Obese patientss with nonalcoholic steatohepatitis (NASH) are particularly prone to developing severe forms of coronavirus disease 19 (COVID-19). The gut-to-lung axis is critical during viral infections of the respiratory tract, and a change in the gut microbiota's composition might have a critical role in disease severity. Here, we investigated the consequences of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the gut microbiota in the context of obesity and NASH. To this end, we set up a nutritional model of obesity with dyslipidemia and NASH in the golden hamster, a relevant preclinical model of COVID-19. Relative to lean non-NASH controls, obese NASH hamsters develop severe inflammation of the lungs and liver. 16S rRNA gene profiling showed that depending on the diet, SARS-CoV-2 infection induced various changes in the gut microbiota's composition. Changes were more prominent and transient at day 4 post-infection in lean animals, alterations still persisted at day 10 in obese NASH animals. A targeted, quantitative metabolomic analysis revealed changes in the gut microbiota's metabolic output, some of which were diet-specific and regulated over time. Our results showed that specifically diet-associated taxa are correlated with disease parameters. Correlations between infection variables and diet-associated taxa highlighted a number of potentially protective or harmful bacteria in SARS-CoV-2-infected hamsters. In particular, some taxa in obese NASH hamsters (e.g. Blautia and Peptococcus) were associated with pro-inflammatory parameters in both the lungs and the liver. These taxon profiles and their association with specific disease markers suggest that microbial patterns might influence COVID-19 outcomes.
Background Varicella-zoster virus (VZV) is one of the main viruses responsible of acute encephalitis. However, data on the prognosis and neurologic outcome of critically ill patients with VZV encephalitis are limited. We aimed to describe the clinical features of VZV encephalitis in the ICU and to identify factors associated with a favorable neurologic outcome. We performed a multicenter cohort study of patients with VZV encephalitis admitted in 18 ICUs in France between 2000 and 2017. Factors associated with a favorable neurologic outcome, defined by a modified Rankin Score (mRS) of 0–2 1 year after ICU admission, were identified by multivariable regression analysis. Results Fifty-five patients (29 (53%) men, median age 53 (interquartile range 36–66)) were included, of whom 43 (78%) were immunocompromised. ICU admission occurred 1 (0–3) day after the onset of neurological symptoms. Median Glasgow Coma Score at ICU admission was 12 (7–14). Cerebrospinal fluid examination displayed a median leukocyte count of 68 (13–129)/mm ³ , and a median protein level of 1.37 (0.77–3.67) g/L. CT scan and MRI revealed brain lesions in 30% and 66% of the cases, respectively. Invasive mechanical ventilation was implemented in 46 (84%) patients for a median duration of 13 (3–30) days. Fourteen (25%) patients died in the ICU. One year after ICU admission, 20 (36%) patients had a favorable neurologic outcome (mRS 0–2), 12 (22%) had significant disability (mRS 3–5), and 18 (33%) were deceased (lost to follow-up n = 5, 9%). On multivariable analysis, age (OR 0.92 per year, (0.88–0.97), p = 0.01), and invasive mechanical ventilation (OR 0.09 CI 95% (0.01–0.84), p = 0.03) reduced the likelihood of favorable neurologic outcome. Conclusion One in every three critically ill patients with VZV encephalitis had a favorable neurologic outcome 1 year after ICU admission. Older age and invasive mechanical ventilation were associated with a higher risk of disability and death.
Aim To provide practice guidelines about fertility preservation (FP) in oncology. Methods We selected 400 articles after a PubMed review of the literature (1987–2019). Recommendations Any child, adolescent and adult of reproductive age should be informed about the risk of treatment gonadotoxicity. In women, systematically proposed FP counselling between 15 and 38 years of age in case of treatment including bifunctional alkylating agents, above 6 g/m2 cyclophosphamide equivalent dose (CED), and for radiation doses on the ovaries ≥3 Gy. For postmenarchal patients, oocyte cryopreservation after ovarian stimulation is the first-line FP technique. Ovarian tissue cryopreservation should be discussed as a first-line approach in case of treatment with a high gonadotoxic risk, when chemotherapy has already started and in urgent cases. Ovarian transposition is to be discussed prior to pelvic radiotherapy involving a high risk of premature ovarian failure. For prepubertal girls, ovarian tissue cryopreservation should be proposed in the case of treatment with a high gonadotoxic risk. In pubertal males, sperm cryopreservation must be systematically offered to any male who is to undergo cancer treatment, regardless of toxicity. Testicular tissue cryopreservation must be proposed in males unable to cryopreserve sperm who are to undergo a treatment with intermediate or severe risk of gonadotoxicity. In prepubertal boys, testicular tissue preservation is: - recommended for chemotherapy with a CED ≥7500 mg/m2 or radiotherapy ≥3 Gy on both testicles. - proposed for chemotherapy with a CED ≥5.000 mg/m2 or radiotherapy ≥2 Gy. If several possible strategies, the ultimate choice is made by the patient.
Aortic dimensions and distensibility are key risk factors for aortic aneurysms and dissections, as well as for other cardiovascular and cerebrovascular diseases. We present genome-wide associations of ascending and descending aortic distensibility and area derived from cardiac magnetic resonance imaging (MRI) data of up to 32,590 Caucasian individuals in UK Biobank. We identify 102 loci (including 27 novel associations) tagging genes related to cardiovascular development, extracellular matrix production, smooth muscle cell contraction and heritable aortic diseases. Functional analyses highlight four signalling pathways associated with aortic distensibility (TGF-β, IGF, VEGF and PDGF). We identify distinct sex-specific associations with aortic traits. We develop co-expression networks associated with aortic traits and apply phenome-wide Mendelian randomization (MR-PheWAS), generating evidence for a causal role for aortic distensibility in development of aortic aneurysms. Multivariable MR suggests a causal relationship between aortic distensibility and cerebral white matter hyperintensities, mechanistically linking aortic traits and brain small vessel disease. Aortic distensibility is a risk factor for multiple cardiovascular events, but the genetic etiology is not well understood. Here, the authors identify genetic variants linked to aortic distensibility, highlighting mechanistic pathways and causal relationships between distensibility and both aortic aneurysms and brain small vessel disease.
Background There are currently few data on the outcome of acute myeloid leukemia (AML) in adolescents after allogeneic HSCT. The aim of this study is to describe the outcome and its specific risk factors for children, adolescents and young adults after a first allogeneic HSCT for AML. Methods In this retrospective study, we compared the outcome of AML patients receiving a first allogeneic HSCT between 2005 and 2017 according to their age at transplantation’s time: children (< 15 years, n = 564), adolescent and post-adolescent (APA) patients (15–25 years, n = 647) and young adults (26–40 years; n = 1434). Results With a median follow-up of 4.37 years (min–max 0.18–14.73 years), the probability of 2-year overall survival (OS) was 71.4% in children, 61.1% in APA patients and 62.9% in young adults ( p = 0.0009 for intergroup difference). Both relapse and non-relapse mortality (NRM) Cumulative Incidence (CI) estimated at 2 years were different between the age groups (30.8% for children, 35.2% for APA patients and 29.4% for young adults— p = 0.0254, and 7.0% for children, 10.6% for APA patients and 14.2% for young adults, p < 0.0001; respectively). Whilst there was no difference between the three groups for grade I to IV acute GVHD CI at 3 months, the chronic GVHD CI at 2 years was higher in APA patients and young adults (31.4% and 36.4%, respectively) in comparison to the children (17.5%) ( p < 0.0001). In multivariable analysis, factors associated with death were AML cytogenetics (HR1.73 [1.29–2.32] for intermediate risk 1, HR 1.50 [1.13–2.01] for intermediate risk 2, HR 2.22 [1.70–2.89] for high cytogenetics risk compared to low risk), use of TBI ≥ 8 Grays (HR 1.33 [1.09–1.61]), disease status at transplant (HR 1.40 [1.10–1.78] for second Complete Remission (CR), HR 2.26 [1.02–4.98] for third CR and HR 3.07 [2.44–3.85] for active disease, compared to first CR), graft source (HR 1.26 [1.05–1.50] for Peripheral Blood Stem Cells compared to Bone Marrow) and donor age (HR 1.01 (1–1.02] by increase of 1 year). Conclusion Age is an independent risk factor for NRM and extensive chronic GVHD. This study suggests that APA patients with AML could be beneficially treated with a chemotherapy-based MAC regimen and bone marrow as a stem cells source.
PurposeTo compare the rate of vaginal birth between double-balloon catheter and oxytocin alone for induction of labor in women with one previous cesarean section and an unfavorable cervix.Materials and methodsA retrospective and observational study was conducted from 2013 to 2017, at the Saint-Etienne University Hospital where women received induction with a double-balloon catheter for 12 h and at the Grenoble Alpes University Hospital where women received induction with a low‐dose oxytocin infusion. Primary outcome was the rate of vaginal birth.ResultsOut of 1920 women eligible for attempting a vaginal birth after one previous cesarean section, 501 had a labor induction. Among women with an unfavorable cervix, 160 received a double-balloon catheter in Saint Etienne and 152 received oxytocin alone in Grenoble. The vaginal birth rate was higher in the double-balloon catheter group (61% versus 47% in the oxytocin group). An induction of labor with oxytocin alone reduced chances of vaginal birth (aOR 0.38 CI-95% [0.22–0.66]) compared to cervical ripening with double-balloon catheter. The perinatal morbidity was similar in the two groups. There was, however, 3.9% uterine rupture in the oxytocin group versus 0.6% in the double-balloon group (p = 0.11).Conclusion For induction of labor in women with one previous cesarean section and with unfavorable cervix, cervical ripening with a double-balloon catheter increases the rate of vaginal birth without increased risk of uterine rupture.
Background Cerebral amyloid angiopathy (CAA) is an age-related small vessel disease, characterised pathologically by progressive deposition of amyloid β in the cerebrovascular wall. The Boston criteria are used worldwide for the in-vivo diagnosis of CAA but have not been updated since 2010, before the emergence of additional MRI markers. We report an international collaborative study aiming to update and externally validate the Boston diagnostic criteria across the full spectrum of clinical CAA presentations. Methods In this multicentre, hospital-based, retrospective, MRI and neuropathology diagnostic accuracy study, we did a retrospective analysis of clinical, radiological, and histopathological data available to sites participating in the International CAA Association to formulate updated Boston criteria and establish their diagnostic accuracy across different populations and clinical presentations. Ten North American and European academic medical centres identified patients aged 50 years and older with potential CAA-related clinical presentations (ie, spontaneous intracerebral haemorrhage, cognitive impairment, or transient focal neurological episodes), available brain MRI, and histopathological assessment for CAA diagnosis. MRI scans were centrally rated at Massachusetts General Hospital (Boston, MA, USA) for haemorrhagic and non-haemorrhagic CAA markers, and brain tissue samples were rated by neuropathologists at the contributing sites. We derived the Boston criteria version 2.0 (v2.0) by selecting MRI features to optimise diagnostic specificity and sensitivity in a prespecified derivation cohort (Boston cases 1994–2012, n=159), then externally validated the criteria in a prespecified temporal validation cohort (Boston cases 2012–18, n=59) and a geographical validation cohort (non-Boston cases 2004–18; n=123), comparing accuracy of the new criteria to the currently used modified Boston criteria with histopathological assessment of CAA as the diagnostic standard. We also assessed performance of the v2.0 criteria in patients across all cohorts who had the diagnostic gold standard of brain autopsy. Findings The study protocol was finalised on Jan 15, 2017, patient identification was completed on Dec 31, 2018, and imaging analyses were completed on Sept 30, 2019. Of 401 potentially eligible patients presenting to Massachusetts General Hospital, 218 were eligible to be included in the analysis; of 160 patient datasets from other centres, 123 were included. Using the derivation cohort, we derived provisional criteria for probable CAA requiring the presence of at least two strictly lobar haemorrhagic lesions (ie, intracerebral haemorrhages, cerebral microbleeds, or foci of cortical superficial siderosis) or at least one strictly lobar haemorrhagic lesion and at least one white matter characteristic (ie, severe visible perivascular spaces in centrum semiovale or white matter hyperintensities in a multispot pattern). The sensitivity and specificity of these criteria were 74·8% (95% CI 65·4–82·7) and 84·6% (71·9–93·1) in the derivation cohort, 92·5% (79·6–98·4) and 89·5% (66·9–98·7) in the temporal validation cohort, 80·2% (70·8–87·6) and 81·5% (61·9–93·7) in the geographical validation cohort, and 74·5% (65·4–82·4) and 95·0% (83·1–99·4) in all patients who had autopsy as the diagnostic standard. The area under the receiver operating characteristic curve (AUC) was 0·797 (0·732–0·861) in the derivation cohort, 0·910 (0·828–0·992) in the temporal validation cohort, 0·808 (0·724–0·893) in the geographical validation cohort, and 0·848 (0·794–0·901) in patients who had autopsy as the diagnostic standard. The v2.0 Boston criteria for probable CAA had superior accuracy to the current Boston criteria (sensitivity 64·5% [54·9–73·4]; specificity 95·0% [83·1–99·4]; AUC 0·798 [0·741–0854]; p=0·0005 for comparison of AUC) across all individuals who had autopsy as the diagnostic standard. Interpretation The Boston criteria v2.0 incorporate emerging MRI markers of CAA to enhance sensitivity without compromising their specificity in our cohorts of patients aged 50 years and older presenting with spontaneous intracerebral haemorrhage, cognitive impairment, or transient focal neurological episodes. Future studies will be needed to determine generalisability of the v.2.0 criteria across the full range of patients and clinical presentations. https://authors.elsevier.com/c/1fPQ45FFzKub~Z
Contexte L'impact de l'exposition d'intérieur à de multiples micro-organismes, de la naissance à l'enfance, sur le développement ultérieur d'asthme demeure irrésolu. Le manque d'études utilisant un échantillonnage standardisé et une analyse microbienne ciblée explique en partie cela. En 2011, la cohorte Étude longitudinale française depuis l'enfance (ELFE) a défini une procédure d'échantillonnage standardisée, utilisée pour le ciblage qPCR de 3193 logements : les dépoussiéreurs électrostatiques (EDC). La cohorte est suivie depuis 2011 et une étude cas-témoin nichée (60 enfants asthmatiques versus 60 enfants non-asthmatiques) a été conçue pour capter les profils microbiens à l’âge de 5 ans et de de les comparer avec les profils microbiens de la même population à la naissance. Méthodes Les réponses des parents à l'étude internationale sur l'asthme et les allergies dans les questionnaires de l'enfance ont été utilisées. La sélection cas-témoins a été effectuée dans la population ayant un EDC exploitable à la naissance et à 5 ans. Les cas d'asthmes ont été diagnostiqués selon les critères stricts d'utilisation de médicaments par inhalateur et de crises de respiration sifflante. Les témoins étaient sains et sans symptômes de la naissance à 5 ans. Résultats Mille sept cent cinquante-trois (1753) enfants avaient un EDC à la naissance ainsi qu’à 5 ans; 52 % sont des garçons, 15 % asthmatiques et 8 % ont des animaux domestiques. Nos critères ont abouti à 402 témoins et 67 cas, qui ont été appariés individuellement selon la saison de naissance et la région d'habitation. Discussion/Conclusion Nous avons détecté 27 % à 88 % de moisissures, 92 % à 98 % de bactéries et 48 % d'acariens. Sur la base de six espèces fongiques, une famille et deux genres de bactéries et un acarien, nous avons réussi à établir six profils d'habitat différents à travers la France. Nous sommes actuellement en train de vérifier les profils microbiologiques des 60 cas et témoins. Déclaration de liens d'intérêts Les auteurs déclarent ne pas avoir de liens d'intérêts.
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.
Objective In comparison to eutrophic fetuses, intra uterine growth restriction fetuses (IUGR) have a higher risk of perinatal morbi-mortality. There are no guidelines on the labor induction of labor (IOL) method to be performed in IUGR. The main objective was to determine fetal and maternal predictive factors of successful induction in IUGR fetuses from 36 weeks. Study design We conducted a retrospective cohort single-center study including 320 women with a cephalic fetal presentation. Labour was induced after 36 weeks for suspected IUGR between January 2013 and December 2019. Results Among the 320 patients, 246 were delivered vaginally (76.9%) and 74 had a cesarean (23.1%). Prognostic factors for successful IUGR induction were nonscarring uterus (OR 8.41; 95%CI [2.92-24.21]), absence of preeclampsia (OR 7.14; 95%CI [2.42-21.03]), multiparity (OR 4.32; 95%CI [1.83-10.18]), normal fetal heart rate before IOL (OR 2.99; 95%CI [1.24-7.22]) and BMI < 30 (OR 3.54; 95%CI [1.62-7.72]). Doppler abnormalities, method and number of line of IOL, cervical evaluation were not significant in our study. Conclusion The prognostic factors for successful IUGR induction are essentially maternal. Thus, a low BMI, multiparity, nonscarring uterus, absence of preeclampsia, and a normal FHR are good prognostic factors in IUGR induction.
Background Since the latest 2017 French guidelines, knowledge about idiopathic pulmonary fibrosis has evolved considerably. Methods Practical guidelines were drafted on the initiative of the Coordinating Reference Center for Rare Lung Diseases, led by the French Language Pulmonology Society (SPLF), by a coordinating group, a writing group, and a review group, with the involvement of the entire OrphaLung network, pulmonologists practicing in various settings, radiologists, pathologists, a general practitioner, a health manager, and a patient association. The method followed the "Clinical Practice Guidelines" process of the French National Authority for Health (HAS), including an online vote using a Likert scale. Results After a literature review, 54 guidelines were formulated, improved, and then validated by the working groups. These guidelines addressed multiple aspects of the disease: epidemiology, diagnostic procedures, quality criteria and interpretation of chest CT scans, lung biopsy indication and procedures, etiological workup, methods and indications for family screening and genetic testing, assessment of the functional impairment and prognosis, indication and use of antifibrotic agents, lung transplantation, management of symptoms, comorbidities and complications, treatment of chronic respiratory failure, diagnosis and management of acute exacerbations of fibrosis. Conclusion These evidence-based guidelines are intended to guide the diagnosis and practical management of idiopathic pulmonary fibrosis.
The French Transplant Health Authority (Agence de la Biomédecine) has broadened its organ- and tissue-donation criteria to include pediatric patients whose death is defined by circulatory criteria and after the planned withdrawal of life-sustaining therapies (WLST) (Maastricht category III). A panel of pediatric experts convened to translate data in the international literature into recommendations for organ and tissue donation in this patient subgroup. The panel estimated that, among children aged 5 years or over with severe irreversible neurological injury (due to primary neurological injury or post-anoxic brain injury) and no progression to brain death, the number of potential donors, although small, deserves attention. The experts emphasized the importance of adhering strictly to the collegial procedure for deciding to withdraw life support. Once this decision is made, the available data should be used to evaluate whether the patient might be a potential donor, before suggesting organ donation to the parents. This suggestion should be reserved for parents who have unequivocally manifested their acceptance of WLST. The discussion with the parents should include both the pediatric intensive care unit (PICU) team under the responsibility of a senior physician and the hospital organ- and tissue-procurement team. All recommendations about family care during the end of life of a child in the PICU must be followed. The course and potential challenges of organ donation in Maastricht-III pediatric patients must be anticipated. The panel of experts recommended strict compliance with French recommendations (by the Groupe Francophone de Réanimation et Urgences Pédiatriques) about WLST and providing deep and continuous sedation until circulatory arrest. The experts identified the PICU as the best place to implement life-support discontinuation and emphasized the importance of returning the body to the PICU after organ donation. French law prohibits the transfer of these patients from one hospital to another. A description of the expert-panel recommendations regarding the organization and techniques appropriate for children who die after controlled circulatory arrest (Maastricht III) is published simultaneously in the current issue of this journal..
Background Empiric antifungal therapy is considered the standard-of-care for high-risk neutropenic patients with persistent fever. The impact of a pre-emptive, diagnostic-driven approach based on galactomannan (GM) screening and chest CT-scan on demand on survival and on the risk of invasive fungal disease (IFD) during the first weeks of high-risk neutropenia is unknown. Methods Patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and allogeneic hematopoietic cell transplant recipients were randomly assigned to receive caspofungin empirically (Arm A) or pre-emptively (Arm B). All patients received fluconazole 400 mg daily as prophylaxis. The primary endpoint of this non-inferiority study was overall survival (OS) 42 days after randomization. Results Of 556 patients recruited, 549 were eligible: 275 in Arm A, 274 in Arm B. Eighty percent of the patients had AML or MDS requiring high-dose chemotherapy and 93% of them were in first induction phase. At day 42, the OS was not inferior in Arm B (96.7%; 95% confidence interval (CI), 93.8 - 98.3%) when compared to Arm A (93.1%; 95% CI, 89.3 - 95.5%). The rates of IFDs at day 84 were not significantly different, 7.7% (95%CI, 4.5–10.8%) in Arm B versus 6.6% (95%CI, 3.6–9.5%) in Arm A, respectively. The rate of patients receiving caspofungin was significantly lower in Arm B (27%) than in Arm A (63%) (p < 0.001). Conclusions The pre-emptive antifungal strategy was safe for high-risk neutropenic patients given fluconazole as prophylaxis, halving the number of patients receiving antifungals without excess mortality or IFDs.
In this study, we aimed to identify the factors related to esophageal impaction following button battery (BB) ingestion in children. PilBouTox, a prospective multicentric observational cohort study, was conducted from French Poison Control Centers between June 1, 2016 and May 31, 2018. Children (0-12 years old) with BB ingestion were included. After ingestion, patients were monitored for 21 days or more if they remained symptomatic (maximum 1 year). Causes of ingestion, clinical manifestations, medical management, and the outcomes were recorded. In total, 415 patients were included; among them, 35 had esophageal impaction and 14 had severe complications or died. Seven symptoms were closely related (relative risk (RR) > 30) to esophageal impaction: anorexia, drooling, dyspnea, fever, hemodynamic instability, pallor, and pain. Furthermore, BBs > 15 mm were related to esophageal impaction (RR = 19, CI95% [4.1; 88]). The absence of initial symptoms was a protective factor for esophageal impaction (RR = 0.013, CI95% [0.002; 0.1]). Nine symptoms were closely related (RR > 30) to major effects and death: dyspnea, cough, dysphagia, drooling, fever, hemodynamic instability, pain, pallor, and vomiting. Seven symptoms were related to esophageal impaction and their rapid recognition could help to ensure that the patient is taken to a health care facility. Nine factors were related to the major effects of BB ingestion. We recommended an X-ray as soon as possible to determine the position of the BB.Trial Registry: Clinical Trial ID: NCT03708250, https://clinicaltrials.gov/ct2/show/NCT03708250.
Background Ventilator-associated lower respiratory tract infections (VA-LRTI) are common in patients with severe SARS-CoV-2 pneumonia. The aim of this ancillary analysis of the coVAPid multicenter observational retrospective study is to assess the relationship between corticosteroid adjuvant administration and the incidence of VA-LRTI. Methods Planned ancillary analysis of a multicenter retrospective European cohort in 36 ICUs. Adult patients receiving invasive mechanical ventilation for more than 48 hours for a SARS-CoV-2 pneumonia were consecutively included between February and May 2020. VA-LRTI diagnosis required strict definition with clinical, radiological and microbiological documentation. We assessed the association of VA-LRTI with corticosteroid administration using univariate and multivariate cause-specific Cox’s proportional hazard models with adjustment on prespecified confounders. Results 545 patients were included, of whom 191 (35%) received corticosteroids. The proportional hazard assumption for the effect of corticosteroids on the incidence of VA-LRTI was violated (p=0.018) indicating that this effect varied during the ICU stay. We found a lower risk of VA-LRTI for corticosteroid treated patients during the first days in the ICU and an increased risk for longer ICU stay. By modeling the effect of corticosteroids with time dependent coefficients, the association between corticosteroids and the incidence of VA-LRTI was not significant (overall effect p=0.068), with time-dependent hazard ratios (95% confidence interval) of 0.45 (0.18 to 1.10) at day 2, 0.89 (0.62 to 1.27) at day 7, 1.38 (0.99 to 1.92) at day 14 and 1.80 (1.08 to 2.98) at day 21. Conclusions No significant association was found between corticosteroid adjuvant therapy and the incidence of VA-LRTI, although a significant time-varying effect of corticosteroids was identified along the 28-day follow-up.
Background Owing to growing number of therapeutic options with similar efficacy and safety, we compared the acceptability of therapeutic maintenance regimens in inflammatory bowel disease (IBD). Methods From a nationwide study (24 public or private centers), IBD patients were consecutively included for 6 weeks. A dedicated questionnaire including acceptability numerical scales (ANS) ranging from 0 to 10 (highest acceptability) was administered to both patients and related physicians. Results Among 1850 included patients (65.9% with Crohn’s disease), the ANS were 8.68 ± 2.52 for oral route (first choice in 65.8%), 7.67 ± 2.94 for subcutaneous injections (first choice in 21.4%), and 6.79 ± 3.31 for intravenous infusions (first choice in 12.8%; P < .001 for each comparison). In biologic-naïve patients (n = 315), the most accepted maintenance regimens were oral intake once (ANS = 8.8 ± 2.2) or twice (ANS = 6.9 ± 3.4) daily and subcutaneous injections every 12 or 8 weeks (ANS = 7.9 ± 3.0 and ANS = 7.2 ± 3.2, respectively). Among 342 patients with prior exposure to subcutaneous biologics, the preferred regimens were subcutaneous injections (≥2 week-intervals; ANS between 9.1 ± 2.3 and 8.1 ± 2.7) and oral intake once daily (ANS = 7.7 ± 3.2); although it was subcutaneous injections every 12 or 8 weeks (ANS = 8.4 ± 3.0 and ANS = 8.1 ± 3.0, respectively) and oral intake once daily (ANS = 7.6 ± 3.1) in case of prior exposure to intravenous biologics (n = 1181). The impact of usual therapeutic escalation or de-escalation was mild (effect size <0.5). From patients’ acceptability perspective, superiority and noninferiority cutoff values should be 15% and 5%, respectively. Conclusions Although oral intake is overall preferred, acceptability is highly impacted by the rhythm of administration and prior medication exposures. However, SC treatment with long intervals between 2 injections (≥8 weeks) and oral intake once daily seems to be the most accepted modalities.
According to experts' guidelines, lymph node surgical excision (SE) is the standard of care for lymphoma diagnosis. However, core needle biopsy (CNB) has widely spread in the lymphoma diagnostic work-up over years. The aim of this study was i) to display the largest multicentric inventory of lymph nodes sampled either by CNB or SE in patients with suspected lymphoma and ii) to compare their diagnostic performance in routine pathological practice. We reviewed 32,285 cases registered in the French Lymphopath network that provides a systematic expert review of all lymphoma diagnoses in France, and evaluated the percentage of CNB and SE cases accurately diagnosed according to the WHO classification. Although CNB led to 92.3% complete diagnoses and appeared to be a reliable method of investigation for most patients with suspected lymphoma, it remained less conclusive than SE that yielded 98.1% of complete diagnoses. Discordance rates between referral and expert diagnoses were higher on CNB (23.1%) than SE (21.2%; P=0.004) and referral pathologists provided more cases with unclassified lymphoma or equivocal lesion through CNB. In such cases, expert review improved the diagnostic work-up by classifying ~90% of cases, with higher efficacy on SE (93.3%) than CNB (81.4%; P<10-6). Moreover, diagnostic concordance for reactive lesions was higher on SE than CNB (P=0.009). Overall, although CNB accurately diagnoses lymphoma in most instances, it increases the risk of erroneous or non-definitive conclusions. This large-scale survey also emphasizes the need for systematic expert review in cases of lymphoma suspicion, especially in those sampled by CNB.
Background Cancer-associated thrombotic microangiopathy (TMA) is a rare disease, with a poor prognosis. The classical treatment is urgent chemotherapy. Few data are available on the efficacy of plasma exchange (PE) and eculizumab in these patients. Methods Cases of cancer-related TMA treated between January 2008 and December 2019 in 12 French treatment centres were retrospectively analysed, excluding cases associated with chemotherapy and stem cell transplantation. Patients were divided into four groups depending on the treatment received: none, PE therapy alone, chemotherapy, with or without PE therapy, or eculizumab, with or without chemotherapy and PE therapy. Results The data of 59 patients with cancer-associated TMA were analysed. Twenty of these cases were related to a cancer recurrence. The cancer was metastatic in 90% of cases (53/59). Bone marrow invasion was observed in 20/41 biopsies. Some laboratory results, including DIC, high ferritin and CRP, were suggestive of cancer. None of the 16 patients whose alternative complement pathway was assessed had abnormal levels of protein expression or activity. The median survival time was 27 days. Chemotherapy was significantly associated with improved survival, with a 30-day survival rate of 85% (17/20) among patients who received PE and chemotherapy, versus 20% (3/15) among patients who received PE alone. Patients treated with eculizumab in addition to chemotherapy and PE therapy did not have longer overall survival or higher haematological remission rates than those treated with chemotherapy and PE therapy alone. Renal remission rates were non-significantly higher, and times to remission non-significantly shorter, in the eculizumab group. Conclusions Nephrologists and oncologists should make themselves aware of cancer diagnoses in patients with TMA and bone marrow biopsies should be performed systematically in these cases. All 59 patients had poor survival outcomes, but patients treated with urgent initiation of chemotherapy survived significantly longer than those who were not.
Importance: The benefit of high-dose dexamethasone and oxygenation strategies vs standard of care for patients with severe acute hypoxemic respiratory failure (AHRF) caused by COVID-19 pneumonia is debated. Objectives: To assess the benefit of high-dose dexamethasone compared with standard of care dexamethasone, and to assess the benefit of high-flow nasal oxygen (HFNo2) or continuous positive airway pressure (CPAP) compared with oxygen support standard of care (o2SC). Design, setting, and participants: This multicenter, placebo-controlled randomized clinical trial was conducted in 19 intensive care units (ICUs) in France from April 2020 to January 2021. Eligible patients were consecutive ICU-admitted adults with COVID-19 AHRF. Randomization used a 2 × 3 factorial design for dexamethasone and oxygenation strategies; patients not eligible for at least 1 oxygenation strategy and/or already receiving invasive mechanical ventilation (IMV) were only randomized for dexamethasone. All patients were followed-up for 60 days. Data were analyzed from May 26 to July 31, 2021. Interventions: Patients received standard dexamethasone (dexamethasone-phosphate 6 mg/d for 10 days [or placebo prior to RECOVERY trial results communication]) or high-dose dexamethasone (dexamethasone-phosphate 20 mg/d on days 1-5 then 10 mg/d on days 6-10). Those not requiring IMV were additionally randomized to o2SC, CPAP, or HFNo2. Main outcomes and measures: The main outcomes were time to all-cause mortality, assessed at day 60, for the dexamethasone interventions, and time to IMV requirement, assessed at day 28, for the oxygenation interventions. Differences between intervention groups were calculated using proportional Cox models and expressed as hazard ratios (HRs). Results: Among 841 screened patients, 546 patients (median [IQR] age, 67.4 [59.3-73.1] years; 414 [75.8%] men) were randomized between standard dexamethasone (276 patients, including 37 patients who received placebo) or high-dose dexamethasone (270 patients). Of these, 333 patients were randomized among o2SC (109 patients, including 56 receiving standard dexamethasone), CPAP (109 patients, including 57 receiving standard dexamethasone), and HFNo2 (115 patients, including 56 receiving standard dexamethasone). There was no difference in 60-day mortality between standard and high-dose dexamethasone groups (HR, 0.96 [95% CI, 0.69-1.33]; P = .79). There was no significant difference for the cumulative incidence of IMV criteria at day 28 among o2 support groups (o2SC vs CPAP: HR, 1.08 [95% CI, 0.71-1.63]; o2SC vs HFNo2: HR, 1.04 [95% CI, 0.69-1.55]) or 60-day mortality (o2SC vs CPAP: HR, 0.97 [95% CI, 0.58-1.61; o2SC vs HFNo2: HR, 0.89 [95% CI, 0.53-1.47]). Interactions between interventions were not significant. Conclusions and relevance: In this randomized clinical trial among ICU patients with COVID-19-related AHRF, high-dose dexamethasone did not significantly improve 60-day survival. The oxygenation strategies in patients who were not initially receiving IMV did not significantly modify 28-day risk of IMV requirement. Trial registration: ClinicalTrials.gov Identifier: NCT04344730; EudraCT: 2020-001457-43.
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