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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.

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 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.

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.

High-risk human papillomaviruses (HPVs) have been identified as the main contributors to cervical cancer. Despite various diagnostic tools available, including the predominant Papanicolaou test (Pap test), technical limitations affect the efficiency of cervical cancer screening. The aim of this study was to evaluate the diagnostic performance of spliced HPV16 E6/E7 mRNA viral loads (VL) for grade 2 or higher cervical intraepithelial neoplasia diagnosis. A new dedicated (quantitative reverse transcription polymerase chain reaction) qRT-PCR assay was developed, allowing selective quantification of several HPV16 E6/E7 mRNA: Full length (FL) with or without all or selected spliced forms (total E6/E7 mRNA corresponding to SP + E6^E7 mRNA (T), + spliced E6/E7 mRNA containing intact E7 ORF (SP), and E6/E7 mRNA containing disrupted E6 and E7 ORFs calculated by the following subtraction T-SP (E6^E7)). Twenty HPV16 DNA and mRNA positive uterine cervical smears representative of all cytological and histological stages of severity were tested. We have shown that all E6/E7 mRNA isoforms expression levels were significantly increased in high grade cervical lesions. Statistical analysis demonstrated that the SP-E6/E7 VL assay exhibited: (i) The best diagnostic performance for identification of both cervical intraepithelial neoplasia (CIN)2+ (90% (56&ndash, 100) sensitivity and specificity) and CIN3+ (100% (72&ndash, 100) sensitivity and 79% (49&ndash, 95) specificity) lesions, (ii) a greater sensitivity compared to the Pap test for CIN2+ lesions detection (80% (44&ndash, 97)), (iii) a predictive value of the histological grade of cervical lesions in 67% of atypical squamous cells of unknown significance (ASC-US) and 100% of low-grade (LSIL) patients. Overall, these results highlight the value of SP-E6/E7 mRNA VL as an innovative tool for improving cervical cancer screening.

Background: Men who have sex with men (MSM) are disproportionately affected by sexually transmitted infection. The aim of this cross-sectional study is to prospectively detect the prevalence of chlamydia trachomatis (CT), neisseria gonorrhoeae (NG), mycoplasma genitalium (MG), and high risk human papillomavirus (HR-HPV), and syphilis in a population of asymptomatic sexually active MSM. Methods: Rectal, pharyngeal, and urine samples for CT, NG, MG, and HR-HPV were analyzed in 116 MSM patients attending the clinic for their routine follow-up during the period the study was conducted: 99 patients were issued from the clinic routine follow-up for their HIV infection, and 17 attended the clinic because they were sexual partners of an HIV infected male. Results: An STI was found in 16% of the patients (19/116), with at least one bacterial strain (CT, NG, or MG) found in one site (the pharynx, rectum, or urine). Conclusions: In this study, 16% of the MSM reporting recent RAI were asymptomatic carriers of rectal CT, NG, or MG. According to the high prevalence of asymptomatic STIs found in our MSM population and in other studies, prevention efforts in the form of counseling about the risk of STI need to be done in the population of MSM.

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.

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

A lack of antiviral response in patients with chronic hepatitis C treated with pegylated (PEG)-interferon (IFN)-α-2a + ribavirin (RIBA) may be explained by neutralizing antibodies to IFN-α-2a. The aim of this study was to assess neutralizing antibodies to IFN-α-2a and IFN levels in non-responder patients who were re-treated by PEG IFN-α-2a and RIBA for 12 weeks. Non-responders to a first-line treatment of PEG IFN-α-2a + RIBA were included for treatment with PEG IFN-α-2a (180 µg/week) + RIBA (1,000 mg/day if

Background: The area under the ROC curve (AUC) is widely used to measure the diagnostic accuracy of noninvasive fibrosis indices. However, use of the AUC assumes a binary gold standard, whereas fibrosis staging is based on an ordinal scale and also depends on the distribution of fibrosis stages in the study sample. We explored other fibrosis staging accuracy measures designed for ordinal gold standards, the C-statistic and the Obuchowski measure. Methods: We performed a simulation study to assess the bias in estimating the accuracy measures when the distribution of fibrosis stages in the study sample do not fit the reference distribution in the population to which the indices are applied. We also estimated the type I error of the tests comparing these measures in 2 samples with different distributions of fibrosis stages. We illustrated the practical use of these measures by reanalyzing real data. Results: Compared with the AUC or the C-statistic, the Obuchowski measure showed limited bias when the distribution of fibrosis stages in the study sample differed from the reference distribution. The type I error was strongly inflated with the AUC or the C-statistic but was preserved in the Obuchowski measure. When we compared noninvasive indices on real data, AUC analysis led to discordant results depending on how the fibrosis stages were grouped together. One single conclusion was drawn from the analysis based on the Obuchowski measure. Conclusions: We recommend using the Obuchowski measure for assessing the diagnostic accuracy of noninvasive indices of fibrosis.

Summary Background Few data are available on the incidence, risk factors and contamination pathways involved in acute indigenous hepatitis E in developed countries. Aims To draw up an overall picture of hepatitis E cases, to confirm whether or not the majority of the cases were indigenous and to attempt to identify the risk factors and contamination pathways involved in hepatitis E. Methods This study was performed in the framework of a national network (ANGH) including 96 participating centres. The 19 centres with at least one case of acute HEV reported a total number of 53 cases. Results A decreasing South-to-North geographic gradient was observed. A nonspecific clinical profile was observed in many cases. Acute hepatitis E was of indigenous origin in 90% of the patients. The most relevant and/or frequent possible risk factors among the 47 indigenous metropolitan cases were water consumption from a personal water supply, uncooked shellfish consumption and the recent acquisition of a pet pig. Conclusions This national survey confirmed that acute indigenous hepatitis E is an emerging disease in developed countries such as France, and suggests that various risk factors are responsible for acute indigenous hepatitis E contamination in non-endemic countries.

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.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.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.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 0.0001) and from 197 ms (IQR: 168 to 220 ms) to 224 ms (IQR: 193 to 250 ms) (p 0001), respectively. After ablation, PV-LAA CL gradients were withdrawn and all PV "rapid fires" were extinguished (without PVI). After 17.2 ± 10 months of follow-up and 1.61 ± 0.75 procedures, 86.3% and 73% of the patients were free from AF and from any arrhythmia (AF/AT), respectively.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.

Introduction: Multi-electrode electrogram temporal activation and fractionation have been used to localize atrial fibrillation (AF) drivers. Yet, the feasibility of a simplified “online” analysis and its usefulness to ablate AF remain to be investigated. Hypothesis: Evaluating a simplified “online” electrogram analysis approach designed to localize and ablate AF drivers. Methods: 105 patients undergoing AF ablation (77% with persistent AF, 3 centres) were prospectively enrolled. AF was first mapped in both atria with the 20-pole contact electrode catheter PentaRay® (Biosense Webster, Inc.) in order to identify regions with a temporal activation pattern compatible with the presence of rapidly rotating rotors. Specifically, regions with consecutive activations spanning the majority of the AF cycle length (including examples of rapid and continuously fractionated electrograms) were visually selected (“hot zone”).The endpoints were AF termination acutely, and freedom from long-term AF (single procedure). Off-line, electrogram cycle length values were compared between “hot” and “non-hot” regions and a numerical simulation of PentaRay-enabled unipolar recordings of a stable rotor driving AF was conducted Results: Visually selected “hot” regions located mostly in the left atrium (6.5 ±4.2/patient; ~70% of ”hot” regions). “Hot” regions were activated at a significantly shorter cycle length than “non-hot” regions (171.8 ± 4.8 vs. 193.0 ± 6.3 ms, p=0.01, N=20). 95.6% of the “hot regions” were automatically labelled CFAEs (automated analysis, Carto). However, 4.5±3.4 distinct CFAEs regions/patient were also labelled in “non-hot” regions. Ablation at “hot” regions terminated AF in 99/104 patients (95.2%), 46 [21-72] min after the 1st radiofrequency application within 20 [10-37] min of RF. Also, numerical simulations show that a simplified PentaRay®-enabled activation analysis is sufficient to distinguish rotor and non-rotor regions. After 9+3 [6-11], months of median [Q1-Q3] follow-up, 87 % were free from AF after 1 procedure and 53 % still under antiarrhythmic drugs. Conclusions: With this simplified “online” analysis, we could successfully localize rotor regions and perform efficient AF ablation. Clinical trial.gov: NCT02093949