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.

Antibiotic prophylaxis for tube thoracostomy placement in trauma: a practice management guideline from the Eastern Association for the Surgery of Trauma.

Background: Antibiotic prophylaxis is routinely administered for most operative procedures, but their utility for certain bedside procedures remains controversial. We performed a systematic review and meta-analysis and developed evidence-based recommendations on whether trauma patients receiving tube thoracostomy (TT) for traumatic hemothorax or pneumothorax should receive antibiotic prophylaxis. Methods: Published literature was searched through MEDLINE (via PubMed), Embase (via Elsevier), Cochrane Central Register of Controlled Trials (via Wiley), Web of Science and ClinicalTrials.gov databases by a professional librarian. The date ranges for our literature search were January 1900 to March 2020. A systematic review and meta-analysis of currently available evidence were performed using the Grading of Recommendations Assessment, Development and Evaluation methodology. Results: Fourteen relevant studies were identified and analyzed. All but one were prospective, with eight being prospective randomized control studies. Antibiotic prophylaxis protocols ranged from a single dose at insertion to 48 hours post-TT removal. The pooled data showed that patients who received antibiotic prophylaxis were significantly less likely to develop empyema (OR 0.47, 95% CI 0.25 to 0.86, p=0.01). The benefit was greater in patients with penetrating injuries (penetrating OR 0.25, 95% CI 0.10 to 0.59, p=0.002, vs blunt OR 0.25, 95% CI 0.06 to 1.12, p=0.07). Administration of antibiotic prophylaxis did not significantly affect pneumonia incidence or mortality. Discussion: In adult trauma patients who require TT insertion, we conditionally recommend antibiotic prophylaxis be given at the time of insertion to reduce incidence of empyema. PROSPERO registration number: CRD42018088759.

Exploring the utility of a novel point-of-care whole blood thrombin generation assay following trauma: A pilot study.

INTRODUCTION: Plasma thrombin generation kinetics as measured by the calibrated automated thrombogram (CAT) assay is a predictor of symptomatic venous thromboembolism after trauma. We hypothesized that data from a new prototype assay for measurement of thrombin generation kinetics in fresh whole blood (near patient testing of thrombin generation), will correlate with the standard CAT assay in the same patients, making it a potential tool in the future care of trauma patients. METHODS: Patients were enrolled from June 2018 to February 2020. Within 12 hours of injury, blood samples were collected simultaneously for both assays. Variables compared and correlated between assays were lag time, peak height, time to peak, and endogenous thrombin potential. Data are presented as median with interquartile range (IQR). Spearman and Pearson correlations were estimated and tested between both assays; a P value of <0.05 was considered to be significant. RESULTS: A total of 64 trauma patients had samples analyzed: injury severity score = 17 (IQR), 10-26], hospital length of stay = 7.5 (IQR), 2-18) days, age = 52 (IQR, 35-63) years, 71.9% male, and 42.2% of patients received a transfusion within 24 hours of injury. Thrombin generation parameters between plasma and whole blood were compared and found that all parameters of the two assays correlate in trauma patients. CONCLUSION: In this pilot study, we have found that a novel point-of-care whole blood thrombin generation assay yields results with modest but statistically significant correlations to those of a standard plasma thrombin generation assay. This finding supports studying this device in a larger, adequately powered study.

Biomarkers of thromboinflammation correlate to COVID-19 infection and admission status in emergency department patients.

Background: COVID-19-associated coagulopathy is incompletely understood. Objectives: To characterize thrombin generation, Von Willebrand Factor (VWF), neutrophil extracellular traps (NETs), and their role in COVID-19 risk stratification in the emergency department (ED). Patients/methods: Plasma samples from 67 ED COVID-19 patients were compared to 38 healthy volunteers (HVs). Thrombin generation (calibrated automated thrombogram, CAT) was expressed as lag time (LT, min), peak height (PH, min), and time to peak (ttPeak, min). Citrullinated nucleosomes and histones were quantified with ELISA, VWF antigen and activity (IU/dL) through latex immunoassay, Factor VIII (IU/dL) through one-stage optical clot detection, and VWF multimers with Western blot densitometry. Wilcoxon testing and multivariable logistic regression were performed. Results presented as median [Q1, Q3]; p < 0.05 significant. Results: COVID-19 patients had longer LT (4.00 [3.26, 4.67]; 2.95 [2.67, 3.10], p < 0.001) and ttPeak (7.33 [6.33, 8.04]; 6.45 [6.00, 7.50], p = 0.004), greater VWF antigen (212 [158, 275]; 110 [91, 128], p < 0.001) and Factor VIII levels (148 [106, 190]; 106 [86, 129], p < 0.001), with decreased high molecular weight multimers (Normalized multimer ratio 0.807 [0.759, 0.869]; 0.891 [0.858, 0.966], p < 0.001), than HVs. COVID-19 patients requiring admission from the ED had longer LT and ttPeak with greater VWF antigen and Factor VIII levels than those not admitted. Two and three variable models of CAT parameters and VWF correlated with COVID-19 and admission status (C-statistics 0.677 to 0.922). Conclusions: Thrombin generation kinetics and VWF levels, independent of NETs, may have a role in predicting admission need for COVID-19 patients.

Randomized trial on the physiologic impact of NOTES.

BACKGROUND: Our previous work revealed significantly less acidosis in swine undergoing natural orifice translumenal endoscopic surgery (NOTES) using endoscopic air insufflation than swine undergoing standard laparoscopy. We wanted to evaluate the differential effects of CO2 versus intra-abdominal pressure as source for this finding. In addition, we investigated the endocrine stress response between swine undergoing NOTES peritoneoscopy with CO2 insufflation and animals undergoing standard diagnostic laparoscopy with CO2. MATERIALS AND METHODS: Twenty-eight (28) female 50-kg domestic pigs were randomly assigned to one of four groups using a permuted block randomization table: Group 1: NOTES using CO2 insufflation, Group 2: NOTES using air insufflation, Group 3: laparoscopy max pressure 12 mmHg and Group 4: laparoscopy with max pressure 7 mmHg. Invasive monitoring lines were placed. Pneumoperitoneum was established by the respective method and maintained for 90 min, visualizing liver, spleen and colon. Arterial blood gas was obtained at baseline and four additional time points. Serum TNF-α for POD (postoperative day) 1 and cumulative urine adrenaline for the procedure were determined by ELISA. ANOVA and t test were used for statistical comparison. The study was Institutional Animal Care and Use Committees approved. RESULTS: All experiments were completed as outlined. Blood pH showed a significant difference between groups. Serum TNF-α revealed higher levels for NOTES CO2 on POD 1 than standard laparoscopy (p = 0.03). CONCLUSION: NOTES animals with CO2 insufflation initially experienced similar pH compared to standard laparoscopy but recovered to levels seen in low-pressure laparoscopy and NOTES with air. NOTES with CO2 appears to elicit a stronger stress response in this study than standard or low-pressure laparoscopy or NOTES with air.

Feasibility of NOTES omental plug repair of perforated peptic ulcers: results from a clinical pilot trial.

BACKGROUND: Ulcer perforation carries up to a 30 % 1-year mortality rate. Intervention-related adverse events are among statistically significant predictors of 1-year mortality. A natural orifice transluminal endoscopic surgical (NOTES) approach may be less invasive and may decrease procedure-related adverse events by diminishing the so-called second hit, thus leading to decreased morbidity and mortality. We sought to assess the feasibility of an endoscopic transluminal omental plug technique in patients with perforated gastroduodenal ulcers under laparoscopic guidance. METHODS: Patients with suspected acute gastroduodenal ulcer perforations were offered participation in this prospective pilot study. Closure of the perforation was attempted using the NOTES omental plug technique. Demographic, clinical, endoscopic, and radiographic data were abstracted, as were data for morbidity, mortality, and pilot data regarding quality of life (QOL). RESULTS: From February 2010 through February 2012, a total of 17 patients presented to a tertiary care center with clinically suspected perforated ulcer. Of seven patients (mean age 79 years, range 64-89 years) who consented to the study, three underwent the study procedure. All patients had multiple comorbidities. Two patients presented with 4-6 mm perforated peptic ulcers and underwent successful laparoscopic-assisted NOTES omental and falciform ligament patch closure, respectively. Postoperative radiographic contrast studies showed no leak, and patients were discharged home on postoperative days 3 and 4. The third patient had undergone enterocutaneous fistula repair with herniorrhaphy 6 weeks before. Although a transluminal endoscopic approach was feasible, the omentum was under too much tension to be secured. This procedure was converted to an open omental patch repair. For all but one patient who provided consent, obtaining QOL data was feasible. CONCLUSIONS: Initial results from a laparoscopic-assisted NOTES approach for closure of perforated peptic ulcers appear promising and enable swift recovery in selected patients. This is especially important in elderly and/or immunocompromised patients. Technical details and patient selection criteria continue to evolve.