Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

The morphology and bridging of the sella turcica in adult orthodontic patients

Abstract Background The purpose of this study was to determine and compare the shapes, sizes, and bridging of the sella turcica in patients with different skeletal patterns and genders. Methods It was a cross-sectional comparative study. The samples were divided into three groups according to the skeletal pattern viz. Class I, Class II and Class III, and each group consisted of 40 samples (20 males and 20 females). The lateral cephalograms were traced and the sella turcica was assessed for its size, shape, and bridging. Results The mean length, anteroposterior diameter and depth of sella turcica were 8.13 ± 2.03 mm, 9.60 ± 1.43 mm and 6.40 ± 1.21 mm respectively. The mean length of sella turcica was 7.91 ± 1.52 mm in Class I, 7.32 ± 1.62 mm in Class II and 9.16 ± .2.42 in Class III skeletal pattern; anteroposterior diameter was 9.30 ± 1.02 mm in Class I, 9.15 ± 1.28 mm in Class II and 10.35 ± 1.64 mm in Class III skeletal pattern; and the depth was 6.40 ± 0.92 mm in Class I, 6.07 ± 1.01 mm in Class II and 6.74 ± .1.54 mm in Class III skeletal pattern. There were significant differences in length and anteroposterior diameter and sella turcica between Class I, Class II and Class III skeletal patterns (p = 0.01), (p = 0.01) respectively. There was no significant difference in size of sella turcica between different genders and age groups. Sixty percent of the patients studied had normal Sella morphology. Partial Sella turcica bridging and Sella turcica bridging was seen in this study in 23.33% and 11.67% of patients respectively. Conclusion Sixty percent of the patients had normal sella turcica. There were significant differences in lengths and anteroposterior diameters among Class I, Class II and Class III patients. The larger size was present in skeletal Class III patients

Histone supply: Multitiered regulation ensures chromatin dynamics throughout the cell cycle

International audienceAs the building blocks of chromatin, histones are central to establish and maintain particular chromatin states associated with given cell fates. Importantly, histones exist as distinct variants whose expression and incorporation into chromatin are tightly regulated during the cell cycle. During S phase, specialized replicative histone variants ensure the bulk of the chromatinization of the duplicating genome. Other non-replicative histone variants deposited throughout the cell cycle at specific loci use pathways uncoupled from DNA synthesis. Here, we review the particular dynamics of expression, cellular transit, assembly, and disassembly of replicative and non-replicative forms of the histone H3. Beyond the role of histone variants in chromatin dynamics, we review our current knowledge concerning their distinct regulation to control their expression at different levels including transcription, posttranscriptional processing, and protein stability. In light of this unique regulation, we highlight situations where perturbations in histone balance may lead to cellular dysfunction and pathologies

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19

International audienc

Notes for genera – Ascomycota

Knowledge of the relationships and thus the classification of fungi, has developed rapidly with increasingly widespread use of molecular techniques, over the past 10--15 years, and continues to accelerate. Several genera have been found to be polyphyletic, and their generic concepts have subsequently been emended. New names have thus been introduced for species which are phylogenetically distinct from the type species of particular genera. The ending of the separate naming of morphs of the same species in 2011, has also caused changes in fungal generic names. In order to facilitate access to all important changes, it was desirable to compile these in a single document. The present article provides a list of generic names of Ascomycota (approximately 6500 accepted names published to the end of 2016), including those which are lichen-forming. Notes and summaries of the changes since the last edition of `Ainsworth Bisby's Dictionary of the Fungi' in 2008 are provided. The notes include the number of accepted species, classification, type species (with location of the type material), culture availability, life-styles, distribution, and selected publications that have appeared since 2008. This work is intended to provide the foundation for updating the ascomycete component of the ``Without prejudice list of generic names of Fungi'' published in 2013, which will be developed into a list of protected generic names. This will be subjected to the XIXth International Botanical Congress in Shenzhen in July 2017 agreeing to a modification in the rules relating to protected lists, and scrutiny by procedures determined by the Nomenclature Committee for Fungi (NCF). The previously invalidly published generic names Barriopsis, Collophora (as Collophorina), Cryomyces, Dematiopleospora, Heterospora (as Heterosporicola), Lithophila, Palmomyces (as Palmaria) and Saxomyces are validated, as are two previously invalid family names, Bartaliniaceae and Wiesneriomycetaceae. Four species of Lalaria, which were invalidly published are transferred to Taphrina and validated as new combinations. Catenomycopsis Tibell Constant. is reduced under Chaenothecopsis Vain., while Dichomera Cooke is reduced under Botryosphaeria Ces. De Not. (Art. 59)