Comparison of open and robotic-assisted partial nephrectomy approaches using multicentric data (UroCCR-47 study).

We compared the outcomes of robotic-assisted partial nephrectomy (RPN) and open partial nephrectomy (OPN) using contemporary data to respond to unmet clinical needs. Data from patients included in the registry who underwent partial nephrectomy between January 01, 2014 and June 30, 2017 within 20 centres of the French Network for Research on Kidney Cancer UroCCR were collected (NCT03293563). Statistical methods included adjusted multivariable analyses. Rates of peri- and post-operative transfusion, and of surgical revision, were lower in the RPN (n = 1434) than the OPN (n = 571) group (2.9% vs. 6.0%, p = 0.0012; 3.8% vs. 11.5%, p < 0.0001; 2.4% vs. 6.7%, p < 0.0001, respectively). In multivariable analyses, RPN was independently associated with fewer early post-operative complications than OPN (overall: odds-ratio [95% confidence interval, CI] = 0.48 [0.35-0.66]; severe: 0.29 [0.16-0.54], p < 0.0001 for both) and shorter hospital stays (34% [30%; 37%], p < 0.0001). RPN was also a significantly associated with a decresedrisk of post-operative acute renal failure, and new-onset chronic kidney disease at 3 and 12 months post-surgery. There were no between-group differences in oncological outcomes. In comparison with OPN, RPN was associated with improved peri- and post-operative morbidity, better functional outcomes, and shorter hospital stays. Our results support the use of RPN, even for large and complex tumours.

Post-stroke pathway analysis and link with one year sequelae in a French cohort of stroke patients: the PAPASePA protocol study.

BACKGROUND: Stroke is a health problem with serious consequences, both in terms of mortality, and after-effects affecting patient quality of life. Stroke requires both urgent and chronic management involving the entire health care system. Although large variability in the management of stroke patients have been noticed, knowledge of the diversity and the scalability of post-stroke pathways, whether it is the care pathway or the life pathway, is currently not sufficient. Moreover the link between post-stroke pathways and patients sequelae have not been yet clearly defined. All this information would be useful to better target the needs to improve stroke patient management. The purposes are to identify the post-stroke life pathways components associated with sequelae (activity limitations - main purpose, cognitive disorders, anxio-depressive disorders, fatigue, participation restrictions) at 3 months and 1 year post-stroke, to define a typology of life pathways of patients during the post-stroke year and to analyze the social and geographical inequalities in the management of stroke. METHODS: Design: a prospective multicenter comparative cohort study with a follow up to 1 year after the acute episode. Participant centers: 13 hospitals in the Aquitaine region (France). STUDY POPULATION: patients diagnosed with a confirmed ischemic or hemorrhagic stroke included in the Aquitaine Observatory of Stroke (ObA2) cohort and voluntary to participate. Data sources are existing databases (ObA2 database and the French National Health Data System - SNDS) to collect information about care pathways, patient characteristics and stroke characteristics and Ad hoc surveys to collect information about life pathways and post-stroke sequelae. The endpoints of the study are post-stroke activity limitations evaluated by the modified Rankin score, other post-stroke sequelae (Cognitive disorders, anxio-depressive disorders, fatigue, restriction of participation) assessed by standardized and validated scales and Clusters of patients responding to pathways with common or similar characteristics.; DISCUSSION: By integrating a longitudinal dimension and relying on a large cohort, the project will make it possible to identify the sources of disturbances and the factors favorable to the outcome of the life pathways, important for the planning of the offer and the management of the public policies concerning stroke pathways. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03865173 , March 6th, 2019.

Cost-effectiveness analysis of mechanical thrombectomy plus tissue-type plasminogen activator compared with tissue-type plasminogen activator alone for acute ischemic stroke in France.

BACKGROUND AND PURPOSE: Recent studies demonstrated the benefit of mechanical thrombectomy (MT) plus intravenous tissue-type plasminogen activator (IV-tPA) (MT-IV-tPA) in acute ischemic stroke. This study aimed to estimate the cost-utility of MT-IV-tPA compared with IV-tPA alone from the perspective of the French National Health Insurance. METHODS: We developed a decision tree for the first 3 months after stroke onset and a Markov model until 10 years post-stroke. The health states of the Markov model were according to the modified Rankin Scale (mRS): independent (mRS=0-2), dependent (mRS=3-5), dead (mRS=6). Recurrent stroke was the fourth health stage of our model. We conducted systematic literature reviews and meta-analyses to estimate the cost and utility of each health state, and the transition probabilities between health states. A microcosting study was conducted to estimate the cost of MT. We estimated the incremental cost-effectiveness ratio of MT-IV-tPA and conducted a probabilistic analysis in order to estimate the probability that MT-IV-tPA is cost-effective compared to IV-tPA, the expected value of perfect information (EVPI), and the expected value of partial perfect information (EVPPI), given the uncertainty surrounding the value of our model's parameters. RESULTS: The total mean (standard deviation (SD) cost of MT was €6708.9 (2357.0). The incremental cost-effectiveness ratio (ICER) of the strategy using IV-tPA combined to MT costs was €14,715 per QALY gained as compared to a strategy using IV-tPA alone. The probabilistic analysis showed that the probability of MT-IV-TPA being cost-effective was 85.4% at threshold willingness-to-pay of €30,000 per QALY gained, reaching 98% at €50,000 per QALY gained. CONCLUSION: Although there is no universally accepted willingness-to-pay threshold in France, our analysis suggest that MT combined to IV-tPA can be considered a cost-effective treatment compared with IV-tPA alone.

[Consensus approach: Prior to the construction of an evaluation scale of risk constipation patients hospitalized for nursing practice]. / Approche par recherche de consensus : un préalable à la construction d'une échelle d'évaluation du risque de constipation des patients hospitalisés destinée à la pratique infirmière.

BACKGROUND: Constipation is a frequent issue during hospitalization. Multiple causes such as the existence of irregular habits, lack of exercise as well as medical history have been identified. Drugs such as strong painkillers, central nervous system therapies and treatments of the digestive tract are a major cause of constipation. Additionally, unbalanced diet, fluid deficiency, and anxiety may aggravate constipation. The consideration of all these risk factors being under the responsibility of nurses. The difficulty to take into account such a multifactorial aetiology in nursing practice and the fact that there is no easy to use and validated tool to assess the risk of constipation in current nurse practice has led us to consider the development of a Risk Assessment scale of Constipation in Patient Hospitalized (ERCoPH) to facilitate preventive management of this trouble. We present here the first step of the elaboration of this scale, the identification of risk factors through a consensus approach after a systematic literature review. METHODS: The key informants consensus-based approach proposed by Pineault and Daveluy is based on five steps: (1) a literature review to identify risk factors for constipation; (2) the elaboration of a questionnaire containing the factors identified in the first step; (3) pre-select a panel of experts; (4) submission the questionnaire to the panel; (5) analysis the results of the consensus survey. Only factors that received a rating>6 by at least 80 % of the experts were retained. RESULTS: The systematic literature review identified 69 risk factors submitted to the 23 experts of the panel. Fifteen risk factors were retained after analyzing the answers of the experts. The Scientific Committee added eight risk factors because of their importance in the literature and decided to group together some factors of the same domain. CONCLUSION: A total of 19 risk factors were selected and grouped by major class (age, physical activity, medication, social data, food/hydration, medical and surgical history and environmental data). These factors have been tested among 300 patients enrolled in different clinical settings as part of the construction and validation of ERCoPH.

A Multi-centre Survey of Acceptability of Newborn Screening for Sickle Cell Disease in Nigeria.

Background Sickle cell disease (SCD) is a major genetic disease that manifests early in life and may lead to significant morbidities. One of the health care services that have been effective in reducing the burden of SCD in developed countries is newborn screening (NBS) followed by pneumococcal vaccines, penicillin prophylaxis, and hydroxyurea treatment. Yet, in sub-Saharan African countries, where about 75% of annual affected babies worldwide are born, NBS programmes are largely unavailable. It is not clear whether this is due to technical challenges associated with setting up such programmes, or significant cultural and social barriers to its acceptance in such settings. Objective Our aim was to ascertain the attitudes to and acceptability of NBS in Nigeria among various socio-demographic groups including health professionals, undergraduate students, parents of children with SCD and SCD patients. Methods Data on socio-demographic characteristics, knowledge of SCD and attitude towards NBS were collected using a semi-structured pre-tested questionnaire from April to July 2014 across 15 health institutions and university campuses in Nigeria. Data were collected from 1,301 respondents across Nigeria. Results There was good knowledge of SCD as an inherited blood disorder. Although 86% of respondents (n = 1,119) supported NBS, there was a statistically significant relationship between support for NBS and age (p = 003), educational status (p = 000) and religion (p = 000). Conclusion This study suggests that there is a good acceptability of NBS across Nigeria. The main barriers to its use are likely to be financial and practical, rather than social or cultural.

Chronic postsurgical pain in children: prevalence and risk factors. A prospective observational study.

BACKGROUND: Chronic postsurgical pain (CPSP) is well known in adults, with prevalence rates ranging from 10 to 50%. Little is known about the epidemiology of CPSP in children. The aim of this prospective observational study was to evaluate the prevalence of CPSP after surgery in children. METHODS: After informed consent, children aged six to18 yr were included. Characteristics and risk factors for CPSP were recorded. Exclusion criteria included ambulatory surgery, refusal, inability to understand and change of address. All eligible children completed a preoperative questionnaire the day before surgery about pain, anxiety and their medical history. All data concerning anaesthetic and surgical procedures, such as acute pain scores (VAS) during the first 24 h were recorded. Three months after surgery all included children were sent a postoperative questionnaire about pain at the surgical site. RESULTS: Altogether, 291 children were enrolled; the mean age was 12 yr, most subjects were male (60%). The most common type of surgery was orthopaedic (63%). In the 258 patients who completed the study, the prevalence of CPSP was 10.9%, most often with a neuropathic origin (64.3%). The two main risk factors were the existence of recent pain before surgery (<1 month) and the severity of acute postoperative pain (VAS >30 mm) in the first 24 h after orthopaedic and thoracic surgeries. Six months after surgery, only five children needed a visit with a chronic pain practitioner. CONCLUSIONS: These results highlight the necessity of evaluating and treating perioperative pain in order to prevent CPSP in children.

Clinical prognostic value of combined analysis of Aldh1, Survivin, and EpCAM expression in colorectal cancer.

BACKGROUND: Tumour aggressiveness might be related to the degree of main cancer hallmark acquirement of tumour cells, reflected by expression levels of specific biomarkers. We investigated the expression of Aldh1, Survivin, and EpCAM, together reflecting main cancer hallmarks, in relation to clinical outcome of colorectal cancer (CRC) patients. METHODS: Immunohistochemistry was performed using a tumour tissue microarray of TNM (Tumour, Node, Metastasis)-stage I-IV CRC tissues. Single-marker expression or their combination was assessed for associations with the clinical outcome of CRC patients (N=309). RESULTS: Increased expression of Aldh1 or Survivin, or decreased expression of EpCAM was each associated with poor clinical outcome, and was therefore identified as clinically unfavourable expression. Analyses of the combination of all three markers showed worse clinical outcome, specifically in colon cancer patients, with an increasing number of markers showing unfavourable expression. Hazard ratios ranged up to 8.3 for overall survival (P<0.001), 36.6 for disease-specific survival (P<0.001), and 27.1 for distant recurrence-free survival (P<0.001). CONCLUSIONS: Our data identified combined expression levels of Aldh1, Survivin, and EpCAM as strong independent prognostic factors, with high hazard ratios, for survival and tumour recurrence in colon cancer patients, and therefore reflect tumour aggressiveness.

Epigenetic status of LINE-1 predicts clinical outcome in early-stage rectal cancer.

BACKGROUND: We evaluated the clinical prognostic value of methylation of two non-coding repeat sequences, long interspersed element 1 (LINE-1) and Alu, in rectal tumour tissues. In addition to DNA methylation, expression of histone modifications H3K27me3 and H3K9Ac was studied in this patient cohort. METHODS: LINE-1 and Alu methylation were assessed in DNA extracted from formalin-fixed paraffin-embedded tissues. A pilot (30 tumour and 25 normal tissues) and validation study (189 tumour and 53 normal tissues) were performed. Histone modifications H3K27me3 and H3K9Ac were immunohistochemically stained on tissue microarrays of the study cohort. RESULTS: In early-stage rectal cancer (stage I-II), hypomethylation of LINE-1 was an independent clinical prognostic factor, showing shorter patient survival (P=0.014; HR: 4.6) and a higher chance of tumour recurrence (P=0.001; HR: 9.6). Alu methylation did not show any significant correlation with clinical parameters, suggesting an active role of LINE-1 in tumour development. Expression of H3K27me3 (silencing gene expression) and H3K9Ac (activating gene expression) in relation to methylation status of LINE-1 and Alu supported this specific role of LINE-1 methylation. CONCLUSION: The epigenetic status of LINE-1, but not of Alu, is prognostic in rectal cancer, indicating an active role for LINE-1 in determining clinical outcome.

Depletion of trypanosome CTR9 leads to gene expression defects.

The Paf complex of Opisthokonts and plants contains at least five subunits: Paf1, Cdc73, Rtf1, Ctr9, and Leo1. Mutations in, or loss of Paf complex subunits have been shown to cause defects in histone modification, mRNA polyadenylation, and transcription by RNA polymerase I and RNA polymerase II. We here investigated trypanosome CTR9, which is essential for trypanosome survival. The results of tandem affinity purification suggested that trypanosome CTR9 associates with homologues of Leo1 and Cdc73; genes encoding homologues of Rtf1 and Paf1 were not found. RNAi targeting CTR9 resulted in at least ten-fold decreases in 131 essential mRNAs: they included several that are required for gene expression and its control, such as those encoding subunits of RNA polymerases, exoribonucleases that target mRNA, RNA helicases and RNA-binding proteins. Simultaneously, some genes from regions subject to chromatin silencing were derepressed, possibly as a secondary effect of the loss of two proteins that are required for silencing, ISWI and NLP1.

[Tolerance and effectiveness of Memokath® 051 ureteral stents : a prospective 3 year follow-up study]. / Efficacité et tolérance des endoprothèses urétérales métalliques Memokath® 051 : étude prospective sur trois ans.

OBJECTIVE: To assess the effectiveness and tolerance of the metallic stent Memokath® 051 in the management of patients with chronic ureteral stricture treated by JJ stenting. PATIENTS AND METHODS: A prospective observational study included 16 patients with chronic ureteral stricture managed with JJ stents. They were all treated with Memokath® 051 metallic stents. The primary endpoint was the medium durability of the stent. Adverse events and complications were prospectively collected. The evolution of the irritative urinary symptoms and lumbar pain after stent insertion were also assessed. RESULTS: Sixteen patients (mean age: 62, standard deviation: 11,4) had a total of 20 stents inserted. It was technically impossible to insert the stent in two patients and one stent was removed one day after insertion. The medium durability of the stents was 13 months (standard deviation: 10,9). Eight stents (40%) were still functioning at the end of the study. Complications were: six migrations (30%) and four obstructions (20%) of the stents. Thirteen of the 14 patients with a Memokath® stent experienced significant improvement of their JJ stent-related symptoms. CONCLUSION: The Memokath® 051 stent was an interesting alternative to JJ stents in the management of chronic ureteral strictures. Their tolerance was good and complications were easily managed without threatening the urologic prognosis of the patients. Larger studies are required to identify the risk factors of complications and the best indications for stent insertion.

Emerging trends in the formation and function of tuberculosis granulomas.

The granuloma is an elaborated aggregate of immune cells found in non-infectious as well as infectious diseases. It is a hallmark of tuberculosis (TB). Predominantly thought as a host-driven strategy to constrain the bacilli and prevent dissemination, recent discoveries indicate the granuloma can also be modulated into an efficient tool to promote microbial pathogenesis. The aim of future studies will certainly focus on better characterization of the mechanisms driving the modulation of the granuloma functions. Here, we provide unique perspectives from both the innate and adaptive immune system in the formation and the role of the TB granuloma. As macrophages (Mϕs) comprise the bulk of granulomas, we highlight the emerging concept of Mϕ polarization and its potential impact in the microbicide response, and other activities, that may ultimately shape the fate of granulomas. Alternatively, we shed light on the ability of B-cells to influence inflammatory status within the granuloma.

An international collaboration to standardize HIV-2 viral load assays: results from the 2009 ACHI(E)V(2E) quality control study.

Accurate HIV-2 plasma viral load quantification is crucial for adequate HIV-2 patient management and for the proper conduct of clinical trials and international cohort collaborations. This study compared the homogeneity of HIV-2 RNA quantification when using HIV-2 assays from ACHI(E)V(2E) study sites and either in-house PCR calibration standards or common viral load standards supplied to all collaborators. Each of the 12 participating laboratories quantified blinded HIV-2 samples, using its own HIV-2 viral load assay and standard as well as centrally validated and distributed common HIV-2 group A and B standards (http://www.hiv.lanl.gov/content/sequence/HelpDocs/subtypes-more.html). Aliquots of HIV-2 group A and B strains, each at 2 theoretical concentrations (2.7 and 3.7 log(10) copies/ml), were tested. Intralaboratory, interlaboratory, and overall variances of quantification results obtained with both standards were compared using F tests. For HIV-2 group A quantifications, overall and interlaboratory and/or intralaboratory variances were significantly lower when using the common standard than when using in-house standards at the concentration levels of 2.7 log(10) copies/ml and 3.7 log(10) copies/ml, respectively. For HIV-2 group B, a high heterogeneity was observed and the variances did not differ according to the type of standard used. In this international collaboration, the use of a common standard improved the homogeneity of HIV-2 group A RNA quantification only. The diversity of HIV-2 group B, particularly in PCR primer-binding regions, may explain the heterogeneity in quantification of this strain. Development of a validated HIV-2 viral load assay that accurately quantifies distinct circulating strains is needed.

Development of a real-time PCR targeting the yidC gene for the detection of Mycoplasma hominis and comparison with quantitative culture.

Mycoplasma hominis is an opportunistic human mycoplasma species that can be either commensal or pathogenic. Its detection by culture is considered to comprise the reference technique. Previously reported PCR techniques target the 16S rRNA or the gap gene, although sequence variations among clinical isolates may lead to variations in clinical sensitivity. The present study aimed to develop a specific TaqMan quantitative real-time PCR assay, targeting a gene conserved in all M. hominis isolates, and to compare it with quantitative culture. With the knowledge of the M. hominis PG21 genome sequence, the yidC gene, encoding a membrane protein translocase, was chosen as target. Its intraspecies heterogeneity was checked at the nucleotide level using 31 reference or clinical strains. The limit of detection, the analytical specificity and the reproducibility of the assay were assessed. Moreover, PCR and culture results were compared using 153 urogenital specimens. The limit of detection was seven copies/µL. The analytical specificity was 100%, with good inter- and intra-assay reproducibility. Among the 153 urogenital specimens, the yidC PCR and culture allowed detection of 55 and 45 M. hominis-positive samples, respectively. Comparison of the bacterial load among the 45 specimens found to be M. hominis-positive by both techniques revealed a statistically significant association between the quantitative results obtained. In conclusion, we developed a specific, sensitive and reproducible real-time PCR to detect all M. hominis clinical isolates. This PCR was shown to have higher sensitivity than culture, although both methods were correlated for quantification of M. hominis loads in urogenital specimens.

Evaluation of five commercial real-time PCR assays for detection of Mycoplasma pneumoniae in respiratory tract specimens.

The performances of five commercial TaqMan real-time PCR assays for the detection of Mycoplasma pneumoniae in respiratory tract specimens were evaluated in comparison with an in-house real-time PCR. All kits allowed prompt and specific results, validated by the use of an internal control. The Nanogen kit showed the best clinical sensitivity.

HIV-2 integrase gene polymorphism and phenotypic susceptibility of HIV-2 clinical isolates to the integrase inhibitors raltegravir and elvitegravir in vitro.

OBJECTIVES: We investigated the in vitro phenotypic susceptibility of HIV-2 isolates from integrase inhibitor (INI)-naive patients to INIs and its relation to HIV-2 integrase gene polymorphism. METHODS: We determined the phenotypic susceptibility to raltegravir and elvitegravir of co-cultured isolates obtained from the HIV-2 ROD reference strain and from 14 clinical isolates. IC(50) values were compared with those for HIV-1 reference strains. HIV-2 integrase gene polymorphism was assessed in isolates from 52 INI-naive patients enrolled in the French HIV-2 cohort. RESULTS: Median raltegravir and elvitegravir IC(50) values for the 14 clinical HIV-2 isolates were 2.4 and 0.7 nM, respectively, and were similar to those observed for HIV-2 ROD and HIV-1 reference strains. Overall, 38% of HIV-2 integrase amino acids were polymorphic. The catalytic triad DDE and the HHCC and RKK motifs were fully conserved, at the same genomic positions as described in HIV-1. In subtype B isolates, the total length of the integrase gene varied, owing to the presence of stop codons at positions 288, 294, 297 and 302. Fourteen of the positions associated with substitutions conferring INI resistance in HIV-1 were polymorphic in HIV-2. CONCLUSIONS: Despite 40% heterogeneity between the HIV-1 and HIV-2 integrase genes, the phenotypic susceptibility of clinical HIV-2 isolates to INIs was similar to that of HIV-1. This new class of antiretroviral drugs thus represents a novel therapeutic possibility for HIV-2-infected patients who otherwise have few treatment options.

Survey of European programmes for the epidemiological surveillance of congenital toxoplasmosis.

The objective of this investigation was to describe systems for the epidemiological surveillance of congenital toxoplasmosis implemented in European countries. In September 2004, a questionnaire, adapted from the evaluation criteria published by the United States Centers for Disease Control and Prevention, was sent to a panel of national correspondents in 35 countries in the European geographical area with knowledge of the epidemiological surveillance systems implemented in their countries. Where necessary, we updated the information until July 2007. Responses were received from 28 countries. Some 16 countries reported routine surveillance for toxoplasmosis. In 12 countries (Bulgaria, Cyprus, Czech Republic, England and Wales, Estonia, Ireland, Latvia, Lithuania, Malta, Poland, Scotland and Slovakia), surveillance was designed to detect only symptomatic toxoplasmosis, whether congenital or not. Four countries reported surveillance of congenital toxoplasmosis, on a regional basis in Italy and on a national basis in Denmark, France and Germany. In conclusion, epidemiological surveillance of congenital toxoplasmosis needs to be improved in order to determine the true burden of disease and to assess the effectiveness of and the need for existing prevention programmes.

Human immunodeficiency virus type 1 (HIV-1) plasma load discrepancies between the Roche COBAS AMPLICOR HIV-1 MONITOR Version 1.5 and the Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 assays.

We compared plasma viral load values obtained with COBAS AMPLICOR human immunodeficiency virus type 1 (HIV-1) MONITOR version 1.5 and with COBAS TaqMan HIV-1 assays. Mean values were 4.2 and 2.9 log(10) copies/ml, respectively, showing the lack of agreement between the two assays.