Safety and feasibility of chemotherapy followed by liver transplantation for patients with definitely unresectable colorectal liver metastases: insights from the TransMet randomised clinical trial.

Background: Despite the increasing efficacy of chemotherapy (C), the 5-year survival rate for patients with unresectable colorectal liver metastases (CLM) remains around 10%. Liver transplantation (LT) might offer a curative approach for patients with liver-only disease, yet its superior efficacy compared to C alone remains to be demonstrated. Methods: The TransMet randomised multicentre clinical trial (NCT02597348) compares the curative potential of C followed by LT versus C alone in patients with unresectable CLM despite stable or responding disease on C. Patient eligibility criteria proposed by local tumour boards had to be validated by an independent committee via monthly videoconferences. Outcomes reported here are from a non-specified interim analysis. These include the eligibility of patients to be transplanted for non resectable colorectal liver metastases, as well as the feasibility and the safety of liver transplantation in this indication. Findings: From February 2016 to July 2021, 94 (60%) of 157 patients from 20 centres in 3 countries submitted to the validation committee, were randomised. Reasons for ineligibility were mainly tumour progression in 50 (32%) or potential resectability in 13 (8%). The median delay to LT after randomisation was 51 (IQR 30-65) days. Nine of 47 patients (19%, 95% CI: 9-33) allocated to the LT arm failed to undergo transplantation because of intercurrent disease progression. Three of the 38 transplanted patients (8%) were re-transplanted, one of whom (3%) died post-operatively from multi-organ failure. Interpretation: The selection process of potential candidates for curative intent LT for unresectable CLM in the TransMet trial highlighted the critical role of an independent multidisciplinary validation committee. After stringent selection, the feasibility of LT was 81%, as 19% had disease progression while on the waiting list. These patients should be given high priority for organ allocation to avoid dropout from the transplant strategy. Funding: No source of support or funding from any author to disclose for this work. The trial was supported by the Assistance Publique - Hôpitaux de Paris (AP-HP).

Incidental diagnosis of lung cancer on chest CT scan performed for suspected or documented COVID-19 infection.

CONTEXT: Recent studies have shown a benefit of chest computed tomography (CT scan) in lung cancer screening. The COVID-19 pandemic has led to many chest CT scan performed on a large population. The objective of this study was to describe the incidence and characteristics of lung cancer detected on chest CT scan, outside the framework of a clinical trial, for a suspected or documented COVID-19 infection. METHODS: We conducted a multicenter study, carried out from the analysis of data from the prospective COVID-19 database of the Clinical Data Warehouse of the Greater Paris University Hospitals (AP-HP). We identified the patients who had been diagnosed with a lung cancer, due to a chest CT scan done for a suspected or confirmed COVID-19 infection. The study period was limited to the first two epidemic lockdowns: (03/01/20 - 05/31/20) and (10/10/20 - 11/30/20). RESULTS: Over the study period, 24 390 patients had at least one chest CT scan. Among them, 72 lung cancer diagnoses were made (incidence 0.30 %; median age 67.4 years old, 50.0 % current smokers, 55.6 % adenocarcinoma). Half of the lung cancer patients (n = 36) did not meet the National Lung Screening Trial inclusion criteria. Twenty-six patients (36.1 %) were diagnosed at an early stage, 25 (34.7 %) of whom received radical curative treatment. Twenty-six patients died during the follow-up (36.1 %) but none in early stages. The median overall survival in lung cancer patients was 693 days [532 - NA]. CONCLUSIONS: A large-scale chest CT scan strategy for suspected or documented COVID-19 infection has allowed a significant proportion of early-stage lung cancer diagnosis, all of which have benefited from curative treatment.

Exploring the impact of ursodeoxycholic acid therapy on COVID-19 in a real-word setting.

Recent data suggest that ursodeoxycholic acid (UDCA) therapy may reduce susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and even improve clinical outcomes when coronavirus disease-2019 (COVID-19) was diagnosed. However, clinical evidence of UDCA's ability to prevent severe forms of COVID-19 remains limited and contradictory. We evaluated the association between UDCA exposure and the risk of hospitalization for COVID-19 in a large multicenter population of patients with chronic liver disease (CLD) followed during the pandemic period before vaccination. An exposed/unexposed cohort study and a nested case-control study were performed. The primary endpoint was severe COVID-19, defined as SARS-CoV2 infection requiring hospitalization. The secondary endpoint was COVID-19-associated intensive care unit (ICU) admission or death. Adjusted odds ratios (aOR) and their confidence intervals (CI) were determined after controlling for age, gender, comorbidities at risk for COVID-19, severity of CLD, and prior hospitalizations. A total of 10 147 patients, including 1322 exposed and 8825 not exposed to UDCA, totaling 21 867 person-years of follow-up, were included in the cohort analysis, while 88 patients hospitalized for COVID-19 and 840 matched controls were eligible for the nested case-control analysis. In both analyses, exposure to UDCA was not associated with a significant reduction in the risk of hospitalization for COVID-19, with aOR (95% confidence interval) values of 0.48 (0.20-1.19) and 0.93 (0.26-3.29), respectively. Furthermore, there was no significant reduction in the risk of ICU admission or death. In this large population of patients with CLD, UDCA exposure was not associated with a reduced risk of severe COVID-19.

Thromboembolic Events With the Woven Endobridge Device: Incidence, Predictive Factors, and Management.

BACKGROUND AND OBJECTIVES: The Woven EndoBridge (WEB) device has been increasingly used to treat wide-neck aneurysms showing a safe and effective profile, but a relatively high number of thromboembolic events (TEEs) have been reported with such treatment. We aimed to evaluate the incidence and management of TEEs and possible predictive factors related to WEB embolization of ruptured and unruptured intracranial aneurysms. METHODS: A single-center database with consecutive aneurysms treated with a WEB device between July 2012 and May 2022 was reviewed for intraoperative and delayed TEEs. Univariate and multivariable analyses were used to determine factors associated with TEEs. RESULTS: A total of 266 independent aneurysms were treated with WEB devices in 245 patients (mean age 55.78 ± 11.64 years, 169 (63.5%) females, 80 (30%) ruptured). The overall rate of TEEs is 13% (35/266), including 8.7% intraoperative. Symptomatic TEEs with clinical sequelae at a 3-month follow-up are reported to be 2.6% (7/266) with no TEE-related mortality. Both the replacement of a WEB device during the procedure (adjusted odds ratio = 2.61, 95% CI 1.24-5.49; P = .01) and ruptured aneurysms (adjusted odds ratio = 2.74, 95% CI 1.31-5.7; P = .007) were independent predictors of TEEs. A case-by-case management of intraprocedural TEE is also presented; tirofiban was successfully used in most cases of this cohort. CONCLUSION: In this study, we demonstrated that ruptured aneurysms and WEB device replacement during the procedure were independent predictive factors for TEEs. As a result, making the correct choice of WEB is crucial for improving treatment outcomes. Moreover, with proper medical management of TEEs, minimal morbidity and no mortality could be achieved, which reinforces the safety of the technique.

CLinical EValuation of WEB 17 device in intracranial aneuRysms (CLEVER): procedural, 30-day and 1-year safety results for ruptured and unruptured aneurysms.

BACKGROUND: Intrasaccular flow disruption is an endovascular approach for the treatment of wide-neck aneurysms and, more specifically, wide-neck bifurcation aneurysms, which are challenging to treat with previously developed technologies. The Woven EndoBridge (WEB) device has demonstrated its efficacy and safety, for both unruptured and ruptured aneurysms. METHODS: The CLEVER study was an observational, multicenter, prospective study conducted in 17 European investigational sites using the WEB 17 device, for the treatment of ruptured and unruptured aneurysms. The study objective was to provide safety and efficacy data on the WEB 17 device in the treatment of wide-neck bifurcation aneurysms. Imaging results were assessed independently by a Corelab and adverse events adjudicated by a Clinical Event Adjudicator. This analysis reports procedural results and safety at 30 days and 12 months. RESULTS: A total of 163 patients (mean age 58.1 years; 68.1% women) with 103 unruptured aneurysms and 60 ruptured aneurysms were enrolled. Most aneurysms were located on the anterior communicating artery (ACom) (37.4%) or the middle cerebral artery (MCA) bifurcation (30.1%). Aneurysm widths ranged from 2.0-9.2 mm, and the mean sac width was 5.0 mm. The WEB procedure was successfully completed in 163 patients (100%). At the 12-month follow-up, major stroke events occurred in 3 of 163 patients (1.8%), and no device-related mortality was observed. CONCLUSION: Endovascular treatment of ruptured and unruptured wide-neck bifurcation aneurysms using WEB 17 is safe, with a low complication rate and no device-related mortality. In particular, none of the ruptured aneurysms bled again up to 1 year of follow-up. TRIAL REGISTRATION NUMBER: NCT03844334.

COVID-19 Hospitalization in Solid Organ Transplant Recipients on Immunosuppressive Therapy.

Importance: Solid organ transplant recipients are at high risk of severe infection with SARS-CoV-2 compared with the general population. However, factors associated with COVID-19-related severity in this population are still insufficiently explored in the literature. Objective: To examine which health conditions and immunosuppressive drugs for preventing graft rejection are associated with the risk of COVID-19-related hospitalization in solid organ transplant recipients. Design, Setting, and Participants: Using the French National Health Data System, this cohort study assessed patients of any age who received transplants between their date of birth and entry into the cohort on February 15, 2020. The cohort was followed up between February 15, 2020, and July 31, 2022. Exposures: Immunosuppressive drugs, including steroids, and health conditions (age, sex, and comorbidities). Main Outcomes and Measures: The main outcome was hospitalization for COVID-19, defined by main diagnostic International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes. Factors associated with the outcome were identified with a nonconditional logistic regression. Confounding by indication was controlled using a multivariable model with adjustment for individual confounders. Each transplanted organ was examined separately. Results: Overall, 60 456 participants (median [IQR] age, 59 [47-67] years; 63.7% male) were included in the study, of whom 41 463 (68.6%) had kidney transplants, 14 464 (23.9%) had liver transplants, 5327 (8.8%) had heart transplants, and 2823 (4.6%) had lung transplants. Among them, 12.7% of kidney transplant recipients, 6.4% of liver transplant recipients, 12.9% of heart transplant recipients, and 18.0% of lung transplant recipients were hospitalized for COVID-19. In kidney transplant recipients, steroids (adjusted odds ratio [AOR], 1.60; 95% CI, 1.49-1.73) and mycophenolic acid (AOR, 1.37; 95% CI, 1.25-1.51) were associated with a high risk of hospitalization. In liver transplant recipients, tacrolimus (AOR, 0.77; 95% CI, 0.61-0.98) was associated with a decreased risk, and steroids (AOR, 1.60; 95% CI, 1.38-1.86) and mycophenolic acid (AOR, 1.61; 95% CI, 1.37-1.90) were associated with an increased risk of hospitalizations. In heart transplant recipients, cyclosporine (AOR, 0.67; 95% CI, 0.47-0.94) was associated with a decreased risk, and steroids (AOR, 1.42; 95% CI, 1.11-1.82), mycophenolic acid (AOR, 1.29; 95% CI, 1.02-1.64), sirolimus (AOR, 2.71; 95% CI, 1.20-6.09), and everolimus (AOR, 1.24; 95% CI, 1.01-1.51) were associated with an increased risk of hospitalization. Only steroids (AOR, 1.72; 95% CI, 1.19-2.48) were associated with a high risk of COVID-19 hospitalization in lung transplant recipients. Conclusions and Relevance: This study suggests that mycophenolic acid, sirolimus, and steroids are associated with an increased risk of COVID-19-related hospitalization in solid organ transplant recipients. These results should be considered by clinicians treating transplant recipients and may help inform epidemic-related decisions for this population in the future.

Effectiveness of homologous/heterologous booster COVID-19 vaccination schedules against severe illness in general population and clinical subgroups in three European countries.

Using 4 data-sources (Spain, Italy, United Kingdom) data and a 1:1 matched cohort study, we aimed to estimate vaccine effectiveness (VE) in preventing SARS-CoV-2 infections with hospitalisations (±30 days) and death (±56 days) in general population and clinical subgroups with homologous/heterologous booster schedules (Comirnaty-BNT and Spikevax-MOD original COVID-19 vaccines) by comparison with unboosted individuals, during Delta and beginning of Omicron variants. Hazard Ratio (HR, by Cox models) and VE ([1-HR]*100) were calculated by inverse probability weights. Between December 2020-February 2022, in adults without prior SARS-CoV-2 infection, we matched 5.5 million people (>1 million with immunodeficiency, 343,727 with cancer) with a booster (3rd) dose by considering doses 1 and 2 vaccine brands and calendar time, age, sex, region, and comorbidities (immunodeficiency, cancer, severe renal disease, transplant recipient, Down Syndrome). We studied booster doses of BNT and MOD administered after doses 1 and 2 with BNT, MOD, or Oxford-AstraZeneca during a median follow-up between 9 and 16 weeks. BNT or MOD showed VE ranging from 70 to 86% across data sources as heterologous 3rd doses, whereas it was 42-88% as homologous 3rd doses. Depending on the severity and available follow-up, 3rd-dose effectiveness lasted between 1 and 5 months. In people with immunodeficiency and cancer, protection across data sources was detected with both heterologous (VE = 54-83%) and homologous (VE = 49-80%) 3rd doses. Overall, both heterologous and homologous 3rd doses with BTN or MOD showed additional protection against the severe effects of SARS-CoV-2 infections for the general population and for patients at potentially high risk of severe COVID-19 (elderly, people with immunodeficiency and cancer) in comparison with two doses schemes during Delta or early Omicron periods. The early VE after vaccination may be due to less testing among vaccinated pairs and unknown confounders, deserving cautious interpretation. The VE wane over time needs further in-depth research to properly envisage when or whether a booster of those vaccines should be administered.

Vaccines and the Risk of Hospitalization for Multiple Sclerosis Flare-Ups.

Importance: Scientific literature is sparse about the association of vaccination with the onset of multiple sclerosis (MS) flare-ups. Immunization by vaccines of the entire population is crucially important for public health. Objective: To evaluate the risk of hospitalization for severe MS flare-ups after vaccination in patients with MS. Design, Setting, Participants: This cohort study included patients diagnosed with MS between January 1, 2007, and December 31, 2017, who were included in the System of National Health Databases, a national health claims database in France. In a nested case-crossover analysis, cases were defined by vaccine exposure prior to the onset of hospitalization due to an MS flare-up, and flare-up rates were compared with those that occurred prior to vaccine exposure in up to 4 control time windows immediately preceding the at-risk time window (ie, the MS flare-up) for each patient. Data were analyzed from January 2022 to December 2022. Exposure: Receipt of at least 1 vaccination, including the diphtheria, tetanus, poliomyelitis, pertussis, or Haemophilus influenzae (DTPPHi) vaccine, influenza vaccine, and pneumococcal vaccine, during follow-up. Main Outcomes and Measures: The primary outcome was the risk of hospitalization for an MS flare-up after receipt of a vaccine. Adjusted odds ratios (AORs) and 95% CIs were derived using conditional logistic regression to measure the risk of hospitalization for an MS flare-up associated with vaccination. Results: A total of 106 523 patients constituted the MS cohort (mean [SD] age, 43.9 [13.8] years; 76 471 females [71.8%]; 33 864 patients [31.8%] had incident MS and 72 659 patients [68.2%] had prevalent MS) and were followed up for a mean (SD) of 8.8 (3.1) years. Of these patients, 35 265 (33.1%) were hospitalized for MS flare-ups during the follow-up period for a total of 54 036 MS-related hospitalizations. The AORs of hospitalization for an MS flare-up and vaccine exposure in the 60 days prior to the flare-up were 1.00 (95% CI, 0.92-1.09) for all vaccines, 0.95 (95% CI, 0.82-1.11) for the DTPPHi, 0.98 (95% CI, 0.88-1.09) for the influenza vaccine, and 1.20 (95% CI, 0.94-1.55) for the pneumococcal vaccine. Conclusions and Relevance: A nationwide study of the French population found no association between vaccination and the risk of hospitalization due to MS flare-ups. However, considering the number of vaccine subtypes available, further studies are needed to confirm these results.

Correction: Impact of a Postintensive Care Unit Multidisciplinary Follow-up on the Quality of Life (SUIVI-REA): Protocol for a Multicenter Randomized Controlled Trial.

[This corrects the article DOI: 10.2196/30496.].

Valproic acid as adjuvant treatment for convulsive status epilepticus: a randomised clinical trial.

BACKGROUND: Generalised convulsive status epilepticus (GCSE) is a medical emergency. Guidelines recommend a stepwise strategy of benzodiazepines followed by a second-line anti-seizure medicine (ASM). However, GCSE is uncontrolled in 20-40% patients and is associated with protracted hospitalisation, disability, and mortality. The objective was to determine whether valproic acid (VPA) as complementary treatment to the stepwise strategy improves the outcomes of patients with de novo established GCSE. METHODS: This was a multicentre, double-blind, randomised controlled trial in 244 adults admitted to intensive care units for GCSE in 16 French hospitals between 2013 and 2018. Patients received standard care of benzodiazepine and a second-line ASM (except VPA). Intervention patients received a 30 mg/kg VPA loading dose, then a 1 mg/kg/h 12 h infusion, whilst the placebo group received an identical intravenous administration of 0.9% saline as a bolus and continuous infusion. Primary outcome was proportion of patients discharged from hospital by day 15. The secondary outcomes were seizure control, adverse events, and cognition at day 90. RESULTS: A total of 126 (52%) and 118 (48%) patients were included in the VPA and placebo groups. 224 (93%) and 227 (93%) received a first-line and a second-line ASM before VPA or placebo infusion. There was no between-group difference for patients hospital-discharged at day 15 [VPA, 77 (61%) versus placebo, 72 (61%), adjusted relative risk 1.04; 95% confidence interval (0.89-1.19); p = 0.58]. There were no between-group differences for secondary outcomes. CONCLUSIONS: VPA added to the recommended strategy for adult GCSE is well tolerated but did not increase the proportion of patients hospital-discharged by day 15. TRIAL REGISTRATION NO: NCT01791868 (ClinicalTrials.gov registry), registered: 15 February 2012.

Management of aneurysmal recurrence after Woven EndoBridge (WEB) treatment.

BACKGROUND: Around 10% of Woven EndoBridge device (WEB)-treated intracranial aneurysms will need retreatment, and it is generally believed to be more challenging than retreatment after an initial coiling. We aim to report retreatment strategies and outcomes after initial WEB embolizations. METHODS: Databases from four treatment centers, containing consecutive aneurysms treated with a WEB between 2013 and 2022, were reviewed. Demographics, aneurysm characteristics, retreatment strategies and outcomes were collected and analyzed. RESULTS: From a 756 WEB database, 57 aneurysms were included. The global retreatment rate was 7.5% (95% CI 5.6% to 9.4%). The retreatment rate was significantly higher in the ruptured compared with the unruptured population (13% vs 3.9%, respectively, P<0.0001). Aneurysms were retreated on average 21.2 months after the initial WEB treatment (range 4.8-70 months). Surgery was performed in 11% and endovascular treatment in 89% of cases, consisting of flow diversion (48%), stent-assisted coiling (30%), coiling (12%), and second WEB placement (10%). Imaging follow-up was available in 88% of all WEB retreatments (50/57) (average 17 months, 49% digital subtraction angiography), demonstrating complete occlusion in 56% and 'adequate' occlusion in 88%. Morbidity was 5.3% (95% CI 0% to 12.0%) and mortality 0%. No patient experienced rebleeding during the follow-up period. CONCLUSION: The retreatment rate after an initial WEB treatment seems to compare favorably with that of coiling. Endovascular treatment of recurrence following WEB implantation is feasible in most situations; it generally requires the use of a stent and leads to a high rate of satisfactory occlusion.

CLinical Assessment of WEB device in Ruptured aneurYSms (CLARYS): 12-month angiographic results of a multicenter study.

BACKGROUND: The CLinical Assessment of WEB device in Ruptured aneurYSms (CLARYS) study has shown that the endovascular treatment of ruptured bifurcation aneurysms with the Woven EndoBridge (WEB) is safe and effective and provides protection against rebleeding at 1 month and 1 year. The 12-month angiographic follow-up is an important endpoint of the study. METHODS: The CLARYS study is a prospective multicenter study conducted in 13 European centers. The study enrolled 60 patients with 60 ruptured aneurysms of the anterior and posterior circulation. The study was conducted with an independent assessment of safety outcomes and imaging. RESULTS: Sixty patients with 60 ruptured bifurcation aneurysms to be treated with the WEB were included. Fifty-three aneurysms (88.3%) had a broad base with a dome to neck ratio <2 (mean 1.6). Of these, 46 patients were evaluated by an independent core laboratory with follow-up imaging performed at 12 months or before eventual retreatment. At 1 year, 19/46 aneurysms (41.3%) were completely occluded (Raymond-Roy grade I), 21/46 (45.7%) had a residual neck and 6/46 (13.0%) had residual aneurysm filling. Adequate occlusion was reported in 40/46 (87%) aneurysms. Six patients underwent target aneurysm retreatment. CONCLUSIONS: The CLARYS study has previously shown that the use of the WEB in the endovascular treatment of ruptured bifurcation aneurysms provides effective protection against rebleeding with a good safety profile. The angiographic occlusion rates at 1 year reported here are comparable to those already seen in previous multicenter studies which primarily included unruptured aneurysms.

Determinants of cerebral aneurysm occlusion after embolization with the WEB device: a single-institution series of 215 cases with angiographic follow-up.

BACKGROUND: Woven EndoBridge (WEB) devices are becoming a reliable option for the treatment of wide-neck bifurcation aneurysms, but clear predictive factors are still missing to understand the one in five aneurysm remnant rate. OBJECTIVE: To evaluate occlusion outcomes after WEB treatment to identify potential determinants of aneurysm occlusion. METHODS: A single-center database with consecutive aneurysms treated with WEB between July 2012 and October 2021 was reviewed for potential determinants of aneurysm adequate occlusion (defined as a Bicêtre Occlusion Scale Score (BOSS) of 0, 0', 1 or 2), through univariate and multivariable analysis. Patients without angiographic follow-up were excluded. RESULTS: 215 of 247 individual aneurysms were included in the final analysis, of which 59 (27%) were ruptured. Mean age of patients was 56 years (range 23-90 years) and 65% were female. Mean angiographic follow-up was at 18 months (range 3-97 months). Adequate and complete occlusion were achieved in 171/215 (79.5%) and 135/215 (62.8%) of cases, respectively. Aneurysm irregular shape (aOR=0.42, 95% CI 0.20 to 0.88; p=0.02), aneurysm height (aOR=0.79, 95% CI 0.66 to 0.94; p<0.01), and WEB shape modification (aOR=0.98, 95% CI 0.97 to 1.00; p=0.02) were all independent predictors of aneurysm recurrence, whereas the WEB oversizing ratio (WEB width/aneurysm mean width) (aOR=16.4, 95% CI 1.4 to 266.7; p=0.04) was an independent predictor of adequate occlusion. CONCLUSION: In this study we demonstrated that a width oversizing strategy of the WEB device was an independent predictor of aneurysm angiographic occlusion. Conversely, aneurysm height, irregular aneurysm, and WEB shape modification were all independent determinants of angiographic aneurysm remnant. These results may help to select aneurysms suitable for the WEB device and WEB sizing.

Does Measles, Mumps, and Rubella (MMR) Vaccination Protect against COVID-19 Outcomes: A Nationwide Cohort Study.

Cross-protection from previous live attenuated vaccines is proposed to explain the low impact of COVID-19 on children. This study aimed to evaluate the effect of live attenuated MMR vaccines on the risk of being hospitalized for COVID-19 in children. An exposed (MMR vaccine)-non-exposed cohort study was conducted using the nationwide French National Health Data System (SNDS). We included children born between 1 January 2009 and 31 December 2019. Exposure was defined as a claim of at least one dose of MMR vaccine since birth. Hospitalization for COVID-19 was defined using main diagnostic ICD10 codes. Non-conditional logistic regression was used to calculate the adjusted odds ratios (aORs) of the association between MMR exposure and hospitalization for COVID-19, controlling for socio-demographic and socio-economic factors, co-morbidities, and general health. In total, 6,800,542 (median age 6 IQR [3-8] years) children exposed to a MMR vaccine and 384,162 (6 [3-9] years) not exposed were followed up with for 18 months. Among them, 873 exposed to the MMR vaccine and 38 who were not exposed were hospitalized for COVID-19. In a multi-variate analysis, the exposure of children to MMR vaccination was not associated with a decreased risk of COVID-19 hospitalization versus non-exposure (aOR (95%CI) = 1.09 [0.81-1.48]). A stratified analysis by age showed an aOR = 1.03 [0.64-1.66] for children aged 1-4, an aOR = 1.38 [0.82-2.31] for those aged 5-9, and an aOR = 1.11 [0.54-2.29] for those aged 10-12. Our study suggests that the live attenuated MMR vaccine does not protect children against COVID-19 hospitalization.

Trace elements repartition in body fluids, hair and organs in an autopsied population evaluated by ICP-MS high resolution.

Exposure to metals and trace elements (TE) is universal and can cause toxicity in case of excessive exposure. We evaluated the concentrations and tissue distribution of 39 TE using high-resolution ICP-MS after total mineralization by microwave in twenty autopsied French subjects. We found a globally homogeneous distribution of TE in the body, with some accumulations in agents, involved in respiratory pathologies and classified as carcinogens, in the lungs. The liver, an organ of metabolism, appeared to concentrate Co, Fe, La, Mn, Mo, Pb and Zn. Fe seemed to accumulate in the spleen, the organ of hematopoiesis. The kidney showed high concentrations of some TE, which can cause nephrotoxicity. The use of microwave mineralization and high-resolution ICP-MS allowed accurate quantification and a very high sensitivity, without spectral interferences. The results obtained in this study could be used to support the interpretation of post-mortem metal concentrations in tissues.

Balloon pulmonary angioplasty versus riociguat for the treatment of inoperable chronic thromboembolic pulmonary hypertension (RACE): a multicentre, phase 3, open-label, randomised controlled trial and ancillary follow-up study.

BACKGROUND: Riociguat and balloon pulmonary angioplasty (BPA) are treatment options for inoperable chronic thromboembolic pulmonary hypertension (CTEPH). However, randomised controlled trials comparing these treatments are lacking. We aimed to evaluate the efficacy and safety of BPA versus riociguat in patients with inoperable CTEPH. METHODS: In this phase 3, multicentre, open-label, parallel-group, randomised controlled trial done in 23 French centres of expertise for pulmonary hypertension, we enrolled treatment-naive patients aged 18-80 years with newly diagnosed, inoperable CTEPH and pulmonary vascular resistance of more than 320 dyn·s/cm5. Patients were randomly assigned (1:1) to BPA or riociguat via a web-based randomisation system, with block randomisation (block sizes of two or four patients) without stratification. The primary endpoint was change in pulmonary vascular resistance at week 26, expressed as percentage of baseline pulmonary vascular resistance in the intention-to-treat population. Safety analyses were done in all patients who received at least one dose of riociguat or had at least one BPA session. Patients who completed the RACE trial continued into an ancillary 26-week follow-up during which symptomatic patients with pulmonary vascular resistance of more than 320 dyn·s/cm5 benefited from add-on riociguat after BPA or add-on BPA after riociguat. This trial is registered at ClinicalTrials.gov, NCT02634203, and is completed. FINDINGS: Between Jan 19, 2016, and Jan 18, 2019, 105 patients were randomly assigned to riociguat (n=53) or BPA (n=52). At week 26, the geometric mean pulmonary vascular resistance decreased to 39·9% (95% CI 36·2-44·0) of baseline pulmonary vascular resistance in the BPA group and 66·7% (60·5-73·5) of baseline pulmonary vascular resistance in the riociguat group (ratio of geometric means 0·60, 95% CI 0·52-0·69; p<0·0001). Treatment-related serious adverse events occurred in 22 (42%) of 52 patients in the BPA group and five (9%) of 53 patients in the riociguat group. The most frequent treatment-related serious adverse events were lung injury (18 [35%] of 52 patients) in the BPA group and severe hypotension with syncope (two [4%] of 53 patients) in the riociguat group. There were no treatment-related deaths. At week 52, a similar reduction in pulmonary vascular resistance was observed in patients treated with first-line riociguat or first-line BPA (ratio of geometric means 0·91, 95% CI 0·79-1·04). The incidence of BPA-related serious adverse events was lower in patients who were pretreated with riociguat (five [14%] of 36 patients vs 22 [42%] of 52 patients). INTERPRETATION: At week 26, pulmonary vascular resistance reduction was more pronounced with BPA than with riociguat, but treatment-related serious adverse events were more common with BPA. The finding of fewer BPA-related serious adverse events among patients who were pretreated with riociguat in the follow-up study compared with those who received BPA as first-line treatment points to the potential benefits of a multimodality approach to treatment in patients with inoperable CTEPH. Further studies are needed to explore the effects of sequential treatment combining one or two medications and BPA in patients with inoperable CTEPH. FUNDING: Programme Hospitalier de Recherche Clinique of the French Ministry of Health and Bayer HealthCare. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Thrombosis of Medium-Sized and Large Arteries During Covid-19 Infection: Results of the COVIVASC Study.

BACKGROUND: COVID-19 infection is associated not only with venous thromboses but also with arterial thromboses (COV-ATs) in relation with an endothelial dysfunction, a coagulopathy and rhythm disorders. The incidence, the topography, and the prognosis of COV-ATs remain poorly known. The objective of this study was to report the overall experience of the Greater Paris University Hospitals (Assistance Publique - Hopitaux de Paris, AP-HP) during the first pandemic wave of COVID-19 infection. METHODS: After approval by the ethics committee, a study using the AP-HP clinical data warehouse was carried out between March and May 2020. Overall, 124,609 patients had a polymerase chain reaction for COVID-19 in our hospitals, of which 25,345 were positive. From 20,710 exploitable stays, patients tested positive for COVID who presented an episode of acute COV-AT (except coronary and intracranial arteries) were selected on the basis of the French medical classification for clinical procedures codes. The data are presented as absolute values with percentages and/or means with standard deviation. RESULTS: Over the studied period, 60 patients (aged 71±14 years, 42 men) presented a COV-AT at the time of their hospitalization, an incidence of 0.2%. The arterial complication occurred 3±7 days after the COVID infection and was inaugural in 30% of the cases (n = 18). The sites of COV-AT were the lower extremities (n = 35%, 58%), the abdominal aorta (n = 10%, 17%), the thoracic aorta (n = 7%, 12%), the upper limbs (n = 7%, 12%), the cerebral arteries (n = 7%, 12%), the digestive arteries (n = 6%, 10%), the renal arteries (n = 2%, 3%), and the ophthalmic artery (n = 1%, 2%). Multiple COV-ATs were observed in 13 patients (22%). At the time of diagnosis, 20 (33%) patients were in intensive care, including six (10%) patients who were intubated. On computed tomography angiography, COVID lesions were classified as moderate and severe in 25 (42%) and 21 (35%) cases, respectively. Revascularization was attempted in 27 patients (45%), by open surgery in 16 cases, using endovascular techniques in 8 cases and with a hybrid approach in three cases. Six patients (22%) required reinterventions. The duration of hospitalization was 12±9 days. Early mortality (in-hospital or at 30 days) was 30% (n = 18). Nine (15%) patients presented severe nonlethal ischemic complications. CONCLUSIONS: Arterial involvement is rare during COVID-19 infection. The aorta and the arteries of the limbs are the privileged sites. The morbi-mortality of these patients is high. Future studies will have to determine if the systematization of anticoagulation therapy decreases the incidence and the severity of the condition.

Impact of a Postintensive Care Unit Multidisciplinary Follow-up on the Quality of Life (SUIVI-REA): Protocol for a Multicenter Randomized Controlled Trial.

BACKGROUND: Critically ill patients are at risk of developing a postintensive care syndrome (PICS), which is characterized by physical, psychological, and cognitive impairments and which dramatically impacts the patient's quality of life (QoL). No intervention has been shown to improve QoL. We hypothesized that a medical, psychological, and social follow-up would improve QoL by mitigating the PICS. OBJECTIVE: This multicenter, randomized controlled trial (SUIVI-REA) aims to compare a multidisciplinary follow-up with a standard postintensive care unit (ICU) follow-up. METHODS: Patients were randomized to the control or intervention arm. In the intervention arm, multidisciplinary follow-up involved medical, psychological, and social evaluation at ICU discharge and at 3, 6, and 12 months thereafter. In the placebo group, patients were seen only at 12 months by the multidisciplinary team. Baseline characteristics at ICU discharge were collected for all patients. The primary outcome was QoL at 1 year, assessed using the Euro Quality of Life-5 dimensions (EQ5D). Secondary outcomes were mortality, cognitive, psychological, and functional status; social and professional reintegration; and the rate of rehospitalization and outpatient consultations at 1 year. RESULTS: The study was funded by the Ministry of Health in June 2010. It was approved by the Ethics Committee on July 8, 2011. The first and last patient were randomized on December 20, 2012, and September 1, 2017, respectively. A total of 546 patients were enrolled across 11 ICUs. At present, data management is ongoing, and all parties involved in the trial remain blinded. CONCLUSIONS: The SUVI-REA multicenter randomized controlled trial aims to assess whether a post-ICU multidisciplinary follow-up improves QoL at 1 year. TRIAL REGISTRATION: Clinicaltrials.gov NCT01796509; https://clinicaltrials.gov/ct2/show/NCT01796509. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/30496.

Performance of Targeted Congenital Cytomegalovirus Screening in Newborns Failing Universal Hearing Screening: A Multicenter Study.

BACKGROUND: Cytomegalovirus (CMV) is the most frequent cause of congenital infection and ≈20% of all infected neonates present or will develop sensorineural hearing loss. Targeted congenital CMV (cCMV) screening in newborns who failed universal newborn hearing screening has been proposed as a strategy to identify neonates with both hearing loss and cCMV infection who could benefit from antiviral treatment implemented within the first month of life. OBJECTIVES: To evaluate the feasibility and performance of cCMV targeted screening in a French setting. METHODS: Neonates were recruited in 5 maternity centers in greater Paris. A saliva sample for CMV polymerase chain reaction (PCR) testing was collected in neonates who failed newborn hearing screening. Outcomes including CMV PCR result and confirmation of hearing loss by an otorhinolaryngologist specialist were documented. RESULTS: Two-hundred thirty-six newborns were included and a saliva sample was collected in 98% (231/236) of them. The result of CMV PCR was available at a median of 9 days (7-10 days) of life and in 96% of cases within the first month of life. Two neonates were infected with CMV. The result of the otorhinolaryngologist assessment was available in 75% (178/236) of cases at a median of 16 days (9-26 days). Hearing loss was confirmed in 2.8% (5/178). The 2 infected neonates had hearing loss confirmed at 5 and 8 days of life and were treated with valganciclovir at days 9 and 16, respectively. CONCLUSIONS: The result of this study confirms that targeted cCMV screening is feasible in these French settings.

CLinical Assessment of WEB device in Ruptured aneurYSms (CLARYS): results of 1-month and 1-year assessment of rebleeding protection and clinical safety in a multicenter study.

BACKGROUND: The primary goal of the CLARYS study is to assess the protection against rebleeding when treating ruptured bifurcation aneurysms with the Woven EndoBridge (WEB) device. METHODS: The CLARYS study is a prospective, multicenter study conducted in 13 European centers. Patients with ruptured bifurcation aneurysms were consecutively included between February 2016 and September 2017. The primary endpoint was defined as the rebleeding rate of the target aneurysm treated with the WEB within 30 days postprocedure. Secondary endpoints included periprocedural and postprocedural adverse events, total procedure and fluoroscopy times, and modified Rankin Scale score at 1 month and 1 year. RESULTS: Sixty patients with 60 ruptured bifurcation aneurysms to be treated with the WEB were included. A WEB device was successfully implanted in 93.3%. The rebleeding rate at 1 month and 1 year was 0%. The mean fluoroscopy time was 27.0 min. Twenty-three periprocedural complications were observed in 18 patients and resolved without sequelae in 16 patients. Two of these complications were attributed to the procedure and/or the use of the WEB, leading to a procedure/device-related intraoperative complication rate of 3.3%. Overall mortality at 1 month and 1 year was 1.7% and 3.8%, respectively and overall morbidity at 1 month and 1 year was 15% and 9.6%, respectively. WEB-related 1-month and 1-year morbidity and mortality was 0%. CONCLUSIONS: The interim results of CLARYS show that the endovascular treatment of ruptured bifurcation aneurysms with the WEB is safe and effective and, in particular, provides effective protection against rebleeding. It may induce profound change in the endovascular management of ruptured bifurcation aneurysms.