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Multiple groups have reported on the usefulness of ablating in atrial regions exhibiting abnormal electrograms during atrial fibrillation (AF). Still, previous studies have suggested that ablation outcomes are highly operator- and center-dependent. This study sought to evaluate a novel machine learning software algorithm named VX1 (Volta Medical), trained to adjudicate multipolar electrogram dispersion.This study was a prospective, multicentric, nonrandomized study conducted to assess the feasibility of generating VX1 dispersion maps. In 85 patients, 8 centers, and 17 operators, we compared the acute and long-term outcomes after ablation in regions exhibiting dispersion between primary and satellite centers. We also compared outcomes to a control group in which dispersion-guided ablation was performed visually by trained operators.The study population included 29% of long-standing persistent AF. AF termination occurred in 92% and 83% of the patients in primary and satellite centers, respectively, p = 0.31. The average rate of freedom from documented AF, with or without antiarrhythmic drugs (AADs), was 86% after a single procedure, and 89% after an average of 1.3 procedures per patient (p = 0.4). The rate of freedom from any documented atrial arrhythmia, with or without AADs, was 54% and 73% after a single or an average of 1.3 procedures per patient, respectively (p 0.001). No statistically significant differences between outcomes of the primary versus satellite centers were observed for one (p = 0.8) or multiple procedures (p = 0.4), or between outcomes of the entire study population versus the control group (p 0.2). Interestingly, intraprocedural AF termination and type of recurrent arrhythmia (i.e., AF vs. AT) appear to be predictors of the subsequent clinical course.VX1, an expertise-based artificial intelligence software solution, allowed for robust center-to-center standardization of acute and long-term ablation outcomes after electrogram-based ablation.

BACKGROUND Careful selection of hepatocellular carcinoma (HCC) patients prior to chemoembolization treatment is a daily reality, and is even more necessary with new available therapeutic options in HCC. AIM To propose two new models to better stratify patients and maximize clinical benefit: “6 and 12” and “pre/post-TACE-predict” (TACE, transarterial chemoembolization). METHODS We evaluated and compared their performance in predicting overall survival with other systems {Barcelona Clinic Liver Cancer (BCLC), Albumin-Bilirubin (ALBI) and NIACE [Number of tumor(s), Infiltrative HCC, alpha-fetoprotein, Child-Pugh (CP), and performance status]} in two HCC French cohorts of different stages enrolled between 2010 and 2018. RESULTS The cohorts included 324 patients classified as BCLC stages A/B (cohort 1) and 137 patients classified as BCLC stages B/C (cohort 2). The majority of the patients had cirrhosis with preserved liver function. “Pre-TACE-predict” and “6 and 12” models identified three distinct categories of patients exhibiting different prognosis in cohort 1. However, their prognostic value was no better than the BCLC system or NIACE score. Liver function based on CP and ALBI grades significantly impacted patient survival. Conversely, the “post-TACE-predict” model had a higher predictive value than other models. The stratification ability as well as predictive performance of these new models in an intermediate/advanced stage population was less efficient (cohort 2). CONCLUSION The newly proposed “Pre-TACE-predict” and “6 and 12” models offer an interesting stratification into three categories in a recommended TACE population, as they identify poor candidates, those with partial control and durable response. The models' contribution was reduced in a population with advanced stage HCCs.

Due to the role of macrophages in glomerular inflammation, macrophage surface molecules such as CD163 and CD11b represent attractive biomarkers for monitoring Lupus Nephritis (LN). We hypothesize that their urinary levels may reflect kidney disease activity. Here, we first analyzed the levels of urinary soluble CD163 (U-sCD163) and CD11b (U-sCD11b) in a cohort of 40 patients with LN including 23 with active disease. U-sCD163 levels were significantly elevated in active LN and correlated with the renal activity score, in contrast to U-sCD11b. Then, we developed the pristane induced LN mouse model to analyze, in a longitudinal way, the evolution of U-sCD163 levels according to the glomerular inflammation progression and response to treatment. We showed an increase of U-sCD163 levels associated with glomerular immune-complex deposits on mouse kidney biopsies at an early stage of the disease and a correlation with inflammatory markers including interferon-α, C-reactive protein and tumor necrosis factor-α. In addition, we showed that U-sCD163 levels decreased following efficient hydroxychloroquine treatment. Altogether our results led us to conclude that U-sCD163 represent a non-invasive biomarker for LN reflecting glomerular inflammation. Although prospective study in patients with LN, active or not, are necessary, U-sCD163 could be proposed to monitor response to treatment.

Peroralcholangio-pancreatoscopy (POCP) is used for diagnosis and treatment of biliopancreatic disease when standard endoscopy (ERCP) or pre-operative imaging workup failed. We aimed to evaluate the diagnostic and therapeutic performance of POCP in complex biliary and pancreatic diseases.Patients with indeterminate biliary or pancreatic duct (PD) strictures, and patients with failure of complex biliary or pancreatic stones removal, were enrolled (six centers). The primary endpoint evaluated malignancy diagnostic performances (accuracy, sensitivity, specificity) and therapeutic performances (biliary or pancreatic stones extraction). Secondary endpoints evaluated: technical success in lesion visualization, ease of maneuvering, image quality and 30-days complications.From November 2016 to March 2018, 66 patients were included: 29/37 women/men, median age (IQR): 73 (64-82). Fifty-three patients had diagnostic POCP and 13 patients therapeutic POCP. One endoscopist with one or two endoscopy nurses performed 94% of the POCP. The 'POCP visual impression' of malignancy showed 92.0% sensitivity, 92.9 % specificity and 92.5 % overall accuracy compared with the final diagnosis. 'POCP-guided samples histological analysis' showed 75.0 % sensitivity and 91.6% specificity. The technical success for lesion visualization was 98.5%. The median VAS scores for insertions in bile and PD were respectively 9.0 (8.1-9.6) and 9.0 (8.8-10.0). Median VAS score for access to the lesion and image quality were respectively 9.0 (7.7-9.6) and 9.0 (7.9-9.7). Only three 30-day minor complications occurred without any major complications.POCP was an effective, safe and easy-to-use tool in routine clinical practice for the management of complex diagnostic and therapeutic biliary and pancreatic diseases (NCT03190343).

The “six-and-twelve” (6&12) score is a new hepatocellular carcinoma (HCC) prognostic index designed for recommended transarterial chemoembolization (TACE) candidates. Quick and easy to use by the sum of tumor size (cm) and number, this model identifies three groups with different survival time (the sum is ≤ 6; or > 6 but ≤ 12; or > 12); a survival benefit with TACE can be expected for HCC patients with a score not exceeding twelve. Recently, Wang ZW et al showed that the “6&12” model was the best system correlated with radiological response after the first TACE. Thus, we wanted to assess its survival prediction ability as well as its prognostic value and compared it to other systems (Barcelona Clinic Liver Cancer, Hong Kong Liver Cancer (HKLC) staging, Albumin-Bilirubin grade, tumor nodularity, infiltrative nature of the tumor, alpha-fetoprotein, Child-Pugh class, and Performance Status score, Cancer of the Liver Italian Program, Model to Estimate Survival for HCC scores, up-to-seven criteria) different from Wang ZW et al study in a multicenter French cohort of HCC including only recommended TACE candidates retrospectively enrolled. As previously demonstrated, we show that the "6&12” score can classify survival within this French cohort, with a prognostic value comparable to that of other systems, except HKLC staging. More importantly, the “6&12” score simplicity and ability in patients’ stratification outperform other systems for a routine clinical practice.

Background: Identifying a specific threshold level of SARS-CoV-2 antibodies that confers protection in immunocompromised patients has been very challenging. The aim was to assess the threshold of 264 binding antibody units (BAU)/ml using four different SARS-CoV-2 antibody assays (Abbott, Beckman, Roche, and Siemens) and to establish a new optimal threshold of protection for each of the four antibody assays. Methods: This study was performed on data retrieved from 69 individuals, who received at least one dose of the Pfizer/BioNTech BNT162b2 or Moderna COVID-19 vaccine (Spikevax) at the Alphabio Laboratory in Marseille, France (European Hospital, Alphabio – Biogroup). The results were compared to the percent inhibition calculated using a functional surrogate of a standardized virus neutralization test (Genscript). Results: Samples from 69 patients were analyzed. For a reference cutoff of 264 BAU/ml, assays showed moderate to good overall concordance with Genscript: 87% concordance for Abbott, 78% for Beckman, 75% for Roche, and 88% for Siemens. Overall concordance increased consistently after applying new thresholds, i.e., 148 BAU/ml (Abbott), 48 (Beckman), 559 (Roche), and 270 (Siemens). Conclusion: We suggest specific adjusted thresholds (BAU/ml) for the four commercial antibody assays that are used to assess pre-exposure prophylaxis in immunocompromised patients.

International audience; Background: During thyroid surgery, preservation of parathyroid gland (PG) feeding vessels is often impossible. The aim of the Fluogreen study was to determine the feasibility of using indocyanine green (ICG)-based intraoperative mapping angiograms of the PG (iMAP) to improve vascular preservation.Study design: This prospective study enrolled all patients undergoing thyroid lobectomy or total thyroidectomy at the Hôpital Européen Marseille between September and December 2018. After exploring the thyroid lobe by autofluorescence to locate the PGs, ICG solution was injected intravenously to locate the PG feeding vessels and guide dissection. A second ICG injection was administered at the end of the lobectomy to assess perfusion of the PGs. The primary outcome was the quality of the angiogram, scaled as iMAP 0 (not informative), iMAP 1 (general vascular pattern visible but no clear vascular pedicle flowing into the PG), or iMAP 2 (clear vascular pedicle flowing into the PG). The secondary outcome was the PG perfusion score at the end of surgery, scaled from ICG 0 (no perfusion) to ICG 2 (intense uptake).Results: A total of 47 adult patients were analyzed, including 34 total thyroidectomies and 13 lobectomies. ICG angiography assessed 76 PGs, which were scored as iMAP 2 in 24 cases (31.6%), iMAP 1 in 46 (60.5%) and iMAP 0 in six (7.9%). At the end of dissection, the ICG perfusion score was significantly better for the PGs with informative angiography (iMAP 1 or 2), than for the PGs with uninformative angiography (iMAP 0), or the PGs not evaluated by vascular angiography (p < 0.05).Conclusion: iMAP is feasible and provides direct vascular information in one-third of the cases. Further improvements to this technology are necessary, and the influence of this technique on patient outcomes during thyroidectomy will need to be further evaluated.

BACKGROUND Conventional transarterial chemoembolization (cTACE) with lipiodol is widely performed in patients with hepatocellular carcinoma (HCC) unsuitable for curative treatment. Additional tumor parameters such as HCC macroscopic appearance based on imaging might be helpful for transarterial chemoembolization prognostication and management. PATIENTS AND METHODS A total of 405 patients with HCC who underwent cTACE between 2008 and 2016 from a real-life multicenter French cohort were retrospectively reviewed. Tumors were classified into two macroscopic types according to HCC gross appearance on imaging: nodular versus non-nodular. The study population was stratified into two groups: derivation and validation cohorts. Independent prognostic factors of survival based on multivariate cox regression models were determined and then assessed in the validation set. Thereafter, time to progression (TTP) and radiological response rate were investigated for each prognostic factors of survival. RESULTS Median overall survival (OS) was 35 months for Barcelona Clinic Liver Cancer (BCLC) stage A, 22 months for BCLC stage B and 12 months for BCLC stage C patients (P < 0.0001). The corresponding TTP for these patients was 12 (7-17) months, 5 (3-6) months and 1.2 (1.2-3) months (P < 0.0001). Multivariate analysis revealed that tumors size and number, non-nodular type, alpha-fetoprotein, aspartate aminotransferase serum levels and impairment of performance status-1 were independent predictors of survival among the study groups. Non-nodular type was the most powerful factor that influences OS, TTP and radiological response rate for the recommended transarterial chemoembolization candidates. TTP was consistent with OS within each stage. CONCLUSION HCC macroscopic appearance on imaging is a determinant predictor of outcome after cTACE in a real-life multicenter cohort.

Background & aim We investigated the combination of rapid antigen detection (RAD) and RT-qPCR assays in a stepwise procedure to optimize the detection of COVID-19. Methods From August 2020 to November 2020, 43,399 patients were screened in our laboratory for COVID-19 diagnostic by RT-qPCR using nasopharyngeal swab. Overall, 4,691 of the 43,399 were found to be positive, and 200 were retrieved for RAD testing allowing comparison of diagnostic accuracy between RAD and RT-qPCR. Cycle threshold (Ct) and time from symptoms onset (TSO) were included as covariates. Results The overall sensitivity, specificity, PPV, NPV, LR-, and LR+ of RAD compared with RT-qPCR were 72% (95%CI 62%–81%), 99% (95% CI95%–100%), 99% (95%CI 93%–100%), and 78% (95%CI 70%–85%), 0.28 (95%CI 0.21–0.39), and 72 (95%CI 10–208) respectively. Sensitivity was higher for patients with Ct ≤ 25 regardless of TSO: TSO ≤ 4 days 92% (95%CI 75%–99%), TSO > 4 days 100% (95%CI 54%–100%), and asymptomatic 100% (95%CI 78–100%). Overall, combining RAD and RT-qPCR would allow reducing from only 4% the number of RT-qPCR needed. Conclusions This study highlights the risk of misdiagnosing COVID-19 in 28% of patients if RAD is used alone. A stepwise analysis that combines RAD and RT-qPCR would be an efficient screening procedure for COVID-19 detection and may facilitate the control of the outbreak.

BackgroundDiagnosing SARS CoV-2 infection with certainty is essential for appropriate case management. We investigated the combination of rapid antigen detection (RAD) and RT-qPCR assays in a stepwise procedure to optimize the detection of COVID-19.MethodsFrom August 2020 to November 2020, 43,399 patients were screened in our laboratory for COVID-19 diagnostic by RT-qPCR using nasopharyngeal swab. Overall, 4,691 of the 43,399 were found to be positive, and 200 were retrieved for RAD testing allowing comparison of diagnostic accuracy between RAD and RT-qPCR. Cycle threshold (Ct) and time from symptoms onset (TSO) were included as covariates.ResultsThe overall sensitivity, specificity, PPV, NPV, LR-, and LR+ of RAD compared with RT- qPCR were 72% (95%CI 62%–81%), 99% (95% CI95%–100%), 99% (95%CI 93%–100%), and 78% (95%CI 70%–85%), 0.28 (95%CI 0.21-0.39), and 72 (95%CI 10-208) respectively. Sensitivity was higher for patients with Ct ≤ 25 regardless of TSO: TSO ≤ 4 days 92% (95%CI 75%–99%), TSO > 4 days 100% (95%CI 54%–100%), and asymptomatic 100% (95%CI 78-100%). Overall, combining RAD and RT-qPCR would allow reducing from only 4% the number of RT-qPCR needed.ConclusionThis study highlights the risk of misdiagnosing COVID-19 in 28% of patients if RAD is used alone. Thus, negative results from RAD needs to be confirmed by RT-qPCR prior to making treatment decisions. A stepwise analysis that combines RAD and RT-qPCR would be an efficient screening procedure for COVID-19 detection and may facilitate the control of the outbreak.

Background & aim Screening for genital infection (GI) such as bacterial vaginosis (BV) and yeast infection, for sexually transmitted infection (STI), and for asymptomatic carriage of group B streptococcus (GBS) in pregnant women are common reason for medical appointments. The diagnosis and control of GIs, STIs, and GBS are major issues, for fertility and overall well-being of affected women. Conventional testing is performed using vaginal/cervical classical sampling (VCS); this procedure requires pelvic examination performed by health care professionals which raises concerns among women. Vaginal-self-sampling (VSS), as an alternative to VCS, might capture more women. The aim was first to show non-inferiority of VSS compared with VCS to screen for GIs, STIs, and GBS; second to determine the feasibility of VSS. Methods VSS and VCS from 1027 women were collected by health care professionals and simultaneously carried out on each patient. GIs, STIs, and GBS were systematically screened in both paired VSS and VCS samples. Non-inferiority of VSS compared with VCS was assessed using z statistic for binomial proportions. Results Prevalence of GIs were 39.7% using VSS and 38.1% using VCS (p = 0.0016). Prevalence of STIs was 8.5% (VSS) vs 8.1% (VCS) (p = 0.0087). Prevalence of GBS was 13.4% (VSS) and 11.5% (VCS) (p = 0.0001). Most participants (84%) recommended the use of VSS. Conclusions This study shows that VSS was not inferior to VCS for the detection of GIs, STIs, and GBS. This study provides evidence that VSS can be used as a universal specimen for detection of lower genital tract infections in women. Study identification number ID-RCB 2014-A01250-4.

Background: Microbiotas play critical roles in human health, yet in most cases scientists lack standardized and reproducible methods. To date, stool sample preservation remains a source of technological bias in metagenomic sequencing, despite newly developed storage solutions. Studying those biases will help in identifying the appropriate stool preservation approach to promote the implementation of standard operating procedure and improve comparability across multiple microbiome studies. Results: Here, we conducted a comparative study of 10 storage methods for human stool over a 15-day period of storage at fluctuating temperatures. We first compared the performance of each stabilizer with observed bacterial composition variation within the same specimen. Then, we identified the nature of the observed variations to determine which bacterial populations were more impacted by the stabilizer. We found that DNA stabilizers display various stabilizing efficacies and affect the recovered bacterial profiles. Furthermore, our results showed that the bias associated with the stabilizers can be linked to the phenotypical characteristics of the bacterial populations present in the studied samples. Conclusions: Although newly developed storage solutions have improved our capacity to stabilize stool microbial content over time, they are nevertheless not devoid of biases. We therefore recommend considering the nature of these technological biases before claiming whether some microbes are beneficial or even deleterious to human health.

Background: Sorafenib is the first-line treatment for advanced hepatocellular carcinoma (HCC). The management of its side effects is improving. This study aimed to assess, in real life, if this translates into a better prognosis. Methods: This was a retrospective study of advanced HCC patients treated with sorafenib between 2007 and 2017. Results: 188 advanced HCC patients received > 4 weeks of sorafenib. Median treatment duration was 5.4 months and median overall survival (mOS) 10 months (95% confidence interval 15–27). Sorafenib was initiated in 65 patients in 2007–2012 and 123 in 2013–2017. Both groups were comparable except for Barcelona Clinic liver cancer class. Tumor progression, disease control (DC) rate, and incidence of toxicity were similar in the 2 periods, but the duration of treatment (4.3 vs. 5.9 months; p < 0.01) and mOS (8 vs. 12 months; p < 0.002) differed. Among progressive disease patients, mOS was similar (7 months) but for those who had DC at 8 weeks, mOS was longer in the recent period (13 vs. 27 months; p < 0.0001). In the univariate analysis of OS, the period of treatment had a prognostic value. Conclusion: When comparing 2 periods of treatment in advanced HCC patients under sorafenib, duration of treatment and mOS were higher in the recent period. While mOS did not differ for patients who progressed, it was 2-fold higher in the recent period for those who had tumor control. Improvements in the use of sorafenib seem to be associated with better outcomes limited to patients with DC.

BACKGROUND Direct-acting antivirals (DAAs) therapy against hepatitis C viral (HCV) infection has markedly improved the sustained viral response. However, recent studies have suggested an unsuspected high rate of hepatocellular carcinoma (HCC) recurrence. PATIENTS AND METHODS A retrospective case-control study was carried out to investigate the impact of DAAs on tumor recurrence in patients with complete response to HCC treatment within our HCV-related cirrhosis cohort. Patients who received [group 1 (G1), n=22] or not [group 2 (G2), n=49] a DAAs therapy were matched 1 : 2 for age, sex, liver function, HCC stage, and treatment. RESULTS Initial HCC were mostly Barcelona Clinic Liver Cancer stage A (95% G1, 94% G2). Sustained viral response with DAAs was achieved in 86% of patients. After a similar median overall follow-up time with similar radiologic surveillance after HCC treatment, 41% of patients developed radiologic tumor recurrence in G1 versus 35% of patients in G2 (P=0.7904). There was no significant difference in time to progression between the two groups [12 (9-16) months G1 vs. 14 (8-21) months G2, P=0.7688], or Barcelona Clinic Liver Cancer stage at recurrence. However, the interval between HCC treatment and antiviral therapy was significantly different among DAAs patients with recurrence and those without recurrence [7.0 (2.5-9.0) months vs. 36.0 (9.0-58.0) months, P=0.0235, respectively]. CONCLUSION In our case-control study, HCV therapy with DAAs does not accelerate or prevent early HCC recurrence compared with untreated patients. The rate of recurrence, time to progression, and HCC pattern are similar. Early DAAs treatment (

Introduction Les inhibiteurs de checkpoints immunitaires (ICI) sont largement utilises en oncologie, en particulier les inhibiteurs de PD-1 et PD-L1. Les donnees sur les patients presentant des conditions auto-immunes preexistantes [1] , de nombreuses comorbidites et/ou un âge avance font defaut. Bien que leurs effets secondaires immuno-induits (irAEs) soient desormais mieux connus, leur gestion reste un defi diagnostique et therapeutique du fait de leur variete et de leur imprevisibilite [2] . Dans notre centre, les oncologues peuvent faire evaluer leurs patients par un medecin interniste (MI) dans le cadre d’un protocole standardise de gestion avant de commencer l’immunotherapie afin d’identifier les eventuels facteurs de risque de developpement des irAEs (pathologies auto-immunes preexistantes ou en cours), d’optimiser les coprescriptions (ex: corticoides) et d’assurer une education therapeutique relative a la gestion des irAEs potentiels les plus courants [3] . En cas de developpement d’irAEs graves et/ou multiples, le MI coordonne une equipe multidisciplinaire comprenant oncologues et autres specialistes en fonction du site de complication. L’objectif de cette etude de cohorte retrospective etait de determiner l’efficacite et la toxicite des inhibiteurs de PD-1/PD-L1 dans une cohorte de patients en vie reelle et d’evaluer l’impact de notre protocole de gestion standardise sur la prise en charge des irAEs. Patients et methodes Les donnees de patients qui ont recu des anti-PD-(L)1 entre aout 2015 et juin 2020 ont ete recueillies dans notre base de donnees pharmaceutique. La reponse clinique et la toxicite ont ete evaluees en utilisant les criteres RECIST et la version 5.0 du CTCAE, respectivement. La survie globale (SG) et la survie sans progression (SSP) ont ete estimees a l’aide de la methode de Kaplan-Meier. Les facteurs pronostiques potentiels ont ete identifies a l’aide du modele de Cox. Resultats Au total, 196 patients ont ete inclus avec un âge median de 66 ans (38-89). Les types de cancer suivants ont ete inclus: cancer du poumon non a petites cellules (73 %), carcinome a cellules transitionnelles (10 %), carcinome a cellules renales (6 %), cancer du poumon a petites cellules (5 %), carcinome epidermoide de la tete et du cou (4 %) et lymphome de Hodgkin classique (1 %). Vingt-cinq patients (12 %) presentaient des affections auto-immunes preexistantes. Le taux de reponse objective etait de 29 %, la SG mediane etait de 10 mois (IQR: 7-15) et la SSP mediane etait de 5 mois (IQR: 1-22). La plupart des irAEs potentiels etaient gastro-intestinaux (n = 82, 21 %), pulmonaires (n = 75, 19 %) ou dermatologiques (n = 70, 18 %). Trente-trois patients (16 %) ont developpe un irAE potentiel grave (grade 3 ou 4) dont 3 (1 %) deces. Un meilleur pronostic en termes de SG (HR = 0,45, p = 0,008) et de PFS (HR = 0,54, p = 0,027) a ete observe chez les patients ayant presente un irAE apres analyse multivariee. 53 (26 %) et 39 (19 %) patients ont recu des corticosteroides systemiques pour traiter respectivement 71 irAEs de grade ≥ 2 et 46 de grade ≥ 3. L’ICI a ete interrompu en raison d’irAEs chez 26 patients (13 %). Notre protocole de gestion standardise concernait 129 patients (64 %). Les irAEs se sont resolus plus rapidement lorsque les patients avaient beneficie du protocole avec MI avant l’initiation de l’ICI avec un delai median de resolution de 14 jours contre 23 jours (HR = 1,50, p = 0,02). Malgre le moins bon pronostic theorique des patients dans le groupe ayant beneficie du protocole standardise de prise en charge avec surrepresentation des cancers du poumon (98 % contre 42 %) et de l’immunochimiotherapie (12 % contre 1 %), l’absence de differences significatives pour la SG ou la SSP (analyses multivariees) pourrait refleter un effet relativement protecteur de l’intervention proposee aux patients juges les plus severes par l’oncologue responsable a l’initiation de l’ICI. Conclusion Notre etude confirme l’efficacite et la securite des inhibiteurs de PD-1 et de PD-L1 dans un contexte de vie reelle. Bien que la survenue d’irAEs soit associee a l’efficacite des anti-PD-(L)1, leur prise en charge precoce et multidisciplinaire est recommandee. Notre etude suggere que la mise en œuvre d’un protocole de gestion standardise avec un MI est un moyen efficace de prendre en charge plus rapidement les irAEs.

Background Peripheral nerve system (PNS) involvement is common in Fabry's disease (FD), predominantly affecting the small nerve fibers that are difficult to investigate with conventional electrophysiological methods. Patients and methods Eighteen patients followed for Fabry's disease underwent a prospective series of electroneurophysiological explorations, including a study of the cardiac parasympathetic autonomic nervous system (ANS) and electrochemical skin conductance (ESC) tests. Data were compared with those obtained in 18 matched healthy controls. Results All patients had at least one clinical sign suggestive of neuropathy: 16 reported an acrosyndrome and 12 had dyshidrosis. Cold hypoesthesia was found in 15 patients and heat hypoesthesia in 13. Electroneurophysiological investigations and study of the cardiac parasympathetic ANS were normal in all patients. The ESC was significantly lower in FD patients compared with controls. Conclusion PNS involvement is common in FD and should be suspected in patients exhibiting an acrosyndrome, dyshidrosis and/or cold hypoesthesia. Conventional electrophysiological investigations are normal. New techniques, such as ESC, provide early diagnosis of small fiber involvement that currently requires more sophisticated tests difficult to apply in routine practice.

Background Recent data have suggested that failure to achieve sustained virological response with direct-acting antiviral therapy is usually due to relapse and is primarily associated with the emergence of resistance-associated substitutions. The aim of this study was to investigate the prevalence and characterization of non-structural-5A resistance-associated substitutions in patients infected with HCV genotypes 1, 3 and 4 treated by direct-acting antiviral therapy, including anti-non-structural-5A, and to characterize the pre-existing resistance-associated substitutions in subjects treated with anti-non-structural-5A inhibitors. Methods From January 2014 to March 2016, 2,995 patients infected with HCV genotypes 1, 3 and 4 were exposed to non-structural-5A inhibitors. Sequencing results at the time of virological failure were available for 61 patients; sequencing at baseline was available for 35 of these patients. Results Among the 35 patients with sequencing results available at baseline, 15 had no resistance-associated substitution, 16 had only one resistance-associated substitution, and 4 had more than one resistance-associated substitution. Resistance-associated substitutions were harbored in 57% of the sequences in the non-structural-5A region. Among the 61 patients sequenced at virological failure, 50 (82%) patients presented at least one resistance-associated substitutions inducing a high level of resistance to non-structural-5A inhibitors (>10-fold resistance). Conclusions This pooled analysis suggests that non-structural-5A resistance-associated substitutions screening should be recommended when considering retreatment with a non-structural-5A inhibitor regimen in patients who have previously experienced failed non-structural-5A treatment.

The Barcelona Clinic Liver Cancer classification is the most widely - used hepatocellular carcinoma (HCC) staging system because it is simple, precise and linked to a treatment algorithm based on randomized studies. But each group includes a broad spectrum of tumors, with limited therapeutic options, particularly for intermediate and advanced stages. Consequently, different additional scoring systems have been proposed to refine the prognosis and/or to improve the management. But until now, there is no consensus. Liu et al proposes a new scoring system, based on a large HCC cohort, with patients at different stages, treated using diverse modalities. This score includes six parameters used in current practice. It is simple to calculate, reliable, with an ability to predict survival superior to other systems, which also works with our European HCC cohort. The MESH score may be especially useful to differentiate subgroups with different prognosis for each treatment modality.

International audience; Importance: Because inadvertent damage of parathyroid glands can lead to postoperative hypocalcemia, their identification and preservation, which can be challenging, are pivotal during total thyroidectomy.Objective: To determine if intraoperative imaging systems using near-infrared autofluorescence (NIRAF) light to identify parathyroid glands could improve parathyroid preservation and reduce postoperative hypocalcemia.Design, setting, and participants: This randomized clinical trial was conducted from September 2016 to October 2018, with a 6-month follow-up at 3 referral hospitals in France. Adult patients who met eligibility criteria and underwent total thyroidectomy were randomized. The exclusion criteria were preexisting parathyroid diseases.Interventions: Use of intraoperative NIRAF imaging system during total thyroidectomy.Main outcomes and measures: The primary outcome was the rate of postoperative hypocalcemia (a corrected calcium

Background: Low gradient (mean gradient, < 40 mmHg) aortic stenosis (AS) may occur in conjunction with a small valve effective orifice area (EOA) < 1 cm2. This discordant grading in AS seve...

Introduction L’Encephalomyelite Myalgique/Syndrome de Fatigue Chronique (EM/SFC) est une pathologie chronique frequente, responsable de limitations fonctionnelles severes compliquant potentiellement l’acces et le maintien dans l’emploi. L’objectif de ce travail etait d’etudier l’impact de la reconnaissance de handicap et des amenagements professionnels sur la situation professionnelle des travailleurs atteints d’EM/SFC. Patients et methodes Il s’agit d’une enquete transversale descriptive, prospective, issues d’une cohorte de patients atteints d’EM/SFC en âge de travailler. Nous avons compare les donnees socio-demographique, la severite de l’atteinte, l’evolution de leur situation professionnelle selon trois criteres principaux : le maintien de l’emploi, la reduction des horaires et le recours aux arrets de travail selon la presence de differentes prestations (aupres de l’assurance maladie (CPAM)), reconnaissance de travailleur handicape (RQTH) et declaration d’inaptitude. Resultats Sur les 47 patients (sex-ratio 2/1, âge moyen de 41,5 ans (SD ± 2,4) inclus, un quart n’exercaient plus d’activite professionnelle. Parmi les patients actifs, 40 % ont ete arretes plus de trois mois en 2019. En terme d’aides, seulement 1/3 des patients beneficiaient d’une RQTH, de prestations de la part des CPAM, ou d’amenagements professionnels. Le niveau financier, la presence d’amenagements professionnels et l’impact fonctionnel de la maladie etaient les facteurs significativement associes au maintien de l’emploi et/ou a la presence d’arrets de travail prolonges. Conclusion Notre etude, demontre un impact important de l’EM/SFC sur le maintien de l’emploi, une tres faible reconnaissance du handicap lie a cette pathologie et des amenagements professionnels limites.

Background The use of intracardiac electrograms to guide atrial fibrillation (AF) ablation has yielded conflicting results. Objectives The authors evaluated the usefulness of spatiotemporal dispersion, a visually recognizable electric footprint of AF drivers, for the ablation of all forms of AF. Methods The authors prospectively enrolled 105 patients admitted for AF ablation. AF was sequentially mapped in both atria with a 20-pole PentaRay catheter. The authors tagged and ablated only regions displaying electrogram dispersion during AF. Results were compared to a validation set in which a conventional ablation approach was used (pulmonary vein isolation/stepwise approach). To establish the mechanism underlying spatiotemporal dispersion of AF electrograms, the authors conducted realistic numerical simulations of AF drivers in a 2-dimensional model and optical mapping of ovine atrial scar-related AF. Results Ablation at dispersion areas terminated AF in 95% of the 105 patients. After ablation of 17 ± 10% of the left atrial surface and 18 months of follow-up, the atrial arrhythmia recurrence rate was 15% after 1.4 ± 0.5 procedures per patient versus 41% in the validation set after 1.5 ± 0.5 procedures per patient (arrhythmia free-survival: 85% vs. 59%; log-rank p Conclusions The clustering of intracardiac electrograms exhibiting spatiotemporal dispersion is indicative of AF drivers. Their ablation allows for a nonextensive and patient-tailored approach to AF ablation. (Substrate Ablation Guided by High Density Mapping in Atrial Fibrillation [SUBSTRATE HD]; NCT02093949)

Objectives This study sought to evaluate the impact of a complex fractionated atrial electrogram (CFAE)–guided ablation strategy on atrial fibrillation (AF) dynamics in patients with persistent AF. Background It is still unclear whether complete pulmonary vein isolation (PVI) is required or if the ablation of well-delineated pulmonary vein (PV) subregions could achieve similar outcomes in persistent AF. Methods CFAE-guided ablations were performed in 76 patients (65.2 ± 10 years of age) with persistent AF. In 47 patients, we measured mean PVs and left atrial appendage (LAA) cycle length (CL) values (PV-CL and LAA-CL), before ablation and before AF termination. We defined “active” PVs as PV-CL ≤ LAA-CL, “rapid fires” as PV-CL ≤80% of LAA-CL, and “PV-LAA CL gradient” as a significant CL difference between the 2 regions. Results AF termination (sinus rhythm [SR] or atrial tachycardia [AT] conversion) occurred in 92% and SR conversion in 75%. The radiofrequency time for AF termination and total radiofrequency time were 26 ± 25 min and 61.1 ± 21.6 min, respectively. Thirty of 47 patients had active PV (with 19 PV “rapid fires”). Ablation significantly increased median CL, both at PVs and LAA from 188 ms (interquartile range [IQR]: 161 to 210 ms) to 227.5 ms (IQR: 200 to 256 ms) (p Conclusions CFAE-guided ablation leads to a large decrease in PV frequency of activation, preceding AF termination. A PV modulation approach, rather than complete PVI, may be preferable for persistent AF.

Background Endoscopic access to common bile duct (CBD) remains difficult in 10% of cases, requiring alternative techniques. This retrospective study with historical controls aimed to evaluate the benefit of the double guidewire (DGW) technique as part of a standardized protocol in CBD access, after failure of standard cannulation and to compare successful CBD access rates, complication rates and length of hospital stay (LOS) in two groups. Method From January 2012 to December 2014, all consecutive patients requiring therapeutic endoscopic retrograde cholangiopancreatography (ERCP) with “difficult” access to CBD were included in a “studied group”. CBD access was “difficult” after either: 5 unsuccessful attempts, 5 unintentional insertions in the pancreatic duct or more than 10-minute-long unsuccessful attempts. This group was compared to a historical control group undergoing ERCP from January 2009 to December 2011. In the studied group, a sequential strategy including DGW technique was performed when the guidewire was unintentional passed into the pancreatic duct. In the control group, only precut technique was used. Results Among the 538 patients with naive papilla eligible for ERCP, 73 had difficult CBD access. Successful CBD access rate was higher in the studied group: 91%(50/55) vs 67%(12/18) p=0.0215. Complication rates were similar in both groups: 28% vs 20%, p=0.5207. LOS was shorter in the studied group (9.2±8.5 days vs. 14.4±7.4 days, p=0.0028). Post-ERCP cholangitis were lower in the study group: 2%(1/55) vs 22%(4/18), p = 0.0118. Conclusion After standard cannulation failure, DGW technique increased successful CBD access rate and decreased LOS without increasing complications. This article is protected by copyright. All rights reserved.

Background Advanced hepatocellular carcinoma (HCC) includes a wide spectrum of tumors and patients' prognosis after treatment is highly variable. Moreover, therapeutic options based on the Barcelona Clinic Liver Cancer (BCLC) staging system algorithm are restricted to one systemic therapy. Aim of the study To refine the stratification among BCLC C HCC patients by establishing a new simple prognostic score. Patients and methods A regression model based on a BCLC stage C population and validated with an external cohort of BCLC C HCC patients defined the score. It was therefore validated among three external cohorts of BCLC C HCC patients treated with sorafenib. Results Five variables had independent prognostic values: the number of nodules, the infiltrating nature of the HCC, alpha-fetoprotein serum level, Child-Pugh score, and Eastern Cooperative Oncology Group Performance Status grade. They were integrated into a new score named NIACE ranging from 0 to 7, well correlated with survival. With the use of one threshold value, this score enables defining of two populations with different survivals among BCLC C patients and specifically among those treated with sorafenib. Conclusion The NIACE score defines different prognostic subgroups after palliative treatment of HCC. It could be an additional tool for BCLC C HCC before inclusion in clinical trials or for the management of patients. These results must be validated in a prospective study

Background The aim of this prospective multicenter study was to compare a flexible 19 G needle with nitinol shaft (19 G Flex) with a standard 22 G needle for transduodenal endoscopic ultrasound (EUS)-guided sampling of pancreatic head tumors. Methods Patients with pancreatic head tumors requiring tissue diagnosis were randomized into two arms: puncture with either a 19 G Flex needle or a 22 G needle. The primary end point was diagnostic accuracy for malignancy. The secondary end points were ergonomic scores, sample cytohistological quality, and complications. A 6-month follow-up was performed. Results 125 patients were randomized and 122 were analyzed: 59 patients in the 19 G Flex arm and 63 patients in the 22 G arm. The final diagnosis was malignancy in 111 patients and benign condition in 11. In intention-to-treat analysis, the diagnostic accuracy for malignancy of the 19 G Flex and 22 G needles was 69.5 % (95 % confidence interval [CI] 56.1 % – 80.8 %) vs. 87.3 % (95 %CI 76.5 % – 94.4 %), respectively (P = 0.02). In per-protocol analysis excluding eight technical failures in the 19 G Flex group, the diagnostic accuracy of the 19 G Flex and 22 G needles was not statistically different: 80.4 % (95 %CI 66.9 % – 90.2 %) vs. 87.3 % (95 %CI 76.5 % – 94.4 %; P = 0.12). Technical success was higher in the 22 G arm than in the 19 G Flex arm: 100 % (95 %CI 94.3 % – 100 %) vs. 86.4 % (95 %CI 75.0 % – 94.0 %), respectively (P = 0.003). Transduodenal EUS-guided sampling was more difficult with the 19 G Flex (odds ratio 0.68, 95 %CI 0.47 – 0.97). Conclusion The 19 G Flex needle was inferior to a standard 22 G needle in diagnosing pancreatic head cancer and more difficult to use in the transduodenal approach.