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The optimal elective colectomy in patients with splenic flexure tumor is debated.This study aimed to compare splenic flexure colectomy, left hemicolectomy, and subtotal colectomy for perioperative, histological, and survival outcomes in this setting.This is a multicenter retrospective cohort study.Patients diagnosed with nonmetastatic splenic flexure tumor who underwent elective colectomy were included.Between 2006 and 2014, 313 consecutive patients were operated on in 15 French Research Group of Rectal Cancer Surgery centers.Propensity score weighting was performed to compare short- and long-term outcomes.The primary end point was disease-free survival. Secondary end points included overall survival, quality of surgical resection, overall postoperative morbidity, surgical postoperative morbidity, and rate of anastomotic leakage.The most performed surgery was splenic flexure colectomy (59%), followed by subtotal colectomy (23%) and left hemicolectomy (18%). Subtotal colectomy was more often performed by laparotomy compared with splenic flexure colectomy and left hemicolectomy (93% vs 61% vs 56%, p0.0001), and was associated with a longer operative time (260 minutes (120-460) vs 180 minutes (68-440) vs 217 minutes (149-480), p0.0001). Postoperative morbidity was similar between the 3 groups, but the median length of hospital stay was significantly longer after subtotal colectomy (13 days (5-56) vs 10 (4-175) vs 9 (4-55), p = 0.0007). The median number of harvested lymph nodes was significantly higher after subtotal colectomy compared with splenic flexure colectomy and left hemicolectomy (24 (8-90) vs 15 (1-81) vs 16 (3-52), p0.0001). The rate of stage III disease and the number of patients treated by adjuvant chemotherapy were similar between the 3 groups. There was no difference in terms of disease-free survival and overall survival between the 3 procedures.The study was limited by its retrospective design.In the elective setting, splenic flexure colectomy is safe and oncologically adequate for patients with nonmetastatic splenic flexure tumor. However, given the oncological clearance after splenic flexure colectomy, it seems that the debate is not completely closed. See Video Abstract at http://links.lww.com/DCR/B703.ANTECEDENTES:La colectomía electiva óptima en pacientes con tumores del ángulo esplénico continua en debate.OBJETIVO:Comparar la colectomía de ángulo esplénico, hemicolectomía izquierda y colectomía subtotal para los resultados perioperatorios, histológicos y de supervivencia en este escenario.DISEÑO:Estudio de cohorte retrospectivo multicéntrico.ESCENARIO:Se incluyeron pacientes diagnosticados de tumores del ángulo esplénico no metastásicos que se sometieron a colectomía electiva.PACIENTES:Entre 2006 y 2014, 313 pacientes consecutivos fueron intervenidos en 15 centros GRECCAR.INTERVENCIONES:Se realizó una ponderación del puntaje de propensión para comparar los resultados a corto y largo plazo.PRINCIPALES MEDIDAS DE RESULTADO:El criterio de valoración principal fue la supervivencia libre de enfermedad. Los criterios de valoración secundarios incluyeron la supervivencia general, la calidad de la resección quirúrgica, la morbilidad posoperatoria general, la morbilidad posoperatoria quirúrgica y la tasa de fuga anastomótica.RESULTADOS:La cirugía más realizada fue la colectomía del ángulo esplénico (59%), seguida de la colectomía subtotal (23%) y la hemicolectomía izquierda (18%). La colectomía subtotal se realizó con mayor frecuencia mediante laparotomía en comparación con la colectomía de ángulo esplénico y la hemicolectomía izquierda (93% frente a 61% frente a 56%, p0.0001), y se asoció con un tiempo quirúrgico más prolongado (260 min [120-460] frente a 180 min [68-440] frente a 217 min [149-480], p0.0001). La morbilidad posoperatoria fue similar entre los tres grupos, pero la duración media de la estancia hospitalaria fue significativamente más prolongada después de la colectomía subtotal (13 días [5-56] frente a 10 [4-175] frente a 9 [4-55], p = 0.0007). La mediana del número de ganglios linfáticos extraídos fue significativamente mayor después de la colectomía subtotal en comparación con la colectomía del ángulo esplénico y la hemicolectomía izquierda (24 [8-90] frente a 15 [1-81] frente a 16 [3-52], p0.0001). La tasa de enfermedad en estadio III y el número de pacientes tratados con quimioterapia adyuvante fueron similares entre los 3 grupos. No hubo diferencias en términos de supervivencia libre de enfermedad y supervivencia general entre los 3 procedimientos.LIMITACIONES:El estudio estuvo limitado por su diseño retrospectivo.CONCLUSIONES:En un escenario electivo, la colectomía del ángulo esplénico es segura y oncológicamente adecuada para pacientes con tumores del ángulo esplénico no metastásicos. Sin embargo, dado el aclaramiento oncológico tras la colectomía del ángulo esplénico, parece que el debate no está completamente cerrado. Consulte Video Resumen en http://links.lww.com/DCR/B703.

International audience; Background: Most cases of left-sided native valve infective endocarditis (IE) involve a single valve and little is known concerning IE that simultaneously affects the aortic and mitral valves. Methods: We aimed to determine the characteristics, identify the prognostic factors, and define the effect of early surgery for patients with left-sided native bivalvular IE. This analysis included 1340 consecutive patients who presented with definite acute left-sided native valve IE in a 2-centre cohort study. Results: A bivalvular involvement was present in 257 patients (19%). Patients with bivalvular IE had more embolic events (P = 0.044), congestive heart failure (P = 0.016), vegetations, and perivalvular complications (both P < 0.001) than those with monovalvular IE. Early surgery was more frequent for patients with bivalvular IE (P < 0.001). Thirty-day mortality was higher for patients with bivalvular IE than for those with monovalvular IE (24.5% vs 17.6%; P = 0.008), even after adjustment (odds ratio, 1.86 [95% confidence interval, 1.26-2.73]; P < 0.001). Estimated 10-year survival was 70% +/- 1% for monovalvular IE and 59% +/- 3% for bivalvular IE (P = 0.002). Bivalvular IE was still associated with mortality in multivariable Cox analysis, after adjustment for covariates including age, neurological events, congestive heart failure, Staphylococcus spp infection, perivalvular complications, and early surgery (hazard ratio, 1.70 [95% confidence interval, 1.31-2.11]; P < 0.001). Early surgery was associated with increased survival for patients with bivalvular IE (79% +/- 4% vs 35% +/- 6%; P < 0.001). Conclusions: Bivalvular involvement is frequent in left-sided native valve IE, is associated with more embolic events and congestive heart failure than monovalvular IE, and patients are at a high risk of death. Early surgery is associated with improved survival and should be systematically discussed in the absence of contraindication.

Objectives Evaluation of left atrial pressure is frequently required for mechanically ventilated critically ill patients. The objective of the present study was to evaluate the 2016 American Society of Echocardiography and the European Association of Cardiovascular Imaging guidelines for assessment of the pulmonary artery occlusion pressure (a frequent surrogate of left atrial pressure) in this population. Design A pooled analysis of three prospective cohorts of patients simultaneously assessed with a pulmonary artery catheter and echocardiography. Settings Medical-surgical intensive care department of two university hospitals in France. Patients Mechanically ventilated critically ill patients. Interventions None. Measurements and main results Of 98 included patients (males: 67%; mean ± SD age: 59 ± 16; and mean Simplified Acute Physiology Score 2: 54 ± 20), 53 (54%) experienced septic shock. Using the 2016 American Society of Echocardiography and the European Association of Cardiovascular Imaging guidelines, the predicted pulmonary artery occlusion pressure was indeterminate in 48 of the 98 patients (49%). Of the 24 patients with an elevated predicted left atrial pressure (grade II/III diastolic dysfunction), only 17 (71%) had a pulmonary artery occlusion pressure greater than or equal to 18 mm Hg. Similarly, 20 of the 26 patients (77%) with a normal predicted left atrial pressure (grade I diastolic dysfunction) had a measured pulmonary artery occlusion pressure less than 18 mm Hg. The sensitivity and specificity of American Society of Echocardiography and the European Association of Cardiovascular Imaging guidelines for predicting elevated pulmonary artery occlusion pressure were both 74%. The agreement between echocardiography and the pulmonary artery catheter was moderate (Cohen's Kappa, 0.48; 95% CI, 0.39-0.70). In a proposed alternative algorithm, the best echocardiographic predictors of a normal pulmonary artery occlusion pressure were a lateral e'-wave greater than 8 (for a left ventricular ejection fraction ≥ 45%) or an E/A ratio less than or equal to 1.5 (for a left ventricular ejection fraction Conclusions The American Society of Echocardiography and the European Association of Cardiovascular Imaging guidelines do not accurately assess pulmonary artery occlusion pressure in ventilated critically ill patients. Simple Doppler measurements gave a similar level of diagnostic performance with less uncertainly.

The objective of this study was to compare the results of transcatheter arterial embolization (TAE) with surgery in terms of efficacy in the context of bleeding duodenal ulcer (BDU) refractory to endoscopic treatment. From January 2006 to December 2016, all patients treated for a BDU refractory to endoscopic treatment were included in this observational, comparative, retrospective, single-center study. Primary endpoint was the overall success of treatment of BDU requiring surgical and/or TAE. The secondary endpoints were pre-interventional data, recurrence rates, feasibility of secondary treatment, morbidity and mortality of surgical and radiological treatment, intensive care unit and length of stay. A systematic review of the literature was performed to compare results of surgery and TAE. 59 out of 396 patients (14.9%) treated for BDU required embolization and/or surgery: 15 patients underwent surgery (group S) including 7 patients after embolization failure and 44 patients underwent TAE (group TAE). The overall treatment success in intention to treat (85.7% vs 67.3%), per protocol (80% vs 79.5%) and bleeding recurrence rates (20% vs 15.9%) were also identical. Mortality (14.2% vs 15.3%) was similar between the two groups. Our study data were pooled with data from eight published studies and suggest that surgery have significant increased overall success (68.3% vs. 55.4%, p

International audience; BACKGROUND: Traditional statistics, based on prediction models with a limited number of prespecified variables, are probably not adequate to provide an appropriate classification of a condition that is as heterogeneous as aortic stenosis (AS). AIMS: To investigate a new classification system for severe AS using phenomapping. METHODS: Consecutive patients from a referral centre (training cohort) who met the echocardiographic definition of an aortic valve area (AVA) ≤q~1~cm(2) were included. Clinical, laboratory and imaging continuous variables were entered into an agglomerative hierarchical clustering model to separate patients into phenogroups. Individuals from an external validation cohort were then assigned to these original clusters using the K nearest neighbour (KNN) function and their 5-year survival was compared after adjustment for aortic valve replacement (AVR) as a time-dependent covariable. RESULTS: In total, 613 patients were initially recruited, with a mean±standard deviation AVA of 0.72±0.17~cm(2). Twenty-six variables were entered into the model to generate a specific heatmap. Penalized model-based clustering identified four phenogroups (A, B, C and D), of which phenogroups B and D tended to include smaller, older women and larger, older men, respectively. The application of supervised algorithms to the validation cohort (n=1303) yielded the same clusters, showing incremental cardiac remodelling from phenogroup A to phenogroup D. According to this myocardial continuum, there was a stepwise increase in overall mortality (adjusted hazard ratio for phenogroup D vs A 2.18, 95% confidence interval 1.46-3.26; P

Crohn's disease (CD) has a significant impact on health status and quality of life, affecting physical and emotional well-being and impairing social and functional abilities. In the era of the treat-to-target concept, endoscopic healing has emerged as the goal to achieve to prevent intestinal damage and disability. It is not clear what level of endoscopic healing is associated with lower disability. We therefore aimed to compare disability associated with complete endoscopic healing to disability with partial endoscopic healing in patients with CD.We conducted a multicenter prospective study, between September 2019 and November 2020, in one university hospital, one general hospital, and one private practice center. Consecutive patients with CD in clinical remission were included, having either complete endoscopic healing (CDEIS = 0) or partial endoscopic healing (CDEIS0 and4). The 10-item IBD-Disk self-assessment questionnaire was used to assess disability. Moderate to severe disability was defined as an overall IBD-Disk score ≥40.A total of 82 patients were included. Forty-four (53%) were women, the median age and disease duration were respectively 35.3 years (interquartile range [IQR], 28.6-45.2) and 8.0 years (IQR, 3.0-17.0). The median overall IBD-Disk score was 26.5 (IQR, 9 -45.0), and 30 (36.6%) patients had moderate to severe disability. Complete endoscopic healing was observed in 48 patients (57.3%). The median IBD-Disk score was respectively 24 (IQR, 9.0-40.5) and 34 (IQR, 9.5-51.5) for patients with complete and partial endoscopic healing (p = 0.068). Respectively, 13/48 (27%) and 17/34 (50%) of patients with complete and partial endoscopic healing had moderate to severe disability (p = 0.039). In multivariate analysis, partial endoscopic healing (OR=5.82, 95% CI [1.65, 24.69], p = 0.0009), female gender (OR=4.0, 95%CI [1.13, 16.58], p = 0.04), and smoking (OR=8.33, 95% CI [1.96, 50.0] p = 0.006) were significantly associated with moderate to severe disability. Among the IBD-Disk sub scores, the defecation score (median, IQR) (0.0 [0.0-3.0] vs 4.0 [0.0-7.5], p = 0.028) and energy score (4.0 [0.0-6.0] vs 6.0 [2.5-8.0], p = 0.023) were significantly lower with complete endoscopic healing.One-third of patient with endoscopic healing reported moderate to severe disability. Complete endoscopic healing (CDEIS = 0) was associated with lower disability than partial endoscopic healing (CDEIS0 and4). Deeper endoscopic healing may be needed to reduce the risk of disability in CD.

Cryoballoon pulmonary vein isolation (PVI) for persistent atrial fibrillation (AF) ablation is an increasingly used strategy. We aimed to determine the results and predictors of arrhythmia recurrence after a single procedure of cryoballoon PVI for patients with persistent and long-standing persistent AF. We included all consecutive patients who underwent cryoballoon PVI for the treatment of persistent symptomatic drug-refractory AF since 2012. All patients were prospectively followed to detect the recurrence of atrial tachyarrhythmia (ATa). Predictors of recurrence were assessed. Cryoballoon PVI was performed on 399 patients with persistent AF, among whom 52 (13%) had long-standing persistent AF. Patients with long-standing persistent AF had a significantly larger left atrium than those with persistent AF. A 28-mm cryoballoon was used for 322 patients (93%). In total, 359 patients (90%) completed the 12-month follow-up visit and the median follow-up was 24 months (interquartile range 43 to 13). The 2-year probability of freedom from ATa recurrence was 51% for persistent AF and 27% for long-standing persistent AF. Long-standing persistent AF and left atrial area/volume were independent predictors of ATa recurrence. Ten patients (2.5%) experienced phrenic nerve palsy, 1 tamponade (0.25%), 2 stroke (0.5%), 2 pericardial effusions (0.5%), and 5 vascular complications (1.25%). In conclusion, 2-year ATa-free survival rates were 51 and 27% for persistent and long-standing persistent AF patients, respectively. Complications were rare. Long-standing persistent AF and left-atrial area/volume were predictors of recurrence.

International audience; Background: Current practice guidelines for red blood cell (RBC) transfusion in ICUs are based on haemoglobin threshold, without consideration of oxygen delivery or consumption. We aimed to evaluate an individual physiological threshold-guided by central venous oxygen saturation (ScvO(2)). Methods: In a randomised study in two French academic hospitals, 164 patients who were admitted to ICU after cardiac surgery with postoperative haemoglobin

International audience; Background: Although some researchers have positioned microdialysis catheters in the soft tissue surrounding bone, the results did not accurately reflect bone metabolism. The present study's objective was to establish the feasibility of microdialysis with a catheter positioned directly in bone.Methods: Thirty‐four patients (19 males, 15 females; median age: 59) were included in a prospective, nonrandomized clinical trial in the Department of Maxillofacial Surgery at Amiens‐Picardie University Hospital (Amiens, France). Fibula or iliac crest free flaps were used in reconstructive head and neck surgery (for cancer, osteoradionecrosis, trauma, or ameloblastoma) and monitored with microdialysis catheters positioned in a hole drilled into the bone. Glucose, lactate, pyruvate, and glycerol concentrations were analyzed for 5 days.Results: All catheters were positioned successfully, and thrombosis did not occur during the monitoring. In two patients, an increase in the lactate concentration and a glucose level close to 0 were associated with signs of flap necrosis, with removal on Days 9 and 50. In viable flaps, the mean glucose level was 2.02 mmol/L, the mean lactate level was 8.36 mmol/L, and the mean lactate/pyruvate ratio was 53. Forty percent of the glucose values were below 1 mmol/L, and 50% of the lactate/pyruvate ratio values were above 50—suggesting a specific metabolic pattern because these values would be considered as alert values in soft tissue.Conclusion: Monitoring bone free flaps with intraosseous microdialysis is feasible. This technique specifically assesses bone viability, and further studies are now necessary to define the alert values in bone.

International audience; Whilst people with schizophrenia have high levels of obesity and metabolic disease, our understanding of their eating behaviors is still limited. Our aim was to evaluate the relationships between eating behavior and clinical data in schizophrenia. A cross-sectional study including 66 schizophrenia outpatients compared to 81 healthy controls was undertaken. Eating behavior was assessed using the shortened 21-item version of the Three-Factor Eating Questionnaire (TFEQ-R21). The patients had a mean of 44 +/- 11 years; a mean BMI of 30.3 +/- 8 kg/m(2) (vs. 24 +/- 3.3 kg/m(2) for controls) and a mean duration of illness of 7.2 +/- 6 years. All mean TFEQ scores were significantly higher in patients (indicating poorer eating behaviors) compared to controls after adjustment for age and sex, BMI and smoking status. Among patients, mean TFEQ scores were not significantly different between men and women samples. The ``cognitive restraint'' factor was significantly higher in schizophrenia patients with a BMI < 25 than in the group of overweight patients with a BMI > 25. Our findings suggest that disordered eating behaviors affect schizophrenia patients regardless of gender or duration of disease compared to controls. More research is needed to help clarify the relationships between eating behaviors and weight-related outcomes in schizophrenia.

BackgroundThe prognostic significance of chronic kidney disease (CKD) in severe aortic stenosis is poorly understood and no studies have yet evaluated the effect of aortic‐valve replacement (AVR) versus conservative management on long‐term mortality by stage of CKD.Methods and ResultsWe included 4119 patients with severe aortic stenosis. The population was divided into 4 groups according to the baseline estimated glomerular filtration rate: no CKD, mild CKD, moderate CKD, and severe CKD. The 5‐year survival rate was 71±1% for patients without CKD, 62±2% for those with mild CKD, 54±3% for those with moderate CKD, and 34±4% for those with severe CKD (PP=0.009 and HR [95% CI]=2.16 [1.67–2.79];PP=0.031 and HR [95% CI]=1.69 [1.18–2.41];P=0.004, respectively) than patients without CKD. Despite more symptoms, AVR was less frequent in moderate (P=0.002) and severe CKD (PPP=0.676) indicating a nondifferentialeffect of AVR across stages of CKD. After propensity matching, AVR was still associated with substantially better survival for each CKD stage relative to conservative management (allPConclusionsIn severe aortic stenosis, moderate and severe CKD are associated with increased mortality and decreased referral to AVR. AVR markedly reduces all‐cause and cardiovascular mortality, regardless of the CKD stage. Therefore, CKD should not discourage physicians from considering AVR.

Background The urine biomarkers tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) have been validated for predicting and stratifying AKI. In this study, we analyzed the utility of these biomarkers for distinguishing between transient and persistent AKI in the early phase of septic shock. Methods We performed a prospective, multicenter study in 11 French ICUs. Patients presenting septic shock, with the development of AKI within the first 6 h, were included. Urine [TIMP-2]*[IGFBP7] was determined at inclusion (0 h), 6 h, 12 h, and 24 h. AKI was considered transient if it resolved within 3 days. Discriminative power was evaluated by receiver operating characteristic (ROC) curve analysis. Results We included 184 patients, within a median [IQR] time of 1.0 [0.0–3.0] h after norepinephrine (NE) initiation; 100 (54%) patients presented transient and 84 (46%) presented persistent AKI. Median [IQR] baseline urine [TIMP-2]*[IGFBP7] was higher in the persistent AKI group (2.21 [0.81–4.90] (ng/ml)2/1000) than in the transient AKI group (0.75 [0.20–2.12] (ng/ml)2/1000; p

Introduction Surgical resection is not curative in Crohn’s disease (CD) and, recurrence after surgery is a common situation. The identification of patients at high risk of recurrence remains disappointing in clinical practice. Objective To evaluate the impact of residual microscopic disease on margins on the risk of recurrence after ileocaecal resection in CD. Patients and methods All patients who underwent ileocaecal resection between January 1992 and December 2016 were prospectively identified. Demographic data, clinical, surgical and histological variables were retrospectively collected. Positive histologic margin was assessed prospectively and defined by the presence of acute inflammatory lesions on margins: erosion, ulceration, chorion infiltration by neutrophils, cryptic abscesses or cryptitis. Results One hundred twenty five patients were included, with a median follow-up of 8 years (Interquartile Range (IQR), 4.3–15.2). Half (49.6%, n = 62) were women, and the median age at surgery was 33 years (IQR, 24–42). Fifty-six (44.8%) had positive inflammatory margins. Five years after surgery, respectively 29 (51%) and 23 (34%) patients with positive and negative margins had clinical recurrence (p = 0.034). At the end of the follow-up, respectively 60% (n = 34) and 47% (n = 33) patients had clinical recurrence (p = 0.07). CD-related hospitalizations were observed in respectively 37.5% (n = 21) and 18.8% (n = 13) with positive and negative margins (p = 0.02). Fourteen patients (25%) with positive intestinal margins had surgical recurrence at the end of the follow-up compared to 5 patients (7%) with negative margins (p = 0.04). Multivariate analysis confirmed that positive intestinal margin was independently associated with surgical recurrence (OR, 4.7 (CI95%, 1.4–15.3), p = 0.01). Conclusion Positive histologic margin was associated with an increased risk of clinical and surgical recurrence after ileocaecal resection for Crohn’s disease.

Background Long-term outcomes in terms of thromboembolic events (TEs) are poorly described after cryoballoon pulmonary vein isolation (cryo-PVI) for atrial fibrillation (AF). We evaluated the long-term incidence and predictive factors of TE after cryo-PVI. Methods All consecutive patients who underwent cryo-PVI for paroxysmal or persistent AF between November 2012 and October 2017 were included. They were prospectively followed for at least 12 months in the ablation center and then by their cardiologist. Data on all ischemic events (stroke, transient ischemic attack (TIA), systemic embolism) were collected. Results In total, 450 patients (78% men, median age 61 years) were included. The mean CHA2DS2-VASc score was 1.6 ± 1.3 and 26 patients (6%) had a history of stroke/TIA before the procedure. OAT was discontinued for 75 patients (17%) after the procedure, among whom 50 (67%) had no indication for long-term anticoagulation. Six patients experienced an ischemic event, all considered as a TE: three strokes, two TIAs, and one acute lower-limb ischemia. The mean follow up was 30 months. Thus, the incidence of TE was 0.53%/year. Three of the six patients who experienced a TE had no recurrence of atrial arrhythmia documented before, at the time, or after the event. All patients who experienced a TE had a class I or class IIa indication for long-term anticoagulation. After multivariate analysis, the CHA2DS2-VASc Score (p = .0005) was a predictor of TEs. Conclusion The long-term incidence of TEs after cryo-PVI was 0.53%/year. The CHA2DS2-VASc Score was the only independent predictor of TEs.

International audience; The purpose of this study was to characterize cognitive impairments and behavioral disorders in a sample of patients with chronic kidney disease (CKD). A total of 52 patients with CKD were prospectively recruited over a 344-day period. Cognitive functions (memory, action speed, executive function, and language) and behavioral characteristics were assessed with a standardized comprehensive battery. The patients' performances were interpreted with a validated method on the basis of normative data from 1,003 healthy control subjects. Brain MRI and biological data were collected. Multivariable linear regression models and bootstrap analyses were used to identify risk factors for cognitive impairment. Cognitive impairment was observed in 32.5% (95% confidence interval: 17%-48%) of the 40 included patients with full data sets. Action speed and executive functions were the most frequently impaired domains. Dysexecutive behavioral disorders were observed in 27% of patients, and depression was observed in 32.5%. Cognitive impairment was independently associated with stroke volume, high serum parathyroid hormone and uric acid levels, and low serum glucose levels (adjusted R-2 = 0.54, p

The aim of this study was to evaluate the impact of frailty in the elderly on response to cardiac resynchronization therapy (CRT).CRT has been shown to improve symptoms and outcome of patients with congestive heart failure (HF) and impaired left ventricular ejection fraction (LVEF). The impact of frailty on the results of CRT is unknown.Frailty defined as 14 of 17 points using the ONCODAGE (Outil de dépistage gériatrique en oncologie) G8 score was assessed before device implantation in candidates for CRT who were70 years of age. The primary endpoint was the response to CRT, defined as an improvement of5% of the LVEF and the absence of hospitalization for HF or cardiovascular death at 9 months.Ninety-two of 151 included patients (61%) were frail, and 89 (59%) were responders. Frailty was more frequent in nonresponders: 45 of 62 (73%) versus 47 of 89 (53%) (p = 0.014) and was identified as an independent predictor of nonresponse to CRT (R = 0.30; 95% confidence interval: 0.02 to 0.59; p = 0.039). Frailty was associated with a higher cumulative probability of hospitalization for HF (log-rank p = 0.032) and of all-cause death (log-rank p = 0.033). A G8 score 10.25 correlated with hospitalization for HF or death at 9 months (area under the curve: 0.75; 95% confidence interval: 0.63 to 0.87; cutoff 10.25; 77% sensitivity, 63% specificity).Frailty is as an independent predictor of nonresponse to CRT. Frail patients implanted with CRT devices have a higher risk of hospitalization for HF and mortality. Routine comprehensive geriatric assessment at the time of screening for device therapy should be recommended to optimize management. (Frailty Score Assessment for Elderly Patients Undergoing Cardiac Resynchronization Therapy [FRAILTY]; NCT02369419).

Background: Myocardial contraction fraction (MCF) is a volumetric measure of myocardial shortening independent of left ventricular size and geometry. This multicenter study investigates the usefulness of MCF for risk stratification in low-gradient severe aortic stenosis with preserved ejection fraction. Methods: We included 643 consecutive patients with low-gradient severe aortic stenosis with preserved ejection fraction in whom MCF was computed at baseline and analyzed mortality during follow-up. Results: Throughout follow-up with medical and surgical management (34.9 [16.1–65.3] months), lower MCF tertiles had higher mortality than the highest tertile. Eighty-month survival was 56±4% for MCF>41%, 41±4% for MCF 30% to 41%, and 40±4% for MCFP 41%. The optimal MCF cutoff point for mortality prediction was 41%. Age, body mass index, Charlson index, peak aortic velocity, and ejection fraction were independently associated with mortality. MCF (χ 2 to improve 10.39; P =0.001), provided greater additional prognostic value over the baseline parameters than stroke volume (SV) index (χ 2 to improve 5.41; P =0.042), left ventricular mass index (χ 2 to improve 2.15; P =0.137), or global longitudinal strain (χ 2 to improve 3.67; P =0.061). MCF outperformed ejection fraction for mortality prediction. When patients were classified by SV index and MCF, mortality risk was low when SV index was ≥30 mL/m 2 and MCF>41%, higher for patients with SV index ≥30 mL/m 2 and MCF≤41% (adjusted hazard ratio, 1.47 [1.05–2.07]) and extremely high for patients with SV index 2 (adjusted hazard ratio, 2.29 [1.45–3.62]). Conclusions: MCF is a valuable marker of risk in low-gradient severe aortic stenosis with preserved ejection fraction and could improve decision-making, especially in normal-flow low-gradient severe aortic stenosis with preserved ejection fraction.

Objectives The objective of this study was to demonstrate and quantify the ultrasound-guided percutaneous tracheostomy (UPDT) learning curve in a single team since the first UPDT. Study design and patients This was a cohort of all consecutive patients undergoing UPDT in the Amiens teaching hospital surgical intensive care unit between 2010 and 2014. Methods The learning process was evaluated according to three aspects: duration of the various steps involved in UPDT, incidence of consecutive complications, and procedure difficulty. Results During the study period, 85 consecutive patients underwent UPDT with no deaths. The mean total procedure time was 22 (10) minutes (range: 7 to 60). Analysis of mean cumulative UPDT procedure times showed that total UPDT time decreased to a stable duration of 25 minutes after 54 procedures. Complications were observed in 24 (28%) of the 85 patients. The overall complication rate decreased to below a stable percentage of 30% after 70 procedures. The minor complication rate decreased below 25% after 64 procedures. The moderate complication rate decreased to below a stable percentage of 10% after 10 procedures. The major complication rate decreased to below a stable percentage of 5% after 20 procedures. Most complications were observed in the first 50 patients (25 [50%] versus 6 [13%], P Conclusions Our study demonstrated that UPDT is associated with a fairly long learning curve. At least 50 procedures are necessary to perform UPDT with an acceptable complication rate and procedure time.

Aim To determine whether the urine biomarkers tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) can identify patients who will develop severe acute kidney injury (AKI) soon after cardiac arrest. Methods We performed a prospective, multicentre study in three French ICUs. The performance of [TIMP-2]*[IGFBP7] was assessed for urine samples collected a median [IQR] of 240 [169–315] minutes post-collapse. The primary end-point was severe AKI (KDIGO stage 3), within 48 h of admission. Results Of the 115 patients analyzed, 32 (28%) developed severe AKI. Eleven of these required renal replacement therapy. The median [IQR] baseline [TIMP-2]*[IGFBP7] level was higher in patients who developed severe AKI (1.57 [0.80–6.62] (ng/ml)2/1000) than in those who did not (0.17 [0.05–0.59] (ng/ml)2/1000; p Conclusion Urine [TIMP-2]*[IGFBP7] effectively identify patients with a risk of severe AKI. Below a cut-off of 0.39 (ng/ml)2/1000, the risk of severe AKI is low.

Data on the benefit or or harmful effects of oxygen level on ischemic reperfusion injuries in cardiac surgery are insufficient. We hypothesized that hyperoxia during cardiopulmonary bypass decreases the incidence of postoperative atrial fibrillation (POAF) and ventricular fibrillation, and therefore decreases cardiovascular morbidity (CARDIOX study). An open-label, randomized clinical trial including adults undergoing elective cardiac surgery, i.e. cardiopulmonary bypass (CPB) randomized 1:1 to an intervention group or standard group at two French University Hospitals from June 2016 to October 2018. The intervention consisted in delivering of an inspired fraction of oxygen of one to one during CPB. The standard care consisted in delivering oxygen to achieve a partial arterial blood pressure less than 150 mmHg. The primary endpoint was the occurrence of POAF and/or ventricular tachycardia/ventricular fibrillation (VT/VF) within the 15 days following cardiac surgery. The secondary endpoint was the occurrence of major adverse cardiovascular events (MACCE: in-hospital mortality, stroke, cardiac arrest, acute kidney injury, and mesenteric ischemia). 330 patients were randomly assigned to either the intervention group (n = 161) or the standard group (n = 163). Mean PaO2 was 447 ± 98 mmHg and 161 ± 60 mmHg during CPB, for the intervention and standard group (p

International audience; BackgroundEndoscopic stent (ES) as a bridge to surgery in obstructed left colon cancer (OLCC) is controversial. Our goal was to compare the operative and oncological results of primary diverting colostomy (PDC) and ES for the curative treatment of OLCC.MethodsBetween 2000 and 2015, patients who underwent PDC or ES in a curative intent for OLCC at member centers of the French Surgical Association were included. Patients with unresectable tumors and/or synchronous metastases were excluded. Comparisons between the two groups were performed after ponderation with propensity score for: demographic and tumor characteristics, operative, and oncological results.ResultsA total of 518 patients were included: PDC (n=327); ES (n=191). The demographic characteristics were similar between the groups. ES failed in 23% of the patients (11% perforation). Cumulative tumor resection rates were 80% and 86% after PDC and ES, respectively (p=0.049). The rates of primary anastomosis were 57% in the PDC group and 40% in the ES group (p

Objectives The ability of voxel-based lesion-symptom mapping (VLSM) to define the functional anatomy of the human brain has not been fully assessed. With a view to assessing VLSM's validity, the present study analyzed the technique's ability to determine the known clinical-anatomic correlates of hemiparesis in stroke patients. Design Lesions (damaged in at least 5 patients) associated with transformed limb motor score (after adjustment on lesion volume) at 6 months were examined in 272 patients using VLSM. The value of additional multivariable linear, logistic and Bayesian analyses was examined. Results We first checked that motor hemiparesis was fully accounted for by corticospinal tract (CST) lesions (sensitivity = 100%; p = 0.0001). Conventional VLSM analysis flagged up 2 regions corresponding to the CST, but also 8 regions located outside the CST. All 10 brain regions achieving statistical significance in the VLSM analysis were submitted to 3 additional analyses. The backward linear regression analysis selected 5 regions, one only corresponding to the CST (R2: 0.03, p = 0.0008). The logistic regression analysis selected correctly the CST (OR: 2.39, 95%CI: 1.44–3.96; 0.001). The Bayesian network analysis selected regions including the CST (in 92% of 3000 bootstrap replications) and identified the source of multicollinearity. These lesions evaluated by structural equation modeling resulted in an excellent fit (p-value = 0.228, chi/df = 1.19, RMSEA = 0.032, CFI = 0.999). Analyses of confusion factors showed that conventional VLSM analyses were strongly influenced by lesion frequency (R2 = 0.377; p = 0.0001) and multicollinearity. Conclusions Conventional VLSM analyses are sensitive but weakened by a type I error due to the combined effects of multicollinearity and lesion frequency. We demonstrate that the addition of a Bayesian network analysis, and to a lesser extent of logistic regression, controlled for this type I error and constituted a reliable means of defining the functional anatomy of the motor system in stroke patients.

ObjectiveTo validate the ability of a specifically developed cognitive risk score to identify patients at risk of poststroke neurocognitive disorders (NCDs) who are eligible for a comprehensive cognitive assessment.MethodsAfter assessing 404 patients (infarct 91.3%) in the Groupe de Réflexion pour l'Evaluation Cognitive VASCulaire (GRECogVASC) cross-sectional study with the National Institute of Neurological Disorders and Stroke–Canadian Stroke Network battery 6 months after stroke, we used multivariable logistic regression and bootstrap analyses to determine factors associated with NCDs. Independent, internally validated factors were included in a cognitive risk score.ResultsCognitive impairment was present in 170 of the 320 patients with a Rankin Scale score ≥1. The backward logistic regression selected 4 factors (≥73% of the permutations): NIH Stroke Scale score on admission ≥7 (odds ratio [OR] 2.73, 95% confidence interval [CI] 1.29–4.3, p = 0.005), multiple strokes (OR 3.78, 95% CI 1.6–8, p = 0.002), adjusted Mini-Mental State Examination (MMSEadj) score ≤27 (OR 6.69, 95% CI 3.9–11.6, p = 0.0001), and Fazekas score ≥2 (OR 2.34, 95% CI 1.3–4.2, p = 0.004). The cognitive risk score computed with these 4 factors provided good calibration, discrimination (overoptimism-corrected C = 0.793), and goodness of fit (Hosmer-Lemeshow test p = 0.99). A combination of Rankin Scale score ≥1, cognitive risk score ≥1, and MMSEadj score ≥21 selected 230 (56.9%) of the 404 patients for a comprehensive assessment. This procedure yielded good sensitivity (96.5%) and moderate specificity (43%; positive predictive value 0.66, negative predictive value 0.91) and was more accurate (p ≤ 0.03 for all) than the sole use of screening tests (MMSE or Montréal Cognitive Assessment).ConclusionThe GRECogVASC cognitive risk score comprises 4 easily documented factors; this procedure helps to identify patients at risk of poststroke NCDs who must therefore undergo a comprehensive assessment.ClinicalTrials.gov identifier:NCT01339195.

Background The risk of early death is particularly high in patients over the age of 65 presenting with antineutrophil cytoplasmic antibody (ANCA)-associated renal vasculitis. We hypothesized that by combining disease severity markers, a comorbidity index and serious adverse event reports, we would be able to identify early predictors of one-year mortality in this population. Methods We performed a multicentre, retrospective study in the nephrology and internal medicine departments of six tertiary hospitals in northern France. A total of 149 patients (median [interquartile range (IQR)] age: 72.7 [68.5–76.8] years) presenting with ANCA-associated vasculitis and renal involvement were included between January 2002 and June 2015. The primary endpoint was the one-year mortality rate. Results Renal function was severely impaired at presentation (median [IQR] peak serum creatinine (SCr): 337 [211–522] μmol/l), and 45 patients required dialysis. The Five-Factor Score (FFS, scored as + 1 point for each poor prognostic factor (age > 65 years, cardiac symptoms, gastrointestinal involvement, SCr ≥150 μmol/L, and the absence of ear, nose, and throat involvement)) was ≥3 in 120 cases. The one-year mortality rate was 19.5%. Most of the deaths occurred before month 6, and most of these were related to severe infections. In a univariate analysis, age, a high comorbidity index, a performance status of 3 or 4, a lack of co-trimoxazole prophylaxis, early severe infection, and disease activity parameters (such as the albumin level, haemoglobin level, peak SCr level, dialysis status, and high FFS) were significantly associated with one-year mortality. In a multivariable analysis, the best predictors were a high FFS (relative risk (RR) [95% confidence interval (CI)] = 2.57 [1.30–5.09]; p = 0.006) and the occurrence of a severe infection during the first month (RR [95%CI] = 2.74 [1.27–5.92]; p = 0.01). Conclusions When considering various disease severity markers in over-65 patients with ANCA-associated renal vasculitis, we found that an early, severe infection (which occurred in about a quarter of the patients) is a strong predictor of one-year mortality. A reduction in immunosuppression, the early detection of infections, and co-trimoxazole prophylaxis might help to reduce mortality in this population. Electronic supplementary material The online version of this article (10.1186/s12882-018-1102-3) contains supplementary material, which is available to authorized users.

The objectives of this study were to characterize the frequencies and profiles of behavioral and cognitive dysexecutive syndromes in PD (based on validated battery and diagnostic criteria) and to develop a shortened diagnostic battery. Eighty-eight non-demented patients with a diagnosis of PD were examined with an executive validated battery. Using a validated framework, the patients' test results were interpreted with respect to normative data from 780 controls. A dysexecutive syndrome was observed in 80.6% of the patients [95% confidence interval: 71.1-90.1]. The dysexecutive profile was characterized by prominent impairments in deduction, flexibility, inhibition and initiation in the cognitive domain, and by global hypoactivity with apathy and hyperactivity in the behavioral domain. This finding implies that patients with PD should be assessed with cognitive tests and a validated inventory for behavioral dysexecutive syndromes. A shortened battery (based on three cognitive tests and three behavioral domains) provided high diagnostic accuracy.

OBJECTIVE: To assess the sensitivity of traditional neuropsychological tests and of a behavioral inventory of executive disorders in a large sample of patients with chronic severe traumatic brain injury. METHODS: A total of 112 patients were compared with 780 healthy controls from a larger database. The GREFEX battery included 7 widely used tests and the Behavioral Dysexecutive Syndrome Inventory (proxy rating). A previously described statistical methodology was used, controlling for age, education, and gender. Summary scores were computed and performance was dichotomized on the basis of 5th percentile cutoffs from controls' z scores. RESULTS: The frequency of cognitive impairment was high (55.4%) but lower than that of behavioral changes (81.5%). Double dissociations were observed between cognitive and behavioral assessments. Behavioral changes exhibited larger effect-sizes as compared with cognitive impairments. Logistic regression analysis showed that 3 cognitive tests (verbal fluency, Stroop reading, and Trail Making Test-B) and 3 behavior z scores (hypoactivity, anticipation, and hyperactivity) best discriminated patients from controls. CONCLUSION: Behavioral changes were more frequent and severe than cognitive deficits, at least as assessed with traditional testing. The present results also suggest that a shortened battery may provide a rapid screening method with reasonable sensitivity to detect deficits of executive functions in patients with severe traumatic brain injury. Language: en

It has been suggested that oxygenation using pressure support ventilation (PSV) before general anaesthesia can reduce the duration of non-hypoxaemic apnoea.The objective was to determine whether or not pre-oxygenation with PSV increases the duration of non-hypoxaemic apnoea in non-obese patients during pan-endoscopy.A randomised, controlled trial.Amiens University Hospital, France.Fifty patients scheduled for ENT pan-endoscopy with a BMI lower than 35 kg m(-2).Patients scheduled for pan-endoscopy were enrolled to receive either 100% oxygen at neutral pressure (the control group) or 100% oxygen with positive-pressure ventilation (a positive inspiratory pressure of 4 cmH2O and a positive end-expiratory pressure of 4 cmH2O; the PSV group) during spontaneous ventilation with a face mask. The goal of pre-oxygenation was to obtain an end-tidal oxygen concentration of more than 90% prior to induction of anaesthesia.The primary efficacy criterion was the duration of non-hypoxaemic apnoea (i.e. before the peripheral capillary oxygen saturation fell to 90%). Secondary outcomes were duration of pre-oxygenation, pre-oxygenation failure and tolerance.The mean (interquartile range) duration of non-hypoxaemic apnoea was longer in the PSV group [598 (447 to 717) s] than in the control group [310 (217 to 451) s] (P 0.001). Oxygenation time was shorter in the PSV group [190 (159 to 225) s] than in the control group [245 (151 to 435) s] (P = 0.037). Pre-oxygenation was unsuccessful (i.e. end-tidal oxygen concentration was90%) in 20% of the patients in the control group but none in the PSV group. The intergroup difference in the duration of pan-endoscopy was not significant. Tolerance was good or very good in all patients.Our results show that pre-oxygenation with PSV is associated with a longer duration of non-hypoxaemic apnoea and a lower frequency of manual reventilation during ENT pan-endoscopy. CLINICALTRIALS.NCT02167334.

The frequency of executive disorders in mild-to-moderate Alzheimer disease (AD) has been demonstrated by the application of a comprehensive battery. The present study analyzed data from 2 recent multicenter studies based on the same executive battery. The objective was to derive a shortened battery by using the GREFEX population as a training dataset and by cross-validating the results in the REFLEX population. A total of 102 AD patients of the GREFEX study (MMSE=23.2±2.9) and 72 patients of the REFLEX study (MMSE=20.8±3.5) were included. Tests were selected and receiver operating characteristic curves were generated relative to the performance of 780 controls from the GREFEX study. Stepwise logistic regression identified 3 cognitive tests (Six Elements Task, categorical fluency and Trail Making Test B error) and behavioral disorders globally referred as global hypoactivity (P=0.0001, all). This shortened battery was as accurate as the entire GREFEX battery in diagnosing dysexecutive disorders in both training group and the validation group. Bootstrap procedure confirmed the stability of AUC. A shortened battery based on 3 cognitive tests and 3 behavioral domains provides a high diagnosis accuracy of executive disorders in mild-to-moderate AD.

International audience; Background: Indoxyl sulfate (IS) is a protein-bound uremic toxin that is known to be associated with the risk of cardiovascular (CV) disease and death in both predialysis and dialysis patients. Data on levels of protein-bound uremic toxins in kidney transplant patients are scarce. The study's objective was to evaluate the levels of IS in kidney transplant patients and the relationship with hard outcomes. Methods and Results: In 311 kidney transplant patients, IS levels were measured immediately before transplantation (T0), and 1 month (M1) and 12 months (M12) afterwards. Over a mean +/- standard deviation follow-up period of 113+/-29 months, a total of 55 deaths, 70 CV events and 71 graft losses were recorded. We observed a rapid significant decrease (below or near the normal value) in IS levels after kidney transplantation. Total and free IS levels at M12 were significantly higher in non-transplant patients than in transplant patients (P=0.003 and

AIM: Although diabetes-related erectile dysfunction (ED) has many etiological factors, little is known about the putative pathophysiological role of advanced glycation end products (AGEs). Skin autofluorescence is a noninvasive marker of AGEs. Recent studies have evidenced a relationship between skin autofluorescence and several complications of diabetes. We hypothesized that AGEs (assessed by skin autofluorescence) are associated with ED in diabetes patients. METHODS: Between March 2014 and April 2015, 42 patients with type 1 diabetes (T1D) and 44 patients with type 2 diabetes (T2D) were consecutively enrolled in a descriptive, cross-sectional study and compared to 54 healthy controls. ED was evaluated via the 5-item version of the International Index of Erectile Function (IIEF-5). Skin autofluorescence was measured on the volar aspect of the arm with an AGE-Reader. RESULTS: Patients with diabetes had a mean±standard deviation age of 50±15 and a mean duration of diabetes of 16±12years. Skin autofluorescence was strongly and significantly correlated with the IIEF-5 score in the T1D subgroup (r=-0.52; P=0.004), the T2D subgroup (r=-0.32; P

Binge drinking is defined as a pattern of drinking leading to intoxication in a single short session and is a serious but preventable public health problem. Only few animal models of voluntary binge drinking using an operant paradigm are available in outbred animals and in general they do not display good face validity. We recently set up a new model of binge drinking behavior using an operant self-administration paradigm in which rats drink to intoxication level in 15-min daily session. Here we tested the current pharmacotherapies of alcohol use disorder: Acamprosate, (R)-Baclofen, gamma-hydroxybutyric acid, Nalmefene and Naltrexone. Our results show that all drugs are effective in reducing ethanol drinking. All drugs except Acamprosate also reduced the motivational properties of ethanol (breakpoint). (R)-Baclofen and gamma-hydroxybutyric acid were effective on ethanol intake at doses devoid of side effects. Among the tested drugs only (R)-Baclofen, gamma-hydroxybutyric acid and Naltrexone reduced reacquisition after a period of abstinence. Interestingly, the efficacy of all drugs except Nalmefene to reduce ethanol drinking was slightly and positively correlated with the basal level of drinking thus revealing heavy drinking as a predictive factor. In summary, all current alcohol use disorder pharmacotherapies were effective in our model of binge drinking behavior thus bringing new data regarding its good predictive validity. The tested drugs display some specificity regarding their effect on motivation, reacquisition and also in terms of individual factors such as basal drinking level. Our new model opens promising perspectives about the development of pharmacotherapies targeting binge drinking behavior.

International audience; Aims In patients with severe aortic stenosis (AS) and preserved left ventricular ejection fraction (LVEF), low flow (LF) is currently defined using Doppler-echocardiography by a stroke volume index (SVi)< 35 mL/m(2). However, the relationship between LF and outcome remains unclear as data on normal reference values defining LF are scarce, and previous studies did not explore the risk associated with other SVi cut-points. We analysed the relationship between LF and mortality in severe AS to establish prognostic LF values associated with mortality risk. Methods and results This study included 1450 consecutive patients with severe AS (aortic valve area < 1 cm(2) and/or < 0.6 cm(2)/m(2)) and preserved LVEF and 1645 controls with normal echocardiograms. Patients were stratified in three groups: (i) SVi > 35 mL/m(2) or SV > 70 mL; (ii) SVi 30-35 mL/m(2) or SV 55-70 mL; and (iii) SVi < 30 mL/m(2) or SV < 55 mL. Mortality with medical and surgical management was analysed. Five-year survival was low for SVi < 30 mL/m(2) and SV < 55mL compared to the other groups (all P-values < 0.001). After adjustment for outcome predictors, including aortic valve replacement, mortality risk was considerable with SVi < 30 mL/m(2) vs. > 35 mL/m(2) [adjusted hazard ratio (HR) 1.60 (1.17-2.18)] and SV < 55mL vs. > 70 mL [adjusted HR 1.84 (1.32-2.58)]. Similar mortality risk was observed for SVi 30-35 mL/m(2) vs. > 35 mL/m(2) [adjusted HR 1.05(0.78-1.41)], and for SV 55-70 mL vs. > 70 mL [adjusted HR 1.22 (0.94-1.58)]. The prognostic impact of SVi < 30 mL/m(2) and SV < 55mL was consistent in subgroups, including asymptomatic patients and patients with low-gradient severe AS. Conclusion Low flow defined as SVi < 30 mL/m(2) or SV < 55mL is an important outcome predictor in severe AS with preserved LVEF under medical and surgical management. Further studies are needed to prospectively test these values for risk stratification and decision making.

International audience

International audience; BACKGROUND: The value of transient elastography for the non-invasive diagnosis of alcohol-related liver fibrosis is subject to debate. We did an individual patient data (IPD) meta-analysis to determine specific diagnostic cutoff values for liver stiffness in alcohol-related fibrosis, and to assess the effect of aminotransferase concentrations, bilirubin concentrations, and presence of asymptomatic and non-severe alcoholic hepatitis on liver stiffness.METHODS: We searched for studies that included patients with alcohol-related liver disease, liver biopsy, and transient elastography, and with a statistical method for determining the diagnostic cutoffs for alcohol-induced liver fibrosis on the basis of the FibroScan results, in PubMed between Jan 1, 2000, and Sept 30, 2017. Native data bases were obtained from corresponding authors in an Excel form. Pooled diagnostic cutoffs for the various fibrosis stages were determined in a two-stage, random-effects meta-analysis. The effects of aspartate aminotransferase (AST) concentrations, bilirubin concentrations, and histological features of asymptomatic and non-severe alcoholic hepatitis on liver stiffness cutoff were assessed in one-stage, random-effects meta-analysis.FINDINGS: Of 188 studies assessed, ten studies comprising 1026 patients were included in the meta-analysis, yielded liver stiffness cutoffs of 7·0 kPa (area under the receiver operating characteristic curve 0·83 [SE 0·02; 95% CI 0·79-0·87]) for F≥1 fibrosis, 9·0 kPa (0·86 [0·02; 0·82-0·90]) for F≥2, 12·1 kPa (0·90 [0·02; 0·86-0·94]) for F≥3, and 18·6 kPa (0·91 [0·04; 0·83-0·99]) for F=4. AST and bilirubin concentrations had a significant effect on liver stiffness, with higher concentrations associated with higher liver stiffness values (pINTERPRETATION: This IPD meta-analysis highlights the link between liver stiffness and the histological features of asymptomatic and non-severe alcoholic hepatitis, reflected by AST and bilirubin concentrations. In alcohol-related liver disease, FibroScan assessments of liver fibrosis should take into account AST and bilirubin concentrations through the use of specifically adjusted liver stiffness cutoffs.FUNDING: None.

International audience; INTRODUCTION:As mortality and morbidity after a curative resection remains high, it is essential to identify pre-operative factors associated with an early death after a major resection.METHODS:Between 1998 and 2008, we selected a population of 331 patients having undergone a major hepatectomy including segment I with a lymphadenectomy and a common bile duct resection for a proven hilar cholangiocarcinoma in 21 tertiary centres. The study's objective was to identify pre-operative predictors of early death (30 mm [odds ratio (OR) 2.471 (95% confidence interval (CI) 1.136-7.339), P = 0.001] and major post-operative complication [OR 3.369 (95% CI 1.038-10.938), P = 0.004] were independently associated with death 30 mm was independently associated with death

Background and Purpose— The prevalence of poststroke neurocognitive disorder (NCD) has yet to be accurately determined. The primary objective of the present study was to optimize operationalization of the criterion for NCD by using an external validity criterion. Methods— The GRECOG-VASC cohort (Groupe de Réflexion pour l'Évaluation Cognitive Vasculaire) of 404 stroke patients with cerebral infarct (91.3%) or hemorrhage (18.7%) was assessed 6 months poststroke and 1003 healthy controls, with the National Institute of Neurological Disorders and Stroke-Canadian Stroke Network standardized battery. Three dimensions of the criterion for cognitive impairment were systematically examined by using the false-positive rate as an external validity criterion. Diagnosis of mild and major NCD was based on the VASCOG criteria (Vascular Behavioral and Cognitive Disorders). The mechanisms of functional decline were systematically assessed. Results— The optimal criterion for cognitive impairment was the shortened summary score (ie, averaged performance for action speed, executive functions, and language) because it was associated with the highest ( P =0.0001) corrected true-positive rate (43.5%) and a false-positive rate ≤5%. Using this criterion, the mean (95% confidence interval) prevalence of poststroke NCD was 49.5% (44.6–54.4), most of which corresponded to mild NCD (39.1%; 95% confidence interval, 34.4–43.9) rather than dementia (10.4%; 95% confidence interval, 7.4–13.4). Conclusions— This study is the first to have optimized the operationalization of the criterion for poststroke cognitive impairment. It documented the prevalence of poststroke NCD in the GRECOG-VASC cohort and showed that mild cognitive impairment accounts for 80% of the affected patients. Finally, the method developed in the present study offers a means of harmonizing the diagnosis of NCD. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT01339195.

Objectives The objective of this study was to test whether assessment of renal resistive index measured after cardiac surgery (RRIT0) can diagnose persistent acute kidney injury (AKI). The predictive value was evaluated using a gray-zone approach. Design A prospective observational study. Setting A teaching university hospital. Participants Eighty-two patients following cardiac surgery with cardiopulmonary bypass. Interventions Measurements of hemodynamic parameters and RRI were obtained before surgery, on admission to the intensive care unit, 6 hours after admission, and on the first postoperative day. AKI was defined according to the renal risk, injury, failure, loss of kidney function, end-stage of kidney disease (RIFLE) classification during the first postoperative week. Persistent AKI was defined as AKI lasting >3 days. Measurements and Main Results Out of the 82 patients, 15 (18%) developed persistent AKI, and 6 (7%) developed transient AKI. The median value and time-course of RRI were significantly different between patients with transient AKI and persistent AKI. Doppler-based RRIT0 predicted persistent AKI with an area under the receiver-operating characteristic curve of 0.93 (95% confidence interval: 0.85-0.98, p

Background Oxidative stress has been intensively studied as a key biochemical system in the pathophysiology of schizophrenia. However, little is known about the implication of oxidative stress in the development of physical illnesses in schizophrenia patients, who are characterized by high cardiovascular risk and decreased life expectancy. Advanced glycation end-products (AGEs) are considered to be markers of oxidative stress and are linked to the development of atherosclerosis. Methods We investigated AGE levels determined by a noninvasive skin autofluorescence (skin AF) method (AGE-Reader™) in schizophrenia patients. Skin AF was assessed in 55 schizophrenia patients without diabetes or renal disease and 55 healthy controls matched for age, gender and smoking status. Nineteen of the 55 schizophrenia patients had a severe form of the disease (Kraepelinian schizophrenia). Results Skin AF was significantly higher in schizophrenia patients compared to controls (2.46 ± 0.52 and 1.90 ± 0.21, respectively, p

Self-expanding metallic stent (SEMS) insertion has been suggested as a promising alternative to emergency surgery for left-sided malignant colonic obstruction (LMCO). However, the literature on the long-term impact of SEMS as "a bridge to surgery" is limited and contradictory.From January 1998 to June 2011, we retrospectively identified patients operated on for LMCO with curative intent. The primary outcome criterion was overall survival. Short-term secondary endpoints included the technical success rate and overall success rate and long-term secondary endpoints included 5-year overall survival, 5-year cancer-specific mortality, 5-year disease-free survival, the recurrence rate, and mean time to recurrence. Patients treated with SEMS were analyzed on an intention-to-treat basis. Overall survival was analyzed after using a propensity score to correct for selection bias.There were 48 patients in the SEMS group and 39 in the surgery-only group. In the overall population, overall survival (P = 0.001) and 5-year overall survival (P = 0.0003) were significantly lower in the SEMS group than in the surgery-only group, and 5-year cancer-specific mortality was significantly higher in the SEMS group (48% vs 21%, respectively (P = 0.02)). Five-year disease-free survival, the recurrence rate, and the mean time to recurrence were better in the surgery-only group (not significant). For patients with no metastases or perforations at hospital admission, overall survival (P = 0.003) and 5-year overall survival (30% vs 67%, respectively, P = 0.001) were significantly lower in the SEMS group than in the surgery-only group.Our study results suggest worse overall survival of patients with LMCO with SEMS insertion compared with immediate surgery.

Purpose To determine the efficacy and safety of bendamustine as a single agent in refractory or relapsed T-cell lymphomas. Patients and Methods Patients with histologically confirmed peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma who progressed after one or more lines of prior chemotherapy received bendamustine at 120 mg/m2 per day on days 1 through 2 every 3 weeks for six cycles. The primary end point was overall response rate (ORR). Secondary end points were duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Results Of the 60 patients included, 27 (45%) were refractory to their last prior chemotherapy, and the median duration of the best previous response was 6.6 months. Histology was predominantly angioimmunoblastic lymphadenopathy and PTCL not otherwise specified. The disease was disseminated in the majority of patients (87%). The median number of previous lines of chemotherapy was one (range, one to three). Twenty patients (33%) received fewer than three cycles of bendamustine, mostly because of disease progression. In the intent-to-treat population, the ORR was 50%, including complete response in 17 patients (28%) and partial response in 13 patients (22%). Bendamustine showed consistent efficacy independent of major disease characteristics. The median values for DoR, PFS, and OS were 3.5, 3.6, and 6.2 months, respectively. The most frequent grade 3 to 4 adverse events were neutropenia (30%), thrombocytopenia (24%), and infections (20%). Conclusion Bendamustine showed an encouraging high response rate across the two major PTCL subtypes, independent of age and prior treatment, with acceptable toxicity in refractory or relapsed T-cell lymphoma.

Since beta-2 microglobulin (B2M) is a surrogate marker for middle molecular weight uremic toxins and the major protein component in dialysis-related amyloidosis, it has been frequently studied in dialysis patients. It is not known, however, whether B2M has an impact in patients with chronic kidney disease (CKD) not yet on dialysis. Here we studied the relationship of plasma B2M levels to clinical and cardiovascular outcomes in 142 patients (mean age of 67 years) at different stages of CKD. B2M levels increased with CKD stage and thus were highest in hemodialysis patients. Baseline B2M levels were associated with vascular calcification but not with arterial stiffness or bone density. During a mean follow-up of 969 days, 44 patients died and 49 suffered a cardiovascular event. Higher B2M levels were independently associated with overall and cardiovascular mortality and cardiovascular events in the whole cohort and with cardiovascular events in the predialysis cohort. Moreover, B2M appeared to be a better predictor than well-established factors associated with outcomes in this population, such as estimated glomerular filtration rate ((eGFR), only for predialysis patients), inflammation biomarkers, and other factors included in a propensity score. Thus, we confirm the strong relationship between B2M levels and eGFR and confirm the power of B2M to predict overall and cardiovascular mortality and cardiovascular events in patients at different stages of CKD.

Ribavirin-induced anemia is the major side effect observed during HCV therapy. In an in vitro study, we recently discovered that DHEA can strongly inhibit this adverse event. We also evaluated a possible link between pre-treatment serum DHEA and hemoglobin during HCV therapy. Among the 108 patients of our cohort serum baseline DHEA levels were associated with hemoglobin levels at week 12 of treatment (r = 0.35; P = 0.0021). Patients with low baseline serum DHEA developed severe anemia. A serum level of DHEA less than 1,500 ng/ml had a sensitivity of 94.3% and a positive predictive value of 93.1% for the detection of hemoglobin less than 11 g/dl during the first 12 week of treatment. With pre-treatment DHEA levels below the cutoff, anemia was observed in 24.4% and 60.5% of patients treated with dual therapy and triple therapy, respectively, versus 0% and 15% of patients with higher DHEA levels. At week 12, the mean difference between patients with serum DHEA below and above the cutoff, in terms of absolute hemoglobin for dual and triple therapy groups were 1.2 and 1.7 g/dl, respectively (P = 0.005 and0.001). Pretreatment DHEA levels are associated with hemoglobin levels during treatment. Based on these data, pretreatment assay of DHEA could be considered systematically in order to propose DHEA supplementation to potentiate the efficacy of the current and future use of ribavirin for HCV and HEV therapy. J. Med. Virol. 89:1033-1039, 2017. © 2016 Wiley Periodicals, Inc.

Purpose Primary plasma cell leukemia (pPCL) is a rare and aggressive malignancy with a poor prognosis. With conventional chemotherapy, patients typically die within 1 year. In all but one of the retrospective studies reported to date, bortezomib and lenalidomide seem to improve survival. We conducted a prospective phase II trial in patients with pPCL to assess the efficacy of an alternate regimen that combines standard chemotherapy, a proteasome inhibitor, and high-dose melphalan and autologous stem cell transplantation (HDM/ASCT) followed by either allogeneic transplantation or bortezomib/lenalidomide maintenance. Patients and Methods Patients 70 years old and younger with newly diagnosed pPCL received four alternating cycles of bortezomib, dexamethasone plus doxorubicin or cyclophosphamide. Peripheral blood stem cells were collected from responding patients with < 1% of circulating plasma cells before HDM/ASCT. As consolidation, young patients received a reduced-intensity conditioning allograft, whereas the remaining patients underwent a second HDM/ASCT followed by 1 year of bortezomib, lenalidomide, dexamethasone. The primary end point was progression-free survival (PFS). Results Forty patients (median age, 57 years; range, 27 to 71 years) were enrolled. The median follow-up was 28.7 months. In the intention-to-treat analysis, the median PFS and overall survival were 15.1 (95% CI, 8.4; -) and 36.3 (95% CI, 25.6; -) months, respectively. The overall response rate to induction was 69%. One patient underwent a syngeneic allograft and 25 HDM/ASCT (16 of whom subsequently received a reduced-intensity conditioning allograft and seven a second ASCT followed by maintenance). Conclusion In this prospective trial in patients with pPCL, we show that bortezomib, dexamethasone plus doxorubicin or cyclophosphamide induction followed by transplantation induces high response rates and appears to significantly improve PFS.

Supplemental Digital Content is available in the text, Cardiac output measurement with pulse contour analysis is a continuous, mini-invasive, operator-independent, widely used, and cost-effective technique, which could be helpful to assess changes in cardiac output. The 4-quadrant plot and the polar plot have been described to compare the changes between 2 measurements performed under different conditions, and the direction of change by using different methods of measurements. However, the 4-quadrant plot and the polar plot present a number of limitations, with a risk of misinterpretation in routine clinical practice. We describe a new trend interchangeability method designed to objectively define the interchangeability of each change of a variable. Using the repeatability of the reference method, we classified each change as either uninterpretable or interpretable and then as either noninterchangeable, in the gray zone or interchangeable. An interchangeability rate can then be calculated by the number of interchangeable changes divided by the total number of interpretable changes. In this observational study, we used this objective method to assess cardiac output changes with 5 arterial pulse contour techniques (Wesseling's method, LiDCO, PiCCO, Hemac method, and Modelflow) in comparison with bolus thermodilution technique as reference method in 24 cardiac surgery patients. A total of 172 cardiac output variations were available from the 199 data points: 88 (51%) were uninterpretable, according to the first step of the method. The second step of the method, based on the 84 (49%) interpretable variations, showed that only 18 (21%) to 30 (36%) variations were interchangeable regardless of the technique used. None of pulse contour cardiac output technique could be interchangeable with bolus thermodilution to assess changes in cardiac output using the trend interchangeability method in cardiac surgery patients. Future studies may consider using this method to assess interchangeability of changes between different methods of measurements.

Background— Current guidelines define severe aortic stenosis in patients with aortic valve area normalized to body surface area (AVA/BSA) 2 /m 2 ; yet, this cutoff has never been validated. Moreover, it is not known whether AVA normalization to other body size indexes allows improved outcome prediction. We aim to test the value of AVA normalized to body size for outcome prediction in asymptomatic aortic stenosis. Methods and Results— We included 289 patients with asymptomatic aortic stenosis, preserved ejection fraction, and AVA2 at diagnosis. The outcome measure was the occurrence of aortic valve replacement or all-cause death or during follow-up. AVA was normalized to BSA, height, weight, and body mass index. For each normalized index, patients in the lowest tertile were at high risk of events whereas outcome was similar for the other tertiles. High risk of events was observed with AVA/BSA 2 /m 2 (adjusted hazard ratio [HR], 3.42 [2.09–5.60]), AVA/height 2 /m (adjusted HR, 3.99 [2.42–6.60]), AVA/weight 2 /kg (adjusted HR, 3.37 [2.07–5.49]), and AVA/body mass index 2 /kg per meter square (adjusted HR, 3.23 [1.99–5.24]). Mortality risk was high with AVA/height 2 /m (adjusted HR, 2.18 [1.28–3.71]), followed by AVA/BSA 2 /m 2 (adjusted HR, 1.84 [1.09–3.11]), AVA/weight 2 /kg (adjusted HR, 1.78 [1.07–2.98]), and AVA/body mass index 2 /kg per meter square (adjusted HR, 1.75 [1.04–2.93]). AVA/height showed better predictive performance than AVA/BSA with improved reclassification and better discrimination (net reclassification improvement: 0.33 versus 0.28; integrated discrimination improvement: 0.10 versus 0.08; C statistic: 0.67 versus 0.65), whereas AVA/weight and AVA/body mass index showed lower predictive capacity. Conclusions— Among AVA normalization methods, AVA/height 2 /m followed by AVA/BSA 2 /m 2 seem as robust parameters for defining high risk in asymptomatic aortic stenosis. The prognostic value of AVA/height deserves future research.

In 18F-fluorodeoxyglucose PET/CT, respiratory motion induces bias in image interpretations (i.e. organ misregistration or lesion omission/underestimation).The present study applied our custom gating method (referred to as 'CT-based gated PET' and that has already been validated by our research group) to PET imaging of the liver and compared its per lesion sensitivity with that of standard clinical (i.e. ungated) PET.A total of 13 patients scheduled for liver surgery were referred to our department for PET/CT imaging. Each patient underwent both ungated and CT-based gated PET imaging protocols. Two independent, blinded observers interpreted the two sets of PET images and reached a consensus when necessary. Image interpretations were combined with histological analysis and/or intraoperative ultrasound examination to compute each method's per lesion sensitivity and true positive fraction. Analyses were also performed by considering lesions according to their size (longest axis over 10 mm or over 15 mm).Forty-eight lesions were confirmed by pathology reports. When considering all the uptakes, the ungated and the CT-based gated PET methods had sensitivities of 54.2 and 64.6% (P=0.025) and true positive fractions of 83.9 and 86.1%, respectively. When considering uptakes greater than 10 mm in size, ungated and CT-based gated PET had sensitivities of 74.3 and 88.6% (P=0.025), respectively. For lesions greater than 15 mm in size, the corresponding sensitivities were 85.2 and 100% (P=0.046).CT-based gated PET yielded a higher lesion-based sensitivity than routine, ungated PET did. Hence, this method improves the detection of intrahepatic colorectal metastases--especially for lesions that are close in size to the detection limit of the PET gantry.

Eastern Cooperative Oncology Group Performance Status (ECOG-PS) is currently an important parameter in the choice of treatment strategy for metastatic pancreatic adenocarcinoma (mPA) patients. However, previous research has shown that patients’ self-reported health-related quality of life (HRQOL) scales provided additional prognostic information in homogeneous groups of patients with respect to ECOG-PS. The aim of this study was to identify HRQOL scales with independent prognostic value in mPA and to propose prognostic groups for these patients. We analysed data from 98 chemotherapy-naive patients with histologically proven mPA recruited from 2007 to 2011 in the FIRGEM phase II study which aimed to compare the effectiveness of two chemotherapy regimen. HRQOL data were assessed with the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire. A random survival forest methodology was used to impute missing data and to identify major prognostic factors for overall survival. Baseline HRQOL assessment was completed by 60 % of patients (59/98). Twelve prognostic variables were identified. The three most important prognostic variables were fatigue, appetite loss, and role functioning, followed by three laboratory variables. The model’s discriminative power assessed by Harrell’s C statistic was 0.65. Fatigue score explained almost all the survival variability. HRQOL scores have prognostic value for mPA patients with good ECOG-PS. Moreover, the patient’s fatigue, appetite loss, and self-perception of daily activities were more reliable prognostic indicators than clinical and laboratory variables. These HRQOL scores, especially the fatigue symptom, should be urgently included for prognostic assessment of mPA patients (with good ECOG-PS).

Sorafenib is the medical reference for treatment of hepatocellular carcinoma (HCC). Multiple forms of cytotoxicity are induced by sorafenib in HCC cells in vitro but it is unclear what extent of apoptosis and necrosis is induced in HCC patients receiving sorafenib.The M30 and M65 biomarkers, which reflect the release of cytokeratin-18 and its apoptotic cleavage fragments, were measured in patients with HCC (n=36) and matched patients with cirrhosis (n=47). A serum sample was collected from 20 patients with HCC four weeks after the onset of treatment with sorafenib.Basal serum levels of M30 and M65 were increased in patients with HCC compared to those with uncomplicated cirrhosis. No statistically significant increase in the level of M30 or M65 was found in the sera of patients with HCC after sorafenib.The findings indicate that sorafenib is not a potent inducer of HCC cell death in most patients.

Background Although a variety of non-invasive methods for measuring cardiovascular (CV) risk (such as carotid intima media thickness, pulse wave velocity (PWV), coronary artery and aortic calcification scores (measured either by CT scan or X-ray) and the ankle brachial index (ABI)) have been evaluated separately in chronic kidney disease (CKD) cohorts, few studies have evaluated these methods simultaneously. Here, we looked at whether the addition of non-invasive methods to traditional risk factors (TRFs) improves prediction of the CV risk in patients at different CKD stages. Methods We performed a prospective, observational study of the relationship between the outputs of non-invasive measurement methods on one hand and mortality and CV outcomes in 143 patients at different CKD stages on the other. During the follow-up period, 44 patients died and 30 CV events were recorded. We used Cox models to calculate the relative risk for outcomes. To assess the putative clinical value of each method, we also determined the categorical net reclassification improvement (NRI) and the integrated discrimination improvement. Results Vascular calcification, PWV and ABI predicted all-cause mortality and CV events in univariate analyses. However, after adjustment for TRFs, only aortic and coronary artery calcification scores were found to be significant, independent variables. Moreover, the addition of coronary artery calcification scores to TRFs improved the specificity of prediction by 20%. Conclusion The addition of vascular calcification scores (especially the coronary artery calcification score) to TRFs appears to improve CV risk assessment in a CKD population.