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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. Antireflux mucosectomy, a new endoscopic treatment for gastroesophageal reflux disease, consists of endoscopic mucosal resection at the esophagogastric junction. This study aim was to evaluate the medium-term efficacy of the antireflux mucosectomy technique for patients with severe gastroesophageal reflux disease symptoms (proton pump inhibitor treatment-dependent or proton pump inhibitor treatment-resistant gastroesophageal reflux disease). Methods. Between January 2017 and June 2018, 13 patients with severe gastroesophageal reflux disease without hiatal hernia, with positive pH reflux, were included in this monocentric prospective pilot study. The primary outcome was clinical success, defined by improvement evaluated by the Gastroesophageal Reflux Disease Health Related Quality of Life Questionnaire at 24 months. Secondary outcomes were technical success, decreased use of proton pump inhibitors, patient satisfaction, and adverse events. Results. Thirteen patients [ females = 8 (62%)], mean age 59 (range, 54-68), were included. The antireflux mucosectomy procedure had technical success in all patients. At 24 months, for 11 patients, gastroesophageal reflux disease symptoms were significantly improved, and mean gastroesophageal reflux disease score decreased from 33 (range, 26-42) to 3 (range, 0-7) ( p = 0.001 ). Ninety-one percent ( n = 10 ) of patients had a lower proton pump inhibitor intake at 24 months. One patient had 3 endoscopic balloon dilatations for EGJ stenosis, two patients had melena ten days after procedure, and seven patients had thoracic or abdominal pain. Patient’s satisfaction at 24 months was 81%. Conclusions. In patients with severe gastroesophageal reflux disease, despite occurrence of several short-term adverse events, antireflux mucosectomy seemed effective in improving gastroesophageal reflux disease symptoms at 24 months. This trial is registered with ClinicalTrials: NCT03357809.

To identify COVID-19-associated immunophenotyping patterns at hospital admission and to determine if some patterns could predict the need for mechanical ventilation (MV).Prospective observational monocentric cohort study.A university-affiliated hospital in Marseille, France.Thirty patients presenting with laboratory-confirmed COVID-19 pneumonia were enrolled within the first 48 hours of hospital admission and compared with 18 healthy controls.None.Whole-blood leukocytes were immunophenotyped with a rapid and simplified one-step flow cytometry method. Thirty-eight immune and five laboratory parameters were compared first between COVID-19 patients and controls and then between the COVID-19 patients who received or not MV during their stays. The variables that significantly discriminated MV from non-MV patients in univariate analysis were entered into a multiple stepwise logistic regression analysis. The COVID-19 patients were predominantly male (87%), aged 61 years (50-71 yr), and 93% received early corticosteroid therapy. Sixteen patients (53%) were managed with noninvasive respiratory support, and 14 (47%) required MV. Compared with controls, COVID-19 patients were characterized by an immune signature featuring: 1) decreased HLA-DR expression on monocytes; 2) reduced basophils, eosinophils, T-cells, NK cells, and nonclassical monocyte count; and 3) up regulation of CD169 on monocytes, CD64 on neutrophils, the adhesion/migration markers (CD62L and CD11b), and the checkpoint inhibitor CD274 on myeloid cells. Among the COVID-19 patients, those who received MV had lower level of CD4 and HLA-DR on monocytes, lower CD8+ T-cell count, and higher lactate dehydrogenase at hospital admission. In multivariate analysis, only CD4 on monocytes (The association of low CD4 on monocytes and low CD8+ T-cell count at hospital admission was highly predictive of the need for MV in hospitalized patients with COVID-19 pneumonia.

BackgroundThe role of atrial fibrillation (AF) drivers located at the left atrium, superior vena cava, crista terminalis and coronary sinus (CS) is well established. While these regions are classically targeted during catheter ablation, the role of right atrial appendage (RAA) drivers has been incompletely investigated.ObjectiveTo determine the prevalence and electrophysiological characteristics of AF driver’s arising from the RAA.Materials and methodsWe conducted a retrospective analysis of clinical and procedural data of 317 consecutive patients who underwent an AF ablation procedure after bi-atrial mapping (multipolar catheter). We selected patients who presented with a per-procedural RAA firing (RAAF). RAAF was defined as the recording of a sustained RAA EGM with a cycle length shorter than 120 ms or 120 < RAAF CL ≤ 130 ms and ratio RAA CL/CS CL ≤ 0.75.ResultsRight atrial/atrium appendage firing was found in 22 patients. The prevalence was estimated at 7% (95% CI, 4–10). These patients were mostly men (72%), median age: 66 yo ± 8 without structural heart disease (77%). RAAFs were predominantly found in paroxysmal AF patients (63%, 32%, and 5% for paroxysmal, short standing and long-standing AF, respectively, p > 0.05). RAAF median cycle length was 117 ms ± 7 while CS cycle length was 180 ms ± 10 (p < 0.01).ConclusionIn 317 consecutive AF ablation patients (22 patients, 7%) the presence of a high-voltage short-cycle-length right atrial appendage driver (RAAF) may conclusively be associated with AF termination. This case series exemplifies the not-so-uncommon role of the RAA in the perpetuation of AF.

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.

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.

Aim To study if one of the two molecules could lead to a lower number of follow up visits and intra-vitreous injection (IVI) with the same efficacy. Methods ELU (or "elected" in French) study is a retrospective study conducted in real life in patients presenting suboptimal response after ranibizumab IVI (phase 1) and secondary switched to aflibercept (phase 2). The number of follow up visits and IVI were compared in both phases. Visual acuity (VA) evolution and "switching" reasons were secondary analyzed. Results We retrospectively included data of 33 patients (38 eyes) with age-related macular degeneration (AMD; mean age: 77±7.7y). The number of monthly follow up visits [median (Q1; Q3)]: was significantly lower with aflibercept (phase 2), respectively 1.0 (0.81; 1.49) visits in phase 1, versus 0.79 (0.67; 0.86) visits in phase 2. The median number of monthly IVI also significantly decreased in phase 2, respectively 0.67 (0.55; 0.90) IVI in phase 1, versus 0.55 (0.45; 0.67) IVI in phase 2. The mean VA evolution (VA final-VA initial) was similar in both phases, (P>0.05). Whatever the reason for "switching" (loss of efficacy, tachyphylaxis, tolerance problems), there was no incidence on VA evolution over the time. Conclusion Our results show that switching from ranibizumab to aflibercept in "suboptimal" patients significantly reduce the number of follow up visits and IVI, with a comparable efficacy. This decrease in visit number could improve patients' quality of life and reduce surgical risk by reducing the number of injections.

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.

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: 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 (

MSM are at particular risk of STIs due to sexual behavior and substance use. HIV PrEP use may increase this risk.Our aim was to comparatively assess incident STIs among different at-risk groups-PLWHIV, HIV-negative PrEP and no-PrEP users-seen at our center early after PrEP implementation.Clinical data were retrospectively collected on 636 MSM seen at the Infectious Diseases Department between September 2016 and October 2018. STI incidence rate was assessed among groups for the whole period, as well as separately for each year of the study.Overall STI incidence rate ratio was higher in HIV-neg when compared to PLWHIV. In multivariate analysis, STI risk was significantly higher among HIV-neg no-PrEP users compared to PLWHIV, while not different between PLWHIV and PrEP users.STI incidence globally increased during the first 2 years after PrEP approval among PLWHIV and no-PrEP users, stated by odds ratio (OR = 1.77 [1.23-2.55], p = 0.0020 and OR = 2.29 [0.91-5.73], p = 0.0774 respectively) while it remained rather stable for HIV-neg PrEP users (OR = 1.19 [0.60-2.38], p = 0.6181). The HIV-neg no-PrEP group remained at higher risk of STI than PLWHIV and PrEP users during the two periods.These results suggest that a proactive approach of an efficient follow-up of MSM participants since PrEP approval may have prevented an increase of the incidence of STIs among PrEP users.

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.

Background & AimLiver fibrosis screening in primary care population is a major public health issue. The FIB-4 index is a simple non-invasive fibrosis test combining age, transaminases, platelets count, developed for the diagnosis of advanced fibrosis. The aim of our study was to evaluate the interest of liver fibrosis screening using systematic calculation of FIB-4 in routine blood analysis.MethodsBetween December 2018 and May 2019, we conducted a prospective screening of liver fibrosis in 134 158 patients during a medical check-up including routine blood analysis. Among these patients, 29 707 had transaminases and platelets counts available and benefited from an automatic calculation of FIB-4. Results were obtained from 21 French clinical laboratories in the Bouches du Rhône region.ResultsAmong the 29 707 patients, 2160 (7.3%) had significant fibrosis (FIB-4>2.67). Individual investigation of patients with FIB-4>2.67 allowed to screen 1267 (1267/2160: 59%) patients who were not managed for any liver disease.ConclusionsThis work demonstrates the interest of FIB-4 for the screening of liver fibrosis in primary care population. Our study strongly supports this easy-to-implement strategy using a simple Fib-4 measure resulting from the use of available routine test results.FundingThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.Clinical Registering NumberMR-0314071019 (INDS: French National Institute for Medical Data)

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.

Introduction Le depistage de la fibrose hepatique dans la population generale represente un enjeu de sante public majeur. Les seules donnees Francaises actuelles sont issues de la cohorte CONSTANCE qui fait etat de 2,6 % des patients qui presentent une fibrose avancee [1] . Il a ete valide que le Fib-4, un score simple combinant l’âge, la mesure de l’activite des ALAT/ASAT et la numeration des plaquettes represente un outil de depistage de la fibrose chez les patients presentant une steatose hepatique [2] . Le but de notre etude est d’evaluer en population generale l’interet du depistage de la fibrose hepatique a l’aide du Fib-4 calcule automatiquement lors d’un bilan biologique au cours duquel un bilan hepatique et la numeration des plaquettes etaient demandes. Patients et methodes Entre decembre 2018 et mai 2019, le Fib-4 a ete calcule de maniere automatisee chez 29 707 patients lors d’un bilan biologique parmi 134 157 patients ayant eu un bilan biologique pendant la meme periode. Le score Easy LIver Fibrosis Test (e-LIFT) [3] a ete etudie chez un sous-groupe de 8341 patients (28,1 %) pour lesquels le TP et les GGT etaient egalement renseignes. La glycemie etait disponible chez 8947 des patients (30,1 %). Les resultats etaient issus des analyses realisees dans 21 laboratoires de biologie medicale des Bouches du Rhone. Les patients sous chimiotherapie etaient exclus de l’etude. Resultats Au total, 2160 (7,3 %) parmi les 29 707 patients ont une fibrose significative (Fib-4 > 2,67), et 22 529 (75,8 %) ont une absence de fibrose (Fib-4 7 mmol/L et les patients diabetiques presentent une fibrose significative (Fib4 > 2,67) significativement plus frequente que les patients non diabetiques, respectivement 17,6 % [IC95 : 16,0–19,3 %] vs 8,6 % [7,9–9,2 %] (p 2,67. Parmi les 2160 patients avec une fibrose significative (Fib-4 > 2,67), 1267 ont ete identifies comme potentiellement non pris en charge pour une hepatopathie (patients non adresses par un hepatologue). Un courrier adresse a leur medecin traitant a permis de mettre en evidence sur les premiers retours (enquete en cours) qu’un peu plus de la moitie des patients ne beneficiait pas d’une prise en charge specialisee. Conclusion Ce travail montre l’interet du Fib-4 et/ou du score e-LIFT pour un depistage de la fibrose en population generale. Ce score peut etre genere automatiquement lors de tout bilan biologique des lors que les ALAT/ASAT et plaquettes sont demandees, et necessite une collaboration entre cliniciens et biologistes afin de depister les hepatopathies avancees et leur prise en charge precoce avant le developpement de complications.

International audience; BACKGROUND & AIMS:Transarterial chemoembolization (TACE) is the standard of care for intermediate stage hepatocellular carcinoma (HCC) and it is the most commonly used treatment for HCC worldwide. However, no prognostic indices, designed to select appropriate candidates for repeat conventional TACE, have been incorporated in the guidelines.METHODS:From January 2007 to April 2012, 139 consecutive HCC patients, mainly with an alcohol- or viral-induced disease, were treated with TACE. Using a regression model on the prognostic variables of our population, we determined a score designed to help for repeat TACE and we validated it in two cohorts. We also compared it to the ART score.RESULTS:In the multivariate analysis, four prognostic factors were associated with overall survival: BCLC and AFP (>200 ng/ml) at baseline, increase in Child-Pugh score by ⩾2 from baseline, and absence of radiological response. These factors were included in a score (ABCR, ranging from -3 to +6), which correlates with survival and identifies three groups. The ABCR score was validated in two different cohorts of 178 patients and proofed to perform better than the ART score in distinguishing between patients' prognosis.CONCLUSIONS:The ABCR score is a simple and clinically relevant index, summing four prognostic variables endorsed in HCC. An ABCR score ⩾4 prior to the second TACE identifies patients with dismal prognosis who may not benefit from further TACE sessions.

We have read with interest the article by Pecorelli et al(1) regarding a new therapeutic approach in intermediate stage hepatocellular carcinoma (HCC). In this retrospective analysis, curative treatments (surgery and percutaneous treatments) offer a better outcome compared to the recommended treatment, transarterial chemoembolization (TACE). The strength of this study is the use of propensity score matching and we would like to make few comments to highlight the relevance as well as the limitations of these findings. This article is protected by copyright. All rights reserved.

Summary Background The impact of the IL28B genotype on the real-life treatment decisions for patients infected with the hepatitis C virus (HCV) is unknown. Objective To prospectively analyze the impact of IL28B genotype in HCV genotype 1 (G1)- or 4 (G4)-infected patients using buccal epithelial cell samples in real-life clinical practices. Patients and methods From October 2011 to March 2013, 1007 CHC patients were included among 127 French clinical centers. Results The IL28B CC, CT, and TT genotype distribution was 252 (25%), 576 (57%), and 177 (18%), respectively. The treatment decisions were recorded and matched with the initial intentions for 433 patients. Multivariate analysis on intention to start treatment showed that patients with HCV G4 were less likely to be intended to be treated than HCV G1 patients (odds ratio [OR] = 0.43 [95% CI 0.19–0.97], P = 0.04); similarly HIV-HCV coinfected patients were less likely to be intended to be treated than HCV monoinfected patients (OR = 0.20 [0.09–0.41], P P = 0.004). Multivariate analysis on final decision to treat showed that Patients with F3–F4 were more likely to be treated than others (OR = 2.06 [1.26–3.38], P = 0.004). Conversely, although P -values are not significant, patients recruited in public hospitals tended to be less treated (OR = 0.65 [0.40–1.04], P = 0.069), similarly to HIV-HCV coinfected patients (OR = 0.55 [0.28–1.11], P = 0.095). Conclusion Our study showed that the IL28B genotype is used for the management of HCV-infected patients. In the context of future treatments, IL28B genotyping may remain useful if it can be used to develop individualized treatment strategies, identifying patients who can be successfully treated with shorter, simpler, or cheaper regimens.

The role of pulmonary veins (PVs) in persistent atrial fibrillation (AF) perpetuation appears less important than in paroxysmal AF. Electrogram-based substrate ablation is not widely performed as a stand-alone strategy.To evaluate PV activity in AF perpetuation and efficacy of our patient-tailored ablation strategy (electrogram-based substrate ablation with or without pulmonary vein isolation [PVI]).One hundred twenty-one patients with paroxysmal (n = 19; 15.7%), persistent (n = 77; 63.6%), or long-standing persistent (n = 25; 20.7%) AF underwent electrogram-based substrate ablation with AF termination end point: sinus rhythm or atrial tachycardia conversion. Before ablation, we classified PVs as "passive" if silent PV or if PV cycle length is greater than left atrial appendage cycle length. No PVI was performed in such cases.Passive PVs were observed in 52 of 121 patients (paroxysmal AF = 0%, persistent AF = 40%, and long-standing persistent AF = 76%; P.0001]). Substrate ablation terminated AF in 95.6% (sinus rhythm conversion in 80.2%). Compared with patients with active PVs, patients with passive PVs had longer AF sustained duration (19.1 ± 29.7 months vs 4.9 ± 11.1 months; P.0001), larger left atrial diameter (46.9 ± 7.3 mm vs 41.9 ± 6.0 mm; P = .0014), lower left ventricular ejection fraction (45.4% ± 13.5% vs 55.1% ± 9.4%; P.0001), and more often structural heart disease (57% vs 33%; P = .02). After a follow-up of 20.39 ± 11.23 months (1.6 procedures per patient), 82% were arrhythmia free with this strategy.PV activity during AF decreases with AF chronicity, left atrial dilatation, and left ventricular ejection fraction. Our patient-tailored ablation strategy without systematic PVI provides good results.

Background and objective The aim of this study was to prospectively evaluate whether the addition of peg-IFN to a stable NA regimen leads to loss of HBsAg in HBeAg-negative patients with chronic hepatitis and HBV DNA fully suppressed by long-term NA treatment. Study design We analyzed HBsAg levels in 10 HBsAg-positive, HBeAg-negative patients who received peg-IFN alpha-2a in addition to a NA regimen. Treatment lasted a maximum of 96 weeks, according to changes in the HBsAg titer. Before peg-IFN therapy, HBV DNA levels had been below the limit of detection for at least three years. Results HBsAg levels declined in nine patients. Among these nine, four became HBsAg-negative after 48 weeks of peg-IFN treatment; these patients received peg-IFN for only 48 weeks. NAs were stopped in these four patients, and these levels remained stable for at least 18 months (loss of HBsAg; HBV-DNA negative). HBs seroconversion was observed in two patients. The remaining five patients received 96 weeks of peg-IFN therapy. One patient became HBsAg-negative at the end of peg-IFN therapy; another became HBsAg-negative six months later. Three patients did not become HBsAg-negative. NAs were stopped in the two patients who became HBsAg-negative with no relapse during 12 months of follow up. Conclusions In HBsAg-positive, HBeAg-negative patients with HBV DNA were fully suppressed by long-term NA treatment, the addition of peg-INF for a maximum of 96 weeks based on HBsAg-titer monitoring led to a loss of HBsAg and cessation of NA therapy in six out of ten patients, with no relapse for 12–18 months of follow up. HBs seroconversion was observed in two patients.

STUDY QUESTION: Can independent predictors of pregnancy-associated plasma protein-A (PAPP-A) levels be identified in a group of women who conceived following IVF/ICSI? SUMMARY ANSWER: The significantly decreased PAPP-A level in IVF and ICSI pregnancies compared with non-IVF/ICSI pregnancies was correlated strongly with the serum estradiol (E2) level at ovulation triggering. WHAT IS KNOWN ALREADY: The first trimester prenatal combined screening test for fetal aneuploidies in pregnancies conceived following assisted reproduction techniques (ART) is complicated by an alteration of the maternal biomarkers free β-hCG and PAPP-A, causing a higher false-positive rate compared with pregnancies which are conceived naturally. The use of controlled ovarian stimulation prior to IVF/ICSI is suggested to be the principle reason for these alterations of biomarkers in ART pregnancies. STUDY DESIGN, SIZE, DURATION: Between January 2010 and December 2011, 1474 women who conceived naturally and 374 women who conceived following IVF (n = 89), ICSI (n = 204) or intrauterine insemination (IUI, n = 81) were included in this retrospective study. Only singleton pregnancies were eligible for this study. For all women, serum analysis was performed in the same clinical laboratory. Measurement of nuchal translucency (NT) thickness was performed by four physicians belonging to the same infertility centre. PARTICIPANTS/MATERIALS, SETTING, METHODS: First-trimester combined screening test of aneuploidy parameters (maternal age, PAPP-A and free β-hCG, NT thickness) were compared between non-ART and ART (IVF, ICSI and IUI) singleton pregnancies. Next, a minimal threshold E2 level at ovulation triggering was suggested for IVF/ICSI pregnancies above which the PAPP-A levels were significantly decreased compared with non-ART pregnancies. Finally, a multivariate analysis was performed to reveal independent predictors of PAPP-A level in IVF/ICSI pregnancies. MAIN RESULTS AND THE ROLE OF CHANCE: We showed a decrease of the multiple of the median (MoM) PAPP-A level in IVF and ICSI singleton pregnancies compared with non-ART singleton pregnancies (P < 0.001), with MoM values of 0.74 (0.16-3.16) and 0.81 (0.12-4.61) versus 0.98 (0.14-5.76), respectively. Analysis of variance of the overall model was highly significant (Fisher test 3.76, P = 0.01), indicating that the model explains a significant portion of the variation in the data. No difference in PAPP-A level was found between non-ART and IUI pregnancies. The free β-hCG level and NT thickness did not differ between ART and non-ART pregnancies. PAPP-A levels in IVF and ICSI pregnancies were strongly correlated with the E2 level at ovulation triggering. We showed by multivariate analysis that an E2 cut-off level of 1300 pg/ml at the time of ovulation could predict a significantly lower PAPP-A level at first trimester combined screening (β -0.239 ± 0.088, P < 0.005). LIMITATION, REASONS FOR CAUTION: The measures of biochemical markers can differ between laboratories and with the used equipment; therefore, extrapolation of the E2 cut-off level to other infertility centres should be undertaken with caution. WIDER IMPLICATIONS OF THE FINDINGS: One should be careful when using correction factors for ART patients undergoing the first trimester combined screening test. The proposed E2 cut-off level may help to identify a subgroup of women within the population of ART patients for whom use of a correction factor is justified. STUDY FUNDING/COMPETING INTEREST(S): None.

BACKGROUND AND AIMS Hepatocellular carcinoma (HCC) prognostic scores could be useful in addition to the Barcelona Clinic Liver Cancer (BCLC) system to clarify patient prognosis and guide treatment decision. The NIACE (tumor Nodularity, Infiltrative nature of the tumor, serum Alpha-fetoprotein level, Child-Pugh stage, ECOG performance status) score distinguishes different prognosis groups among BCLC A, B, and C HCC patients. Our aims are to evaluate the NIACE score and its additive value in two HCC cohorts treated either by surgery or by chemoembolization, and then according to the BCLC recommendations. PATIENTS AND METHODS This was a retrospective multicenter study with two BCLC A, B, and C HCC cohorts treated either by surgery (n=207) or by chemoembolization (n=168) carried out between 2008 and 2013. We studied survival time according to the baseline NIACE score and compared it with the Cancer of the Liver Italian Program score and the BCLC system. RESULTS The NIACE score differentiates between subgroups of patients with different prognosis within each BCLC class. Among BCLC A patients treated by surgery and BCLC B patients treated by chemoembolization, the NIACE score differentiates between two subgroups with a significant difference in survival time: 68 (55-81) months versus 35 (21-56) months (P=0.0004) and 20 (17-24) months versus 13 (7-17) months (P=0.0008), respectively. Among those subgroups, the NIACE score has a significantly better prognostic value than the BCLC system or the Cancer of the Liver Italian Program score. CONCLUSION In this study, among HCC patients treated according to the BCLC recommendations, the NIACE score predicts more accurately than any other system the survival time.

The clinical impact of intraoperative autofluorescence-based identification of parathyroids using a near-infrared camera remains unknown.In a before and after controlled study, we compared all patients who underwent total thyroidectomy by the same surgeon during Period 1 (January 2015 to January 2016) without near-infrared (near-infrared- group) and those operated on during Period 2 (February 2016 to September 2016) using a near-infrared camera (near-infrared+ group). In parallel, we also compared all patients who underwent surgery without near-infrared during those same periods by another surgeon in the same unit (control groups). Main outcomes included postoperative hypocalcemia, parathyroid identification, autotransplantation, and inadvertent resection.The near-infrared+ group displayed significantly lower postoperative hypocalcemia rates (5.2%) than the near-infrared- group (20.9%; P .001). Compared with the near-infrared- patients, the near-infrared+ group exhibited an increased mean number of identified parathyroids and reduced parathyroid autotransplantation rates, although no difference was observed in inadvertent resection rates. Parathyroids were identified via near-infrared before they were visualized by the surgeon in 68% patients. In the control groups, parathyroid identification improved significantly from Period 1 to Period 2, although autotransplantation, inadvertent resection and postoperative hypocalcemia rates did not differ.Near-infrared use during total thyroidectomy significantly reduced postoperative hypocalcemia, improved parathyroid identification and reduced their autotransplantation rate.

Le Dual-Knife® (Olympus) est un nouveau couteau frequemment utilise pour la dissection sous-muqueuse du fait de sa surete et de sa precision. L’objet de cette etude etait d’evaluer l’efficacite et la tolerance du traitement endoscopique du diverticule de Zenker avec le Dual-Knife® assiste d’un diverticuloscope (Cook®). De fevrier 2009 a octobre 2011, 21 patients (14 hommes et sept femmes) dont l’âge moyen etait de 70,7 ± 10,2 ans, presentant un diverticule de Zenker symptomatique, ont ete inclus dans une etude prospective multicentrique non randomisee. La myotomie du muscle cricopharyngien etait realisee avec le Dual-Knife® apres exposition du septum diverticulaire grâce au diverticuloscope. En fin de procedure, un ou deux clips etaient positionnes a l’extremite distale de la dissection. Tous les patients decrivaient des symptomes incluant une dysphagie (n = 15; 71,4 %), des regurgitations et/ou troubles de la deglutition (n = 19; 90 %). Seize patients (75 %) avaient un diverticule dont la profondeur etait superieure ou egale a 30 mm. Toutes les complications etaient notees. Les symptomes des patients (dysphagie, regurgitation, troubles de la deglutition et inhalations) etaient evalues lors de consultations de surveillance regulieres ou par telephone. Le test utilise determine la probabilite que les deux parametres soient fortement lies au seuil p = 0,05 (test CMH). Une p-value inferieure a 0,05 indique une forte liaison entre les deux parametres, donc on accepte l’hypothese qu’il n’y a pas d’effet traitement. Les donnees ont ete analysees a l’aide du logiciel SAS (version 9.2; SAS Institute Inc, Cary, NC). Tous les patients ont ete traites avec succes lors de la premiere session. Nous n’avons eu aucune complication grave. Une hemorragie immediate a ete traitee endoscopiquement avec succes a l’aide d’une pince d’hemostase. Tous les patients sont sortis dans les 48 heures suivant l’intervention. A un mois et au moment de l’evaluation de suivi (7,85 mois [3–12]), la dysphagie et les regurgitations etaient significativement ameliorees (p = 0,48/0,18 et 0,68/,041 respectivement). Dix-huit patients (85,7 %) n’avaient plus aucun symptome. Pour trois patients, la dysphagie et/ou les regurgitations persistaient de manieres plus moderees. La dysphagie et/ou les regurgitations ont recidive pour deux patients (9,5 %). Un deuxieme traitement endoscopique a ete necessaire et un patient a ete opere. Au final, le traitement endoscopique etait efficace dans 90,4 % des cas. La diverticulotomie endoscopique au Dual-Knife® aide du diverticuloscope est une alternative therapeutique sure et efficace pour des patients atteints d’un diverticule de Zenker symptomatique.

We appreciate the interest of Dr. Gianni and colleagues in our paper [(1)][1] and their invitation to a careful consideration of history. Classic anatomy-based approach may be insufficient for treating persistent atrial fibrillation (AF) (reference #1 in our article [[1]][1]). Gianni and colleagues

BACKGROUND: Recent studies have suggested that host genetics may be useful for predicting drug response and have supported the recommendation that single polynucleotide polymorphisms (SNPs) of IL28B should be investigated when treating hepatitis C virus (HCV)-1 infected patients. The aim of this study was to determine whether a single IL-28B genotype SNP rs8099917 or rs12979860 determination is sufficient to predict treatment failure in patients with chronic HCV. METHODS: A total of 198 patients were included; mean (±standard deviation) age was 47±12 years and 140 (71%) were men. One hundred and fifty-six (79%) patients were infected with HCV genotype 1 and 42 (21%) with HCV genotypes 2 or 3. One hundred and eight (55%) patients had sustained virologic response (SVR). Two SNPs in the IL-28B were analyzed (rs8099917 and rs12979860). RESULTS: A total of 115 (58%) patients had rs8099917 TT genotype and 61 (31%) had rs12979860 CC genotype. Rs8099917 TT and rs12979860 CC genotypes were associated with SVR in HCV genotype 1 patients [odds ratio=2.60 (1.36-5.00), P=0.004 and odds ratio=3.30 (1.58-6.90), P=0.03 respectively]. No association was found between SNPs and SVR in HCV genotype 2 or 3 patients. CONCLUSION: This study confirms that SNPs rs8099917 and rs12979860 used alone may be useful for predicting the outcome of HCV treatment. In a rational and cost-effective approach, determination of only one of these two SNPs is sufficient for predicting SVR. Because of the highest predictive SVR associated with rs12979860 CC compared with the rs8099917 TT (respective positive predictive value: 72% vs. 63%, P=ns), rs12979860 determination alone is sufficient for predicting interferon response.