Overriding water table control on managed peatland greenhouse gas emissions.

Global peatlands store more carbon than is naturally present in the atmosphere1,2. However, many peatlands are under pressure from drainage-based agriculture, plantation development and fire, with the equivalent of around 3 per cent of all anthropogenic greenhouse gases emitted from drained peatland3-5. Efforts to curb such emissions are intensifying through the conservation of undrained peatlands and re-wetting of drained systems6. Here we report eddy covariance data for carbon dioxide from 16 locations and static chamber measurements for methane from 41 locations in the UK and Ireland. We combine these with published data from sites across all major peatland biomes. We find that the mean annual effective water table depth (WTDe; that is, the average depth of the aerated peat layer) overrides all other ecosystem- and management-related controls on greenhouse gas fluxes. We estimate that every 10 centimetres of reduction in WTDe could reduce the net warming impact of CO2 and CH4 emissions (100-year global warming potentials) by the equivalent of at least 3 tonnes of CO2 per hectare per year, until WTDe is less than 30 centimetres. Raising water levels further would continue to have a net cooling effect until WTDe is within 10 centimetres of the surface. Our results suggest that greenhouse gas emissions from peatlands drained for agriculture could be greatly reduced without necessarily halting their productive use. Halving WTDe in all drained agricultural peatlands, for example, could reduce emissions by the equivalent of over 1 per cent of global anthropogenic emissions.

The impact of psoriasis on professional life: PsoPRO, a French national survey.

BACKGROUND: The physical, social and mental burden of psoriasis is well known, but its occupational impact has been less investigated. OBJECTIVE: To assess the impact of psoriasis on the working life of patients compared with the general population. METHODS: A national survey compared people with and without psoriasis using online questionnaires. In addition to the demographic, medical and professional characteristics, data on recent absenteeism and presenteeism were captured using the validated WPAI-PSO questionnaire. RESULTS: The patient sample comprised 714 with psoriasis (PsO), including 81 treated with systemic therapies (PsoST), and 84 with associated psoriatic arthritis (PsO + PsA). The control sample comprised 604 active subjects representative of the French population. Compared to controls, the impact of the disease on working life was no greater in PsO patients. Conversely, unemployment within the past 5 years and mean number of sick leaves within the previous year were more frequent in PsO + PsA. In patients with active psoriasis skin lesions, all aspects of the WPAI questionnaire were negatively impacted in PsoST and PsO + PsA patients, but not in PsO patients: Levels of absenteeism were 3.3% in controls, 5.6% in PsO (NS), 8.3% in PsoST (P < 0.05) and 13.0% in Ps0 + PsA (P < 0.05); impairment in presenteeism reached 27.0%, 21.2% (NS), 43.5% (P < 0.05) and 53.2% (P < 0.05), respectively, while overall work impairment was 27.9%, 22.2% (NS), 46.3% (P < 0.05) and 57.6% (P < 0.05), respectively. Nevertheless, a higher proportion of PsoST and PsO + PsA patients reported that work was more important than any other activity in their life. CONCLUSION: The occupational impact of psoriasis is important and significant in patients who receive systemic therapy or have concurrent PsA but minimal or absent in other psoriasis patients. The findings show that psoriasis patients have a high level of motivation to work.

[Comparison of medical and economic benefits of antipsychotics in the treatment of schizophrenia in France]. / Comparaison des bénéfices médico-économiques des antipsychotiques dans la prise en charge de la schizophrénie en France.

INTRODUCTION: The course of schizophrenia can vary widely, and patients experience remission phases alternating with relapse episodes, which generally lead to hospitalisation and have a significant impact on the burden of disease. The prevalence of schizophrenia in France is estimated to be approximately 600,000 people, with an incidence of 10,000 new patients per year. Patients with schizophrenia represent the largest group of hospitalised patients in French public institutions and specialised centres, and the French authorities recognise that the management of schizophrenia is a major public health concern. The Haute Autorité de Santé (HAS) and most of the evidence-based guidelines for the maintenance treatment of schizophrenia recommend long-acting injectable (LAI) antipsychotics to be used predominantly in the prevention of relapse for non-compliant patients; however, in clinical practice, the use of LAIs remains low. OBJECTIVE: This analysis aimed to estimate and to compare the cost-effectiveness of the most common antipsychotic strategies in France in the management of schizophrenia. METHODS: A Markov model was developed to simulate the progression of a cohort of patients with schizophrenia through four health states (stable treated, stable non-treated, relapse and death) and considered up to three lines of treatment to account for changes in treatment management. Antipsychotics including aripiprazole LAI (ALAI), olanzapine LAI (OLAI), paliperidone LAI (PLAI), risperidone LAI (RLAI), haloperidol decanoate (HD) and oral olanzapine (OO) were compared in terms of costs and clinical outcomes. Thus, costs, quality-adjusted life-years (QALYs) and number of relapses were assessed over five years based on three-month cycles from a French health insurance perspective with a discount rate of 4 %. Patients were considered to be stabilised after clinical decompensation and would enter the model at an initiation phase, followed by a prevention of relapse phase if successful. Data (e.g. relapse or discontinuation rates) for the initiation phase came from randomised clinical trials, whereas relapse rates in the prevention phase were derived from hospitalisation risks based on French real-life data in order to capture adherence effects. Safety and utility data were derived from international publications. Additionally costs were retrieved from French health insurance databases and publications. Robustness of results was assessed through deterministic and probabilistic sensitivity analyses. RESULTS: First and second generations of LAIs were found to have similar costs over five years; i.e. approximately € 55,000, except for PLAI which was associated with a discounted cost of € 50,880. Oral antipsychotics were found to be less costly (i.e. OO cost € 50,379 after five years) but associated with a lower number of QALYs gained and relapse avoided. PLAI and RLAI were associated with the greatest number of QALYs gained; i.e. PLAI dominated ALAI, OLAI and HD and was associated with an incremental costs-effectiveness ratio (ICER) of € 2411 per QALY gained versus OO. Finally, PLAI and OLAI were associated with the lowest number of relapses; i.e. PLAI dominated RLAI, ALAI and HLAI and was associated with an ICER of € 1782 per avoided relapse compared to OO. OO and HD were found to have led to the highest number of relapses. CONCLUSION: This analysis, to the best of our knowledge, is the first of its kind to assess the cost-effectiveness of antipsychotics based on French observational data. PLAI was associated with the highest probability of being the optimal treatment from the French health insurance perspective.

[Neuropsychological benefit of cataract surgery among sight impaired Alzheimer's patient]. / Modifications des troubles du comportement après l'opération de la cataracte chez les patients Alzheimer.

PURPOSE: Evaluation of neuropsychological benefits of cataract surgery for 46 Alzheimer patients on the basis of neuropsychiatric index (NPI), as the principal criterion of analysis of the VIVA study. METHODS: Prospective, monocentric neuropsychiatric study, performed from 2005 to 2011. All Alzheimer's patients with 10

MGMT expression predicts response to temozolomide in pancreatic neuroendocrine tumors.

Temozolomide (TEM) showed encouraging results in well-differentiated pancreatic neuroendocrine tumors (WDPNETs). Low O(6)-methylguanine-DNA methyltransferase (MGMT) expression and MGMT promoter methylation within tumors correlate with a better outcome under TEM-based chemotherapy in glioblastoma. We aimed to assess whether MGMT expression and MGMT promoter methylation could help predict the efficacy of TEM-based chemotherapy in patients with WDPNET. Consecutive patients with progressive WDPNET and/or liver involvement over 50% who received TEM between 2006 and 2012 were retrospectively studied. Tumor response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines. Nuclear expression of MGMT was assessed by immunochemistry (H-score, 0-300) and MGMT promoter methylation by pyrosequencing. Forty-three patients (21 men, 58years (27-84)) with grade 1 WDPNET (n=6) or 2 (n=36) were analyzed. Objective response, stable disease, and progression rates were seen in 17 patients (39.5%), 18 patients (41.9%), and 8 patients (18.6%), respectively. Low MGMT expression (≤50) was associated with radiological objective response (P=0.04) and better progression-free survival (PFS) (HR=0.35 (0.15-0.81), P=0.01). Disease control rate at 18months of treatment remained satisfying with an MGMT score up to 100 (74%) but dropped with a higher expression. High MGMT promoter methylation was associated with a low MGMT expression and longer PFS (HR=0.37 (0.29-1.08), P=0.05). Low MGMT score (≤50) appears to predict an objective tumor response, whereas an intermediate MGMT score (50-100) seems to be associated with prolonged stable disease.

OC-06 - Pro-thrombotic biomarkers in pancreatic diseases: are they specific of cancer?

INTRODUCTION: Venous thrombo-embolic events (VTE) occur frequently in patients with pancreatic cancer and contribute to elevated morbidity and mortality. Clinical risk factors for thrombosis such as cancer stage and tumor grade have been clearly identified. Recently, several biomarkers have been proposed which may help identifying cancer patients at high risk of thrombosis. Those biomarkers have been studied in heterogeneous cohorts of patients with different cancer types. AIM: To compare pro-thrombotic biomarkers in pancreatic cancer and in chronic pancreatitis to determine whether these biomarkers are related to cancer or inflammation and to validate their association with thrombotic risk in a pancreatic cancer population. MATERIALS AND METHODS: 45 patients with pancreatic cancer, 49 with intraductal papillary mucinous tumor of the pancreas (IPMN), a precancerous lesion, and 50 with chronic pancreatitis were recruited. Plasma levels of factor VIII, D-dimers, thrombin-antithrombin complexes, soluble p-selectin, tissue factor-dependent procoagulant activity of MP (TF-MP), free Tissue Factor Pathway Inhibitor (TFPI) and extracellular DNA were measured. Thrombin generation triggered by 1pM of TF was evaluated with the Calibrated Automated Thrombogram assay. RESULTS: Levels of factor VIII, D-dimers, TF-MP, TFPI and extracellular DNA were significantly higher in cancer patients compared to IPMN or chronic pancreatitis (Table 1). Patients with metastatic cancer (n=27) presented higher levels of D-dimers (mean±sd 1.77±1.28 vs 0.80±0.96 µg/ml, p=0.004) and MP-TF (54.3±53.2 vs 15.8±10.4 fM, p=0.02) compared to patients with localized lesions (n=18). Among cancer patients, 42 were followed for a median duration of 187 days (min 21-max 802 days). VTE occurred in 10 (23%) patients. All had metastatic cancer at the time of thrombosis. Only D-dimers were significantly elevated in cancer patients with VTE compared to patients without VTE (median 1.85 vs 0.7 µg/ml, p=0.02). CONCLUSIONS: Elevation of factor VIII, D-dimers, TF-MP, TFPI and extracellular DNA seems to be related to cancer process, not to local or systemic inflammation as these parameters differentiate cancer from chronic pancreatitis. Interestingly, D-dimers and TF-MP are related to the disseminated cancer stage, suggesting that vascular invasion is a prerequisite to the release of TF-MP from the primary tumor into the bloodstream and to coagulation activation. However, only D-dimers are associated with the occurrence of future VTE. We propose that D-dimers could be a useful tool to predict thrombotic events in pancreatic cancer patients. This should be confirmed in a larger population.

Metabolic reprogramming: a hallmark of viral oncogenesis.

More than 1 in 10 cases of cancer in the world are due to chronic viral infections. Viruses induce oncogenesis by targeting the same pathways known to be responsible for neoplasia in tumor cells, such as control of cell cycle progression, cell migration, proliferation and evasion from cell death and the host's immune defense. In addition, metabolic reprogramming has been identified over a century ago as a requirement for growth of transformed cells. Renewed interest in this topic has emerged recently with the discovery that basically all metabolic changes in tumor cells are finely orchestrated by oncogenes and tumor suppressors. Indeed, cancer cells activate biosynthetic pathways in order to provide them with sufficient levels of energy and building blocks to proliferate. Interestingly, viruses introduce into their host cells similar metabolic adaptations, and importantly, it seems that they depend on these changes for their persistence and amplification. The central carbon metabolism, for example, is not only frequently altered in tumor cells but also modulated by human papillomavirus, hepatitis B and C viruses, Epstein-Barr virus and Kaposi's Sarcoma-associated virus. Moreover, adenoviruses (Ad) and human cytomegalovirus, which are not directly oncogenic but present oncomodulatory properties, also divert cellular metabolism in a tumor cell-like mnner. Thus, metabolic reprogramming appears to be a hallmark of viral infection and provides an interesting therapeutic target, in particular, for oncogenic viruses. Therapeutic targeting of metabolic pathways may not only allow to eliminate or control the viral infection but also to prevent virus-induced carcinogenesis.

Impact of exercise training without caloric restriction on inflammation, insulin resistance and visceral fat mass in obese adolescents.

BACKGROUND: Exercise training has been shown to improve cardiometabolic health in obese adolescents. OBJECTIVES: Evaluate the impact of a 12-week exercise-training programme (without caloric restriction) on obese adolescents' cardiometabolic and vascular risk profiles. METHODS: We measured systemic markers of oxidation, inflammation, metabolic variables and endothelial function in 20 obese adolescents (OB) (age: 14.5 ± 1.5 years; body mass index: 34.0 ± 4.7 kg m(-2) ) and 20 age- and gender-matched normal-weight adolescents (NW). Body composition was assessed by magnetic resonance imagery. Peak aerobic capacity and maximal fat oxidation were evaluated during specific incremental exercise tests. OB participated in a 12-week exercise-training programme. RESULTS: OB presented lower peak aerobic capacity (24.2 ± 5.9 vs. 39.8 ± 8.3 mL kg(-1) min(-1) , P < 0.05) and maximal fat oxidation compared with NW (P < 0.05). OB displayed greater F2t-Isoprostanes (20.5 ± 6.7 vs. 13.4 ± 4.2 ng mmol(-1) creatinine), Interleukin-1 receptor antagonist (IL-1Ra) (1794.8 ± 532.2 vs. 835.1 ± 1027.4 pg mL(-1) ), Tumor Necrosis Factor-α (TNF-α) (2.1 ± 1.2 vs. 1.5 ± 1.0 pg mL(-1) ), Soluble Tumor Necrosis Factor-α Type II Receptor (sTNFαRII), leptin, insulin, homeostasis model assessment of insulin resistance, version 2 (HOMA2-IR), high-sensitive C-reactive protein, triglycerides and lower adiponectin and high-density lipoprotein cholesterol (all P < 0.05). After exercise training, despite lack of weight loss, VO2peak (mL.kg(-1) .min(-1) ) and maximal fat oxidation increased (P < 0.05). IL-1Ra and IFN-gamma-inducible protein 10 (IP-10) decreased (P < 0.05). Insulin and HOMA2-IR decreased (14.8 ± 1.5 vs. 10.2 ± 4.2 µUI mL(-1) and 1.9 ± 0.8 vs. 1.3 ± 0.6, respectively, P < 0.05). Change in visceral fat mass was inversely associated with change in maximal fat oxidation (r = -0.54; P = 0.024). The subgroup of participants that lost visceral fat mass showed greater improvements in triglycerides, insulin resistance and maximal fat oxidation. CONCLUSION: Our data confirms the role of exercise training on improving the inflammatory profile and insulin resistance of OB in the absence of weight loss. However, those who lost a greater amount of visceral fat mass showed greater benefits in terms of insulin profile, triglycerides and maximal fat oxidation.

[Cardiovascular morbidity associated with obstructive sleep apnea syndrome]. / Morbidité cardiovasculaire associée au syndrome d'apnée obstructive du sommeil.

INTRODUCTION: The obstructive sleep apnoea syndrome (OSAS) had become a major public health concern in modern society due to its high prevalence but, above all, to its associated morbidity, especially cardiovascular. BACKGROUND: Untreated OSAS is associated with an increased incidence of fatal (myocardial infarction and stroke) (odds ratio: 2.87) and non-fatal cardiovascular events (myocardial infarction, stroke, coronary artery bypass surgery and coronary angiography) (odds ratio: 3.17). Moreover, the prevalence of hypertension in patients with OSAS is high, between 35 and 80%. The pathophysiological mechanisms leading to these complications are mainly due to intermittent hypoxia secondary to repeated episodes of apnoea/hypopnoea during sleep. These mechanisms include sympathetic hyperactivation, impairment of vasomotor reactivity, vascular inflammation, oxidative stress and metabolic disorders. In patients with OSAS, the impact of continuous positive pressure is proven in terms of prevention of cardiovascular events although blood pressure reduction is limited. Obviously these effects are proportional to observance. CONCLUSION: OSAS does increase the cardiovascular risk, independently of other risk factors. Although the impact of treatment is relatively low in decreasing blood pressure, it seems essentially effective in preventing cardiovascular morbidity. Therefore, OSAS screening, and the association of specific treatments in cardio-metabolic patients and OSAS patients respectively, should be included in clinical strategies.

Relation between nasal carriage of Staphylococcus aureus and surgical site infection in orthopedic surgery: the role of nasal contamination. A systematic literature review and meta-analysis.

UNLABELLED: Staphylococcus aureus is the pathogen most frequently implicated in infection on orthopedic hardware; various strategies are deployed to limit the risk of transmission and surgical infection. OBJECTIVES: The present study is based on a meta-analysis assessing firstly the relationship between nasal carriage of S. aureus and the development of osteo-articular infection and secondly current methods of decolonization. RESULTS: The meta-analysis showed increased risk of surgical site infection in case of nasal carriage of S. aureus: OR=5.92, 95% CI [1.15-30.39]; P=0.033. For cross-transmission, a scientifically proven reduction in surgical site S. aureus levels is ensured by associated mupirocin and 2% chlorhexidine antiseptic solution in subjects with positive nasal screening results for all surgical procedures taken together; the reduction was not, however, significant in the orthopedic surgery subgroup. The meta-analysis confirmed these findings: OR=0.60, 95% CI [0.34-1.06]; P=0.08. CONCLUSION: The literature review confirmed that nasal carriage of S. aureus is a major risk factor for surgical site infection. The efficacy of eradication could not be demonstrated for orthopedic surgery as samples were too small. The positive trend found, however, should encourage further studies with sufficient power and risk/benefit should meanwhile be assessed on a case-by-case basis. LEVEL OF EVIDENCE: Level 2. Meta-analysis.

Severe sepsis in the emergency department: an observational cohort study from the university hospital of the West Indies / Sepsis severa en la sala de emergencias: un estudio observacional de cohorte en el hospital universitario de West Indies

OBJECTIVE: To describe the incidence, treatment and outcomes of patients with severe sepsis and septic shock in a setting where early goal directed therapy (EGDT) is not routinely performed. METHOD: An observational study of all adult patients admitted from the emergency department (ED) of the University Hospital of the West Indies (UHWI) with a diagnosis of severe sepsis and septic shock from July 5, 2007 to September 1, 2008 was conducted. Baseline parameters, treatment patterns and inhospital outcomes were evaluated. RESULTS: A total of 58 011 patients were seen and 762 (1.3%) had sepsis, 117 (15.4%) of whom were classified as severe sepsis or septic shock. Mean (SD) age was 59.2 (23.3) years and 49% were female. Medical history included hypertension (29%), diabetes mellitus (26%), stroke (8%), heart failure (6%) and HIV (6%). The most common sources of sepsis were pneumonia (67%) and urinary tract infection (46%). Median, interquartile range (IQR) time from triage to antibiotic administration was 126 (88, 220) minutes and antibiotics were given to 65.7% within three hours. Overall, organisms were sensitive to empirical antibiotics in 69%. Median (IQR) lactate was 5.3 (4.5, 7.5) mmol/L. Most patients (95%) were admitted to the ward; 1% went to the intensive care unit (ICU) and 2% died in the ED. Mean (SD) length of hospital stay was 9.5 (10.3) days. Inhospital mortality was 25% and survival correlated inversely with age (r pb = 0.25; p = 0.006). CONCLUSION: Despite a lack of EGDT, sepsis treatment patterns were consistent with "bestpractice" and mortality was lower than international comparators.

OBJETIVO: Describir la incidencia, el tratamiento y los resultados para pacientes con sepsis severa y shock séptico en un entorno donde la terapia dirigida por metas tempranas (TDMT) no se realiza de modo rutinario. MÉTODO: Se realizó un estudio observacional de todos los pacientes adultos con diagnóstico de sepsis severa y shock séptico, ingresados en la Sala de Emergencias del Hospital Universitario de West Indies (HUWI) desde el 5 de julio de 2007 al 1ero. de septiembre de 2008. Se evaluaron los parámetros iniciales de referencia, los patrones de tratamiento, y la evolución intrahospitalaria. RESULTADOS: Un total de 58 011 pacientes fueron vistos, 762 (1.3%) de ellos con sepsis. De estos casos con sepsis, 117 (15.4%) fueron clasificados como sepsis severa o shock séptico. La edad media (SD) fue 59.2 (23.3) años y 49% eran mujeres. Historia clínica incluía hipertensión (29%), diabetes (26%), accidente cerebrovascular (8%), insuficiencia cardíaca (6%) y VIH (6%). Las fuentes más comunes de la sepsis fueron neumonía (67%) e infección del tracto urinario (46%). La mediana del tiempo (IQR) transcurrido desde la selección (triaje) hasta la administración de antibióticos fue 126 (88, 220) minutos, y los antibióticos fueron entregados al 65.7% dentro de las tres horas. En general, los organismos fueron sensibles a los antibióticos empíricos en 69%. La mediana del lactato (IQR) fue 5.3 (4.5, 7.5) mmol/L. La mayoría de los pacientes (95%) fueron ingresados a la sala; 1% se destinó a la unidad de cuidados intensivos (UCI), y el 2% murió en la Sala de Emergencias. El promedio (SD) de la estancia hospitalaria fue de 9.5 (10.3) días. La mortalidad intrahospitalaria fue de 25%, y la supervivencia se halló en correlación inversa con la edad (rpb = .25; p = 0.006). CONCLUSIÓN: A pesar de la falta de TDMT, los patrones del tratamiento de sepsis fueron consistentes con las "mejores prácticas", y la mortalidad fue menor comparada con los datos de comparación a nivel internacional.

FOLFIRI regimen: an effective second-line chemotherapy after failure of etoposide-platinum combination in patients with neuroendocrine carcinomas grade 3.

Patients with neuroendocrine carcinomas (NECs) grade 3 have a poor prognosis. Etoposide-platinum combination is the standard chemotherapy but the role of a second-line therapy remains unknown. Irinotecan alone or in combination has shown some efficacy in patients treated for small cell lung cancer which had pathological similarities with neuroendocine tumors. The aim of this study is to determine safety and efficacy of the FOLFIRI regimen in patients with NECs grade 3 after failure of etoposide-platinum combination. This study was retrospective, including patients with NECs grade 3 and treated with the FOLFIRI regimen after progression or toxicity of etoposide-platinum combination in first-line. Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≥3 and/or serum alkaline phosphatase ≥5×upper limit of normal value (ULN) and/or bilirubin ≥1.5×ULN were excluded. Among 39 patients who failed etoposide-platinum combination, 19 (49%; 12 women, median age 53 (29-78) years) received the FOLFIRI regimen with a median number of 6 (1-16) courses. Six patients (31%) had at least one episode of grades 3-4 toxicity (neutropenia, n=3; diarrhea, n=3) without toxic death. Six patients (31%) had objective response, 6 (31%) stable disease, and 7 (38%) tumor progression. Median progression-free survival under FOLFIRI was 4 months. Overall survival was 18 vs 6.8 months in noneligible patients. FOLFIRI regimen is a safe and potentially efficient chemotherapy given as second-line in patients with NECs grade 3 who remain in good condition and with correct liver tests after failure of etoposide-platinum combination. These results should be confirmed in a future prospective study.

Prospective multicenter evaluation of colon capsule examination indicated by colonoscopy failure or anesthesia contraindication.

BACKGROUND AND STUDY AIMS: In France, in about 5% of cases colonoscopies are incomplete or temporarily contraindicated.We tested the diagnostic yield of colon capsule endoscopy (CCE) in these patients. PATIENTS AND METHODS: In a prospective study, in 17 French centers, inclusion criteria were colonoscopy failure or general disease that excluded colonoscopy with anesthesia. Patients underwent CCE using the first-generation PillCam Colon capsule. The main end point was CCE diagnostic yield, defined as identification of a colorectal lesion that directly explained symptoms or necessitated a diagnostic or therapeutic examination. A secondary objective was to test a simplified Movi-Prep colon cleansing. Follow-up to identify missed symptomatic cancer was scheduled. RESULTS: CCE showed positive findings in 36 patients (diagnostic yield 33.6 %), among whom 23 subsequently underwent therapeutic intervention. Among 64 patients with negative capsule findings, 9 had a complementary procedure showing adenomas in only 1 case. CCE was incomplete in 7/107 patients. Colonoscopy was done in one patient to retrieve a capsule retained in the left colon, and sigmoidoscopy in 11 because the rectum was not reached. No colorectal cancer was diagnosed during the follow-up period. Colon cleansing with MoviPrep was rated good or excellent in 75.9% of cases. CONCLUSION: This study shows the feasibility and the usefulness of CCE in the situation of colonoscopy failure or contraindication. The colon capsule modality should be tested against other available approaches, such as virtual colonoscopy or repeat colonoscopy by an expert.

Gene expression signature of advanced pancreatic ductal adenocarcinoma using low density array on endoscopic ultrasound-guided fine needle aspiration samples.

AIMS: The purpose of this study was to investigate the clinical feasibility and utility of low-density array analysis on samples obtained from endoscopic ultrasound-guided fine needle aspiration biopsy in locally advanced and/or metastatic pancreatic ductal adenocarcinoma and chronic pancreatitis. PATIENTS AND METHODS: In this prospective multicenter study, we quantified candidate gene expression in biopsies sampled from 44 locally advanced and/or metastatic pancreatic carcinoma and from 17 pseudotumoural chronic pancreatitis using dedicated low-density array microfluidic plates. RESULTS: We first demonstrated that 18S gene expression is stable and comparable in normal pancreas and pancreatic cancer tissues. Next, we found that eight genes (S100P, PLAT, PLAU, MSLN, MMP-11, MMP-7, KRT7, KRT17) were significantly over expressed in pancreatic cancer samples when compared to pseudotumoural chronic pancreatitis (p value ranging from 0.0007 to 0.0215): Linear discriminative analysis identified S100P, PLAT, MSLN, MMP-7, KRT7 as highly explicative variables. The area under receiver operating curve establishes the clinical validity of the potential diagnostic markers identified in this study (values ranging from 0.69 to 0.76). In addition, combination of S100P and KRT7 gave better diagnosis performances (Area Under Receiver Operating Curve 0.81, sensitivity 81%, specificity 77%). CONCLUSION: We demonstrate that molecular studies on EUS-guided FNA material are feasible for the identification and quantification of markers in PDAC patients diagnosed with non-resectable tumours. Using low-density array, we isolated a molecular signature of advanced pancreatic carcinoma including mostly cancer invasion-related genes. This work stems for the use of novel biomarkers for the molecular diagnosis of patient with solid pancreatic masses.

[Toric IOL's]. / Les implants toriques.

Toric intraocular lenses have been increasingly utilized in cataract surgery and are considered "premium lenses" They provide a reliable and effective option for patients with astigmatism undergoing cataract surgery. We present various methods for the correction of astigmatism during cataract surgery. We present the available models of pseudophakic toric IOL's, including monofocal and multifocal lenses. We present indications for toric IOL's in cases of regular and irregular astigmatism.

Ki-67 index, tumor differentiation, and extent of liver involvement are independent prognostic factors in patients with liver metastases of digestive endocrine carcinomas.

The prognosis remains ill-defined in patients with liver metastases of well-differentiated (WD) digestive endocrine carcinomas (DEC) with high Ki-67 index. The objectives of this study were to determine whether Ki-67 index, tumor differentiation, and extent of liver involvement are independent prognostic factors in patients with DEC, and whether chemotherapy commonly used in patients with poorly differentiated (PD) carcinomas might be applied to those with high Ki-67 index but well-differentiated DEC. Sixty-three patients with DEC metastatic to the liver were retrospectively studied and divided into three prognostic groups. Group 1 comprised patients with well-differentiated carcinomas and Ki-67 index<15% (n=28), group 2 comprised those with well-differentiated carcinomas and Ki-67 index≥15% (n=17), and group 3 comprised those with poorly differentiated carcinomas (n=18). Therapeutic strategy was decided in accordance to guidelines, and tumoral response rate was assessed by computed tomography scan (RECIST). Prognostic factors were determined by uni/multivariate analysis. The 5-year survival rates were 89, 36, and 6% in groups 1, 2, and 3 respectively (P<0.001). Multivariate analysis showed that Ki-67 index≥15%, poor tumor differentiation, and large liver tumor burden were independent predictors of poorer survival. Disease control rates after etoposide-cisplatin were 50 and 53% in groups 2 and 3 respectively (NS). In conclusion, Ki-67 index, tumor differentiation, and extent of liver involvement are independent prognostic factors in patients with liver metastases of DEC. Patients with well-differentiated carcinomas with high Ki-67 index (≥15%) have intermediate prognosis and a similar response rate to the etoposide-cisplatin combination as those with poorly differentiated carcinomas.

14 nights of intermittent hypoxia elevate daytime blood pressure and sympathetic activity in healthy humans.

Obstructive sleep apnoea syndrome (OSAS) causes nocturnal chronic intermittent hypoxia (IH) that contributes to excess cardiovascular morbidity. To explore the consequences of IH, we used our recently developed model of nocturnal IH in healthy humans to characterise the profile of this blood pressure increase, to determine if it is sustained and to explore potential physiological mechanisms. We performed 24-h ambulatory monitoring of blood pressure in 12 healthy subjects before and after 2 weeks of IH exposure. We also assessed systemic haemodynamics, muscle sympathetic nerve activity (MSNA), ischaemic calf blood flow responses and baroreflex gain. We obtained blood samples for inflammatory markers before, during and after exposure. IH significantly increased daytime ambulatory blood pressure after a single night of exposure (3 mmHg for mean and diastolic) and further increased daytime pressures after 2 weeks of exposure (8 mmHg systolic and 5 mmHg diastolic). Mean ± sd MSNA increased across the exposure (17.2 ± 5.1 versus 21.7 ± 7.3 bursts·min⁻¹; p < 0.01) and baroreflex control of sympathetic outflow declined from -965.3 ± 375.1 to -598.4 ± 162.6 AIU·min⁻¹ ·mmHg⁻¹ (p < 0.01). There were no evident changes in either vascular reactivity or systemic inflammatory markers. These data are the first to show that the arterial pressure rise is sustained throughout the waking hours beyond the acute phase immediately after exposure. Moreover, they may suggest that sympathoactivation induced by IH likely contributes to blood pressure elevation and may derive from reduced baroreflex inhibition. These mechanisms may reflect those underlying the blood pressure elevation associated with OSAS.

Ultra-long duration of a peripheral nerve block: a possible consequence of intraneural (subepineural) local anaesthetic injection.

A 29-year-old patient was scheduled for bilateral halllux valgus surgery and a lateral sciatic popliteal nerve block was performed on each side using ropivacaine and lidocaine using nerve stimulation. Although the sensory and motor block had usual duration on the left side, the block lasted more than 48 hours on the right side with both sensory and motor impairment. An MRI performed on day 2 on the blocked side showed extra- and intraneural fluid accumulation with cephalad and distal spread. Sensory and motor function progressively recovered within the next day and was complete on the fourth day. We postulate that this case of extremely long duration of a peripheral nerve block can be ascribed to subepineural trapping of the local anaesthetic. Part of the variability in the duration of the sensory and motor block after peripheral nerve blocks might be explained by the variable amount of drug injected intraneurally.

Effect of ABCB1 C3435T polymorphism on docetaxel pharmacokinetics according to menopausal status in breast cancer patients.

BACKGROUND: It can be hypothesised that inherited polymorphisms in the drug-transporter ABCB1 gene may interfere with interindividual variations in drug response in breast cancer patients. Docetaxel is a substrate for ABCB1 whose function has been shown to be modulated by oestrogen and progesterone. METHODS: Whether ABCB1 polymorphisms including T-129C, A61G, C1236T, G2677T/A and C3435T polymorphisms could account for variations in the disposition of docetaxel and whether menopausal status at the time of diagnosis might interact with this effect were analysed in women receiving neoadjuvant chemotherapy for breast cancer (n=86). RESULTS: A highly significant association was observed, but restricted to premenopausal women (n=53), between the pharmacokinetics of docetaxel and C3435T polymorphism, as patients with CC genotype had lower mean values of the area under the plasma concentration-time curve (AUC) of docetaxel than patients with CT and TT genotypes (P<0.0001). Comparison between pre- and postmenopausal women with the same C3435T genotype yielded a significant difference in docetaxel AUC only for CC genotype (P<0.0001). CONCLUSION: These results suggest that C3435T polymorphism genotyping and menopausal status at the time of diagnosis might be useful when considering chemotherapy regimens including docetaxel in breast cancer patients.