Pathophysiology of COVID-19-associated acute respiratory distress syndrome: a multicentre prospective observational study

Background Patients with COVID-19 can develop acute respiratory distress syndrome (ARDS), which is associated with high mortality. The aim of this study was to examine the functional and morphological features of COVID-19-associated ARDS and to compare these with the characteristics of ARDS unrelated to COVID-19.Methods This prospective observational study was done at seven hospitals in Italy. We enrolled consecutive, mechanically ventilated patients with laboratory-confirmed COVID-19 and who met Berlin criteria for ARDS, who were admitted to the intensive care unit (ICU) between March 9 and March 22, 2020. All patients were sedated, paralysed, and ventilated in volume-control mode with standard ICU ventilators. Static respiratory system compliance, the ratio of partial pressure of arterial oxygen to fractional concentration of oxygen in inspired air, ventilatory ratio (a surrogate of dead space), and D-dimer concentrations were measured within 24 h of ICU admission. Lung CT scans and CT angiograms were done when clinically indicated. A dataset for ARDS unrelated to COVID-19 was created from previous ARDS studies. Survival to day 28 was assessed.Findings Between March 9 and March 22, 2020, 301 patients with COVID-19 met the Berlin criteria for ARDS at participating hospitals. Median static compliance was 41 mL/cm H2O (33\u201352), which was 28% higher than in the cohort of patients with ARDS unrelated to COVID-19 (32 mL/cm H2O [25\u201343]; p<0\ub70001). 17 (6%) of 297 patients with COVID-19-associated ARDS had compliances greater than the 95th percentile of the classical ARDS cohort. Total lung weight did not differ between the two cohorts. CT pulmonary angiograms (obtained in 23 [8%] patients with COVID-19-related ARDS) showed that 15 (94%) of 16 patients with D-dimer concentrations greater than the median had bilateral areas of hypoperfusion, consistent with thromboembolic disease. Patients with D-dimer concentrations equal to or less than the median had ventilatory ratios lower than those of patients with D-dimer concentrations greater than the median (1\ub766 [1\ub732\u20131\ub795] vs 1\ub790 [1\ub750\u20132\ub733]; p=0\ub70001). Patients with static compliance equal to or less than the median and D-dimer concentrations greater than the median had markedly increased 28-day mortality compared with other patient subgroups (40 [56%] of 71 with high D-dimers and low compliance vs 18 [27%] of 67 with low D-dimers and high compliance, 13 [22%] of 60 with low D-dimers and low compliance, and 22 [35%] of 63 with high D-dimers and high compliance, all p=0\ub70001).Interpretation Patients with COVID-19-associated ARDS have a form of injury that, in many aspects, is similar to that of those with ARDS unrelated to COVID-19. Notably, patients with COVID-19-related ARDS who have a reduction in respiratory system compliance together with increased D-dimer concentrations have high mortality rate

Prevalence and death rate of COVID-19 in systemic autoimmune diseases in the first three pandemic waves. Relationship to disease subgroups and ongoing therapies

Objective: Autoimmune systemic diseases (ASD) represent a predisposing condition to COVID-19. Our prospective, observational multicenter telephone survey study aimed to investigate the prevalence, prognostic factors, and outcomes of COVID-19 in Italian ASD patients. Methods: The study included 3,918 ASD pts (815 M, 3103 F; mean age 59 +/- 12SD years) consecutively recruited between March 2020 and May 2021 at the 36 referral centers of COVID-19 and ASD Italian Study Group. The possible development of COVID-19 was recorded by means of a telephone survey using a standardized symptom assessment questionnaire. Results: ASD patients showed a significantly higher prevalence of COVID-19 (8.37% vs. 6.49%; p<0.0001) but a death rate statistically comparable to the Italian general population (3.65% vs. 2.95%). Among the 328 ASD patients developing COVID-19, 17% needed hospitalization, while mild-moderate manifestations were observed in 83% of cases. Moreover, 12/57 hospitalized patients died due to severe interstitial pneumonia and/or cardiovascular events; systemic sclerosis (SSc) patients showed a significantly higher COVID-19-related death rate compared to the general population (6.29% vs. 2.95%; p=0.018). Major adverse prognostic factors to develop COVID-19 were: older age, male gender, SSc, pre-existing ASD-related interstitial lung involvement, and long-term steroid treatment. Of note, patients treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) showed a significantly lower prevalence of COVID-19 compared to those without (3.58% vs. 46.99%; p=0.000), as well as the SSc patients treated with low dose aspirin (with 5.57% vs. without 27.84%; p=0.000). Conclusion: During the first three pandemic waves, ASD patients showed a death rate comparable to the general population despite the significantly higher prevalence of COVID-19. A significantly increased COVID-19-related mortality was recorded in only SSc patients' subgroup, possibly favored by preexisting lung fibrosis. Moreover, ongoing long-term treatment with csDMARDs in ASD might usefully contribute to the generally positive outcomes of this frail patients' population

Prevalence and death rate of COVID-19 in systemic autoimmune diseases in the first three pandemic waves. Relationship to disease subgroups and ongoing therapies

none84noAutoimmune systemic diseases (ASD) represent a predisposing condition to COVID-19. Our prospective, observational multicenter telephone survey study aimed to investigate the prevalence, prognostic factors, and outcomes of COVID-19 in Italian ASD patients.Ferri, Clodoveo; Raimondo, Vincenzo; Gragnani, Laura; Giuggioli, Dilia; Dagna, Lorenzo; Tavoni, Antonio; Ursini, Francesco; L'Andolina, Massimo; Caso, Francesco; Ruscitti, Piero; Caminiti, Maurizio; Foti, Rosario; Riccieri, Valeria; Guiducci, Serena; Pellegrini, Roberta; Zanatta, Elisabetta; Varcasia, Giuseppe; Olivo, Domenico; Gigliotti, Pietro; Cuomo, Giovanna; Murdaca, Giuseppe; Cecchetti, Riccardo; De Angelis, Rossella; Romeo, Nicoletta; Ingegnoli, Francesca; Cozzi, Franco; Codullo, Veronica; Cavazzana, Ilaria; Colaci, Michele; Abignano, Giuseppina; De Santis, Maria; Lubrano, Ennio; Fusaro, Enrico; Spinella, Amelia; Lumetti, Federica; De Luca, Giacomo; Bellando-Randone, Silvia; Visalli, Elisa; Bosco, Ylenia Dal; Amato, Giorgio; Giannini, Daiana; Bilia, Silvia; Masini, Francesco; Pellegrino, Greta; Pigatto, Erika; Generali, Elena; Mariano, Giuseppa Pagano; Pettiti, Giorgio; Zanframundo, Giovanni; Brittelli, Raffaele; Aiello, Vincenzo; Caminiti, Rodolfo; Scorpiniti, Daniela; Ferrari, Tommaso; Campochiaro, Corrado; Brusi, Veronica; Fredi, Micaela; Moschetti, Liala; Cacciapaglia, Fabio; Paparo, Sabrina Rosaria; Ragusa, Francesca; Mazzi, Valeria; Elia, Giusy; Ferrari, Silvia Martina; Di Cola, Ilenia; Vadacca, Marta; Lorusso, Sebastiano; Monti, Monica; Lorini, Serena; Aprile, Maria Letizia; Tasso, Marco; Miccoli, Mario; Bosello, Silvia; D'Angelo, Salvatore; Doria, Andrea; Franceschini, Franco; Meliconi, Riccardo; Matucci-Cerinic, Marco; Iannone, Florenzo; Giacomelli, Roberto; Salvarani, Carlo; Zignego, Anna Linda; Fallahi, Poupak; Antonelli, AlessandroFerri, Clodoveo; Raimondo, Vincenzo; Gragnani, Laura; Giuggioli, Dilia; Dagna, Lorenzo; Tavoni, Antonio; Ursini, Francesco; L'Andolina, Massimo; Caso, Francesco; Ruscitti, Piero; Caminiti, Maurizio; Foti, Rosario; Riccieri, Valeria; Guiducci, Serena; Pellegrini, Roberta; Zanatta, Elisabetta; Varcasia, Giuseppe; Olivo, Domenico; Gigliotti, Pietro; Cuomo, Giovanna; Murdaca, Giuseppe; Cecchetti, Riccardo; De Angelis, Rossella; Romeo, Nicoletta; Ingegnoli, Francesca; Cozzi, Franco; Codullo, Veronica; Cavazzana, Ilaria; Colaci, Michele; Abignano, Giuseppina; De Santis, Maria; Lubrano, Ennio; Fusaro, Enrico; Spinella, Amelia; Lumetti, Federica; De Luca, Giacomo; Bellando-Randone, Silvia; Visalli, Elisa; Bosco, Ylenia Dal; Amato, Giorgio; Giannini, Daiana; Bilia, Silvia; Masini, Francesco; Pellegrino, Greta; Pigatto, Erika; Generali, Elena; Mariano, Giuseppa Pagano; Pettiti, Giorgio; Zanframundo, Giovanni; Brittelli, Raffaele; Aiello, Vincenzo; Caminiti, Rodolfo; Scorpiniti, Daniela; Ferrari, Tommaso; Campochiaro, Corrado; Brusi, Veronica; Fredi, Micaela; Moschetti, Liala; Cacciapaglia, Fabio; Paparo, Sabrina Rosaria; Ragusa, Francesca; Mazzi, Valeria; Elia, Giusy; Ferrari, Silvia Martina; Di Cola, Ilenia; Vadacca, Marta; Lorusso, Sebastiano; Monti, Monica; Lorini, Serena; Aprile, Maria Letizia; Tasso, Marco; Miccoli, Mario; Bosello, Silvia; D'Angelo, Salvatore; Doria, Andrea; Franceschini, Franco; Meliconi, Riccardo; Matucci-Cerinic, Marco; Iannone, Florenzo; Giacomelli, Roberto; Salvarani, Carlo; Zignego, Anna Linda; Fallahi, Poupak; Antonelli, Alessandr

Adjunctive Brivaracetam in Older Patients with Focal Seizures: Evidence from the BRIVAracetam add‑on First Italian netwoRk Study (BRIVAFIRST)

BACKGROUND: The management of epilepsy in older adults has become part of daily practice because of an aging population. Older patients with epilepsy represent a distinct and more vulnerable clinical group as compared with younger patients, and they are generally under-represented in randomized placebo-controlled trials. Real-world studies can therefore be a useful complement to characterize the drug's profile. Brivaracetam is a rationally developed compound characterized by high-affinity binding to synaptic vesicle protein 2A and approved as adjunctive therapy for focal seizures in adults with epilepsy. OBJECTIVE: The aim of this study was to assess the 12-month effectiveness and tolerability of adjunctive brivaracetam in older patients (≥65 years of age) with epilepsy treated in a real-world setting. METHODS: The BRIVAFIRST (BRIVAracetam add-on First Italian netwoRk STudy) was a 12-month retrospective multicenter study including adult patients prescribed adjunctive brivaracetam. Effectiveness outcomes included the rates of seizure response (≥50% reduction in baseline seizure frequency), seizure freedom, and treatment discontinuation. Safety and tolerability outcomes included the rate of treatment discontinuation due to adverse events and the incidence of adverse events. Data were compared for patients aged ≥65 years of age ('older') vs those aged <65 years ('younger'). RESULTS: There were 1029 patients with focal epilepsy included in the study, of whom 111 (10.8%) were aged ≥65 years. The median daily dose of brivaracetam at 3 months was 100 [interquartile range, 100-175] mg in the older group and 100 [100-200] mg in the younger group (p = 0.036); it was 150 [100-200] mg in both groups either at 6 months (p = 0.095) or 12 months (p = 0.140). At 12 months, 49 (44.1%) older and 334 (36.4%) younger patients had a reduction in their baseline seizure frequency by at least 50% (p = 0.110), and the seizure freedom rates were 35/111 (31.5%) and 134/918 (14.6%) in older and younger groups, respectively (p < 0.001). During the 1-year study period, 20 (18.0%) patients in the older group and 245 (26.7%) patients in the younger group discontinued brivaracetam (p = 0.048). Treatment withdrawal because of insufficient efficacy was less common in older than younger patients [older: n = 7 (6.3%), younger: n = 152 (16.6%); p = 0.005]. Adverse events were reported by 24.2% of older patients and 30.8% of younger patients (p = 0.185); the most common adverse events were somnolence, nervousness and/or agitation, vertigo, and fatigue in both study groups. CONCLUSIONS: Adjunctive brivaracetam was efficacious, had good tolerability, and no new or unexpected safety signals emerged when used to treat older patients with uncontrolled focal seizures in clinical practice. Adjunctive brivaracetam can be a suitable therapeutic option in this special population

Sustained seizure freedom with adjunctive brivaracetam in patients with focal onset seizures

The maintenance of seizure control over time is a clinical priority in patients with epilepsy. The aim of this study was to assess the sustained seizure frequency reduction with adjunctive brivaracetam (BRV) in real-world practice. Patients with focal epilepsy prescribed add-on BRV were identified. Study outcomes included sustained seizure freedom and sustained seizure response, defined as a 100% and a >= 50% reduction in baseline seizure frequency that continued without interruption and without BRV withdrawal through the 12-month follow-up. Nine hundred ninety-four patients with a median age of 45 (interquartile range = 32-56) years were included. During the 1-year study period, sustained seizure freedom was achieved by 142 (14.3%) patients, of whom 72 (50.7%) were seizure-free from Day 1 of BRV treatment. Sustained seizure freedom was maintained for >= 6, >= 9, and 12 months by 14.3%, 11.9%, and 7.2% of patients from the study cohort. Sustained seizure response was reached by 383 (38.5%) patients; 236 of 383 (61.6%) achieved sustained >= 50% reduction in seizure frequency by Day 1, 94 of 383 (24.5%) by Month 4, and 53 of 383 (13.8%) by Month 7 up to Month 12. Adjunctive BRV was associated with sustained seizure frequency reduction from the first day of treatment in a subset of patients with uncontrolled focal epilepsy

Use of hydroxychloroquine in hospitalised COVID-19 patients is associated with reduced mortality: Findings from the observational multicentre Italian CORIST study

Hydroxychloroquine (HCQ) was proposed as potential treatment for COVID-19

Risk of Guillain-Barr\ue9 syndrome after 2010-2011 influenza vaccination

Influenza vaccination has been implicated in Guillain Barr\ue9 Syndrome (GBS) although the evidence for this link is controversial. A case-control study was conducted between October 2010 and May 2011 in seven Italian Regions to explore the relation between influenza vaccination and GBS. The study included 176 GBS incident cases aged 6518 years from 86 neurological centers. Controls were selected among patients admitted for acute conditions to the Emergency Department of the same hospital as cases. Each control was matched to a case by sex, age, Region and admission date. Two different analyses were conducted: a matched case-control analysis and a self-controlled case series analysis (SCCS). Case-control analysis included 140 cases matched to 308 controls. The adjusted matched odds ratio (OR) for GBS occurrence within 6 weeks after influenza vaccination was 3.8 (95 % CI: 1.3, 10.5). A much stronger association with gastrointestinal infections (OR = 23.8; 95 % CI 7.3, 77.6) and influenza-like illness or upper respiratory tract infections (OR = 11.5; 95 % CI 5.6, 23.5) was highlighted. The SCCS analysis included all 176 GBS cases. Influenza vaccination was associated with GBS, with a relative risk of 2.1 (95 % CI 1.1, 3.9). According to these results the attributable risk in adults ranges from two to five GBS cases per 1,000,000 vaccinations

Measurement of the lifetime of the B-c(+) meson using the B-c(+) -> J/psi pi(+) decay mode

The difference in total widths between the B-c(+) and B+ mesons is measured using a data sample corresponding to an integrated luminosity of 3.0 fb(-1) collected by the LHCb experiment in 7 and 8 TeV centre-of-mass energy proton-proton collisions at the LHC. Through the study of the time evolution of B-c(+) -> J/psi pi(+) and B+ -> J/psi K+ decays, the width difference is measured to be Delta Gamma = Gamma(Bc+) - Gamma(Bc+) = 4.46 +/- 0.14 +/- 0.07 mm(-1) c, where the first uncertainty is statistical and the second systematic. The known lifetime of the B+ meson is used to convert this to a precise measurement of the B-c(+) clifetime, tau(Bc+) = 513.4 +/- 11.0 +/- 5.7 fs, where the first uncertainty is statistical and the second is systematic. (C) 2015 The Authors. Published by Elsevier B.V

Identification of beauty and charm quark jets at LHCb

Identification of jets originating from beauty and charm quarks is important for measuring Standard Model processes and for searching for new physics. The performance of algorithms developed to select b- and c-quark jets is measured using data recorded by LHCb from proton-proton collisions at root s = 7TeV in 2011 and at root s = 8TeV in 2012. The efficiency for identifying a b (c) jet is about 65%(25%) with a probability for misidentifying a light-parton jet of 0.3% for jets with transverse momentum pT > 20GeV and pseudorapidity 2 : 2 < eta < 4.2. The dependence of the performance on the pT and eta of the jet is also measured