Prostate cancer outcomes in France: treatments, adverse effects and two-year mortality

BACKGROUND: This very large population-based study investigated outcomes after a diagnosis of prostate cancer (PCa) in terms of mortality rates, treatments and adverse effects. METHODS: Among the 11 million men aged 40 years and over covered by the general national health insurance scheme, those with newly managed PCa in 2009 were followed for two years based on data from the national health insurance information system (SNIIRAM). Patients were identified using hospitalisation diagnoses and specific refunds related to PCa and PCa treatments. Adverse effects of PCa treatments were identified by using hospital diagnoses, specific procedures and drug refunds. RESULTS: The age-standardised two-year all-cause mortality rate among the 43,460 men included in the study was 8.4%, twice that of all men aged 40 years and over. Among the 36,734 two-year survivors, 38% had undergone prostatectomy, 36% had been treated by hormone therapy, 29% by radiotherapy, 3% by brachytherapy and 20% were not treated. The frequency of treatment-related adverse effects varied according to age and type of treatment. Among men between 50 and 69 years of age treated by prostatectomy alone, 61% were treated for erectile dysfunction and 24% were treated for urinary disorders. The frequency of treatment for these disorders decreased during the second year compared to the first year (erectile dysfunction: 41% vs 53%, urinary disorders: 9% vs 20%). The frequencies of these treatments among men treated by external beam radiotherapy alone were 7% and 14%, respectively. Among men between 50 and 69 years with treated PCa, 46% received treatments for erectile dysfunction and 22% for urinary disorders. For controls without PCa but treated surgically for benign prostatic hyperplasia, these frequencies were 1.5% and 6.0%, respectively. CONCLUSIONS: We report high survival rates two years after a diagnosis of PCa, but a high frequency of PCa treatment-related adverse effects. These frequencies remain underestimated, as they are based on treatments for erectile dysfunction and urinary disorders and do not reflect all functional outcomes. These results should help urologists and general practitioners to inform their patients about outcomes at the time of screening and diagnosis, and especially about potential treatment-related adverse effects

Quantitative isotope-dilution high-resolution-mass-apectrometry analysis of multiple intracellular metabolites in Clostridium autoethanogenum with uniformly 13C-labeled standards derived from Spirulina

We have investigated the applicability of commercially available lyophilized spirulina (Arthrospira platensis), a microorganism uniformly labeled with 13C, as a readily accessible source of multiple 13C-labeled metabolites suitable as internal standards for the quantitative determination of intracellular bacterial metabolites. Metabolites of interest were analyzed by hydrophilic-interaction liquid chromatography coupled with high-resolution mass spectrometry. Multiple internal standards obtained from uniformly (U)-13C-labeled extracts from spirulina were used to enable isotope-dilution mass spectrometry (IDMS) in the identification and quantification of intracellular metabolites. Extraction of the intracellular metabolites of Clostridium autoethanogenum using 2:1:1 chloroform/methanol/water was found to be the optimal method in comparison with freeze–thaw, homogenization, and sonication methods. The limits of quantification were ≤1 μM with excellent linearity for all of the calibration curves (R2 ≥ 0.99) for 74 metabolites. The precision and accuracy were found to be within relative standard deviations (RSDs) of 15% for 49 of the metabolites and within RSDs of 20% for all of the metabolites. The method was applied to study the effects of feeding different levels of carbon monoxide (as a carbon source) on the central metabolism and Wood–Ljungdahl pathway of C. autoethanogenum grown in continuous culture over 35 days. Using LC-IDMS with U-13C spirulina allowed the successful quantification of 52 metabolites in the samples, including amino acids, carboxylic acids, sugar phosphates, purines, and pyrimidines. The method provided absolute quantitative data on intracellular metabolites that was suitable for computational modeling to understand and optimize the C. autoethanogenum metabolic pathways active in gas fermentation

Quantitative Bioreactor Monitoring of Intracellular Bacterial Metabolites in Clostridium autoethanogenum Using Liquid Chromatography–Isotope Dilution Mass Spectrometry

We report a liquid chromatography–isotope dilution mass spectrometry method for the simultaneous quantification of 131 intracellular bacterial metabolites of Clostridium autoethanogenum. A comprehensive mixture of uniformly 13C-labeled internal standards (U-13C IS) was biosynthesized from the closely related bacterium Clostridium pasteurianum using 4% 13C–glucose as a carbon source. The U-13C IS mixture combined with 12C authentic standards was used to validate the linearity, precision, accuracy, repeatability, limits of detection, and quantification for each metabolite. A robust-fitting algorithm was employed to reduce the weight of the outliers on the quantification data. The metabolite calibration curves were linear with R2 ≥ 0.99, limits of detection were ≤1.0 μM, limits of quantification were ≤10 μM, and precision/accuracy was within RSDs of 15% for all metabolites. The method was subsequently applied for the daily monitoring of the intracellular metabolites of C. autoethanogenum during a CO gas fermentation over 40 days as part of a study to optimize biofuel production. The concentrations of the metabolites were estimated at steady states of different pH levels using the robust-fitting mathematical approach, and we demonstrate improved accuracy of results compared to conventional regression. Metabolic pathway analysis showed that reactions of the incomplete (branched) tricarboxylic acid “cycle” were the most affected pathways associated with the pH shift in the bioreactor fermentation of C. autoethanogenum and the concomitant changes in ethanol production

A genome-scale model of Clostridium autoethanogenum reveals optimal bioprocess conditions for high-value chemical production from carbon monoxide

Clostridium autoethanogenum is an industrial microbe used for the commercial-scale production of ethanol from carbon monoxide. While significant progress has been made in the attempted diversification of this bioprocess, further improvements are desirable, particularly in the formation of the high-value platform chemicals, such as 2,3-butanediol. A new, experimentally parameterised genome scale model of C. autoethanogenum predicts dramatically increased 2,3-butanediol production under non-carbon-limited conditions when thermodynamic constraints on hydrogen production are considered

Whole genome sequence and manual annotation of Clostridium autoethanogenum, an industrially relevant bacterium

Clostridium autoethanogenum is an acetogenic bacterium capable of producing high value commodity chemicals and biofuels from the C1 gases present in synthesis gas. This common industrial waste gas can act as the sole energy and carbon source for the bacterium that converts the low value gaseous components into cellular building blocks and industrially relevant products via the action of the reductive acetyl-CoA (Wood-Ljungdahl) pathway. Current research efforts are focused on the enhancement and extension of product formation in this organism via synthetic biology approaches. However, crucial to metabolic modelling and directed pathway engineering is a reliable and comprehensively annotated genome sequence

Current challenges in providing bariatric surgery in France

International audienceBariatric surgery is a well-accepted procedure for severe and massive obesity management. We aimed to determine trends, geographical variations, and factors influencing bariatric surgery and the choice of procedure in France in a large observational study.The Health Insurance Fund for Salaried Workers (Caisse National Assurance Maladie Travailleurs Salariés) covers about 86% of the French population. The Système National d'Information Inter-régimes de l'Assurance Maladie database contains individualized and anonymized patient data on all reimbursements for healthcare expenditure. All types of primary bariatric procedures (Roux-en-Y gastric bypass [RYGB] or omega loop, adjustable gastric banding [AGB], or longitudinal sleeve gastrectomy [LSG]) performed during 2011 to 2013 were systematically recorded. Surgical techniques performed by region of residence and age-range relative risks with 95% confidence intervals of undergoing LSG or RYGB versus AGB were computed.In 2013, LSG was performed more frequently than RYGB and AGB (57% vs 31% and 13%, respectively). A total of 41,648 patients underwent a bariatric procedure; they were predominantly female (82%) with a mean (±standard deviation) age of 40 (±12) years and a body mass index ≥40 kg/m for 68% of them. A total of 114 procedures were performed in patients younger than 18 years and 2381 procedures were performed in patients aged 60 years and older. Beneficiaries of the French universal health insurance coverage for low-income patients were more likely to undergo surgery than the general population. Large nationwide variations were observed in the type choice of bariatric surgical procedures. Significant positive predictors for undergoing RYGB compared to those for undergoing AGB were as follows: referral to a center performing a large number of surgeries or to a public hospital, older age, female gender, body mass index ≥50 kg/m, and treatment for obstructive sleep apnea syndrome, diabetes, or depression. Universal health insurance coverage for low-income patients was inversely correlated with the probability of RYGB.Differences in access to surgery have been observed in terms of the patient's profile, geographical variations, and predictors of types of procedures. Several challenges must be met when organizing the medical care of this growing number of patients, when delivering surgery through qualified centers while assuring the quality of long-term follow-up for all patients

The morphogenic protein CopD controls the spatio-temporal dynamics of PBP1a and PBP2b in Streptococcus pneumoniae

International audiencePenicillin-binding proteins (PBPs) are key to the assembly of peptidoglycan, the major component of the bacterial cell wall. Although several PBP-specific regulatory proteins have been identified in different species, little is known about how the activity of PBPs is controlled and coordinated during the cell cycle. In this study, we characterize the unknown function protein Spr1400 and demonstrate its regulatory function on two PBPs in Streptococcus pneumoniae. For that, we use a combination of technics ranging from bacterial genetics and protein biochemistry to microscopy imaging. First, we show that pneumococcal Spr1400 localizes late to the cell division septum. Furthermore, deletion of spr1400 results in wider cells. Using co-immunoprecipitation and bacterial two hybrid (B2H), we observe that Spr1400 interacts with two PBPs, the class A PBP PBP1a and the class B PBP PBP2b, which are required for cell elongation. Microscale thermophoresis combined with B2H further reveals that these interactions occur through their transmembrane domains. We also show that Spr1400 co-localizes with PBP1a and PBP2b throughout the cell cycle. Strikingly, deletion of spr1400 alters the dynamics of PBP1a and PBP2b. Indeed, the two PBPs persist longer at the division site and localize later at the division site of daughter cells. Collectively, these data demonstrate that Spr1400, thus named CopD for coordinator of PBP1a and 2b dynamics, is a spatio-temporal regulator of PBP1a and PBP2b required for pneumococcal morphogenesis

To What Extent Does Posthospital Discharge Chemoprophylaxis Prevent Venous Thromboembolism After Bariatric Surgery?

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Do sleeve gastrectomy and gastric bypass influence treatment with proton pump inhibitors 4 years after surgery? A nationwide cohort

International audienceGastroesophageal reflux disease (GERD) is a common obesity-related co-morbidity that routinely is treated by continuous proton pump inhibitor (PPI) therapy. A number of concerns have been raised regarding the risk of de novo GERD or exacerbation of preexisting GERD after sleeve gastrectomy (SG).OBJECTIVE:To assess PPI use at 4 years after bariatric surgery.SETTING:French National Health Insurance.METHODS:Data were extracted from the French National Health Insurance database. All adult obese patients who had undergone gastric bypass (GBP) (n = 8250) or SG (n = 11,923) in 2011 in France were included. Patients were considered to be on continuous PPI therapy when PPIs were dispensed≥6 times per year. Logistic regression models were used to compute odds ratios for potential risk factors for PPI reimbursement 4 years after surgery.RESULTS:Overall, continuous use of PPIs increased from baseline to 4 years after SG and GBP, from 10.9% to 26.5% (P<.001) and from 11.4% to 21.9% (P<.001), respectively. Among patients who underwent PPI therapy before surgery, those who had undergone SG were more likely to continue PPI therapy 4 years after surgery compared with those who underwent GBP (72.7% versus 59.2%; P<.001). In multivariate analyses, the major risk factors for persistent continuous PPI treatment 4 years after surgery were the following: SG (odds ratio [OR] = 1.87; 95% confidence interval [CI] 1.55-2.25), higher body mass index (OR 1.85; 95% CI 1.35-2.5), and preoperative antidepressant treatment (OR 1.89; 95% CI 1.56-2.29).CONCLUSION:At a nationwide scale, continuous PPI treatment is used by 1 of 10 obese patients before bariatric surgery, but by 1 of 4 patients 4 years after surgery. SG compared with GBP, higher body mass index, and other coexisting conditions are the 3 major risk factors for medium-term continuous PPI therapy