P1245 Polymorphic Variants of HSD3B1 Gene Confer Different Outcome in Specific Subgroups of Patients Infected With SARS-CoV-2

Introduction: Severe respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the androgen receptor (AR), through ACE2 receptor and TMPRSS2, to enter nasal and upper airways epithelial cells. Genetic analyses revealed that HSD3B1 P1245C polymorphic variant increases dihydrotestosterone production and upregulation of TMPRSS2 with respect to P1245A variant, thus possibly influencing SARS-CoV-2 infection. Our aim was to characterize the HSD3B1 polymorphism status and its potential association with clinical outcomes in hospitalized patients with COVID-19 in Southern Switzerland. Materials and Methods: The cohort included 400 patients hospitalized for COVID-19 during the first wave between February and May 2020 in two different hospitals of Canton Ticino. Genomic DNA was extracted from formalin-fixed paraffin-embedded tissue blocks, and HSD3B1 gene polymorphism was evaluated by Sanger sequencing. Statistical associations were verified using different test. Results: HSD3B1 polymorphic variants were not associated with a single classical factor related to worse clinical prognosis in hospitalized patients with SARS-CoV-2. However, in specific subgroups, HSD3B1 variants played a clinical role: intensive care unit admission was more probable in patients with P1245C diabetes compared with P1245A individuals without this comorbidity and death was more associated with hypertensive P1245A>C cases than patients with P1245A diabetes without hypertension. Discussion: This is the first study showing that HSD3B1 gene status may influence the severity of SARS-CoV-2 infection. If confirmed, our results could lead to the introduction of HSD3B1 gene status analysis in patients infected with SARS-CoV-2 to predict clinical outcome. Keywords: HSD3B1 gene polymorphism; Likelihood-ratio tests; SARS-CoV-2; androgen receptor; direct sequencing

Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy.

We delineate a KMT2E-related neurodevelopmental disorder on the basis of 38 individuals in 36 families. This study includes 31 distinct heterozygous variants in KMT2E (28 ascertained from Matchmaker Exchange and three previously reported), and four individuals with chromosome 7q22.2-22.23 microdeletions encompassing KMT2E (one previously reported). Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. One-quarter of individuals met criteria for autism. Additional common features include macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. More than 70% of the individuals were male, and expressivity was variable by sex; epilepsy was more common in females and autism more common in males. The four individuals with microdeletions encompassing KMT2E generally presented similarly to those with truncating variants, but the degree of developmental delay was greater. The group of four individuals with missense variants in KMT2E presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E might explain this divergence in phenotype, but requires independent validation. Disruptive variants in KMT2E are an under-recognized cause of neurodevelopmental abnormalities

Relevance of Chest Ultrasound in Mechanically Ventilated Patients

Bedside ultrasonography can be very useful in the evaluation and management of mechanically ventilated patients. In intensive care units the role of ultrasound is not limited to diagnosis but can be used as a guide for management of mechanical ventilation from early stages to weaning. To obtain a comprehensive functional evaluation of critical care patients during mechanical ventilation, chest ultrasonography should include the examinations of the lungs, heart, and diaphragm. Lung ultrasound is an emerging and increasingly used imaging tool to investigate both in a semiquantitative and quantitative way lung aeration during mechanical ventilation, thus helping physicians to determine the best ventilator settings to reexpand collapsed lung regions, avoiding pulmonary stress and strain. Echocardiography is important to assess right and left ventricular function, to guide ventilation strategies such as low-plateau pressures, best positive end-expiratory pressure, pronation, and permissive hypoxia and hypercapnia. Monitoring the effects of mechanical ventilation on cardiac-lung interaction may prompt lung-heart protective ventilation strategy to avoid right ventricular failure, which is correlated with worse outcomes. Moreover, during weaning from mechanical ventilation chest ultrasound may give much information to the clinician, because weaning failure is due to cardiac reasons in a number of patients. Early echocardiography assessment and monitoring of weaning may lead to therapeutic interventions to improve left ventricular diastolic function and choose the best timing. Furthermore, ultrasound evaluation of diaphragm excursion and contractility may predict weaning failure

A randomized clinical trial of ultrasound-guided infra-clavicular cannulation of the subclavian vein in cardiac surgical patients: short-axis versus long-axis approach

PURPOSE: The aim of this study was to compare the success rate and safety of short-axis versus long-axis approaches to ultrasound-guided subclavian vein cannulation. METHODS: A total of 190 patients requiring central venous cannulation following cardiac surgery were randomized to either short-axis or long-axis ultrasound-guided cannulation of the subclavian vein. Each cannulation was performed by anesthesiologists with at least 3 years' experience of ultrasound-guided central vein cannulation (>150 procedures/year, 50% short-axis and 50% long-axis). Success rate, insertion time, number of needle redirections, number of separate skin or vessel punctures, rate of mechanical complications, catheter misplacements, and incidence of central line-associated bloodstream infection were documented for each procedure. RESULTS: The subclavian vein was successfully cannulated in all 190 patients. The mean insertion time was significantly shorter (p = 0.040) in the short-axis group (69 \ub1 74 s) than in the long-axis group (98 \ub1 103 s). The short-axis group was also associated with a higher overall success rate (96 vs. 78%, p < 0.001), first-puncture success rate (86 vs. 67%, p = 0.003), and first-puncture single-pass success rate (72 vs. 48%, p = 0.002), and with fewer needle redirections (0.39 \ub1 0.88 vs. 0.88 \ub1 1.15, p = 0.001), skin punctures (1.12 \ub1 0.38 vs. 1.28 \ub1 0.54, p = 0.019), and complications (3 vs. 13%, p = 0.028). CONCLUSIONS: The short-axis procedure for ultrasound-guided subclavian cannulation offers advantages over the long-axis approach in cardiac surgery patients