Long-term outcome of COVID-19 patients treated with helmet noninvasive ventilation vs. high-flow nasal oxygen: a randomized trial

Background: Long-term outcomes of patients treated with helmet noninvasive ventilation (NIV) are unknown: safety concerns regarding the risk of patient self-inflicted lung injury and delayed intubation exist when NIV is applied in hypoxemic patients. We assessed the 6-month outcome of patients who received helmet NIV or high-flow nasal oxygen for COVID-19 hypoxemic respiratory failure. Methods: In this prespecified analysis of a randomized trial of helmet NIV versus high-flow nasal oxygen (HENIVOT), clinical status, physical performance (6-min-walking-test and 30-s chair stand test), respiratory function and quality of life (EuroQoL five dimensions five levels questionnaire, EuroQoL VAS, SF36 and Post-Traumatic Stress Disorder Checklist for the DSM) were evaluated 6 months after the enrollment. Results: Among 80 patients who were alive, 71 (89%) completed the follow-up: 35 had received helmet NIV, 36 high-flow oxygen. There was no inter-group difference in any item concerning vital signs (N = 4), physical performance (N = 18), respiratory function (N = 27), quality of life (N = 21) and laboratory tests (N = 15). Arthralgia was significantly lower in the helmet group (16% vs. 55%, p = 0.002). Fifty-two percent of patients in helmet group vs. 63% of patients in high-flow group had diffusing capacity of the lungs for carbon monoxide < 80% of predicted (p = 0.44); 13% vs. 22% had forced vital capacity < 80% of predicted (p = 0.51). Both groups reported similar degree of pain (p = 0.81) and anxiety (p = 0.81) at the EQ-5D-5L test; the EQ-VAS score was similar in the two groups (p = 0.27). Compared to patients who successfully avoided invasive mechanical ventilation (54/71, 76%), intubated patients (17/71, 24%) had significantly worse pulmonary function (median diffusing capacity of the lungs for carbon monoxide 66% [Interquartile range: 47–77] of predicted vs. 80% [71–88], p = 0.005) and decreased quality of life (EQ-VAS: 70 [53–70] vs. 80 [70–83], p = 0.01). Conclusions: In patients with COVID-19 hypoxemic respiratory failure, treatment with helmet NIV or high-flow oxygen yielded similar quality of life and functional outcome at 6 months. The need for invasive mechanical ventilation was associated with worse outcomes. These data indicate that helmet NIV, as applied in the HENIVOT trial, can be safely used in hypoxemic patients. Trial registration Registered on clinicaltrials.gov NCT04502576 on August 6, 202

Oestrogenic repression of human coagulation factor VII expression mediated through an oestrogen response element sequence motif in the promoter region

Reporter gene analysis of two regions of the human factor VII (FVII) gene promoter (residues –658 to –1 and –348 to –1, where +1 is the start site of translation) in the mammalian liver-derived cell line HepG2 showed reduced transcriptional activity in the presence of oestrogenic factors. This effect was independent of promoter polymorphic haplotype. Similar analysis using a smaller region of the promoter spanning residues –187 to –1 failed to show any evidence of oestrogenic suppression. Electrophoretic mobility shift assays and supershift assays using recombinant oestrogen receptor α and anti-oestrogen receptor antibody localized the sequence motif to which oestrogen receptor was binding to residues –225 to –212 of the FVII promoter. The lack of oestrogenic suppression in a reporter gene construct spanning residues –658 to –1 modified to abolish oestrogen receptor binding at this site, confirmed the functional significance of this motif. Although superficially similar to the classical oestrogen response element (ORE), comprising two half sites separated by three spacer nucleotides, the FVII ORE represents an alternative type of ORE in which the two half sites are separated by just two spacer nucleotides. EMSAs indicated that increasing spacer nucleotide number from two to three in the FVII ORE, or decreasing it from three to two in a consensus ORE sequence motif, had a small effect on the binding affinity for oestrogen receptor. These data correlate with and provide a plausible mechanism for the inverse relationship between FVII and oestradiol levels observed during the menstrual cycle

4G/5G Promoter PAI-1 Gene Polymorphism Is Associated with Plasmatic PAI-1 Activity in Italians: A Model of Gene-Environment Interaction

SummaryThe PAI-1 gene promoter 4G/5G polymorphism was found to be associated with plasma PAI-1 activity in Northern and Central Europe populations, but no data are available on the association between this polymorphism and PAI-1 levels in Southern Europe countries (such as Italy) where the incidence of ischemic disorders is lower. This study shows that among populations with different incidence of atherothrombotic disorders the 4G/5G PAI-1 gene promoter polymorphism has the same importance in the regulation of plasma PAI-1 activity.Moreover, we have analysed some gene-environmental interactions: the correlation between PAI-1 and cholesterol in non dyslipidemic subjects and the correlation between PAI-1 activity and tryglicerides in dyslipidemic subjects differed according to the 4G/5G genotype class. Thus, our findings suggest that, among subjects with or without metabolic disorders such as dyslipidemia, completely different gene-environment interactions may occur.</jats:p

4G/5G promoter PAI-1 gene polymorphism is associated with plasmatic PAI-1 activity in Italians: a model of gene-environment interaction

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