PFCCS instructor training included the following steps: (1) US PFCCS consultant and content experts presented PFCCS course to Georgian instructor candidates. (2) Simulation learning principles were taught and basic equipment was acquired. (3) Instructor candidates presented PFCCS to Georgian learners, mentored by PFCCS course consultants. Objective evaluation and debriefing with instructor candidates concluded each visit. Between training visits Georgian instructors translated PFCCS slides to the Georgian language. Six candidates were identified and completed PFCCS instructor training. These Georgian instructors independently presented the PFCCS course to 15 Georgian medical students. Student test scores improved significantly from pretest results (n = 14) (pretest: 38.7 ± 7 vs. posttest 62.7 ± 6, p < 0.05). A Likert-type scale of 1 to 5 (1 = not useful or effective, 5 = extremely useful or effective) was used to evaluate each student's perception regarding (1) relevance of course content to clinical work students rated as median (IQR): (a) relevance of PFCCS content to clinical work, 5 (4-5); (b) effectiveness of lecture delivery, 4 (3-4); and (c) value of skill stations for clinical practice, 5 (4-5). Additionally, the mean (±SD) responses were 4.6 (±0.5), 3.7 (±0.6), and 4.5 (±0.6), respectively. Training local PFCCS instructors within an international environment is an effective method for establishing a uniform, reproducible, and sustainable approach to educating health-care providers in the fundamentals of pediatric critical care. Future collaborations will evaluate the clinical impact of PFCCS throughout the Georgian health-care system.

Factors that contribute to physician variability in decisions to limit life support in the ICU: a qualitative study.

PURPOSE: Our aim was to explore reasons for physician variability in decisions to limit life support in the intensive care unit (ICU) utilizing qualitative methodology. METHODS: Single center study consisting of semi-structured interviews with experienced physicians and nurses. Seventeen intensivists from medical (n = 7), surgical (n = 5), and anesthesia (n = 5) critical care backgrounds, and ten nurses from medical (n = 5) and surgical (n = 5) ICU backgrounds were interviewed. Principles of grounded theory were used to analyze the interview transcripts. RESULTS: Eleven factors within four categories were identified that influenced physician variability in decisions to limit life support: (1) physician work environment-workload and competing priorities, shift changes and handoffs, and incorporation of nursing input; (2) physician experiences-of unexpected patient survival, and of limiting life support in physician's family; (3) physician attitudes-investment in a good surgical outcome, specialty perspective, values and beliefs; and (4) physician relationship with patient and family-hearing the patient's wishes firsthand, engagement in family communication, and family negotiation. CONCLUSIONS: We identified several factors which physicians and nurses perceived were important sources of physician variability in decisions to limit life support. Ways to raise awareness and ameliorate the potentially adverse effects of factors such as workload, competing priorities, shift changes, and handoffs should be explored. Exposing intensivists to long term patient outcomes, formalizing nursing input, providing additional training, and emphasizing firsthand knowledge of patient wishes may improve decision making.

Quantification of hypercoagulable state after blunt trauma: microparticle and thrombin generation are increased relative to injury severity, while standard markers are not.

BACKGROUND: Major trauma is an independent risk factor for developing venous thromboembolism. While increases in thrombin generation and/or procoagulant microparticles have been detected in other patient groups at greater risk for venous thromboembolism, such as cancer or coronary artery disease, this association has yet to be documented in trauma patients. This pilot study was designed to characterize and quantify thrombin generation and plasma microparticles in individuals early after traumatic injury. METHODS: Blood was collected in the trauma bay from 52 blunt injured patients (cases) and 19 uninjured outpatients (controls) and processed to platelet poor plasma to allow for (1) isolation of microparticles for identification and quantification by flow cytometry, and (2) in vitro thrombin generation as measured by calibrated automatic thrombography. Data collected are expressed as either mean ± standard deviation or median with interquartile range. RESULTS: Among the cases, which included 39 men and 13 women (age, 40 ± 17 years), the injury severity score was 13 ± 11, the international normalized ratio was 1.0 ± 0.1, the thromboplastin time was 25 ± 3 seconds, and platelet count was 238 ± 62 (thousands). The numbers of total (cell type not specified) procoagulant microparticles, as measured by Annexin V staining, were increased compared to nontrauma controls (541 ± 139/µL and 155 ± 148/µL, respectively; P < .001). There was no significant difference in the amount of thrombin generated in trauma patients compared to controls; however, peak thrombin was correlated to injury severity (Spearman correlation coefficient R, 0.35; P = .02). CONCLUSION: Patients with blunt trauma have greater numbers of circulating procoagulant microparticles and increased in vitro thrombin generation. Future studies to characterize the cell-specific profiles of microparticles and changes in thrombin generation kinetics after traumatic injury will determine whether microparticles contribute to the hypercoagulable state observed after injury.