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

Parathyroid hormone in pediatric patients with β-thalassemia major and its relation to bone mineral density; a case control study

Background: Thalassemia syndromes are heterogeneous groups of inherited anemias. Its treatment depends on recurrent blood transfusion with a problem of iron overload, which leads to multiple endocrinopathies including hypoparathyroid. The aim of the study is to estimate the level of serum parathyroid hormone and its relation to bone mineral density in transfusion dependent beta-thalassemia major children. Subjects and methods: We measured serum calcium, phosphorus and parathyroid hormone in a sample of pediatric patients with thalassemia, compared them with age and sex matched healthy control. Measurement of bone mineral density by dual-energy X-ray absorptiometry was done in 2 sites: lumbar spine (L2–L4) in the anteroposterior position and left femur neck using Lunar Densitometry in osteoporosis Unit Ain Shams University Hospital for thalassemia patients. Results: Thalassemic patients had significantly higher alkaline phosphatase and lower bone mineral density. Conclusion: Osteopenia in β-thalassemia major patients is multifactorial and is mainly predisposed by defective function of the parathyroid gland and excessive iron deposition

Pancreatic surgery outcomes: multicentre prospective snapshot study in 67 countries

Background: Pancreatic surgery remains associated with high morbidity rates. Although postoperative mortality appears to have improved with specialization, the outcomes reported in the literature reflect the activity of highly specialized centres. The aim of this study was to evaluate the outcomes following pancreatic surgery worldwide.Methods: This was an international, prospective, multicentre, cross-sectional snapshot study of consecutive patients undergoing pancreatic operations worldwide in a 3-month interval in 2021. The primary outcome was postoperative mortality within 90 days of surgery. Multivariable logistic regression was used to explore relationships with Human Development Index (HDI) and other parameters.Results: A total of 4223 patients from 67 countries were analysed. A complication of any severity was detected in 68.7 percent of patients (2901 of 4223). Major complication rates (Clavien-Dindo grade at least IIIa) were 24, 18, and 27 percent, and mortality rates were 10, 5, and 5 per cent in low-to-middle-, high-, and very high-HDI countries respectively. The 90-day postoperative mortality rate was 5.4 per cent (229 of 4223) overall, but was significantly higher in the low-to-middle-HDI group (adjusted OR 2.88, 95 per cent c.i. 1.80 to 4.48). The overall failure-to-rescue rate was 21 percent; however, it was 41 per cent in low-to-middle-compared with 19 per cent in very high-HDI countries.Conclusion: Excess mortality in low-to-middle-HDI countries could be attributable to failure to rescue of patients from severe complications. The authors call for a collaborative response from international and regional associations of pancreatic surgeons to address management related to death from postoperative complications to tackle the global disparities in the outcomes of pancreatic surgery (NCT04652271; ISRCTN95140761)

Characteristics and outcomes of COVID-19 patients admitted to hospital with and without respiratory symptoms

Background: COVID-19 is primarily known as a respiratory illness; however, many patients present to hospital without respiratory symptoms. The association between non-respiratory presentations of COVID-19 and outcomes remains unclear. We investigated risk factors and clinical outcomes in patients with no respiratory symptoms (NRS) and respiratory symptoms (RS) at hospital admission. Methods: This study describes clinical features, physiological parameters, and outcomes of hospitalised COVID-19 patients, stratified by the presence or absence of respiratory symptoms at hospital admission. RS patients had one or more of: cough, shortness of breath, sore throat, runny nose or wheezing; while NRS patients did not. Results: Of 178,640 patients in the study, 86.4 % presented with RS, while 13.6 % had NRS. NRS patients were older (median age: NRS: 74 vs RS: 65) and less likely to be admitted to the ICU (NRS: 36.7 % vs RS: 37.5 %). NRS patients had a higher crude in-hospital case-fatality ratio (NRS 41.1 % vs. RS 32.0 %), but a lower risk of death after adjusting for confounders (HR 0.88 [0.83-0.93]). Conclusion: Approximately one in seven COVID-19 patients presented at hospital admission without respiratory symptoms. These patients were older, had lower ICU admission rates, and had a lower risk of in-hospital mortality after adjusting for confounders

Inclusive nonresonant multilepton probes of new phenomena at s\sqrt{s} = 13 TeV

An inclusive search for nonresonant signatures of beyond the standard model (SM) phenomena in events with three or more charged leptons, including hadronically decaying $\tau$ leptons, is presented. The analysis is based on a data sample corresponding to an integrated luminosity of 138 fb$^{-1}$ of proton-proton collisions at $\sqrt{s}$ = 13 TeV, collected by the CMS experiment at the LHC in 2016-2018. Events are categorized based on the lepton and b-tagged jet multiplicities and various kinematic variables. Three scenarios of physics beyond the SM are probed, and signal-specific boosted decision trees are used for enhancing sensitivity. No significant deviations from the background expectations are observed. Lower limits are set at 95% confidence level on the mass of type-III seesaw heavy fermions in the range 845-1065 GeV for various decay branching fraction combinations to SM leptons. Doublet and singlet vector-like $\tau$ lepton extensions of the SM are excluded for masses below 1045 GeV and in the mass range 125-150 GeV, respectively. Scalar leptoquarks decaying exclusively to a top quark and a lepton are excluded below 1.12-1.42 TeV, depending on the lepton flavor. For the type-III seesaw as well as the vector-like doublet model, these constraints are the most stringent to date. For the vector-like singlet model, these are the first constraints from the LHC experiments. Detailed results are also presented to facilitate alternative theoretical interpretations

Measurement of the inclusive and differential ttˉγ\mathrm{t\bar{t}}\gamma cross sections in the dilepton channel and effective field theory interpretation in proton-proton collisions at s\sqrt{s} =13 TeV

The production cross section of a top quark pair in association with a photon is measured in proton-proton collisions in the decay channel with two oppositely charged leptons (e$^\pm\mu^\mp$, e$^+$e$^-$, or $\mu^+\mu^-$). The measurement is performed using 138 fb$^{-1}$ of proton-proton collision data recorded by the CMS experiment at $\sqrt{s}$ =13 TeV during the 2016-2018 data-taking period of the CERN LHC. A fiducial phase space is defined such that photons radiated by initial-state particles, top quarks, or any of their decay products are included. An inclusive cross section of 173.5 $\pm$ 2.5 (stat) $\pm$ 6.3 (syst) fb is measured in a signal region with at least one jet coming from the hadronization of a bottom quark and exactly one photon with transverse momentum above 20 GeV. Differential cross sections are measured as functions of several kinematic observables of the photon, leptons, and jets, and compared to standard model predictions. The measurements are also interpreted in the standard model effective field theory framework, and limits are found on the relevant Wilson coefficients from these results alone and in combination with a previous CMS measurement of the $\mathrm{t\bar{t}}\gamma$ production process using the lepton+jets final state

Measurement and QCD analysis of double-differential inclusive jet cross sections in proton-proton collisions at s \sqrt{s} = 13 TeV

International audienceA measurement of the inclusive jet production in proton-proton collisions at the LHC at $\sqrt{s}$ = 13 TeV is presented. The double-differential cross sections are measured as a function of the jet transverse momentum p$_{T}$ and the absolute jet rapidity |y|. The anti-k$_{T}$ clustering algorithm is used with distance parameter of 0.4 (0.7) in a phase space region with jet p$_{T}$ from 97 GeV up to 3.1 TeV and |y| < 2.0. Data collected with the CMS detector are used, corresponding to an integrated luminosity of 36.3 fb$^{−1}$ (33.5 fb$^{−1}$). The measurement is used in a comprehensive QCD analysis at next-to-next-to-leading order, which results in significant improvement in the accuracy of the parton distributions in the proton. Simultaneously, the value of the strong coupling constant at the Z boson mass is extracted as α$_{S}$(m$_{Z}$) = 0.1170±0.0019. For the first time, these data are used in a standard model effective field theory analysis at next-to-leading order, where parton distributions and the QCD parameters are extracted simultaneously with imposed constraints on the Wilson coefficient c$_{1}$ of 4-quark contact interactions.[graphic not available: see fulltext

Measurement and QCD analysis of double-differential inclusive jet cross sections in proton-proton collisions at s\sqrt{s} = 13 TeV

A measurement of the inclusive jet production in proton-proton collisions at the LHC at $\sqrt{s}$ = 13 TeV is presented. The double-differential cross sections are measured as a function of the jet transverse momentum $p_\mathrm{T}$ and the absolute jet rapidity $\lvert y \rvert$. The anti-$k_\mathrm{T}$ clustering algorithm is used with distance parameter of 0.4 (0.7) in a phase space region with jet $p_\mathrm{T}$ from 97 GeV up to 3.1 TeV and $\lvert y \rvert\lt$ 2.0. Data collected with the CMS detector are used, corresponding to an integrated luminosity of 36.3 fb$^{-1}$ (33.5 fb$^{-1}$). The measurement is used in a comprehensive QCD analysis at next-to-next-to-leading order, which results in significant improvement in the accuracy of the parton distributions in the proton. Simultaneously, the value of the strong coupling constant at the Z boson mass is extracted as $\alpha_\mathrm{S}$(Z) = 0.1170 $\pm$ 0.0019. For the first time, these data are used in a standard model effective field theory analysis at next-to-leading order, where parton distributions and the QCD parameters are extracted simultaneously with imposed constraints on the Wilson coefficient $c_1$ of 4-quark contact interactions

Measurement and QCD analysis of double-differential inclusive jet cross sections in proton-proton collisions at s\sqrt{s} = 13 TeV

A measurement of the inclusive jet production in proton-proton collisions at the LHC at $\sqrt{s}$ = 13 TeV is presented. The double-differential cross sections are measured as a function of the jet transverse momentum $p_\mathrm{T}$ and the absolute jet rapidity $\lvert y \rvert$. The anti-$k_\mathrm{T}$ clustering algorithm is used with distance parameter of 0.4 (0.7) in a phase space region with jet $p_\mathrm{T}$ from 97 GeV up to 3.1 TeV and $\lvert y \rvert\lt$ 2.0. Data collected with the CMS detector are used, corresponding to an integrated luminosity of 36.3 fb$^{-1}$ (33.5 fb$^{-1}$). The measurement is used in a comprehensive QCD analysis at next-to-next-to-leading order, which results in significant improvement in the accuracy of the parton distributions in the proton. Simultaneously, the value of the strong coupling constant at the Z boson mass is extracted as $\alpha_\mathrm{S}$(Z) = 0.1170 $\pm$ 0.0019. For the first time, these data are used in a standard model effective field theory analysis at next-to-leading order, where parton distributions and the QCD parameters are extracted simultaneously with imposed constraints on the Wilson coefficient $c_1$ of 4-quark contact interactions

Inclusive nonresonant multilepton probes of new phenomena at s\sqrt{s} = 13 TeV

An inclusive search for nonresonant signatures of beyond the standard model (SM) phenomena in events with three or more charged leptons, including hadronically decaying $\tau$ leptons, is presented. The analysis is based on a data sample corresponding to an integrated luminosity of 138 fb$^{-1}$ of proton-proton collisions at $\sqrt{s}$ = 13 TeV, collected by the CMS experiment at the LHC in 2016-2018. Events are categorized based on the lepton and b-tagged jet multiplicities and various kinematic variables. Three scenarios of physics beyond the SM are probed, and signal-specific boosted decision trees are used for enhancing sensitivity. No significant deviations from the background expectations are observed. Lower limits are set at 95% confidence level on the mass of type-III seesaw heavy fermions in the range 845-1065 GeV for various decay branching fraction combinations to SM leptons. Doublet and singlet vector-like $\tau$ lepton extensions of the SM are excluded for masses below 1045 GeV and in the mass range 125-150 GeV, respectively. Scalar leptoquarks decaying exclusively to a top quark and a lepton are excluded below 1.12-1.42 TeV, depending on the lepton flavor. For the type-III seesaw as well as the vector-like doublet model, these constraints are the most stringent to date. For the vector-like singlet model, these are the first constraints from the LHC experiments. Detailed results are also presented to facilitate alternative theoretical interpretations