A novel lipase with dual localisation in Trypanosoma brucei.

Phospholipases are esterases involved in lipid catabolism. In pathogenic micro-organisms (bacteria, fungi, parasites) they often play a critical role in virulence and pathogenicity. A few phospholipases (PL) have been characterised so far at the gene and protein level in unicellular parasites including African trypanosomes (AT). They could play a role in different processes such as host-pathogen interaction, antigenic variation, intermediary metabolism. By mining the genome database of AT we found putative new phospholipase candidate genes and here we provided biochemical evidence that one of these has lipolytic activity. This protein has a unique non-canonical glycosome targeting signal responsible for its dual localisation in the cytosol and the peroxisomes-related organelles named glycosomes. We also show that this new phospholipase is excreted by these pathogens and that antibodies directed against this protein are generated during an experimental infection with T. brucei gambiense, a subspecies responsible for infection in humans. This feature makes this protein a possible tool for diagnosis.

Steroids in cardiac surgery: a systematic review and meta-analysis.

BACKGROUND: Cardiopulmonary bypass (CPB) induces a systemic inflammatory reaction that may contribute to postoperative complications. Preventing this reaction with steroids may improve outcomes. We performed a systematic review to evaluate the impact of prophylactic steroids on clinical outcomes in patients undergoing on-pump cardiac surgery. METHODS: We searched MEDLINE, EMBASE, and Cochrane CENTRAL for randomised controlled trials (RCTs) comparing perioperative corticosteroid administration with a control group in adults undergoing CPB. Outcomes of interest included mortality, myocardial infarction, and new onset atrial fibrillation. We assessed the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Fifty-six RCTs published between 1977 and 2015 were included in this meta-analysis. Mortality was not significantly different between groups [3.0% (215/7258 patients) in the steroid group and 3.5% (252/7202 patients) in the placebo group; relative risk (RR), 0.85; 95% confidence interval (CI), 0.71-1.01; P=0.07; I2 = 0%]. Myocardial injury was more frequent in the steroid group [8.0% (560/6989 patients), compared with 6.9% (476/6929 patients); RR, 1.17, 95% CI, 1.04-1.31; P=0.008; I2=0%]. New onset atrial fibrillation was lower in the steroid group [25.7% (1792/6984 patients) compared with 28.3% (1969/6964 patients), RR, 0.91, 95% CI, 0.86-0.96, P=0.0005, I2=43%]; this beneficial effect was limited to small trials (P for interaction <0.00001). CONCLUSIONS: After randomising 16 013 patients, steroid administration at the time of cardiac surgery had an unclear impact on mortality, increased the risk of myocardial injury, and the impact on atrial fibrillation should be viewed with caution given that large trials showed no effect.

Incidental findings in CT imaging of coronary artery bypass grafts: results from a Canadian multicenter prospective cohort.

OBJECTIVE: To assess the prevalence and clinical significance of incidental findings identified during computed tomography imaging of coronary artery bypass grafts. RESULTS: This prospective study includes 144 patients undergoing coronary graft patency assessment using computed tomography. Incidental findings were classified as significant if they were considered to need an immediate action or treatment, short-term work-up or follow-up, or minor. A total of 211 incidental findings were present in 109 (75.7%) patients. Seventy-one incidental findings (33.6%) were cardiac and 140 (66.4%) were extracardiac. Most common cardiac incidental findings were atrial dilatation [39 patients, 48 incidental findings (67.6%)] and aortic valve calcifications (7 patients, 9.9%). Among the 140 extracardiac incidental findings, the most common were lung nodules (51 patients, 54 nodules, 38.6%), and emphysema (21 patients, 15%). Thirty-six (25.7%) extracardiac incidental findings were significant and notably, 23 (63.9%) were lung nodules. Follow-up was recommended in 37 cases, among which all patients with significant lung nodules (23 patients, 62.2%). In conclusion, most common computed tomography incidental findings in patients with coronary grafts were lung nodules and emphysema.

[Tumour sequencing: Evolutions and revolutions]. / Séquençage des tumeurs : évolutions et révolutions.

For some years now, we have entered the genomic age of tumour genotyping from a medical point of view. Technological breakthroughs in both biology and information science now allow a genomic analysis of cancers in everyday medical practice with, in some case, a major impact on patient care not only for the choice of therapy (i.e. EGFR mutations in lung adenocarcinoma), but also for diagnosis and monitoring of the disease. Tumour genotyping is performed from formalin-fixed paraffin-embedded tissues used for diagnosis of cancer. However, new approaches have emerged, with for example the more and more spread use of "liquid biopsies". Genotyping of a gene panel implicated in carcinogenesis is now routinely performed in some cancer types, with the help of high-throughput sequencers, and it is likely that improvement of these machines will make tumour genotyping easier and more accessible in the near future. Nevertheless, the current challenge is not anymore detection of molecular alterations, but their relevant interpretation, so as to be the most useful in patient care.

Community structure and nutrient level control the tolerance of autotrophic biofilm to silver contamination.

Autotrophic biofilms are complex and fundamental biological compartments of many aquatic ecosystems. Since microbial species differ in their sensitivity to stressors, biofilms have long been proposed for assessing the quality of aquatic ecosystems. Among the many stressors impacting aquatic ecosystems, eutrophication and metal pollution are certainly the most common. Despite that these stressors often occur together, their effects on biofilms have been far much studied separately than interactively. In this study, we evaluated the interactive effects of silver (Ag), a reemerging contaminant, and phosphorus (P), a nutrient often associated with freshwater eutrophication, on the structure and functioning of two types of autotrophic biofilms, one dominated by diatoms and another one dominated by cyanobacteria. We hypothesized that P would alleviate the toxic effects of Ag, either directly, through the contribution of P in metal detoxification processes, or indirectly, through P-mediated shifts in biofilm community compositions and associated divergences in metal tolerance. Results showed that Ag impacted biofilm community structure and functioning but only at unrealistic concentrations (50 µg/L). P availability led to significant shifts in biofilm community composition, these changes being more pronounced in diatom- than those in cyanobacteria-dominated biofilm. In addition, P tended to reduce the impact of Ag but only for the cyanobacteria-dominated biofilm. More generally, our results highlight the preponderant role of the initial community structure and nutrient level on biofilm response to metallic pollutants.

Influence of the natural growth environment on the sensitivity of phototrophic biofilm to herbicide.

Ecotoxicological experiments were performed in laboratory-scale microcosms to investigate community-level structural responses of river phototrophic biofilms from different environments to herbicide exposure. Biofilms were initially cultivated on artificial supports placed in situ for 4 weeks at two sites, site M, located in an agricultural watershed basin and site S, located in a forested watershed basin. The biofilms were subsequently transferred to microcosms and, after an acclimatisation phase of 7 days were exposed to alachlor at 10 and 30 µg L(-1) for 23 days. Alachlor effects were assessed by a combination of structural parameters, including biomass (ash-free dry mass and chlorophyll a), molecular fingerprinting of the bacterial community (polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis (DGGE)) and diatom species composition. Alachlor impacted the chlorophyll a and ash-free dry mass levels of phototrophic biofilms previously cultivated at site S. The structural responses of bacterial and diatom communities were difficult to distinguish from changes linked to the microcosm incubation period. Phototrophic biofilms from site S exposed at 30 µg L(-1) alachlor were characterised by an increase of Achnanthidium minutissimum (K-z.) Czarnecki abundance, as well as a higher proportion of abnormal frustules. Thus, phototrophic biofilms with different histories, exhibited different responses to alachlor exposure demonstrating the importance of growth environment. These observations also confirm the problem of distinguishing changes induced by the stress of pesticide toxicity from temporal evolution of the community in the microcosm.

Cost implications of the use of basal insulin glargine in people with early dysglycemia: the ORIGIN trial.

AIMS: The cost implications of the Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial were evaluated using a prespecified analysis plan. METHODS: Purchasing power parity-adjusted country-specific costs were applied to consumed healthcare resources by participants from each country. Subgroup analyses were conducted on subgroups based on baseline metabolic status and diabetes duration. RESULTS: The total undiscounted cost per participant in the insulin glargine arm was $13,491 ($13,080 to $14,254) versus $11,189 ($10,568 to $12,147) for standard care, an increase of $2303 ($1370 to $3235; p < 0.0001); the discounted increase was $2099 ($1276 to $2923; P < 0.0001). The greater number of mainly generic oral anti-diabetic agents in the standard group partially offset the higher cost of basal insulin glargine. As the trial progressed and the standard group required more anti-diabetic medications, the annual cost difference decreased, reaching $68 (-$160 to $295) in the last year. The subgroup whose baseline diabetes duration was ≥ 6 years achieved cost-savings during the trial. CONCLUSIONS: From a global perspective basal insulin glargine use in ORIGIN incurred greater costs than standard care using older generic drugs. Nevertheless, the cost difference fell with time such that the intervention was cost-neutral by the last year.

Neuropathic complications after 157 procedures of continuous popliteal nerve block for hallux valgus surgery. A retrospective study.

BACKGROUND: Continuous peripheral nerve block (CPNB), in particular at the popliteal fossa, is widely used in orthopedic surgery, allowing good postoperative analgesia. Possible neuropathic complications, however, remain poorly known. OBJECTIVE: To review the characteristics of peripheral neuropathy (PN) after sciatic CPNB at the popliteal fossa, estimating prevalence, severity, evolution and possible risk factors, especially those relating to the procedure. METHODS: Retrospective study of PN associated with popliteal fossa CPNB for hallux valgus surgery, between November 1st, 2005 and November 1st, 2009. All procedures were analyzed (type of anesthesia, approach, nerve location technique, number of procedures by operator) with, for each case of PN, analysis of clinical and electromyographic data. RESULTS: One hundred and fifty seven sciatic CPNBs were performed (92% women; mean age, 55 years). The approach was lateral (n=62), posterior (n=74) or unknown (n=21). Ultrasound guidance was combined to neurostimulation for 69 patients (44%). Three women (prevalence=1.91%), aged 19, 24 and 65 years respectively, developed associated common superficial peroneal and sural nerve injury (2), axonal on electromyography, with motor (n=1) and/or sensory (n=3) residual dysfunction. DISCUSSION: The higher prevalence found in the present study than in the literature (0 to 0.5%) raises questions of methodological bias or technical problems. The common peroneal and sural nerves seem to be exposed, unlike the tibial. Several mechanisms can be suggested: anesthetic neurotoxicity, direct mechanical lesion, or tourniquet-related ischemia and conduction block. Further studies are necessary to determine the ideal anesthetic procedure. CONCLUSION: Patients should be informed of the potential risk, however rare, even during mild surgery. The best possible technique should be implemented, with reinforced surveillance.

[Proposal of a rating scale of posture for simple dysfunctional dysphonia: "S-TRAV"]. / Proposition d'une échelle d'évaluation de la posture pour les dysphonies dysfonctionnelles simples: "S-TRAV".

OBJECTIVE: This work aims to create a scale to evaluate posture, quick and easy to perform during the assessment of voice in patients with simple dysfunctional dysphonia. MATERIAL AND METHOD: The "S-TRAV" scale was evaluated on 60 subjects with dysphonia and 60 control subjects. It assesses "the overall severity" of the alteration of posture, the "Tension", the "Breathing", the "Ground anchoring" and the "Verticality" both quantitatively (score 0-3) and qualitatively. The patient also assesses his voice disorder and his posture. Postural observation was carried out in five conditions: at rest, conversational voice, reading, projected voice and singing voice. The comparison between the dysphonic subjects and control subjects was used to assess the sensitivity of this tool. Two reviewers rated the scale to determine its reproducibility. RESULTS: The scale is sensible for the majority of criteria with a significance coefficient less than 0.05. The most discriminate criteria relate to the cervical spine, the overall score of postural severity assessed by the therapist and verticality. All criteria have a low level of variability between the reviewers under all conditions. Most criteria are correlated with the criterion "Overall Severity" of postural alterations under all conditions. Non-sensible criteria were eliminated from the final scale). CONCLUSION: This tool is sensitive, reproducible and relevant in assessing the severity of postural alterations and their location. Further studies will validate the scale on a consistent population.

TP53 mutations predict disease control in metastatic colorectal cancer treated with cetuximab-based chemotherapy.

Recent studies have suggested that activation of the EGFR pathway leads to malignant transformation only if the p53 protein is inactivated. Therefore, we evaluated the impact of TP53 mutations on cetuximab-based chemotherapy (CT) sensitivity in combination with KRAS mutations that have been associated with cetuximab resistance. KRAS and TP53 status were assessed in tumours from 64 metastatic colorectal cancer patients treated with cetuximab-based CT and correlated to clinical response using the Fisher's exact test. Times to progression (TTPs) according to gene status were calculated using the Kaplan-Meier method and compared with log-rank test. TP53 mutations were found in 41 patients and were significantly associated with controlled disease (CD), as defined as complete response, partial response or stable disease (P=0.037) and higher TTP (20 vs 12 weeks, P=0.004). Remarkably, in the subgroup of 46 patients without KRAS mutation, but not in patients with KRAS mutation, TP53 mutations were also associated with CD (P=0.008) and higher TTP (24 vs 12 weeks, P=0.0007). This study suggests that TP53 mutations are predictive of cetuximab sensitivity, particularly in patients without KRAS mutation, and that TP53 genotyping could have a clinical interest to select patients who should benefit from cetuximab-based CT.

Cardiac surgery in patients with haemophilia B: a case report and review of the literature.

Cardiac surgery for coronary heart disease, and for calcific and degenerative valvular heart disease, will likely become more frequent with an ageing haemophilia population. Our report describes the successful management of an individual with mild haemophilia B undergoing elective aortic valve replacement using a continuous infusion of recombinant factor IX. Emphasis is placed on the multidisciplinary coordination of care required across three hospital sites to ensure an uncomplicated peri- and postoperative course. We also provide a review of the current literature on cardiac surgery in patients with haemophilia B.

Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy.

The predictive value of KRAS mutation in metastatic colorectal cancer (MCRC) patients treated with cetuximab plus chemotherapy has recently been suggested. In our study, 59 patients with a chemotherapy-refractory MCRC treated with cetuximab plus chemotherapy were included and clinical response was evaluated according to response evaluation criteria in solid tumours (RECIST). Tumours were screened for KRAS mutations using first direct sequencing, then two sensitive methods based on SNaPshot and PCR-ligase chain reaction (LCR) assays. Clinical response was evaluated according to gene mutations using the Fisher exact test. Times to progression (TTP) were calculated using the Kaplan-Meier method and compared with log-rank test. A KRAS mutation was detected in 22 out of 59 tumours and, in six cases, was missed by sequencing analysis but detected using the SNaPshot and PCR-LCR assays. Remarkably, no KRAS mutation was found in the 12 patients with clinical response. KRAS mutation was associated with disease progression (P=0.0005) and TTP was significantly decreased in mutated KRAS patients (3 vs 5.5 months, P=0.015). Our study confirms that KRAS mutation is highly predictive of a non-response to cetuximab plus chemotherapy in MCRC and highlights the need to use sensitive molecular methods, such as SNaPshot or PCR-LCR assays, to ensure an efficient mutation detection.

Molecular profiling of bladder tumors based on the detection of FGFR3 and TP53 mutations.

PURPOSE: On a routine basis we performed systematic molecular screening for FGFR3 and TP53 mutations in 121 bladder tumors. We then specifically analyzed the predictive value of the recurrence of FGFR3 and TP53 genotypes in superficial lesions. MATERIALS AND METHODS: The FGFR3 gene was analyzed by direct sequencing of exons 7, 10 and 15, whereas TP53 status was determined using the p53 functional assay in yeast. RESULTS: We identified a missense FGFR3 mutation in 66% of pTa, 26% of pT1 and 12% of pT2 tumors. Of activating FGFR3 mutations 54% and 85% were found in low G1 and intermediate G2 grade tumors, respectively, but in only 20% of high grade G3 tumors. We detected inactivating TP53 mutations in 10% of pTa, 42% of pT1 and 58% of pT2 tumors. Moreover, TP53 mutations were found only in 23% of grade G1 and 3% of grade G2 tumors but in 44% of high grade G3 tumors. When the 2 genotypes were combined, we observed that 58% of pTa tumors had the (mutant FGFR3, WT TP53) genotype, whereas 58% of invasive lesions harbored the inverse genotype (WT FGFR3, mutant TP53). The (mutant FGFR3, WT TP53) genotype and the (WT FGFR3, mutant TP53) genotype were detected in 23% and 38% of pT1G3 tumors, respectively. In the subgroup of 92 patients with superficial pTa-T1 bladder tumors we did not find that the TP53 or FGFR3 genotype alone or combined had a predictive value for tumor recurrence. CONCLUSIONS: Our data again represent solid proof for the pivotal role of FGFR3 and TP53 mutations in superficial and invasive bladder tumors, respectively. However, other molecular markers should be identified for borderline pT1G3 bladder tumors, which are probably at the crossroads of these 2 distinct molecular pathways.

Bicycle helmet prevalence two years after the introduction of mandatory use legislation for under 18 year olds in Alberta, Canada.

OBJECTIVE: To determine changes in helmet use in cyclists following the introduction of a bicycle helmet law for children under age 18. METHODS: Cyclists were observed by two independent observers from July to August 2004 (post-legislation) in Edmonton, Alberta. The data were compared with a similar survey completed at the same locations and days in July to August 2000 (pre-legislation). Data were collected for 271 cyclists in 2004 and 699 cyclists in 2000. RESULTS: The overall prevalence of helmet use increased from 43% (95% CI 39 to 47%) in 2000 to 53% (95% CI 47 to 59%) in 2004. Helmet use increased in those under 18, but did not change in those 18 and older. In the cluster adjusted multivariate Poisson regression model, the prevalence of helmet use significantly increased for those under age 18 (adjusted prevalence ratio (APR) 3.69, 95% CI 2.65 to 5.14), but not for those 18 years and older (APR 1.17, 95% CI 0.95 to 1.43). CONCLUSION: Extension of legislation to all age groups should be considered.

The Canadian off-pump coronary artery bypass graft registry: a one-year prospective comparison with on-pump coronary artery bypass grafting.

BACKGROUND: The authors sought to examine in-hospital and one-year outcomes of off-pump coronary artery bypass grafting (CABG) and to determine the subgroups of patients most likely to benefit from the off-pump procedure in a regular surgical practice. METHODS: From March 2001 to December 2002, 1657 consecutive patients were treated with off-pump CABG and 1693 consecutive patients were treated with on-pump CABG. Propensity score modelling was performed to control for treatment and selection bias. A propensity-matched analysis was performed to identify factors associated with survival benefit from the off-pump procedure. RESULTS: The mortality was similar postoperatively and at one year after surgery. The rate of stroke was decreased in the off-pump group postoperatively (OR=0.49, 95% CI 0.23 to 1.06) and significantly at one year after surgery (OR=0.49, 95% CI 0.27 to 0.90). A significant reduction in acute renal dialysis and a significant increase in myocardial infarction rates were seen in off-pump patients during the initial hospitalization but these differences disappeared during the follow-up period. The number of grafts completed was significantly lower in off-pump CABG than in on-pump CABG (2.62+/-1.00 versus 3.36+/-0.92, respectively; P<0.001). Hospital length of stay and the percentage of patients who required mechanical ventilation were significantly lower in the off-pump group than in the on-pump group. At one year after surgery, the adjusted rate of coronary angiogram and revascularization was similar between the two groups, and the adjusted rate of self-reported angina and memory status was significantly better in the off-pump CABG group. Almost all subgroups of patients had a neutral effect or a survival benefit with the off-pump technique. CONCLUSIONS: The results from a Canada-wide multicentre registry showed the safety and effectiveness of off-pump CABG in most subgroups of patients in a regular surgical practice.

[Perineal necrotizing cellulitis disclosing rectal adenocarcinoma]. / Cellulite nécrosante périnéale révélant un adénocarcinome rectal.

We report one case of rectal cancer disclosed by a perineal cellulitis in a diabetic woman. This infrequent association has a bad prognosis. Diagnosis is mainly clinical. Treatment is urgent with large spectrum antibiotic therapy, surgical debridement, colostomy and hyperbaric oxygen if available. Surgical treatment of the rectal cancer can be done immediately or delayed.

[Pudendal hernia of the labia]. / Hernie de la grande lèvre.

A case of hernia is reported with a brief review of perineal hernia.