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Objetivos: Descrever ocorrência rara de infiltração do sistema nervoso central (SNC) por linfoma Hodgkin (LH) clássico simulando meningioma e fazer uma revisão de literatura sobre este evento. Materiais e métodos: Relato de caso com revisão de informações de prontuário e revisão de dados da literatura. Resultados: Homem, 33 anos, com diagnóstico de LH clássico subtipo celularidade mista, estadio IIA, há 7 anos. Os tratamentos incluíram quimioterapia (QT) de 1ª linha com 6 ciclos de BEACOPP padrão e radioterapia (RT) de campo envolvido. Findado tratamento, houve abandono de seguimento por 53 meses com readmissão por recaída tardia histologicamente comprovada de LH clássico com massa bulky paravertebral lombar e infiltração pulmonar e isquiosacral (estadio IVX). Tratamento de 2ª linha consistiu de QT com esquema ICE (ifosfamida, carboplatina e etoposideo). Paciente recusou terapia de consolidação por autotransplante e aceitou RT de áreas bulky, após o que ocorreu nova perda de seguimento. Após 6 meses, paciente cursou com disfagia, cefaléia e convulsões tônico-clônicas. Foram identificadas adenomegalias cervicais e paralisia facial central à direita. Estudo por ressonância nuclear magnética de crânio evidenciou volumosa (10 × 8,8 × 4 cm) lesão expansiva frontal extra-axial com invasão do seio sagital superior e sinais de hipertensão intracraniana. Para a elucidação, biópsia da lesão em SNC foi realizada. Achados de biópsia de congelação favoreceram o diagnóstico de meningioma e a ressecção completa da massa foi realizada. Ao anatomopatológico da lesão de SNC evidenciou-se neoplasia fusocelular, sem atipias, permeada por linfócitos pequenos e células atípicas com núcleo grande e hipercromático, considerando-se as hipóteses de LH ou meningioma rico em células linfoplasmocitárias. À imuno-histoquímica revelou marcação CD30+, CD15+, PAX5+, Receptor de Progesterona e Somatostatin Receptor 2 negativos em grandes células sugestivas de células de Hodgkin, achados compatíveis com LH, e semelhantes aos encontrados em nova biópsia de adenomegalia cervical. Paciente permanece em seguimento irregular com adesão insatisfatória à terapia com dexametasona e brentuximabe vedotina, havendo, por isto, a progressão de déficits neurológicos com comprometimento de status performance, logo, cuidados com a intenção não curativa. Discussão: O envolvimento do SNC pelo LH é considerado raro e a incidência estimada é de 0,02-0,07% dos casos. Quando da infiltração do SNC, alteração do estado mental, déficits neurológicos e cefaleia são as alterações mais encontradas. Fundamental a comprovação diagnóstica por meio de biópsia mediante os diagnósticos diferenciais a serem considerados. As evidências sugerem uma variedade de terapias, incluindo RT para envolvimento isolado de SNC e RT associada a QT contendo agentes com penetração em SNC. Metotrexato intratecal, ressecção completa do tumor e autotransplante são também descritos. A infiltração do SNC por LH compromete grandemente o prognóstico e a sobrevida global estimada de 29 a 43 meses. Conclusão: O envolvimento do SNC por LH é raro. A ocorrência de alterações neurológicas não previstas em associação a LH primariamente refratário ou com recaída pode representar cenários em que a suspeita de infiltração do SNC deva ser considerada. A raridade da ocorrência em associação com a ausência de terapia específica torna o prognóstico sombrio.

Plastic pollution is widely recognized as one of the major threats to marine ecosystems. However, our knowledge on the ecological interactions between plastic and marine fauna is still limited. Here, we analyzed the substrate preferences for oviposition in the small-spotted catshark (Scyliorhinus canicula) and explored the influence of pollution, environmental conditions, and fishing pressure as potential drivers. For the first time, we report this catshark species using marine debris for oviposition, unraveling a behavioral shift in the oviposition substrate preferences towards plastics, particularly ghost fishing gear, when biological substrates are unavailable. Our results indicate that this behavioral change may be driven by the combined effects of plastic pollution and habitat degradation. Preferences also change with depth, with a larger preference for the hydrozoan Lytocarpia myriophyllum on the continental shelf, followed by sponges, as in this region mesophotic and deep benthic communities are still more abundant although impacted by human pressures. In contrast, on the continental slope, the preference shifts to tube-dwelling polychaetes and plastics, primarily ghost fishing gear, due to the limited availability of biological substrates in this region. We highlight that plastic-fish interactions may become increasingly recurrent as plastic substrates increase and habitat forming invertebrates decline due to trawl fishing and other anthropogenic activities, especially in the Mediterranean Sea. The implications of this behavior for catshark fitness are still largely unknown, which prompts further research concerning the potential impact on its survival and/or dispersal in the plastic age and highlights the urgency of preserving biogenic habitats., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Study Objective: Monitoring anaesthesia-related severe morbidity constitutes a good opportunity for assessing quality and safety of care in anaesthesia. Several recent studies attempted to describe and define indicators for anaesthesia-related severe morbidity with limitations: no formal experts' consensus process, overlap with surgical complications, no consensual definitions, inapplicability in clinical practice. The aim of this study was to provide a set of indicators for anaesthesia-related severe morbidity based on outcomes and using clinically useful consensual definitions., Design: 1/ scoping review of studies published in 2010-2021 on outcomes of anaesthesia-related severe morbidity with different definitions; 2/ International experts' consensus on indicators for anaesthesia-related severe morbidity with specific definitions using a Delphi process., Main Results: After including 142 studies, 68 outcomes for anaesthesia-related severe morbidity were identified and organized in 34 indicators divided into 8 categories (cardiovascular, respiratory, sepsis, renal, neurological, medication error, digestive and others). The indicators were then submitted to the experts. After 2 Delphi rounds, the 26 indicators retained by the experts with their corresponding consensual definition were: acute heart failure, cardiogenic shock, acute respiratory distress syndrome, pulmonary embolism and thrombosis, bronchospasm or laryngospasm, pneumonia, inhalation pneumonitis, pneumothorax, difficult or impossible intubation, atelectasis, self-extubation or accidental extubation, sepsis or septic shock, transient ischemic attack, postoperative confusion or delirium, post-puncture headache, medication error, liver failure, unplanned intensive care unit admission, multiple-organ failure., Conclusions: This study provides a new consensual set of indicators for anaesthesia-related severe morbidity with specific definitions, that could be easily applied in clinical practice as in research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Despite improved management of traumatic brain injury (TBI), it still leads to lifelong sequelae and disability, particularly in children. Chronic neuroinflammation (the so-called tertiary phase), in particular, microglia/macrophage and astrocyte reactivity, is among the main mechanisms suspected of playing a role in the generation of lesions associated with TBI. The role of acute neuroinflammation is now well understood, but its persistent effect and impact on the brain, particularly during development, are not. Here, we investigated the long-term effects of pediatric TBI on the brain in a mouse model., Methods: Pediatric TBI was induced in mice on postnatal day (P) 7 by weight-drop trauma. The time course of neuroinflammation and myelination was examined in the TBI mice. They were also assessed by magnetic resonance, functional ultrasound, and behavioral tests at P45., Results: TBI induced robust neuroinflammation, characterized by acute microglia/macrophage and astrocyte reactivity. The long-term consequences of pediatric TBI studied on P45 involved localized scarring astrogliosis, persistent microgliosis associated with a specific transcriptomic signature, and a long-lasting myelination defect consisting of the loss of myelinated axons, a decreased level of myelin binding protein, and severe thinning of the corpus callosum. These results were confirmed by reduced fractional anisotropy, measured by diffusion tensor imaging, and altered inter- and intra-hemispheric connectivity, measured by functional ultrasound imaging. In addition, adolescent mice with pediatric TBI showed persistent social interaction deficits and signs of anxiety and depressive behaviors., Conclusions: We show that pediatric TBI induces tertiary neuroinflammatory processes associated with white matter lesions and altered behavior. These results support our model as a model for preclinical studies for tertiary lesions following TBI., (Copyright © 2024. Published by Elsevier Inc.)

Microplastics in aquatic ecosystems harbor numerous microorganisms, including pathogenic species. The ingestion of these microplastics by commercial fish poses a threat to the ecosystem and human livelihood. Coastal lagoons are highly vulnerable to microplastic and microbiological pollution, yet limited understanding of the risks complicates management. Here, we present the main bacterial groups, including potentially pathogenic species, identified on microplastics in waters, sediments, and commercial fish from Ciénaga Grande de Santa Marta (CGSM), the largest coastal lagoon in Colombia. DNA metabarcoding allowed identifying 1760 bacterial genera on microplastics, with Aeromonas and Acinetobacter as the most frequent and present in all three matrices. The greatest bacterial richness and diversity were recorded on microplastics from sediments, followed by waters and fish. Biochemical analyses yielded 19 species of potentially pathogenic culturable bacteria on microplastics. Aeromonas caviae was the most frequent and, along with Pantoea sp., was found on microplastics in all three matrices. Enterobacter roggenkampii and Pseudomonas fluorescens were also found on microplastics from waters and fish. We propose management strategies for an Early Warning System against microbiological and microplastic pollution risks in coastal lagoons, illustrated by CGSM. This includes forming inter-institutional alliances for research and monitoring, accompanied by strengthening governance and health infrastructures., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate the performance of the 4PEPS score in the diagnosis of pulmonary embolism at the University Hospital of Bogodogo from January 1, 2021 to July 31, 2023., Methodology: This was a cross-sectional descriptive and analytical diagnostic study, running from January 1, 2021 to July 31, 2023. It took place in the infectious and tropical diseases departments, including a pneumology unit and a cardiology unit, of the Bogodogo University Hospital. Patients of both sexes with suspected pulmonary embolism who had undergone CT scan were included. The 4PEPS score was calculated and dichotomized into probable and improbable. It thus constituted the diagnostic test. CT scan was the gold standard. The accuracy of the diagnostic test was judged by the area under the ROC curve. An area under the curve between 0.70 and 1 would mean that the score was moderately informative to perfect., Results: Our study included 472 patients with suspected pulmonary embolism out of a total population of 1228 patients. Hospital prevalence was 21.7%. The mean age of patients was 54.3 years. Females accounted for 52.1% of cases, with a sex ratio of 0.93. The prevalence of pulmonary embolism in the different probability levels of the 4PEPS score was 13.3% for the very low level, 11.7% for the low level, 84.6% for the intermediate level and 93.3% for the high level. Sensitivity and specificity were 92.1% and 86.82% respectively. The positive and negative predictive values were 90.1% and 89.4% respectively. The area under the ROC curve was 0.91., Conclusion: In our study, the 4PEPS score showed good negative and positive predictive values. The use of this score will enable practitioners faced with diagnostic difficulties to make therapeutic decisions, reducing inappropriate prescriptions for thoracic angioscan., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Objectives: The value of C-reactive protein point-of-care testing (CRP POCT) to guide antibiotic prescriptions in adults has previously been emphasized. The aim of this study was to assess the impact of CRP POCT on antibiotic prescriptions by general practitioners (GPs) for suspected lower respiratory tract infections in children ≥3 years old and in adults., Methods: This was an open-label randomized trial (NCT03540706) conducted in 26 GPs in France between October 2019 and March 2023. Of the 404 participating patients, 207 (51.2%) were randomized to the CRP POCT group and 197 (48.8%) to the control group (i.e. no CRP POCT). During consultations, GPs measured CRP levels in patients randomized to the CRP POCT group. The primary endpoint was the proportion of patients in each group who were prescribed antibiotics by their GP during the consultation. Z-tests were used for comparisons., Results: The overall proportion of patients treated with antibiotics was similar in the CRP POCT (n = 89/207, 43% CI: 36.2, 50.0) and in the control group (n = 94/197, 47.7% CI: 40.6, 54.9), difference: -4.7 CI: -14.4, 5.0; p 0.3. Overall, 75% of the GPs followed CRP-based antibiotic prescription recommendations in the CRP POCT group., Discussion: CRP POCT did not reduce antibiotic prescriptions in this trial., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In the last decade, much attention was given to the study of physiological amyloid fibrils. These structures include A-bodies, which are the nucleolar fibrillar formations that appear in the response to acidosis and heat shock, and disassemble after the end of stress. One of the proteins involved in the biogenesis of A-bodies, regardless of the type of stress, is Von-Hippel Lindau protein (VHL). Known also as a tumor suppressor, VHL is capable to form amyloid fibrils both in vitro and in vivo in response to the environment acidification. As with most amyloidogenic proteins fusion with various tags is used to increase the solubility of VHL. Here, we first performed AFM-study of fibrils formed by VHL protein and by VHL fused with GST-tag (GST-VHL) at acidic conditions. It was shown that formed by full-length VHL fibrils are short heterogenic structures with persistent length of 2400 nm and average contour length of 409 nm. GST-tag catalyzes VHL amyloid fibril formation, superimpose chirality, increases length and level of hierarchy, but decreases rigidity of amyloid fibrils. The obtained data indicate that tagging can significantly affect the fibrillogenesis of the target protein., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: We evaluate the predictive and prognostic value of insulin-like growth factor-I (IGF-1), IGF binding protein-2 (IGFBP-2) and -3 (IGFBP-3) in patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC)., Methods: This is a retrospective analysis of a multi-institutional database comprising 753 patients who underwent RNU for UTUC and had a preoperative plasma available. Logistic and Cox regression analyses were performed. The discriminative ability and clinical utility of the models was calculated using the lasso regression test, area under receiver operating characteristics curves, C-index, and decision curve analysis (DCA)., Results: Lower preoperative plasma levels of IGFBP-2 and -3 independently correlated with increased risks of lymph node metastasis, pT3/4 disease, nonorgan confined disease, and worse recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) (all P ≤ .004). The addition of both IGFBP-2 and -3 to a postoperative multivariable model, that included standard clinicopathologic characteristics, improved the model's concordance index by 10%, 9%, and 8% for RFS, CSS, and OS, respectively. On DCA, addition of both IGFBP-2 and -3 to base models improved their performance for RFS, CSS, and OS by a statistically and clinically significant margin. Plasma IGF-1 was not associated with any of outcomes., Conclusions: We confirmed that a lower plasma levels of IGFBP-2 and -3 both are independent and clinically significant predictors of adverse pathological features and survival outcomes in UTUC patients treated with RNU. These findings might help guide the clinical decision-making regarding perioperative systemic therapy and follow-up scheduling., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Although all patients with cancer-associated thrombosis (CAT) have a high morbidity and mortality risk, certain groups of patients are particularly vulnerable. This may expose the patient to an increased risk of thrombotic recurrence or bleeding (or both), as the benefit-risk ratio of anticoagulant treatment may be modified. Treatment thus needs to be chosen with care. Such vulnerable groups include older patients, patients with renal impairment or thrombocytopenia, and underweight and obese patients. However, these patient groups are poorly represented in clinical trials, limiting the available data on which treatment decisions can be based. Meta-analysis of data from randomised clinical trials suggests that the relative treatment effect of direct oral factor Xa inhibitors (DXIs) and low molecular weight heparin (LMWH) with respect to major bleeding could be affected by advanced age. No evidence was obtained for a change in the relative risk-benefit profile of DXIs compared to LMWH in patients with renal impairment or of low body weight. The available, albeit limited, data do not support restricting the use of DXIs in patients with TAC on the basis of renal impairment or low body weight. In older patients, age is not itself a critical factor for choice of treatment, but frailty is such a factor. Patients over 70 years of age with CAT should undergo a systematic frailty evaluation before choosing treatment and modifiable bleeding risk factors should be addressed. In patients with renal impairment, creatine clearance should be assessed and monitored regularly thereafter. In patients with an eGFR less than 30mL/min/1.72m 2 , the anticoagulant treatment may need to be adapted. Similarly, platelet count should be assessed prior to treatment and monitored regularly. In patients with grade 3-4, thrombocytopenia (less than 50,000platelets/μL) treatment with a LMWH at a reduced dose should be considered. For patients with CAT and low body weight, standard anticoagulant treatment recommendations are appropriate, whereas in obese patients, apixaban may be preferred., (Copyright © 2024. Published by Elsevier Masson SAS.)

Background & Aims: Serum prealbumin is considered to be a sensitive predictor of clinical outcomes and a quality marker for nutrition support. However, its susceptibility to inflammation restricts its usage in critically ill patients according to current guidelines. We assessed the performance of the initial value of prealbumin and dynamic changes for predicting the ICU mortality and the effectiveness of nutrition support in critically ill patients., Methods: This monocentric study included patients admitted to the ICU between 2009 and 2016, having at least one initial prealbumin value available. Prospectively recorded data were extracted from the electronic ICU charts. We used both univariable and multivariable logistic regressions to estimate the performance of prealbumin for the prediction of ICU mortality. Additionally, the association between prealbumin dynamic changes and nutrition support was assessed via a multivariable linear mixed-effects model and multivariable linear regression. Performing subgroup analysis assisted in identifying patients for whom prealbumin dynamic assessment holds specific relevance., Results: We included 3136 patients with a total of 4942 prealbumin levels available. Both prealbumin measured at ICU admission (adjusted odds-ratio (aOR) 0.04, confidence interval (CI) 95% 0.01-0.23) and its change over the first week (aOR 0.02, CI 95 0.00-0.19) were negatively associated with ICU mortality. Throughout the entire ICU stay, prealbumin dynamic changes were associated with both cumulative energy (estimate: 33.2, standard error (SE) 0.001, p < 0.01) and protein intakes (1.39, SE 0.001, p < 0.01). During the first week of stay, prealbumin change was independently associated with mean energy (6.03e-04, SE 2.32e-04, p < 0.01) and protein intakes (1.97e-02, SE 5.91e-03, p < 0.01). Notably, the association between prealbumin and energy intake was strongest among older or malnourished patients, those suffering from increased inflammation and those with high disease severity. Finally, prealbumin changes were associated with a positive mean nitrogen balance at day 7 only in patients with SOFA <4 (p = 0.047)., Conclusion: Prealbumin measured at ICU admission and its change during the first-week serve as an accurate predictor of ICU mortality. Prealbumin dynamic assessment may be a reliable tool to estimate the effectiveness of nutrition support in the ICU, especially among high-risk patients., Competing Interests: Conflict of interest E.P. received a research grant from Nestle Health Science, speaking honoraria from Fresenius Kabi & Baxter, and congressional reimbursement from Fresenius Kabi and Nutricia., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

This article addresses the management of venous thromboembolism in patients with malignant brain tumours, including both primary and secondary (metastatic) tumours. The available data on patients on venous thromboembolism recurrence and bleeding risks in patients with brain tumours is limited, since these patients have been excluded from most randomised, interventional, head-to-head, clinical trials comparing low molecular weight heparins to vitamin K antagonists or to direct oral factor Xa inhibitors. More information is available from retrospective observational studies, which however were generally small, and carried a high risk of confounding. Their findings suggest that direct factor Xa inhibitor use is associated with lower rates of intracranial haemorrhage compared with low molecular weight heparins. Overall, the safety profile of direct oral factor Xa inhibitors when used to prevent venous thromboembolism recurrence in patients with either primary or secondary brain tumours appears to be favourable. The available data are in favour of using an anticoagulant at a full therapeutic dose in patients with primary and secondary brain tumours experiencing a venous thromboembolism, although they are not yet sufficiently robust to permit recommending a direct factor Xa inhibitor over low-molecular weight heparin., (Copyright © 2024. Published by Elsevier Masson SAS.)

Resting-state eyes-closed electroencephalographic (rsEEG) alpha rhythms are dominant in posterior cortical areas in healthy adults and are abnormal in subjective memory complaint (SMC) persons with Alzheimer's disease amyloidosis. This exploratory study in 161 SMC participants tested the relationships between those rhythms and seed-based resting-state functional magnetic resonance imaging (rs-fMRI) connectivity between thalamus and visual cortical networks as a function of brain amyloid burden, revealed by positron emission tomography and cognitive reserve, measured by educational attainment. The SMC participants were divided into 4 groups according to 2 factors: Education (Edu+ and Edu-) and Amyloid burden (Amy+ and Amy-). There was a statistical interaction (p < 0.05) between the two factors, and the subgroup analysis using estimated marginal means showed a positive association between the mentioned rs-fMRI connectivity and the posterior rsEEG alpha rhythms in the SMC participants with low brain amyloidosis and high CR (Amy-/Edu+). These results suggest that in SMC persons, early Alzheimer's disease amyloidosis may contrast the beneficial effects of cognitive reserve on neurophysiological oscillatory mechanisms at alpha frequencies and connectivity between the thalamus and visual cortical networks., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Interneuronopathies are a group of neurodevelopmental disorders characterized by deficient migration and differentiation of gamma-aminobutyric acidergic interneurons resulting in a broad clinical spectrum, including autism spectrum disorders, early-onset epileptic encephalopathy, intellectual disability, and schizophrenic disorders. SP9 is a transcription factor belonging to the Krüppel-like factor and specificity protein family, the members of which harbor highly conserved DNA-binding domains. SP9 plays a central role in interneuron development and tangential migration, but it has not yet been implicated in a human neurodevelopmental disorder., Methods: Cases with SP9 variants were collected through international data-sharing networks. To address the specific impact of SP9 variants, in silico and in vitro assays were carried out., Results: De novo heterozygous variants in SP9 cause a novel form of interneuronopathy. SP9 missense variants affecting the glutamate 378 amino acid result in severe epileptic encephalopathy because of hypomorphic and neomorphic DNA-binding effects, whereas SP9 loss-of-function variants result in a milder phenotype with epilepsy, developmental delay, and autism spectrum disorder., Conclusion: De novo heterozygous SP9 variants are responsible for a neurodevelopmental disease. Interestingly, variants located in conserved DNA-binding domains of KLF/SP family transcription factors may lead to neomorphic DNA-binding functions resulting in a combination of loss- and gain-of-function effects., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: the study's objective was to determine impact of COVID-19 on the prognosis of pulmonary embolism., Patients and Methods: An analytical multicenter cross-sectional study with retrospective data collection was carried out in three university hospitals and a private clinic in Ouagadougou from March, 2020 to July 2021. It included consecutive patients hospitalized for PE confirmed on chest CT angiography or by the association an acute cor pulmonale on echocardiography-Doppler with deep vein thrombosis on venous ultrasound-Doppler of the lower limbs and having carried out a COVID-19 test (RT-PCR or rapid diagnostic test). Control cases consisted of all COVID-19 negative PE cases. Data comparison was carried out using the Epi info 7 software. A univariate then multivariate analysis allowed the comparison of the prognosis of the two subpopulations. The significance level retained was p < 0.05., Results: 96 patients with COVID-19+ and 70 COVID-19- PE were included. The prevalence of PE in patients hospitalized for COVID-19 was 7.05%. The average patient age was 61.5±17 years for COVID-19+ patients and 49.6±15.9 years for COVID-19- patients. Pulmonary condensation syndrome (p=0.007), desaturation (p=0.0003) and respiratory distress syndrome (p=0.006) were more common in COVID-19+ patients. The hospital death rate was 27.1% in COVID-19+ patients and 10% in COVID-19- patients (p=0.0024). Age > 65 years and COVID-19 pneumonia were the independent factors of death., Conclusion: COVID-19 is associated with clinical severity and excess mortality in patients with pulmonary embolism., Competing Interests: Déclaration de liens d'intérêts Les auteurs déclarent n'avoir aucun lien d'intérêt., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Competing Interests: Declaration of interests We declare no competing interests.

The determination of boron isotopes (δ 11 B) represents a powerful tool for a variety of applications such as the reconstruction of past ocean pH and atmospheric pCO 2 from the analysis of marine biogenic carbonates. In recent years, MC-ICP-MS has gained popularity over other techniques thanks to its superior sample throughput and high ionization efficiency. This study evaluates, for the first time, the performance of the Nu Instruments Plasma 3 MC-ICP-MS for measuring δ 11 B using different sample introduction systems and detector configurations. The main goal is to provide a detailed methodology for nanogram-scale boron isotope analysis through a straightforward approach that can be easily adopted. Boron (B) purification from the carbonate matrix was performed through micro-distillation, using a temperature of 95 °C and a minimum heating duration of 15 h, allowing the full recovery of B from up to 3 mg of carbonate mass. We attained blank values (on average 14 ± 6 pg, 1 SD, n = 27) comparable to the lowest micro-distillation blanks reported in the literature. Three sample introduction systems were tested, and the 30 μL min -1 nebuliser system outperformed the 50 and 170 μL min -1 systems in terms of signal intensity per mass of B. Two detector configurations were used based on the total boron signal intensity achieved: (1) FC11/FC12, with two Faraday cups fitted to 10 11  Ω and 10 12  Ω amplifier resistors to detect 11 B and 10 B ion beams, respectively, and (2) FC12/IC, with which we investigated, for the first time, the feasibility of combining an ion counter for detecting 10 B, and a Faraday cup fitted to a 10 12  Ω amplifier for 11 B. The FC12/IC configuration provided accurate results compared to the use of two Faraday cups for total boron signals lower than 0.35 V (∼12 ng of B in the analysed solution). The proposed analytical procedure was validated through the analysis of several reference materials with varying boron amounts, including clam JCt-1, coral JCp-1, NIST RM 8301 Foram and Coral solutions, and boric acid ERM-AE121. Furthermore, the long-term reproducibility was assessed with two in-house standards (coral CLD-1 and foraminifera GINF-1), providing values of 25.68 ± 0.23 ‰ (2SD, n = 53; with 14-36 ng of B) and 14.90 ± 0.16 ‰ (2SD, n = 12; with 11-16 ng of B), respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Acute chest syndrome (ACS) is a life-threatening complication of sickle cell disease (SCD). Although respiratory pathogens are frequently detected in children with ACS, their respective role in triggering the disease is still unclear. We hypothesized that the incidence of ACS followed the unprecedented population-level changes in respiratory pathogen dynamics after COVID-19-related nonpharmaceutical interventions (NPIs)., Research Question: What is the respective role of respiratory pathogens in ACS epidemiology?, Study Design and Methods: This study was an interrupted time series analysis of patient records from a national hospital-based surveillance system. All children aged < 18 years with SCD hospitalized for ACS in France between January 2015 and May 2022 were included. The monthly incidence of ACS per 1,000 children with SCD over time was analyzed by using a quasi-Poisson regression model. The circulation of 12 respiratory pathogens in the general pediatric population over the same period was included in the model to assess the fraction of ACS potentially attributable to each respiratory pathogen., Results: Among the 55,941 hospitalizations of children with SCD, 2,306 episodes of ACS were included (median [interquartile range] age, 9 [5-13] years). A significant decrease was observed in ACS incidence after NPI implementation in March 2020 (-29.5%; 95% CI, -46.8 to -12.2; P = .001) and a significant increase after lifting of the NPIs in April 2021 (24.4%; 95% CI, 7.2 to 41.6; P = .007). Using population-level incidence of several respiratory pathogens, Streptococcus pneumoniae accounted for 30.9% (95% CI, 4.9 to 56.9; P = .02) of ACS incidence over the study period and influenza 6.8% (95% CI, 2.3 to 11.3; P = .004); other respiratory pathogens had only a minor role., Interpretation: NPIs were associated with significant changes in ACS incidence concomitantly with major changes in the circulation of several respiratory pathogens in the general population. This unique epidemiologic situation allowed determination of the contribution of these respiratory pathogens, in particular S pneumoniae and influenza, to the burden of childhood ACS, highlighting the potential benefit of vaccine prevention in this vulnerable population., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: N. O. reports travel grants from GlaxoSmithKline, Pfizer, and Sanofi. A. R. reports travel grants from Pfizer and AstraZeneca and personal fees from MSD outside the submitted work. A. V. reports personal fees from Sanofi, Moderna, GlaxoSmithKline, and MSD. R. C. reports speaking and lecture fees from Pfizer, Sanofi, GlaxoSmithKline, and MSD; and funding and travel grants from Pfizer. E. V. reports grants from Santé Publique France, Pfizer, and MSD. F. A. reports honoraria from Pfizer, GlaxoSmithKline, MSD, and Sanofi outside the submitted work. None declared (Z. A., Z. V., F. K., A. L., L.-L. P., L. L., A. F., M. C., C. L., F. G., B. K.)., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Treatment options are limited for patients with high-risk non-muscle-invasive bladder cancer (NMIBC) with disease recurrence after bacillus Calmette-Guérin (BCG) treatment and who are ineligible for/refuse radical cystectomy. FGFR alterations are commonly detected in NMIBC. We evaluated the activity of oral erdafitinib, a selective pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, versus intravesical chemotherapy in patients with high-risk NMIBC and select FGFR3/2 alterations following recurrence after BCG treatment., Patients and Methods: Patients aged ≥18 years with recurrent, BCG-treated, papillary-only high-risk NMIBC (high-grade Ta/T1) and select FGFR alterations refusing or ineligible for radical cystectomy were randomized to 6 mg daily oral erdafitinib or investigator's choice of intravesical chemotherapy (mitomycin C or gemcitabine). The primary endpoint was recurrence-free survival (RFS). The key secondary endpoint was safety., Results: Study enrollment was discontinued due to slow accrual. Seventy-three patients were randomized 2 : 1 to erdafitinib (n = 49) and chemotherapy (n = 24). Median follow-up for RFS was 13.4 months for both groups. Median RFS was not reached for erdafitinib [95% confidence interval (CI) 16.9 months-not estimable] and was 11.6 months (95% CI 6.4-20.1 months) for chemotherapy, with an estimated hazard ratio of 0.28 (95% CI 0.1-0.6; nominal P value = 0.0008). In this population, safety results were generally consistent with known profiles for erdafitinib and chemotherapy., Conclusions: Erdafitinib prolonged RFS compared with intravesical chemotherapy in patients with papillary-only, high-risk NMIBC harboring FGFR alterations who had disease recurrence after BCG therapy and refused or were ineligible for radical cystectomy., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Monitoring delirium in critically ill patients is recognized as a major challenge. Although involving certified nursing assistants could be a valuable help in this field, such strategy has never been formally investigated., Objectives: Following theoretical training, we conducted a prospective multicenter study assessing the diagnostic accuracy of a CAM-ICU delirium screening strategy performed by CNAs in clinical settings, compared to parallel blinded evaluations conducted by nurses and physicians., Methods: From October 2020 to June 2022, adult intensive care patients admitted in three French University teaching hospitals with Richmond Agitation Sedation Scale ≥-2 were independently assessed for delirium by the three members of the care team (clinical nursing assistant, nurse and physician) using CAM-ICU in a random order. Physician's assessment served as the reference standard for comparisons., Results: We analyzed results from 268 triplets of CAM-ICU assessments performed sequentially on 203 patients. Prevalence of delirium was 22%. Compared to physician's assessments, clinical nursing assistants demonstrated a sensitivity (Se) of 88% CI95% [80-96] and a specificity (Sp) of 95% [92-98] in detecting delirium. There was no significant difference in the performance of clinical nursing assistants and nurses (Se = 90 % [82-97] p = 0.77, Sp = 98 % [95-100] p = 0.19). We observed high agreement between results obtained by physicians and clinical nursing assistants (ĸ = 0.82) and clinical nursing assistants performance remained consistent in the subgroups at higher risk of delirium., Conclusion: Evaluation of the CAM-ICU by clinical nursing assistants is feasible and should be seen as an opportunity to increase routine monitoring of delirium in intensive care patients., Implication for Clinical Practice: Delirium is a severe and underestimated complication of intensive care unit stay. This study results demonstrate the great performance of trained clinical nursing assistants in detecting delirium using the CAM-ICU. Further research is needed to define the most effective role for clinical nursing assistants in the routine management of delirium in intensive care patients., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JM-C reports personal fees and non-financial support from Drager, GE Healthcare, Sedana Medical, Baxter, and AOP Health; personal fees from Fisher and Paykel Healthcare, GSK, Guilead, Orion, Philips Medical, and Fresenius Medical Care; and non-financial support from LFB and Bird Corporation, outside of the submitted work., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To study the 6MWT and NT-proBNP contribution to the prognosis evaluation of patients with NYHA class II-III heart failure in the Yalgado Ouédraogo Teaching Hospital., Methods: We carried out a nine months prospective observational cohort from the 1 st February to the 31 st October 2020. Patients with NYHA class II-III HF who consented to participate were included in the study. We identified two variables of interest: death and readmission., Results: We included 50 patients with congestive heart failure representing 37.3% of heart failure. The average follow up time of patients was 154.58 ± 74.8 days. Twelve patients (24%) were readmited and 11 passed away with five during hospitalisation. On admission, The average distance on the 6MWT (194.6 ± 85.5 m) on admission and average NT-proBNP (5812.1±4729.4 ng/L) measured on admission and before discharge wasn't significantly correlated to the risk of death and re-hospitalisation. The average distance on the 6MWT before discharge (306.2±84.6) was significantly correlated to an increase risk of death and re-hospitalisation. Patients with an increase in NT-proBNP superior to 30% from measurement on admission to the one before discharge had a high risk of re-hospitalisation and death compare to those with a decrease of more than 30% with a moderate to good correlation coefficient of 0.6 between the two., Conclusion: 6MWT and NT-proBNP variations from admission to discharge have been necessary to evaluate the prognosis of patients with CHF., Competing Interests: Conflit d'intérêts Les auteurs ne déclarent aucun conflit d'intérêts., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Increasing amount of anthropogenic litter in the marine environment has provided an enormous number of substrates for a wide range of marine organisms, thus serving as a potential vector for the transport of fouling organisms. Here, we examined the fouling organisms on different types of stranded litter (plastic, glass, rubber, foam sponge, cloth, metal and wood) on eight beaches along the southeast coast of India. In total, 17 encrusting species belonging to seven phyla (Arthropoda, Bryozoa, Mollusca, Annelida, Cnidaria, Chlorophyta and Foraminifera) were identified on 367 items, with one invasive species, the mussel Mytella strigata, detected. The most common species associated with marine litter were the cosmopolitan bryozoans Jellyella tuberculata (%O = 31.64 %) and J. eburnea (28.61 %), the barnacle species Lepas anserifera (29.97 %), Amphibalanus amphitrite (22.34 %) and Amphibalanus sp. (14.16 %), and the oyster species Saccostrea cucullata (13.62 %) and Magallana bilineata (5.44 %). We also reported the first records on stranded litter of four species: the gastropod species Pirenella cingulata and Umbonium vestiarium, the foraminiferan Ammonia beccarii, and the oyster M. bilineata. This study is thus the first documentation of marine litter as a vector for species dispersal in India, where the production and consumption of plastic rank among the highest in the world. We also highlight the increasing risk of invasions by non-indigenous organisms attached to debris along the southeast coast of India. Comprehensive monitoring efforts are thus needed to elucidate the type of vectors responsible for the arrival of invasive species in this region. Raising awareness and promoting education are vital components in fostering sustainable solutions to combat plastic pollution in the country and globally., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Sequential anti-programmed cell death protein 1 (PD-1) or anti-programmed death-ligand 1 (PD-L1) followed by small targeted therapy use is associated with increased prevalence of adverse events (AEs) in NSCLC. KRASG12C inhibitor sotorasib may trigger severe immune-mediated hepatotoxicity when used in sequence or in combination with anti-PD-(L)1. This study was designed to address whether sequential anti-PD-(L)1 and sotorasib therapy increases the risk of hepatotoxicity and other AEs., Methods: This is a multicenter, retrospective study of consecutive advanced KRAS G12C -mutant NSCLC treated with sotorasib outside clinical trials in 16 French medical centers. Patient records were reviewed to identify sotorasib-related AEs (National Cancer Institute Common Classification Criteria for Adverse Events-Version 5.0). Grade 3 and higher AE was considered as severe. Sequence group was defined as patients who received an anti-PD-(L)1 as last line of treatment before sotorasib initiation and control group as patients who did not receive an anti-PD-(L)1 as last line of treatment before sotorasib initiation., Results: We identified 102 patients who received sotorasib, including 48 (47%) in the sequence group and 54 (53%) in the control group. Patients in the control group received an anti-PD-(L)1 followed by at least one treatment regimen before sotorasib in 87% of the cases or did not receive an anti-PD-(L)1 at any time before sotorasib in 13% of the cases. Severe sotorasib-related AEs were significantly more frequent in the sequence group compared with those in the control group (50% versus 13%, p < 0.001). Severe sotorasib-related AEs occurred in 24 patients (24 of 48, 50%) in the sequence group, and among them 16 (67%) experienced a severe sotorasib-related hepatotoxicity. Severe sotorasib-related hepatotoxicity was threefold more frequent in the sequence group compared with that in the control group (33% versus 11%, p = 0.006). No fatal sotorasib-related hepatotoxicity was reported. Non-liver severe sotorasib-related AEs were significantly more frequent in the sequence group (27% versus 4%, p < 0.001). Severe sotorasib-related AEs typically occurred in patients who received last anti-PD-(L)1 infusion within 30 days before sotorasib initiation., Conclusions: Sequential anti-PD-(L)1 and sotorasib therapy are associated with a significantly increased risk of severe sotorasib-related hepatotoxicity and severe non-liver AEs. We suggest avoiding starting sotorasib within 30 days from the last anti-PD-(L)1 infusion., (Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background & Aims: After a prolonged intensive care unit (ICU) stay patients experience increased mortality and morbidity. The primary aim of this study was to assess the prognostic value of nutritional status, body mass composition and muscle strength, as assessed by body mass index (BMI), bioelectrical impedance analysis (BIA), handgrip (HG) test, and that of the biological features to predict one-year survival at the end of a prolonged ICU stay., Methods: This was a multicenter prospective observational study. Survivor patients older than 18 years with ICU length of stay >72 h were eligible for inclusion. BIA and HG were performed at the end of the ICU stay. Malnutrition was defined by BMI and fat-free mass index (FFMI). The primary endpoint was one-year mortality. Multivariable logistic regression was performed to determine parameters associated with mortality., Results: 572 patients were included with a median age of 63 years [53.5; 71.1], BMI of 26.6 kg/m 2 [22.8; 31.3], SAPS II score of 43 [31; 58], and ICU length of stay of 9 days [6; 15]. Malnutrition was observed in 142 (24.9%) patients. During the 1-year follow-up after discharge, 96 (18.5%) patients died. After adjustment, a low HG test score (aOR = 1.44 [1.11; 1.89], p = 0.01) was associated with 1-year mortality. Patients with low HG score, malnutrition, and Albuminemia <30 g/L had a one-year death rate of 41.4%. Conversely, patients with none of these parameters had a 1-year death rate of 4.1%., Conclusion: BIA to assess FFMI, HG and albuminemia at the end of ICU stay could be used to predict 1-year mortality. Their ability to identify patients eligible for a structured recovery program could be studied., Competing Interests: Conflicts of interest The authors declare that they have no conflict of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Current evidence-based clinical practice guidelines recommend the use of both low-molecular-weight heparin (LMWH) and direct factor Xa inhibitors (apixapan, edoxaban and rivaroxaban) as first-line options for the treatment of venous thromboembolism (VTE) in patients with cancer. However, most of these guidelines refer to the general cancer patient population and provide limited guidance for specific subgroups of patients at particularly high risk of bleeding, such as those with gastrointestinal cancers, primary or metastatic brain tumors, thrombocytopenia, or renal impairment. In these complex populations, the management of cancer-associated thrombosis (CAT) poses unique challenges and requires a nuanced approach based on the primum non nocere principle. This comprehensive review critically examines the relevant literature and discusses the therapeutic options currently available for the management of CAT in these special situations., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Objective: Our aim was to compare the prevalence of biofilm formation on antibiotic-impregnated (AIC) versus standard (SC) external ventricular drain (EVD) catheters., Methods: From March 2018 to November 2020, all consecutive EVD catheters inserted in adult patients were included. After removal, EVD catheters were analyzed under scanning electronic microscopy, on both extraluminal and intraluminal faces. Standard culture of catheter tips was also performed., Results: Overall, 114 catheters were included in 101 patients. There were 48 AICs and 66 SCs. Standard culture showed that ventriculostomy-related colonization was more frequent in SC than in AIC (26 vs. 10%; P = 0.06). Gram-negative rods accounted for 25% of ventriculostomy-related colonization in AICs, and none was documented in SCs. Scanning electronic microscopy observation showed mature biofilm on more than 80% of catheters, without significant difference between catheter type. Also, there was no difference between extraluminal and intraluminal colonization rate. There were 2 ventriculostomy-related infections in each group (5% and 3% among AICs and SCs respectively; P = 1)., Conclusions: Mature biofilm presence on the intraluminal and the extraluminal faces is similar on AICs and SCs. Accordingly, AICs do not seem to efficiently prevent biofilm formation on EVD catheters. The impact of AICs on the microbiological epidemiology of colonizing biofilm should be further evaluated., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Mangroves in estuaries are highly vulnerable to the impacts of plastic litter pollution, because their location at river mouths and the high capacity of mangrove trees to trap plastic items. Here, we present new results on the abundance and characteristics of plastic litter during high and low rainfall seasons in mangrove waters and sediments of the Saija and Timbiqui River estuaries in the Colombian Pacific. In both estuaries, microplastics were the most common size (50-100 %), followed by mesoplastics (13-42 %) and macroplastics (0-8 %). Total abundances of plastic litter were higher during the high rainfall season (0.17-0.53 items/m -3 in surface waters and 764-832 items/m -2 in sediments), with a moderately positive relationship between plastic abundances recorded in both environmental matrices. The most common microplastics were foams and fragments. Continuous research and monitoring are required for a better understanding and management of these ecosystems and their threats., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The dumping of an estimated amount of 57 million tons of hazardous sulfide mine waste from 1957 to 1990 into Portmán's Bay (SE Spain) caused one of the most severe cases of persistent anthropogenic impact in Europe's costal and marine environments. The resulting mine tailings deposit completely infilled Portmán's Bay and extended seawards on the continental shelf, bearing high levels of metals and As. The present work, where Synchrotron XAS, XRF core scanner and other data are combined, reveals the simultaneous presence of arsenopyrite (FeAsS), scorodite (FeAsO₄·2H₂O), orpiment (As 2 S 3 ) and realgar (AsS) in the submarine extension of the mine tailings deposit. In addition to arsenopyrite weathering and scorodite formation, the, the presence of realgar and orpiment is discussed, considering both potential sourcing from the exploited ores and in situ precipitation from a combination of inorganic and biologically mediated geochemical processes. Whereas the formation of scorodite relates to the oxidation of arsenopyrite, we hypothesize that the presence of orpiment and realgar is associated to scorodite dissolution and subsequent precipitation of these two minerals within the mine tailings deposit under moderately reducing conditions. The occurrence of organic debris and reduced organic sulfur compounds evidences the activity of sulfate-reducing bacteria (SRB) and provides a plausible explanation to the reactions leading to the formation of authigenic realgar and orpiment. The precipitation of these two minerals in the mine tailings, according to our hypothesis, has important consequences for As mobility since this process would reduce the release of As into the surrounding environment. Our work provides for the first time valuable hints on As speciation in a massive submarine sulfide mine tailings deposit, which is highly relevant for similar situations worldwide., Competing Interests: Declaration of competing interest This manuscript has not been published and is not under consideration for publication elsewhere. We have no conflicts of interest to disclose., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Non-invasive ventilation (NIV) and oxygen therapy (high-flow nasal oxygen [HFNO] or standard oxygen) following extubation have never been compared in critically ill patients with obesity. We aimed to compare NIV (alternating with HFNO or standard oxygen) and oxygen therapy (HFNO or standard oxygen) following extubation of critically ill patients with obesity., Methods: In this multicentre, parallel group, pragmatic randomised controlled trial, conducted in 39 intensive care units in France, critically ill patients with obesity undergoing extubation were randomly assigned (1:1) to either the NIV group or the oxygen therapy group. Two randomisations were performed: first, randomisation to either NIV or oxygen therapy, and second, randomisation to either HFNO or standard oxygen (also 1:1), which was nested within the first randomisation. Blinding of the randomisation was not possible, but the statistician was masked to group assignment. The primary outcome was treatment failure within 3 days after extubation, a composite of reintubation for mechanical ventilation, switch to the other study treatment, or premature discontinuation of study treatment. The primary outcome was analysed by intention to treat. Effect of medical and surgical status was assessed. The reintubation within 3 days was analysed by intention to treat and after a post-hoc crossover analysis. This study is registered with ClinicalTrials.gov, number NCT04014920., Findings: From Oct 2, 2019, to July 17, 2021, of the 1650 screened patients, 981 were enrolled. Treatment failure occurred in 66 (13·5%) of 490 patients in the NIV group and in 130 (26·5%) of 491 patients in the oxygen-therapy group (relative risk 0·43; 95% CI 0·31-0·60, p<0·0001). Medical or surgical status did not modify the effect of NIV group on the treatment-failure rate. Reintubation within 3 days after extubation was similar in the non-invasive ventilation group and in the oxygen therapy group in the intention-to-treat analysis (48 (10%) of 490 patients and 59 (12%) of 491 patients, p=0·26) and lower in the NIV group than in the oxygen-therapy group in the post-hoc cross-over (51 (9%) of 560 patients and 56 (13%) of 421 patients, p=0·037) analysis. No severe adverse events were reported., Interpretation: Among critically ill adults with obesity undergoing extubation, the use of NIV was effective to reduce treatment-failure within 3 days. Our results are relevant to clinical practice, supporting the use of NIV after extubation of critically ill patients with obesity. However, most of the difference in the primary outcome was due to patients in the oxygen therapy group switching to NIV, and more evidence is needed to conclude that an NIV strategy leads to improved patient-centred outcomes., Funding: French Ministry of Health., Competing Interests: Declaration of interests SJ reports receiving consulting fees from Drager, Medtronic, Mindray, Fresenius, Baxter, and Fisher & Paykel. ADJ reports receiving remuneration for presentations from Medtronic, Drager and Fisher & Paykel. VL reported being a member of a research group that has received grants from Alexion, Baxter, MSD, Gilead, Sanofi, Celgène. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Nearly 1% to 2% of NSCLCs harbor RET fusions. Characterization of this rare population is still incomplete., Methods: This retrospective multicenter study included patients with any-stage RET positive (RET+) NSCLC from 31 cancer centers. Molecular profiling included DNA/RNA sequencing or fluorescence in situ hybridization analyses. Clinicobiological features and treatment outcomes (per investigator) with surgery, chemotherapy (CT), immune checkpoint blockers (ICBs), CT-ICB, multityrosine kinase inhibitors, and RET inhibitors (RETis) were evaluated., Results: For 218 patients included between February 2012 and April 2022, median age was 63 years, 56% were females, 93% had adenocarcinoma, and 41% were smokers. The most frequent fusion partner was KIF5B (72%). Median tumor mutational burden was 2.5 (range: 1-4) mutations per megabase, and median programmed death-ligand 1 expression was 10% (range: 0%-55%). The most common metastatic sites were the lung (50%), bone (43%), and pleura (40%). Central nervous system metastases were found at diagnosis of advanced NSCLC in 21% of the patients and at last follow-up or death in 31%. Overall response rate and median progression-free survival were 55% and 8.7 months with platinum doublet, 26% and 3.6 months with single-agent CT, 46% and 9.6 months with CT-ICB, 23% and 3.1 months with ICB, 37% and 3 months with multityrosine kinase inhibitor, and 76% and 16.2 months with RETi, respectively. Median overall survival was longer in patients treated with RETi versus no RETi (50.6 mo [37.7-72.1] versus 16.3 mo [12.7-28.8], p < 0.0001)., Conclusions: Patients with RET+ NSCLC have mainly thoracic and bone disease and low tumor mutational burden and programmed death-ligand 1 expression. RETi markedly improved survival, whereas ICB may be active in selected patients., (Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Introduction: We aimed to describe management and survival of patients with endometrial cancer (EC) ≥80 years to identify poor prognosis criteria., Methods: We collected clinical, histologic, surgical and follow-up data for patients with EC ≥ 80 years included in a multicenter French cohort (FRANCOGYN) who underwent primary surgical treatment from 1999 to 2019. The outcomes were overall survival (OS) and disease-free survival (DFS). We performed a descriptive analysis then a survival time analysis and comparison using the Kaplan Meier method and log-rank test., Results: Of the 1647 patients with EC who received treatment during the study period, 184 (11.17%) were ≥80 years. The mean age was 84 years (±3.34). Thirty-three patients (25.4%) died during the follow-up period and 26 relapsed (18.4%). Forty-nine patients were lost to follow-up (27.37%). The median follow-up time was 15.3 months (4.9-28.8). The median OS and DFS was 16.4 months (6.3-24.9) and 13.6 months (4.5-26.6), respectively. Eighty-three patients received adjuvant therapy (45.11%), out of 95 who had a formal or relative indication. Four patients received adjuvant chemotherapy (2.6%), out of 61 who had a formal or relative indication. Inappropriate or underuse of chemotherapy was significantly associated with a lower median OS of 12.6 months [3.73-24] versus 17.3 months [7.93-41.77] when performed appropriately (HR = 4.14, CI 95% [1.62-10.56]), and a lower median DFS of 10.83 months [3.73-24] versus 17.3 months [7.93-28.5] (HR = 9.04, CI 95% [2.04-40.12])., Conclusion: Our results suggest that very elderly patients with EC should receive adjuvant chemotherapy according to the standard care guidelines., Competing Interests: Declaration of competing interest I have no conflicts of interest to disclose., (Copyright © 2023 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Surgical resection of esophageal carcinoma is one of the mainstays of curative treatment for these cancers. During the last decade, numerous improvements in surgical approaches and perioperative management of these patients have resulted in a decrease in postoperative morbidity and mortality. Thus, centralization of patients with esophagogastric adenocarcinoma in high volume center, development of minimally invasive surgery and improvements in surgical imaging have led to reduce mortality rate, major pulmonary complication rate and postoperative chylothorax rate. Optimization of postoperative management with enhanced recovery programs has meanwhile reduced the rate of major postoperative complication and the hospital length of stay. The objective of this review is to give an overview of novelties and challenges regarding surgical management of patients with esophageal carcinoma., (Copyright © 2022 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Research Question: Can a saliva-based miRNA signature for endometriosis-associated infertility be designed and validated by analysing the human miRNome?, Design: The prospective ENDOmiARN study (NCT04728152) included 200 saliva samples obtained between January 2021 and June 2021 from women with pelvic pain suggestive of endometriosis. All patients underwent either laparoscopy, magnetic resonance imaging, or both. Patients diagnosed with endometriosis were allocated to one of two groups according to their fertility status. Data analysis consisted of identifying a set of miRNA biomarkers using next-generation sequencing, and development of a saliva-based miRNA signature of infertility among patients with endometriosis based on a random forest model., Results: Among the 153 patients diagnosed with endometriosis, 24% (n = 36) were infertile and 76% (n = 117) were fertile. Small RNA-sequencing of the 153 saliva samples yielded approximately 3712 M raw sequencing reads (from ∼13.7 M to ∼39.3 M reads/sample). Of the 2561 known miRNAs, the feature selection method generated a signature of 34 miRNAs linked to endometriosis-associated infertility. After validation, the most accurate signature model had a sensitivity, specificity and area under the curve of 100%., Conclusion: A saliva-based miRNA signature for endometriosis-associated infertility is reported. Although the results still require external validation before using the signature in routine practice, this non-invasive tool is likely to have a major effect on care provided to women with endometriosis., (Copyright © 2022 Reproductive Healthcare Ltd. All rights reserved.)

The SFE-AFCE-SFMN 2022 consensus deals with the management of thyroid nodules, a condition that is a frequent reason for consultation in endocrinology. In more than 90% of cases, patients are euthyroid, with benign non-progressive nodules that do not warrant specific treatment. The clinician's objective is to detect malignant thyroid nodules at risk of recurrence and death, toxic nodules responsible for hyperthyroidism or compressive nodules warranting treatment. The diagnosis and treatment of thyroid nodules requires close collaboration between endocrinologists, nuclear medicine physicians, surgeons, and other specialists. Therefore, this consensus statement was established jointly by 3 societies: the French Society of Endocrinology (SFE), French Association of Endocrine Surgery (AFCE) and French Society of Nuclear Medicine (SFMN); the various working groups included experts from other specialties (pathologists, radiologists, pediatricians, biologists, etc.). This section deals with the follow-up of thyroid nodules, low-grade tumors and microcarcinomas., (Copyright © 2022. Published by Elsevier Masson SAS.)

The SFE-AFCE-SFMN 2022 consensus deals with the management of thyroid nodules, a condition that is a frequent reason for consultation in endocrinology. In more than 90% of cases, patients are euthyroid, with benign non-progressive nodules that do not warrant specific treatment. The clinician's objective is to detect malignant thyroid nodules at risk of recurrence and death, toxic nodules responsible for hyperthyroidism or compressive nodules warranting treatment. The diagnosis and treatment of thyroid nodules requires close collaboration between endocrinologists, nuclear medicine physicians and surgeons, but also involves other specialists. Therefore, this consensus statement was established jointly by 3 societies: the French Society of Endocrinology (SFE), French Association of Endocrine Surgery (AFCE) and French Society of Nuclear Medicine (SFMN); the various working groups included experts from other specialties (pathologists, radiologists, pediatricians, biologists, etc.). Because of the emerging role of molecular fine-needle cytology diagnostics, the French Endocrine Society convened a panel of experts to review the evidence for the diagnostic value of molecular tests performed on cytologically indeterminate thyroid nodules., (Copyright © 2022. Published by Elsevier Masson SAS.)

The SFE-AFCE-SFMN 2022 consensus deals with the management of thyroid nodules, a condition that is a frequent reason for consultation in endocrinology. In more than 90% of cases, patients are euthyroid, with benign non-progressive nodules that do not warrant specific treatment. The clinician's objective is to detect malignant thyroid nodules at risk of recurrence and death, toxic nodules responsible for hyperthyroidism or compressive nodules warranting treatment. The diagnosis and treatment of thyroid nodules requires close collaboration between endocrinologists, nuclear medicine physicians and surgeons, but also involves other specialists. Therefore, this consensus statement was established jointly by 3 societies: the French Society of Endocrinology (SFE), French Association of Endocrine Surgery (AFCE) and French Society of Nuclear Medicine (SFMN); the various working groups included experts from other specialties (pathologists, radiologists, pediatricians, biologists, etc.). This section deals with thermal ablation, which may constitute an alternative to thyroid surgery in selected patients., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

The SFE-AFCE-SFMN 2022 consensus deals with the management of thyroid nodules, a condition that is a frequent reason for consultation in endocrinology. In more than 90% of cases, patients are euthyroid, with benign non-progressive nodules that do not warrant specific treatment. The clinician's objective is to detect malignant thyroid nodules at risk of recurrence and death, toxic nodules responsible for hyperthyroidism or compressive nodules warranting treatment. The diagnosis and treatment of thyroid nodules requires close collaboration between endocrinologists, nuclear medicine physicians and surgeons, but also involves other specialists. Therefore, this consensus statement was established jointly by 3 societies: the French Society of Endocrinology (SFE), French Association of Endocrine Surgery (AFCE) and French Society of Nuclear Medicine (SFMN); the various working groups included experts from other specialties (pathologists, radiologists, pediatricians, biologists, etc.). This section deals with epidemiology and challenges in the management of thyroid nodules., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

The SFE-AFCE-SFMN 2022 consensus deals with the management of thyroid nodules, a condition that is a frequent reason for consultation in endocrinology. In more than 90% of cases, patients are euthyroid with benign and non-progressive nodules that do not warrant specific treatment. The clinician's objective is to detect malignant thyroid nodules at risk of recurrence and death, toxic nodules responsible for hyperthyroidism or compressive nodules warranting treatment. The diagnosis and treatment of thyroid nodules requires close collaboration between endocrinologists, nuclear medicine physicians and surgeons but also involves other specialists. Therefore, this consensus statement was established jointly by 3 societies, the French Society of Endocrinology (SFE), the French Association of Endocrine Surgery (AFCE) and the French Society of Nuclear Medicine (SFMN); the various working groups included experts from other specialties (pathologists, radiologists, pediatricians, biologists, etc.). This specific text is a summary chapter taking up the recommendations from specific sections and presenting algorithms for the exploration and management of thyroid nodules., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Introduction: Multiple sclerosis (MS) is often associated with urological disorders, mainly urinary incontinence and retention, the management of which being necessary to improve patient's quality of life (QOL) and to reduce potential urological complications. Besides the classical treatments based mainly on anticholinergics and/or self-catheterization, several neuromodulation techniques have been tried in recent years to improve these urinary disorders. By this review, we aim at providing an overview of neuromodulation and electrostimulation approaches to manage urinary symptoms in MS patients., Materials and Methods: A literature search using MEDLINE was performed. Only papers in English, and describing the effects of neuromodulation in MS patients, were considered., Results: A total of 18 studies met inclusion criteria and were reviewed. Of them, four related to sacral neuromodulation (SNM), seven to percutaneous tibial nerve stimulation (PTNS), six to spinal cord stimulation (SCS), and one to transcranial magnetic stimulation (TMS)., Discussion: PTNS and SNM seem to be effective and safe therapeutic options for treating lower urinary tract symptoms in MS patients principally in case of overactive bladder (OAB) symptoms. Similarly, also SCS and TMS have been shown to be effective, despite the very limited number of patients and the small number of studies found in the literature. Interestingly, these techniques are effective even in patients who do not respond well to conservative therapies, such as anticholinergics. Furthermore, given their safety and efficacy, stimulations such as PTNS could be considered as a first-line treatment for OAB in MS patients, also considering that they are often preferred by patients to other commonly used treatments., (Copyright © 2022 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Ammonia is one of the main players in the pathogenesis of hepatic encephalopathy (HE) in patients with chronic liver diseases. The usefulness of measuring ammonemia has been debated since many years. New data reveal that besides helping in the differential diagnosis of HE, ammonemia could be a prognostic marker not only in patients with HE, but also in patients without any neurological symptoms, suggesting a potential toxic role of ammonia beyond the brain. Finally, targeting ammonemia while monitoring therapeutic response could be a way to improve outcomes in patients with HE., Competing Interests: Declaration of competing interest Dominique Thabut declares having received consultant fees from MedDay Pharmaceuticals, Gore, Alfasigma and Owkin. Nicolas Weiss declares having received consultant fees from MedDay Pharmaceuticals and Owkin., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Study Objective: Fibrinogen concentrate is used to treat severe postpartum hemorrhage despite limited evidence of its effectiveness in obstetric settings. We aimed to explore the association between its administration and maternal outcomes in women with severe postpartum hemorrhage., Design, Setting and Patients: This secondary analysis of the EPIMOMS prospective population-based study, exploring severe maternal morbidity, as defined by national expert consensus (2012-2013, 182,309 deliveries, France), included all women with severe postpartum hemorrhage and transfused with red blood cells during active bleeding., Measurements: The primary endpoint was maternal near-miss or death, and the secondary endpoint the total number of red blood cells units transfused., Interventions: We studied fibrinogen concentrate administration as a binary variable and then by the timing of its administration. We used multivariable analysis and propensity score matching to account for potential indication bias., Main Results: Among the 730 women with severe postpartum hemorrhage and transfused, 313 (42.9%) received fibrinogen concentrate, and 142 (19.5%) met near-miss criteria or died. The risk of near-miss or death was not significantly lower among the women treated with fibrinogen concentrate than among those not treated, in either the multivariable analysis (adjusted RR = 1.03; 95% CI, 0.72-1.49; P = 0.855) or the propensity score analysis (RR = 0.85; 95% CI, 0.55-1.32; P = 0.477). Among women treated with fibrinogen concentrate, administration more than three hours after red blood cell transfusion started was associated with a higher risk of near-miss or death than administration before or within 30 min after the transfusion began (adjusted RR = 2.07; 95% CI, 1.10-3.89; P = 0.024). Results were similar for the secondary endpoint., Conclusions: The use of fibrinogen concentrate in severe postpartum hemorrhage needing red blood cell transfusion during active bleeding is not associated with improved maternal outcomes., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Bladder cancer is currently ranked as the 8th most common cancer in France. However, the patient care pathway for this cancer is still not well known., Methods: A telephone survey was conducted with fifteen healthcare professionals, ten patients, and five family caregivers between November 2020 and March 2021. The objectives of this survey were to identify the major steps in the care pathway according to the medical, emotional and societal dimensions, for patients with locally advanced or metastatic bladder cancer, the associated barriers, and the initiatives to be implemented to improve it., Results: Several barriers were identified at different stages of the overall care pathway, including lack of knowledge of risk factors and warning signs of the disease by the general population and some healthcare professionals, difficulties linked to the announcement consultation, lack of psychological support for patients and their caregivers, and lack of information given about the disease and supportive care., Discussion: These results allowed us to identify three major initiatives which could improve the overall care pathway and the quality of life of patients and their caregivers: 1/implementation of a public awareness campaign on bladder cancer; 2/creation of booklets for patients and their caregivers to provide them with a source of reliable information; and 3/the creation of communication tools between healthcare professionals and patients to facilitate exchanges during consultations., (Copyright © 2022 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background: Although non-invasive ventilation (NIV) is recommended for immunocompromised patients with acute respiratory failure in the intensive care unit (ICU), it might have deleterious effects in the most severe patients. High-flow nasal oxygen (HFNO) alone might be an alternative method to reduce mortality. We aimed to determine whether HFNO alone could reduce the rate of mortality at day 28 compared with HFNO alternated with NIV., Methods: FLORALI-IM is a multicentre, open-label, randomised clinical trial conducted in 29 ICUs (28 in France and one in Italy). Adult immunocompromised patients with acute respiratory failure, defined as respiratory rate of 25 breaths per min or more and a partial pressure of arterial oxygen to inspired fraction of oxygen ratio of 300 mm Hg or lower, were randomly assigned (1:1) to HFNO alone (HFNO alone group) or NIV alternating with HFNO (NIV group). Key exclusion criteria were severe hypercapnia above 50 mm Hg, patients who could strongly benefit from NIV (ie, those with underlying chronic lung disease, with cardiogenic pulmonary oedema, or who were postoperative), severe shock, impaired consciousness defined as Glasgow coma score ≤12, urgent need for intubation, do not intubate order, and contraindication to NIV. Patients were assigned using computer-generated permuted blocks and were stratified according to centre and to the type of immunosuppression using a centralised web-based management system. In the HFNO alone group, patients were continuously treated by HFNO with a gas flow rate of 60 L/min or the highest tolerated. In the NIV group, patients were treated with NIV with a first session of at least 4 h, and then by sessions for a minimal duration of 12 h a day, with a dedicated ventilator, targeting a tidal volume below 8 mL/kg of predicted bodyweight, and with a positive end-expiratory level of at least 8 cm H 2 O. NIV sessions were interspaced with HFNO delivered as in the HFNO alone group. The primary outcome was mortality at day 28 and was assessed in the intention-to-treat population. Secondary outcomes were mortality in the ICU, in hospital, at day 90 and at day 180, intubation at day 28, length of stay in the ICU and in hospital, number of ventilator-free days at day 28, number of oxygenation technique-free days at day 28, and efficacy and tolerance of oxygenation techniques. The trial is registered with ClinicalTrials.gov, NCT02978300, and is complete., Findings: Between Jan 21, 2017 to March 4, 2019, of 497 eligible patients, 300 were randomly assigned but one patient withdrew consent, leaving 299 patients included in the intention-to-treat analysis (154 assigned to the HFNO alone group and 145 assigned to NIV group). Mortality rate at day 28 was 36% (95% CI 29·2 to 44·2; 56 of 154 patients) in the HFNO alone group and 35% (27·9 to 43·2; 51 of 145 patients) in the NIV group (absolute difference 1·2% [95% CI -9·6 to 11·9]; p=0·83). None of the other prespecified secondary outcomes were different between groups except for greater decreased discomfort after initiation of HFNO than with NIV (-4 mm on visual analogic scale [IQR -18 to 4] vs 0 mm [-16 to 17]; p=0·040)., Interpretation: In critically ill immunocompromised patients with acute respiratory failure, the mortality rate did not differ between HFNO alone and NIV alternating with HFNO. However, study power was limited, so results should be interpreted with caution., Funding: French Ministry of Health., Competing Interests: Declaration of interests RC reports grants from French Ministry of Health, grants from Le nouveau souffle, and grants from AADAIRC (Association Prestataire de Santé à Domicile) during the conduct of the study; grants from European Respiratory Society, non-financial support from Fisher & Paykel Healthcare, and non-financial support from Merck Sharp & Dohme outside of the submitted work. J-PF reports grants and non-financial support from Fisher & Paykel Healthcare during the conduct of the study; grants, personal fees, and non-financial support from Aerogen Ltd outside of the submitted work. SE reports grants and non-financial support from Fisher & Paykel Healthcare during the conduct of the study; grants, personal fees, and non-financial support from Aerogen Ltd outside of the submitted work. FP reports grants from ALEXION and personal fees from GILEAD outside of the submitted work. NT reports personal fees from Pfizer outside of the submitted work. CGi reports travel expense coverage to attend scientific meetings, personal fees, and logistic support from Fisher & Paykel, Resmed, and Lowenstein Medical. SJ reports personal fees for lectures from Hamilton Medical and Nihon Kohden. SN reports personal fees from Pfizer, Gilead, MSD, BioMérieux, Fischer & Paykel, and Bio Rad outside of the submitted work. GC reports personal fees from GSK outside of the submitted work. GG reports grants and personal fees from Fisher & Paykel outside of the submitted work. AWT reports travel expense coverage to attend scientific meetings and payment for lectures from Fisher & Paykel, Covidien, Maquet-Getinge, General Electric Healthcare. MD, GP, CGa, DC, AG, JB, CV, JD, GL, AH, J-PQ, JD, DBe, EV, DT, DBo, MA, CGu, TL, AK, and SR report no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)