Search

Background and Objectives: Primary spinal glioblastoma (PsGBM) is extremely rare. The dramatic neurologic deterioration and unresectability of PsGBM makes it a particularly disabling malignant neoplasm. Because it is a rare and heterogeneous disease, the assessment of prognostic factors remains limited., Methods: PsGBMs were identified from the French Brain Tumor Database and the Club de Neuro-Oncologie of the Société Française de Neurochirurgie retrospectively. Inclusion criteria were age 18 years or older at diagnosis, spinal location, histopathologic diagnosis of newly glioblastoma according to the 2016 World Health Organization classification, and surgical management between 2004 and 2016. Diagnosis was confirmed by a centralized neuropathologic review. The primary outcome was overall survival (OS). Therapeutic interventions and neurologic outcomes were also collected., Results: Thirty-three patients with a histopathologically confirmed PsGBM (median age 50.9 years) were included (27 centers). The median OS was 13.1 months (range 2.5-23.7), and the median progression-free survival was 5.9 months (range 1.6-10.2). In multivariable analyses using Cox model, Eastern Cooperative Oncology Group (ECOG) performance status at 0-1 was the only independent predictor of longer OS (hazard ratio [HR] 0.13, 95% CI 0.02-0.801; p = 0.02), whereas a Karnofsky performance status (KPS) score <60 (HR 2.89, 95% CI 1.05-7.92; p = 0.03) and a cervical anatomical location (HR 4.14, 95% CI 1.32-12.98; p = 0.01) were independent predictors of shorter OS. The ambulatory status (Frankel D-E) (HR 0.38, 95% CI 0.07-1.985; p = 0.250) was not an independent prognostic factor, while the concomitant standard radiochemotherapy with temozolomide (Stupp protocol) (HR 0.35, 95% CI 0.118-1.05; p = 0.06) was at the limit of significance., Discussion: Preoperative ECOG performance status, KPS score, and the location are independent predictors of OS of PsGBMs in adults. Further analyses are required to capture the survival benefit of concomitant standard radiochemotherapy with temozolomide., (© 2023 American Academy of Neurology.)

Objective: This study aimed to assess if quantitative diffusion magnetic resonance imaging analysis would improve prognostication of individual patients with severe traumatic brain injury., Methods: We analyzed images of 30 healthy controls to extract normal fractional anisotropy ranges along 18 white-matter tracts. Then, we analyzed images of 33 patients, compared their fractional anisotropy values with normal ranges extracted from controls, and computed severity of injury to white-matter tracts. We also asked 2 neuroradiologists to rate severity of injury to different brain regions on fluid-attenuated inversion recovery and susceptibility-weighted imaging. Finally, we built 3 models: (1) fed with neuroradiologists' ratings, (2) fed with white-matter injury measures, and (3) fed with both input types., Results: The 3 models respectively predicted survival at 1 year with accuracies of 70%, 73%, and 88%. The accuracy with both input types was significantly better (P < 0.05)., Conclusions: Quantifying severity of injury to white-matter tracts complements qualitative imaging findings and improves outcome prediction in severe traumatic brain injury., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The aim of this study was to compare the quality of life (mental health) and voice in patients with or without permanent hypoparathyroidism after total thyroidectomy., Summary Background Data: Permanent hypoparathyroidism is an underestimated complication of thyroid surgery owing to suppression of parathormone secretion. Few studies have evaluated the consequences of hypoparathyroidism on quality of life and none has studied its effects on voice., Methods: The QoL-hypopara study (ClinicalTrial.gov NCT04053647) was a national observational study. Adult thyroidectomized patients were included between January and June 2020. A serum parathormone level <15 pg/mL >6 months after surgery defined permanent hypoparathyroidism. Patients answered the MOS-36-item short-form health (SF-36), the Voice Handicap Index (VHI) surveys, and a list of questions regarding their symptoms., Results: A total of 141 patients were included, 45 with permanent hypoparathyroidism. The median period between thyroid surgery and the questionnaire was 6 (Q1-Q3 4-11) and 4 (4-5) years in hypoparathyroid patients and controls respectively. Hypoparathyroid patients presented a reduced median mental score ratio (SF-36) [0.88 (Q1-Q3 0.63-1.01) vs 1.04 (0.82-1.13), P = 0.003] and a lower voice quality (incidence rate ratio for total VHI 1.83-fold higher, P < 0.001). In multivariable analysis, hypoparathyroidism [-0.17 (95% confidence interval -0.28 to -0.07), P = 0.002], but not age, female sex, thyroid cancer, or abnormal TSH level, was associated with the reduced mental score ratio. Myalgia, joint pain, paresthesia, tetany, anxiety attack, and exhaustion were the most common symptoms among hypoparathyroid patients (>50%)., Conclusions: Hypoparathyroid patients present significantly impaired quality of life, lower voice quality, and frequent symptoms. These results reinforce the importance of preventing this complication., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Liver transplantation (LT) from controlled donation after circulatory death (cDCD) was initiated in France in 2015 under a protocol based on the use of normothermic regional perfusion (NRP) before organ procurement. The aim was to compare outcomes following cDCD LT with NRP and donation after brain death (DBD) LT., Methods: This is a multicenter retrospective study comparing cDCD LT with NRP and DBD LT. A case-matched study (1:2) was performed using the variables such as recipient and donor age, indication of LT., Results: A total of 50 patients from the cDCD group were matched to 100 patients from the DBD group. From postoperative days 1-4, serum transaminase release was significantly lower in the cDCD group compared to the DBD group (P < 0.05). Early allograft dysfunction (cDCD: 18% versus DBD: 32%; P = 0.11), acute kidney injury (26% versus 33%; P = 0.49), 90-d graft loss (2% versus 5%; P = 0.66), and arterial (4% versus 12%; P = 0.19) and biliary (16% versus 17%; P = 0.94) complications were similar between the 2 groups. The 2-y graft survival was 88% for cDCD group and 85% for DBD group (P = 0.91). The 2-y patient survival was 90% for cDCD group and 88% for DBD group (P = 0.68)., Conclusions: This study provides evidence that cDCD LT following postmortem NRP can be safely and effectively performed in selected recipients with similar graft and patient survival outcomes, without increased rates of biliary complications and early graft dysfunction compared to DBD LT.

Objective: Chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infections are associated with increased risks of lymphomas in the non-HIV setting. Their impacts on HIV-associated lymphomas deserved further studies in the modern combined antiretroviral therapy (cART) era., Design: We evaluated the associations between HCV, HBV and HIV-related lymphomas in the Lymphovir-ANRS-CO16 cohort., Methods: Prevalence of HCV seropositivity and chronic HBV infections were compared with those observed in the French Hospital Database on HIV (FHDH-ANRS-CO4)., Results: Between 2008 and 2015, 179 patients with HIV-related lymphomas from 32 French hospitals were enrolled, 69 had Hodgkin's lymphoma (39%), and 110 non-Hodgkin's lymphoma (NHL) (61%). The prevalence of HCV infection was higher in patients with NHL than in the FHDH-ANRS-CO4 [26 versus 14%, odd ratio (OR): 2.15; 95% confidence interval (1.35-3.32)] whereas there was no association between Hodgkin's lymphoma and chronic HCV infection. Chronic HBV infection was not associated with NHL in our cohort with a prevalence of 5 versus 7% in FHDH-ANRS-CO4 but tended to be associated with Hodgkin's lymphoma [prevalence of 14%, OR: 2.16 (0.98-4.27)]. Chronic HCV infection tended to pejoratively impact 2-year overall survival in patients with NHL: 72% [57%, 91%] versus 82% [74%, 91%], hazard ratio: 2.14 [0.95-4.84]. In contrast, chronic HBV infection did not correlate with outcome., Conclusion: In the modern cART era, chronic HCV infection is associated with an increased risk of NHL in PLWHIV and tends to pejoratively impact overall survival. HBV infection is not associated with the risk of NHL but with a borderline increase of Hodgkin's lymphoma risk.

Objective: In this study, we compared the effectiveness of teriflunomide (TRF) and dimethyl fumarate (DMF) on both clinical and MRI outcomes in patients followed prospectively in the Observatoire Français de la Sclérose en Plaques., Methods: A total of 1,770 patients with relapsing-remitting multiple sclerosis (RRMS) (713 on TRF and 1,057 on DMF) with an available baseline brain MRI were included in intention to treat. The 1- and 2-year postinitiation outcomes were relapses, increase of T2 lesions, increase in Expanded Disability Status Scale score, and reason for treatment discontinuation. Propensity scores (inverse probability weighting) and logistic regressions were estimated., Results: The confounder-adjusted proportions of patients were similar in TRF- compared to DMF-treated patients for relapses and disability progression after 1 and 2 years. However, the adjusted proportion of patients with at least one new T2 lesion after 2 years was lower in DMF compared to TRF (60.8% vs 72.2%, odds ratio [OR] 0.60, p < 0.001). Analyses of reasons for treatment withdrawal showed that lack of effectiveness was reported for 8.5% of DMF-treated patients vs 14.5% of TRF-treated patients (OR 0.54, p < 0.001), while adverse events accounted for 16% of TRF-treated patients and 21% of DMF-treated patients after 2 years (OR 1.39, p < 0.001)., Conclusions: After 2 years of treatment, we found similar effectiveness of DMF and TRF in terms of clinical outcomes, but with better MRI-based outcomes for DMF-treated patients, resulting in a lower rate of treatment discontinuation due to lack of effectiveness., Classification of Evidence: This study provides Class III evidence that for patients with RRMS, TRF and DMF have similar clinical effectiveness after 2 years of treatment., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: Initial blood lactate and base deficit have been shown to be prognostic biomarkers in trauma, but their respective performances have not been compared., Methods: Blood lactate levels and base deficit were measured at admission in trauma patients in three level 1 trauma centers. This was a retrospective analysis of prospectively acquired data. The association of initial blood lactate and base deficit with mortality was tested using receiver operating characteristics curve, logistic regression using triage scores (Revised Trauma Score and Mechanism Glasgow scale and Arterial Pressure score), and Trauma Related Injury Severity Score as a reference standard. The authors also used a reclassification method., Results: The authors evaluated 1,075 trauma patients (mean age, 39 ± 18 yr, with 90% blunt and 10% penetrating injuries and a mortality of 13%). At admission, blood lactate was elevated in 425 (39%) patients and base deficit was elevated in 725 (67%) patients. Blood lactate was correlated with base deficit (R = 0.54; P < 0.001). Using logistic regression, blood lactate was a better predictor of death than base deficit when considering its additional predictive value to triage scores and Trauma Related Injury Severity Score. This result was confirmed using a reclassification method but only in the subgroup of normotensive patients (n = 745)., Conclusions: Initial blood lactate should be preferred to base deficit as a biologic variable in scoring systems built to assess the initial severity of trauma patients.

Background: The collapsibility index of inferior vena cava (cIVC) is widely used to decide fluid infusion in spontaneously breathing intensive care unit patients. The authors hypothesized that high inspiratory efforts may induce false-positive high cIVC values. This study aims at determining a value of diaphragmatic motion recorded by echography that could predict a high cIVC (more than or equal to 40%) in healthy volunteers., Methods: The cIVC and diaphragmatic motions were recorded for three levels of inspiratory efforts. Right and left diaphragmatic motions were defined as the maximal diaphragmatic excursions. Receiver operating characteristic curves evaluated the performance of right diaphragmatic motion to predict a cIVC more than or equal to 40% defining the best cutoff value., Results: Among 52 included volunteers, interobserver reproducibility showed a generalized concordance correlation coefficient (ρc) above 0.9 for all echographic parameters. Right diaphragmatic motion correlated with cIVC (r = 0.64, P < 0.0001). Univariate analyses did not show association between cIVC and age, sex, weight, height, or body mass index. The area under the receiver operating characteristic curves for cIVC more than or equal to 40% was 0.87 (95% CI, 0.81 to 0.93). The best diaphragmatic motion cutoff was 28 mm (Youden Index, 0.65) with sensitivity of 89% and specificity of 77%. The gray zone area was 25 to 43 mm., Conclusions: Inferior vena cava collapsibility is affected by diaphragmatic motion. During low inspiratory effort, diaphragmatic motion was less than 25 mm and predicted a cIVC less than 40%. During maximal inspiratory effort, diaphragmatic motion was more than 43 mm and predicted a cIVC more than 40%. When diaphragmatic motion ranged from 25 to 43 mm, no conclusion on cIVC value could be done.

The aim of this study was to estimate the prevalence of psychostimulant use in the French medical community and their motives. A population-based cross-sectional study using a self-administered online survey was done. A total of 1718 French students and physicians (mean age, 26.84±7.19 years, 37.1% men) were included. Self-reported lifetime use, motives, socio-demographic and academic features for over the counter (OTC), medically prescribed (MPP), and illicit (IP) psychostimulant users were reported. Lifetime prevalence of psychostimulant use was 33% (29.7% for OTC, 6.7% for MPP, and 5.2% for IP). OTC consumption mainly aimed at increasing academic performance and wakefulness during competitive exams preparation. OTC consumption started early and was predictive of later MPP use. Corticoids were the most frequently consumed MPP (4.5%) before methylphenidate and modafinil. Motives for MPP consumption were increased academic performance, concentration, memory, and wakefulness. Psychostimulant use is common among French medical community. Our results suggest that restrictions on methylphenidate and modafinil prescriptions are effective at limiting their use. However, these restrictions may explain the observed rates of corticoids consumption, which raise a new public health problem, given that corticoids may have severe side effects.

Background: An accurate risk score able to predict in-hospital mortality in patients undergoing surgery may improve both risk communication and clinical decision making. The aim of the study was to develop and validate a surgical risk score based solely on preoperative information, for predicting in-hospital mortality., Methods: From January 1, 2010, to December 31, 2010, data related to all surgeries requiring anesthesia were collected from all centers (single hospital or hospitals group) in France performing more than 500 operations in the year on patients aged 18 yr or older (n = 5,507,834). International Statistical Classification of Diseases, 10th revision codes were used to summarize the medical history of patients. From these data, the authors developed a risk score by examining 29 preoperative factors (age, comorbidities, and surgery type) in 2,717,902 patients, and then validated the risk score in a separate cohort of 2,789,932 patients., Results: In the derivation cohort, there were 12,786 in-hospital deaths (0.47%; 95% CI, 0.46 to 0.48%), whereas in the validation cohort there were 14,933 in-hospital deaths (0.54%; 95% CI, 0.53 to 0.55%). Seventeen predictors were identified and included in the PreOperative Score to predict PostOperative Mortality (POSPOM). POSPOM showed good calibration and excellent discrimination for in-hospital mortality, with a c-statistic of 0.944 (95% CI, 0.943 to 0.945) in the development cohort and 0.929 (95% CI, 0.928 to 0.931) in the validation cohort., Conclusion: The authors have developed and validated POSPOM, a simple risk score for the prediction of in-hospital mortality in surgical patients.

Background: Treatment of acute antibody-mediated rejection (AMR) is based on a combination of plasma exchange (PE), IVIg, corticosteroids (CS), and rituximab, but the place of rituximab is not clearly specified in the absence of randomized trials., Methods: In this phase III, multicenter, double-blind, placebo-controlled trial, we randomly assigned patients with biopsy-proven AMR to receive rituximab (375 mg/m) or placebo at day 5. All patients received PE, IVIg, and CS. The primary endpoint was a composite of graft loss or no improvement in renal function at day 12., Results: Among the 38 patients included, at 1 year, no deaths occurred, but 1 graft loss occurred in each group. The primary endpoint frequency was 52.6% (10/19) and 57.9% (11/19) in the rituximab and placebo groups, respectively (P = 0.744). Renal function improved in both groups, as soon as day 12 with no difference in serum creatinine level and proteinuria at 1, 3, 6, and 12 months. Supplementary administration of rituximab and total number of IVIg and PE treatments did not differ between the 2 groups. Both groups showed improved histological features of AMR and Banff scores at 1 and 6 months, with no significant difference between groups but with a trend in favor of the rituximab group. Both groups showed decreased mean fluorescence intensity of donor-specific antibodies as soon as day 12, with no significant difference between them but with a trend in favor of the rituximab group at 12 months., Conclusions: After 1 year of follow-up, we observed no additional effect of rituximab in patients receiving PE, IVIg, and CS for AMR. Nevertheless, our study was underpowered and important differences between groups may have been missed. Complementary trials with long-term follow-up are needed.

Objectives: The length of stay in the emergency department (ED) has been proposed as an indicator of performance in many countries. We conducted a survey of length of stay in two large areas in France and tested the hypothesis that patient and ED-related variables may influence it., Patients and Methods: During 2007, we examined lengths of stay in ambulatory patients, that is, excluding admitted patients. The following variables were considered: (a) at the patient level, age, sex, the day and month of the visit, and the French clinical classification of emergency patients (CCEP) class; (b) at the ED level, annual ED total number of visits, mean age, the proportions of patients less than 15 and more than 75 years, and the proportions of admitted and clinically stable patients with CCEP class 1 and 2. A multilevel hierarchical analysis was carried out., Results: We analyzed 988 591 visits in 53 EDs. The ED-specific median length of stay was 98 (IQR: 62-137) min and the ED-specific median proportion of patients with length of stay of more than 4 h was 15 (5-24) %. There was a strong correlation between the ED-specific median length of stay and the ED-specific proportion of patients with a length of stay of more than 4 h (R=0.96, P<0.001). Using a multilevel analysis, only three variables were associated significantly with the length of stay: the age and the CCEP class of the patient, and the ED census., Conclusion: We observed that the length of stay in the ED needs to be stratified by case mix and the total number of visits of the ED.

Background: Delayed graft function is a major determinant of long-term renal allograft survival. Despite considerable efforts to improve donor selection and matching, incidence of delayed graft function remains close to 25%. As neutrophil gelatinase-associated lipocalin (NGAL) has been shown to predict acute renal failure, the authors tested the hypothesis that NGAL measurement in brain-dead donors predicts delayed graft function in kidney recipients., Methods: In a prospective, multicenter, observational study, serum NGAL was measured in donors at the time of transfer to operating room. The primary endpoint was the delayed graft function, defined as the need for renal replacement therapy during the first week posttransplantation., Results: Among 159 included brain-dead donors, 146 were analyzable leading to 243 renal transplantations. Of these, 56 (23%) needed renal replacement therapy. Donors' NGAL values were similar in case of both delayed and normal graft function in recipients. The area under the receiver-operating curve for NGAL to predict the need for renal replacement therapy before day 8 was 0.50 (95% CI, 0.42 to 0.59). The area under curve for NGAL to predict failure to return to a normal graft function at day 8 was 0.51 (95% CI, 0.44 to 0.59). Using multivariate analysis, NGAL was not associated to the need for renal replacement therapy (odds ratio, 0.99; 95% CI, 0.98 to1.00) or failure to return to a normal graft function at day 8 (odds ratio, 1.00; 95% CI, 0.99 to 1.00)., Conclusion: NGAL measurement in brain-dead donors at the time of recovery failed to predict delayed or normal graft function in kidney recipients.

Background: No externally validated risk score for postoperative pulmonary complications (PPCs) is currently available. The authors tested the generalizability of the Assess Respiratory Risk in Surgical Patients in Catalonia risk score for PPCs in a large European cohort (Prospective Evaluation of a RIsk Score for postoperative pulmonary COmPlications in Europe)., Methods: Sixty-three centers recruited 5,859 surgical patients receiving general, neuraxial, or plexus block anesthesia. The Assess Respiratory Risk in Surgical Patients in Catalonia factors (age, preoperative arterial oxygen saturation in air, acute respiratory infection during the previous month, preoperative anemia, upper abdominal or intrathoracic surgery, surgical duration, and emergency surgery) were recorded, along with PPC occurrence (respiratory infection or failure, bronchospasm, atelectasis, pleural effusion, pneumothorax, or aspiration pneumonitis). Discrimination, calibration, and diagnostic accuracy measures of the Assess Respiratory Risk in Surgical Patients in Catalonia score's performance were calculated for the Prospective Evaluation of a RIsk Score for postoperative pulmonary COmPlications in Europe cohort and three subsamples: Spain, Western Europe, and Eastern Europe., Results: The full Prospective Evaluation of a RIsk Score for postoperative pulmonary COmPlications in Europe data set included 5,099 patients; 725 PPCs were recorded for 404 patients (7.9%). The score's discrimination was good: c-statistic (95% CI), 0.80 (0.78 to 0.82). Predicted versus observed PPC rates for low, intermediate, and high risk were 0.87 and 3.39% (score <26), 7.82 and 12.98% (≥ 26 and <45), and 38.13 and 38.01% (≥ 45), respectively; the positive likelihood ratio for a score of 45 or greater was 7.12 (5.93 to 8.56). The score performed best in the Western Europe subsample-c-statistic, 0.87 (0.83 to 0.90) and positive likelihood ratio, 11.56 (8.63 to 15.47)-and worst in the Eastern Europe subsample. The predicted (5.5%) and observed (5.7%) PPC rates were most similar in the Spain subsample., Conclusions: The Assess Respiratory Risk in Surgical Patients in Catalonia score predicts three levels of PPC risk in hospitals outside the development setting. Performance differs between geographic areas.

Objective: To describe characteristics, risk factors, and treatment outcome of progressive multifocal leukoencephalopathy (PML) complicating sarcoidosis., Methods: A retrospective chart and literature review was performed. Patients were identified through records from physicians of the Groupe Sarcoïdose Francophone. Each case was compared with 3 controls., Results: Ten cases were found (8 men). The median age at sarcoidosis diagnosis was 34.9 (±6) years. PML and sarcoidosis were diagnosed concomitantly in 2 cases, while sarcoidosis was previously known in 8 cases, including 7 cases treated with steroids (mean time between sarcoidosis diagnosis and PML was 114 [±99] months). The mean CD4 cell count was 215 (±139)/mm(3). Neurosarcoidosis was thought to be the problem in 8 cases and treatment was intensified, delaying PML diagnosis by 4.5 (±3.9) months. Eight patients received PML-specific treatment. On the whole, 6 patients died of PML within a mean time of 8 (±4.3) months. Patients with PML were significantly younger than controls. When combining our 10 patients with another 20 from the literature, we found that 17 patients (57%) died from sarcoidosis-associated PML; thus, the fatality rate was 57%., Conclusions: PML during sarcoidosis is often misdiagnosed. It is not associated with severe CD4 lymphocytopenia. Fatality rate is high in comparison with PML associated with other conditions. Interrupting immunosuppression remains the mainstay of treatment.

Background: Significant postprocedural aortic regurgitation (AR) is observed in 10% to 20% of cases after transcatheter aortic valve replacement (TAVR). The prognostic value and the predictors of such a complication in balloon-expandable (BE) and self-expandable (SE) TAVR remain unclear., Methods and Results: TAVR was performed in 3195 consecutive patients at 34 hospitals. Postprocedural transthoracic echocardiography was performed in 2769 (92%) patients of the eligible population, and these patients constituted the study group. Median follow-up was 306 days (Q1-Q3=178-490). BE and SE devices were implanted in 67.6% (n=1872) and 32.4% (n=897). Delivery was femoral (75.3%) or nonfemoral (24.7%). A postprocedural AR≥grade 2 was observed in 15.8% and was more frequent in SE (21.5%) than in BE-TAVR (13.0%, P=0.0001). Extensive multivariable analysis confirmed that the use of a SE device was one of the most powerful independent predictors of postprocedural AR≥grade 2. For BE-TAVR, 8 independent predictors of postprocedural AR≥grade 2 were identified including femoral delivery (P=0.04), larger aortic annulus (P=0.0004), and smaller prosthesis diameter (P=0.0001). For SE-TAVR, 2 independent predictors were identified including femoral delivery(P=0.0001). Aortic annulus and prosthesis diameter were not predictors of postprocedural AR for SE-TAVR. A postprocedural AR≥grade 2, but not a postprocedural AR=grade 1, was a strong independent predictor of 1-year mortality for BE (hazard ratio=2.50; P=0.0001) and SE-TAVR (hazard ratio=2.11; P=0.0001). Although postprocedural AR≥grade 2 was well tolerated in patients with AR≥grade 2 at baseline (1-year mortality=7%), it was associated with a very high mortality in other subgroups: renal failure (43%), AR

Background: Pulmonary hypertension (PH) is associated with poor prognosis in patients with severe aortic stenosis. The aim of this multicenter study was to describe clinical outcome after transcatheter aortic valve implantation., Methods and Results: The FRANCE 2 Registry included all patients undergoing transcatheter aortic valve implantation in France in 2010 and 2011. Patients were divided into 3 groups depending on systolic pulmonary artery pressure (sPAP) estimated in transthoracic echocardiography: group I, sPAP <40 mm Hg (no PH); group II, sPAP 40 to 59 mm Hg (mild-to-moderate PH); and group III, sPAP ≥60 mm Hg (severe PH). Patients were followed up for 1 year. A total of 2435 patients whose pre-transcatheter aortic valve implantation sPAP was reported were included. A total of 845 were in group I (34.7%), 1112 in group II (45.7%), and 478 in group III (19.6%). Procedural success, early complications, and 30-day mortality were statistically similar across sPAP groups. One-year mortality was higher in groups II and III (group I, 22%; group II, 28%; and group III, 28%; P=0.032). Mild-to-moderate and severe PH were identified as an independent factor of all-cause mortality. The major adverse cardiovascular event rates did not differ according to sPAP. New York Health Association functional class improved significantly in all groups., Conclusions: PH (sPAP ≥40 mm Hg) in patients with aortic stenosis undergoing transcatheter aortic valve implantation was associated with increased 1-year mortality especially when severe (sPAP ≥60 mm Hg) but not with increased 30-day mortality, and functional status was significantly improved regardless of PAP level.

Objective: To report that homoplasmic deleterious mutations in the mitochondrial DNA MT-ATP6/8 genes may be responsible for acute episodes of limb weakness mimicking periodic paralysis due to channelopathies and dramatically responding to acetazolamide., Methods: Mitochondrial DNA sequencing and restriction PCR, oxidative phosphorylation functional assays, reactive oxygen species metabolism, and patch-clamp technique in cultured skin fibroblasts., Results: Occurrence of a typical MELAS (mitochondrial encephalopathy with lactic acidosis and stroke-like episodes) syndrome in a single member of a large pedigree with episodic weakness associated with a later-onset distal motor neuropathy led to the disclosure of 2 deleterious mitochondrial DNA mutations. The MT-ATP6 m.9185T>C p.Leu220Pro mutation, previously associated with Leigh syndrome, was present in all family members, while the MT-TL1 m.3271T>C mutation, a known cause of MELAS syndrome, was observed in the sole patient with MELAS presentation. Significant defect of complexes V and I as well as oxidative stress were observed in both primary fibroblasts and cybrid cells with 100% m.9185T>C mutation. Permanent plasma membrane depolarization and altered permeability to K(+) in fibroblasts provided a link with the paralysis episodes. Screening of 9 patients, based on their clinical phenotype, identified 4 patients with similar deleterious MT-ATP6 mutations (twice m.9185T>C and once m.9176T>C or m.8893T>C). A fifth patient presented with an original potentially deleterious MT-ATP8 mutation (m.8403T>C). All mutations were associated with almost-normal complex V activity but significant oxidative stress and permanent plasma membrane depolarization., Conclusion: Homoplasmic mutations in the MT-ATP6/8 genes may cause episodic weakness responding to acetazolamide treatment.

Purpose of Review: Heart involvement during sarcoidosis is a medical emergency. The review focuses on published data analysis of clinical management and therapy involving a multidisciplinary monitoring of cardiac sarcoidosis., Recent Findings: With the emergence of new modalities, especially MRI and FDG PET scan, cardiac sarcoidosis is most often suspected and confirmed even in atypical cases. Laboratory investigations may help to diagnose and survey. Cardiac sarcoidosis drastically changes functional and vital prognosis. Recent studies define earlier detrimental predictable criteria to underline how beneficial is the combination of immunosuppressive therapy and cardiac treatment to patients. There are no large prospective studies, but case reports and small series support an appropriate therapeutic approach, which includes corticosteroids and immunosuppressive agents., Summary: Our review illustrates the importance of looking for cardiac sarcoidosis in all sarcoidosis patients and to propose more specific and sensitive investigations when suspected on clinical and/or electrical signs. It emphasizes the need for more adapted criteria and even more prognostic criteria to choose the best therapeutic option.

Background: It has been suggested that predicting difficult tracheal intubation is useless because of the poor predictive capacity of individual signs and scores. The authors tested the hypothesis that an accurate prediction of difficult tracheal intubation using simple clinical signs is possible using a computer-assist model., Methods: In a cohort of 1,655 patients, the authors analyzed the predictive properties of each of the main signs (Mallampati score, mouth opening, thyromental distance, and body mass index) to predict difficult tracheal intubation. They built the best score possible using a simple logistic model (SCOREClinic) and compared it with the more recently described score in the literature (SCORENaguib). Then they used a boosted tree analysis to build the best score possible using computer-assisted calculation (SCOREComputer)., Results: Difficult tracheal intubation occurred in 101 patients (6.1%). The predictive properties of each sign remain low (maximum area under the receiver operating characteristic curve 0.70). Using receiver operating characteristic curve, the global prediction of the SCOREClinic (0.74, 95% CI: 0.72-0.76) was greater than that of the SCORENaguib (0.66, 95% CI: 0.60-0.72, P<0.001) but significantly lower than that of the SCOREComputer (0.86, 95% CI: 0.84-0.91, P<0.001). The proportion of patients in the inconclusive zone was 71% using SCORENaguib, 56% using SCOREClinic, and only 32 % using SCOREComputer (all P<0.001)., Conclusion: Computer-assisted models using complex interaction between variables enable an accurate prediction of difficult tracheal intubation with a low proportion of patients in the inconclusive zone. An external validation of the model is now required.

Background: Lactate has been shown to be a prognostic biomarker in trauma. Although lactate clearance has already been proposed as an intermediate endpoint in randomized trials, its precise role in trauma patients remains to be determined., Methods: Blood lactate levels and lactate clearance (LC) were calculated at admission and 2 and 4 h later in trauma patients. The association of initial blood lactate level and lactate clearance with mortality was tested using receiver-operating characteristics curve, logistic regression using triage scores, Trauma Related Injury Severity Score as a reference standard, and reclassification method., Results: The authors evaluated 586 trauma patients (mean age 38±16 yr, 84% blunt and 16% penetrating, mortality 13%). Blood lactate levels at admission were elevated in 327 (56%) patients. The lactate clearance should be calculated within the first 2 h after admission as LC0-2 h was correlated with LC0-4 h (R=0.55, P<0.001) but not with LC2-4 h (R=0.04, not significant). The lactate clearance provides additional predictive information to initial blood lactate levels and triage scores and the reference score. This additional information may be summarized using a categorical approach (i.e., less than or equal to -20 %/h) in contrast to initial blood lactate. The results were comparable in patients with high (5 mM/l or more) initial blood lactate., Conclusions: Early (0-2 h) lactate clearance is an important and independent prognostic variable that should probably be incorporated in future decision schemes for the resuscitation of trauma patients.

Background: The determinants of prognosis in patients with heart failure and preserved ejection fraction (HF-PEF) are poorly documented., Methods and Results: We evaluated data from 4128 patients in the I-PRESERVE trial (Irbesartan in Heart Failure with Preserved Ejection Fraction Study). Multivariable Cox regression models were developed using 58 baseline demographic, clinical, and biological variables to model the primary outcome of all-cause mortality or cardiovascular hospitalization (1505 events), all-cause mortality (881 events), and HF death or hospitalization (716 events). Log N-terminal pro-B-type natriuretic peptide, age, diabetes mellitus, and previous hospitalization for HF were the most powerful factors associated with the primary outcome and with the HF composite. For all-cause mortality, log N-terminal pro-B-type natriuretic peptide, age, diabetes mellitus, and left ventricular EF were the strongest independent factors. Other independent factors associated with poor outcome included quality of life, a history of chronic obstructive lung disease, log neutrophil count, heart rate, and estimated glomerular filtration rate. The models accurately stratified the actual 3-year rate of outcomes from 8.1% to 59.9% (primary outcome) 2.7% to 36.5% (all-cause mortality), and 2.1% to 38.9% (HF composite) for the lowest to highest septiles of predicted risks., Conclusions: In a large sample of elderly patients with HF and preserved EF enrolled in I-Preserve, simple clinical, demographic, and biological variables were associated with outcome and identified subgroups at very high and very low risk of events.

Background: alpha-Internexin (INA) is a proneural gene encoding a neurofilament interacting protein that is upregulated in some gliomas, particularly oligodendrogliomas., Methods: INA expression was evaluated by immunohistochemistry in a series of 122 gliomas, and correlated to the 1p19q codeletion, a favorable prognostic marker of oligodendroglial tumors., Results: INA expression was strong (>10% positive cells) in 22 cases (22 oligodendroglial tumors and 0 astrocytic tumors), weak (<10% cells) in 14 cases (12 oligodendroglial tumors, 2 glioblastoma with an oligodendroglial component, and 0 astrocytic tumors), and negative in 86 cases (49 oligodendroglial tumors, 9 glioblastoma with an oligodendroglial component, and 28 astrocytic tumors). Among the 27 tumors exhibiting the 1p19q codeletion (all with an oligodendroglial phenotype), INA was detected in 96% (26/27, 18 strong, 8 weak) as compared to 11% (10/95, 4 strong, 6 weak) in the tumors without 1p19q codeletion (with an oligodendroglial or an astrocytic phenotype) (p < 0.001). In oligodendroglial tumors, INA expression specificity for 1p19q codeletion was 86%, sensitivity 96%, positive predictive value 76%, and negative predictive value was 98%. The prognostic impact of INA expression could be evaluated in grade III oligodendroglial tumors. Similar to 1p19q deletion, positive INA expression was correlated with better progression-free survival (52.6 vs 8.7 months [p = 0.001]) and overall survival (121.1 vs 31.4 months [p = 0.0001])., Conclusion: alpha-Internexin (INA) expression appears to be a simple, reliable prognostic marker and a surrogate marker of 1p19q codeletion.

Background: In diabetic cardiomyopathy, diastolic dysfunction results in part from sarcoplasmic reticulum abnormalities affecting both phospholamban and sarcoplasmic reticulum Ca2+ uptake (SERCA2a). Consequently, the positive lusitropic effect of beta-adrenoceptors stimulation could be altered, and beta3-adrenoceptor over-expression may play a role, as previously demonstrated with an altered positive inotropic effect. In this study, we tested the hypothesis that the beta-adrenergic positive lusitropic effect is altered in diabetic cardiomyopathy, and that beta3-adrenoceptor over-expression is involved., Methods: beta-adrenergic responses were investigated in vivo (dobutamine-echocardiography) and in vitro (papillary muscle preparation) in healthy and diabetic rats killed 4 (4W) and 12 (12W) wk after IV streptozotocin injection. The effect of beta3-adrenoceptor pathway inhibition by S-cyanopindolol (selective beta3-adrenoceptor antagonist) or by NG-nitro-L-arginine-methyl-ester (nonselective nitric oxide synthase inhibitor) on the lusitropic response to isoproterenol (nonselective beta-adrenoceptors agonist) was studied in vitro. Western blots were performed to quantify the protein expressions of beta1- and beta3-adrenoceptors, phospholamban, and SERCA2a. Data are presented as mean percentages of baseline+/-sd., Results: Despite the increased phospholamban/SERCA2a protein ratio and documented diastolic dysfunction, the positive lusitropic effect of beta-adrenoceptors stimulation was preserved in vivo (dobutamine) and in vitro (isoproterenol) in 4W and 12W diabetic, compared with healthy, rats. The beta3-adrenoceptor was up-regulated whereas beta1-adrenoceptor was down-regulated in 4W and 12W diabetic, compared with healthy, rats. Nevertheless, S-cyanopindolol or NG-nitro-L-arginine-methyl-ester had no lusitropic effect., Conclusions: The positive lusitropic effect of beta-adrenoceptor stimulation was preserved in diabetic cardiomyopathy. beta3-adrenoceptor over-expression does not seem to affect this process.

Objective: We compared the usefulness of plasma N-terminal-pro B-type natriuretic peptide and troponin I levels for risk stratification of patients with pulmonary embolism., Methods: This was a prospective study performed in an emergency department. N-terminal-B-type natriuretic peptide assay and troponin I were performed blindly at admission in patients with pulmonary embolism confirmed by imaging tests. A complicated pulmonary embolism was defined as any of the following: death, cardiopulmonary resuscitation, requirement for mechanical ventilation, use of pressors, thrombolysis, surgical embolectomy or admission in an intensive care unit., Results: Sixty patients (mean age+/-standard deviation of 72+/-15 years) were included. Seventeen (28%) patients had adverse events: all were admitted in intensive care unit, one was treated with surgical embolectomy and one with thrombolysis, and three died. The median N-terminal-pro B-type natriuretic peptide level (95% confidence interval) was higher in the group of patients with complicated pulmonary embolism, 4086 pg/ml (505-8998) versus 352 pg/ml (179-662), respectively (P<0.05). The mean value of troponin I was similar in the complicated pulmonary embolism group, 0.09+/-0.17 microg/l versus 0.08+/-0.41 microg/l, respectively (P=0.93). The best threshold value of N-terminal-pro B-type natriuretic peptide was 1000 pg/ml, and the receiver operating characteristic curve demonstrated that N-terminal-pro B-type natriuretic peptide significantly predicted the complicated pulmonary embolism with an area under the receiver operative curve of 0.72 (0.58-0.83) (P<0.05), whereas troponin I did not [area under the receiver operative curve of 0.58 (0.42-0.71)]., Conclusion: Unlike troponin I, N-terminal-pro B-type natriuretic peptide may be an accurate marker of in-hospital complication after pulmonary embolism.

In this study, we assessed the relationship between brain estimated specific gravity (eSG) and clinical symptoms, therapeutic intensity level, and outcome in human traumatic brain injury (TBI). Brain weight, volume, and eSG of the noncontused hemispheric areas were measured from computed tomography (CT) DICOM images on the initial (5 +/- 6 h) CT of 120 patients with severe TBI. Control values were obtained from 40 healthy patients. The eSG of the noncontused hemispheric areas was significantly higher in TBI patients than in controls. eSG was higher in patients having a Marshall CT classification of 3 or 4 or a low initial Glasgow coma score. Two groups were defined according to the eSG of the noncontused hemispheric areas: less than (n = 83, 69%) or more than (n = 37, 31%) the threshold of normality (defined as 1.96 sd above normal = 1.0355 g/mL). The occurrence of mydriasis, use of osmotherapy at the scene of the accident, and therapeutic intensity level were higher in the increased eSG group. The outcome at intensive care unit discharge was worse in patients with an increased eSG although the difference was no longer significant at 1 yr. eSG determination by CT analysis might be relevant in the early management of TBI.

Objective: To prospectively evaluate the impact of subthalamic nucleus (STN) stimulation on social adjustment in patients with Parkinson disease (PD)., Methods: Before and 18 to 24 months after bilateral STN stimulation, the authors assessed 29 patients with PD for motor disability, cognition (Mattis dementia rating scale, frontal score), psychiatric morbidity (Mini-5.0.0, MADRS, BAS), quality of life (PDQ-39), social adjustment (Social Adjustment Scale), and psychological status using unstructured in-depth interviews., Results: Despite marked improvement in parkinsonian motor disability, the absence of significant changes in cognitive status, and improvement of activities of daily living and quality of life by the end of the study, social adjustment did not improve. Several kinds of problems with social adjustment were observed, affecting the patients' perception of themselves and their body, marital situation, and professional life. Marital conflicts occurred in 17/24 couples. Only 9 out of 16 patients who had a professional activity before the operation went back to work after surgery., Conclusion: After STN stimulation, patients experienced difficulties in their relations with themselves, their spouses, their families, and their socio-professional environment. The authors suggest a multidisciplinary psychosocial preparation and follow-up to help patients and their entourage cope with the sudden changes in their existence following successful neurosurgery.

Proliferation of vascular smooth muscle cells (VSMC) is a primary cause of vascular disorders and is associated with major alterations in Ca2+ handling supported by loss of the sarco/endoplasmic reticulum calcium ATPase, SERCA2a. To determine the importance of SERCA2a in neointima formation, we have prevented loss of its expression by adenoviral gene transfer in a model of balloon injury of the rat carotid artery. Two weeks after injury, the intima/media ratio was significantly lower in SERCA2a-infected than in injured noninfected or injured beta-galactosidase-infected carotids (0.29+/-0.04 versus 0.89+/-0.19 and 0.72+/-0.14, respectively; P<0.05), and was comparable to that observed in control carotids (0.21+/-0.03). The pathways leading to proliferation were analyzed in serum-stimulated VSMC. Forced expression of SERCA2a arrested cell cycle at the G1 phase and prevented apoptosis. SERCA2a inhibits proliferation through inactivation of calcineurin (PP2B) and its target transcription factor NFAT (nuclear factor of activated T-cells) resulting in lowering of cyclin D1 and pRb levels. By using NFAT-competing peptide VIVIT, we showed that NFAT activity is strongly required to promote VSMC proliferation. In conclusion, we provide the first evidence that increasing SERCA2a activity inhibits VSMC proliferation and balloon injury-induced neointima formation.

Objectives: We tested the hypothesis that colloid-induced hemodilution can induce hypocalcemia in the early phase of severe trauma resuscitation and tried to assess other potential causative factors of that hypocalcemia., Design: Prospective cohort., Setting: Level I academic trauma center., Patients: Consecutive severe trauma patients (n = 212, mean Injury Severity Score 34) resuscitated in the prehospital phase without any blood transfusion., Interventions: At admission, ionized calcium (corrected to an arterial pH = 7.40) was measured., Measurements and Main Results: Hypocalcemia was defined as a value <1.15 mmol/L and severe hypocalcemia as a value <0.9 mmol/L. A normal ionized calcium concentration was observed in 56 (26%) patients, a mild ionized hypocalcemia (1.05 +/- 0.06 mmol/L) in 135 (64%) patients, and a severe ionized hypocalcemia (0.77 +/- 0.10 mmol/L) in 21 (10%) patients. There were significant correlations between ionized calcium concentration with the amount of infused colloid (R = .658, p < .001) and arterial pH (R = .760, p < 0.001) but not with the amount of infused crystalloid (R = .007, not significant). Despite taking into account hemodilution, arterial pH, binding of calcium to lactates, and colloids, some patients had marked differences (>15%) between calculated and observed ionized calcium, and these patients had more severe trauma and more frequently had acidosis and/or prehospital cardiac arrest. Using the TRISS methodology, survival was not significantly different from that expected in this trauma population., Conclusion: Hypocalcemia frequently occurs on arrival at the hospital in severe trauma patients, and colloid-induced hemodilution and severe shock and/or ischemia-reperfusion appear to be important causative factors.

In heart failure, the renin-angiotensin-aldosterone and the sympathetic systems are overactivated and lead to formation of cardiac fibrosis, which contributes to the aggravation of cardiac function. The aim of the present study was to evaluate the role of aldosterone and angiotensin II on formation of left ventricular fibrosis induced by chronic beta-adrenergic stimulation with isoproterenol (iso) in the rat heart failure model induced by myocardial infarction (MI). Rats were submitted to chronic treatment with either the aldosterone receptor antagonist potassium canrenoate (pc, 20 mg/kg/d) or both aldosterone and angiotensin II receptor antagonists with addition of losartan (los, 10 mg/kg/d). Isoproterenol induced cardiac hypertrophy, which was completely inhibited by potassium canrenoate alone in atria and by potassium canrenoate plus losartan in infarcted ventricles. Isoproterenol also induced cardiac fibrosis, which was completely inhibited in infarcted rats by potassium canrenoate alone in right and left ventricles. In left ventricle, extent of fibrosis was, for control MI, 1.30 +/- 0.34%; MI + iso, 2.50 +/- 0.27%; MI + iso + pc, 0.82 +/- 0.11%; and MI + iso + pc + los, 1.47 +/- 0.31%. The deleterious effects of beta-adrenoceptor stimulation on cardiac fibrosis seem therefore to involve aldosterone action. These results suggest a transregulation between the adrenergic and mineralocorticoid pathways, most likely at the nucleus level, with activation of profibrotic genes.

Unlabelled: Major surgery evokes a stress response that can produce deleterious consequences, especially in a population at high risk for those complications. We tested the hypothesis that decreasing or eliminating one of the sources of stress by providing intense analgesia in the immediate postoperative period via application of neuraxial opioids would decrease major nonsurgical complications. Two-hundred-seventeen patients scheduled to undergo abdominal aortic surgery were randomly allocated to receive either general anesthesia alone (control) or general anesthesia combined with intrathecal opioid (1 micro g/kg sufentanil with 8 micro g/kg preservative-free morphine injected at the L4-5 interspace). Postoperative care was identical in the two groups, including patient-controlled analgesia. Each patient provided an assessment of postoperative pain using a visual analog scale. Postopera-tive complications were recorded according to criteria established a priori. The administration of intrathecal opioid provided more intense analgesia than patient-controlled analgesia during the first 24 h postoperatively (P < 0.05). There was no difference between groups for the incidence of combined major cardiovascular, respiratory, and renal complications (P > 0.05) or mortality (P > 0.05). The incidence of myocardial damage or infarction, as defined by abnormal plasma concentration of troponin I, did not differ between the two groups (P > 0.05). In patients undergoing major abdominal vascular surgery, decrease of one contributor to postoperative stress, by provision of intense analgesia for the intraoperative and initial postoperative period, via application of neuraxial opioid, does not alter the combined major cardiovascular, respiratory, and renal complication rate., Implications: Provision of intense analgesia for the initial postoperative period after major abdominal vascular surgery, via the administration of neuraxial opioid, does not alter the combined incidence of major cardiovascular, respiratory, and renal complications.

Background: Upper limb trauma occurs frequently in elderly patients for whom peripheral nerve blocks are often preferred for anesthesia. The characteristics of such regional blocks have, however, never been described in an elderly population. Therefore, the authors assessed prospectively the onset and duration of upper extremity peripheral nerve block (the mid-humeral block) in elderly and young patients undergoing emergency upper extremity surgery., Methods: Consecutive patients aged > 70 yr or < 70 yr received a mid-humeral block with a small volume of ropivacaine, 0.75%. Five milliliters was injected onto each of the musculocutaneous, radial, ulnar, and median nerves. Time to complete sensory and motor block and durations of complete sensory and motor block were assessed. Results are shown as median and its 95% confidence interval., Results: Median ages were 77 yr (95% CI, 72-81 yr) and 39 yr (95% CI, 27-46 yr) in the two groups. Both groups had similar times to complete sensory blockade. The elderly group had longer durations of complete sensory (390 min [range, 280-435 min] vs.150 min [range, 105-160 min]; P< 0.05) and motor (357 min [range, 270-475 min] vs. 150 min [range, 90-210 min]; P< 0.05) blockade. Duration of complete sensory block was significantly correlated with age (rho = 0.56; P< 0.05)., Conclusions: Age is a major determinant of duration of complete motor and sensory blockade with peripheral nerve block, perhaps reflecting increased sensitivity to conduction failure from local anesthetic agents in peripheral nerves in the elderly population.

The effect on the nociceptive tail-flick (TF) reflex of cardiopulmonary chemoreceptor and arterial baroreceptor activation, producing Bezold-Jarisch like- and baro-reflex responses, respectively, was analysed in lightly halothane-anaesthetized rats. Intra-cardiac administration of phenylbiguanide (5-100 microg/kg, into the right atrium) or veratrine (30-150 microg/kg, into the left ventricle), which both elicited the characteristic Bezold-Jarisch-like cardiovascular reflex responses (hypotension and bradycardia), produced a dose-dependent increase in TF latency. A similar inhibitory influence on the TF reflex was noted upon baroreflex activation by acute administration of phenylephrine (15-50 microg/kg i.v.) or aortic depressor nerve stimulation (100-400 microA). As expected from the involvement of local excitatory amino acid receptors in both vagally mediated cardiovascular reflex responses and inhibition of the TF reflex, microinjections of kynurenic acid (3 nmol/0.1 microl), an N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonist, into the nucleus tractus solitarius, prevented the cardiovascular responses as well as the concomitant increase in TF latency produced by cardiopulmonary chemoreceptor and baroreceptor stimulations. The present data show that induction of the cardiopulmonary chemoreceptor and baroreceptor reflexes produces an antinociceptive effect which can be assessed using the TF test, and that glutamate ionotropic receptors within the nucleus tractus solitarius mediate this effect., (Copyright 2002 International Association for the Study of Pain)

Unlabelled: We investigated the effects of sevoflurane (0.7 to 3.6 vol%) on inotropy and lusitropy in left ventricular papillary muscles of healthy hamsters and genetically induced cardiomyopathic (strain BIO 14.6) hamsters in vitro (29 degrees C, pH 7.40, Ca(2+) 2.5 mM, stimulation frequency three per minute) under low (isotony) and high (isometry) loads. Sevoflurane induced a moderate positive inotropic effect in healthy hamsters (maximum unloaded shortening velocity and isometric active force at 3.6 vol%: 115% +/- 12% and 128% +/- 21% of baseline values, respectively; P < 0.01) and in cardiomyopathic hamsters (maximum unloaded shortening velocity and isometric active force at 3.6 vol%: 115% +/- 20% and 124% +/- 31% of baseline values, respectively; P < 0.05). This positive inotropic effect did not differ between healthy and cardiomyopathic hamsters, even when sevoflurane concentrations were corrected for minimum alveolar anesthetic concentration values in each strain, and was unchanged after alpha- and beta-adrenoceptor blockade. After calcium-channel blockade, this positive inotropic effect was abolished in healthy hamsters but enhanced in cardiomyopathic hamsters. In both strains, sevoflurane induced a moderate negative lusitropic effect under low and high loads., Implications: A paradoxical moderate positive inotropic effect of sevoflurane was observed in hamster ventricular muscle. This effect was likely related to calcium channel interaction, because after calcium-channel blockade, it was abolished in healthy hamsters and enhanced in cardiomyopathic hamsters.

Background: Although the existence of a motor defect in discogenic sciatica is a sign of severity, the literature does not provide evidence for an immediate requirement for surgery., Objective: To assess the course of sciatica with discogenic paresis and to determine possible prognostic factors for recovery or improvement., Study Design: This open prospective multicenter study included patients with discogenic sciatica with paresis that had been developing for less than 1 month and was rated < or =3 on a 5-grade scale. Pain, the strength of 11 muscles, return to work, and analgesic intake were assessed at 1, 3, and 6 months. Recovery and improvement were defined by pain not exceeding 20 mm or < or =50% of the initial pain score and a score of either 5 (recovery) or 4 (improvement) for the weakest muscle at inclusion., Results: Sixty-seven patients were enrolled; 39 (58%) patients were treated surgically and 28 (42%) medically. Surgically treated patients differed from medically treated patients by a higher rate of extruded herniation, a higher number of paretic muscles (6.3 vs. 5; P = 0.051), and a longer course of sciatica (31.4 vs. 17.3 days; P = 0.034). At 6 months, 7 (10.4%) patients were lost to follow-up; 32 (53.3%) had improved, including 18 (30%) recovered, 33 (85%) back to work and having a professional activity, and 22 (39%) still taking analgesics. The only significant difference between recovered and not recovered patients was mean age at inclusion (43 vs. 51 years, P = 0.034). There were no significant differences between improved and not improved patients. Moreover, the outcome was not different in the two treatment groups: there were 17 (53%) improvements in surgically treated patients, including 8 (25%) recoveries, and 14 (56%) improvements in medically treated patients, including 8 (40%) recoveries., Conclusion: This pilot study showed no difference between surgical or medical management for recovery or improvement in patients with discogenic paresis. These results need confirmation by a randomized study.

The possible participation of glutamate and NO/cGMP in the pressor response to 5-HT3 receptor activation in the nucleus tractus solitarii (NTS) was investigated using selective antagonists in urethane-anaesthetized rats. Intra-NTS administration of NMDA and non-NMDA receptor antagonists, but not metabotropic glutamate receptor antagonists, markedly reduced (70%) the increase in blood pressure caused by local application of the potent 5-HT3 receptor agonist, 1-(m-chlorophenyl)-biguanide. The 5-HT3 receptor-mediated pressor response was also significantly attenuated by the local blockade of nitric oxide synthase and soluble guanylyl cyclase. These data suggest that ionotropic glutamate receptors and the associated NO/cGMP transduction mechanism contribute downstream to the pressor effect elicited by 5-HT3 receptor stimulation in the NTS.

A task requiring dynamic postural stabilisation during locomotion in a conflicting visual vestibular environment (rotating beam), has been devised to assess anxiety-related balance impairments and postural changes in mice. The model, already validated with acutely administered diazepam, was used to assess the action of two chronically administered selective serotonin reuptake inhibitors (SSRIs), fluoxetine and paroxetine. On three behavioural measures (imbalance, elevation of trunk and angle of tail), observed in anxious BALB/cByJ mice, both compounds had the same diazepam-like effects: reduction in number of imbalances, higher elevation of trunk and increase in tail angle. These data suggest, for the first time, that SSRIs should be useful in the treatment of anxiety-induced balance impairments.

Unlabelled: Hydroxyethyl starch (HES) solutions are effective plasma volume expanders. Impairment of coagulation occurs with large HES volumes infused perioperatively. Therefore, a lower substituted novel HES (Voluven; Fresenius Kabi, Bad Homburg, Germany) was developed to minimize hemostatic interactions, and was compared with HAES-steril (Fresenius Kabi) (pentastarch) regarding safety and efficacy. We performed a prospective, randomized, double-blinded study in 100 major orthopedic surgery patients. Because the 95% confidence interval (-330 mL; +284 mL) for the treatment contrast Voluven-HAES-steril was entirely included in the predefined equivalence range (+/- 500 mL), comparable efficacy was established. Voluven interfered significantly less than HAES-steril with coagulation factor VIII levels and partial thromboplastin time postoperatively. Total amounts of red blood cells transfused were comparable between the Voluven and HAES-steril groups, but a significantly reduced need for homologous red blood cells was observed in the Voluven group. We conclude that in large-blood-loss surgery, Voluven has a comparable efficacy with HAES-steril and may reduce coagulation impairment, possibly leading to a smaller number of allogeneic blood transfusions., Implications: Hydroxyethyl starches are common plasma volume expanders, but may interfere with coagulation at large doses. We tested a novel hydroxyethyl starch specification (Voluven; Fresenius Kabi, Bad Homburg, Germany) which was developed to reduce hemostatic interactions while preserving its efficacy in restoring plasma volume in comparison to HAES-steril (pentastarch; Fresenius Kabi) in major orthopedic surgery.

Unlabelled: We studied the effects of protamine (10-300 microg. mL(-1)) as well as its interaction with heparin in rat left ventricular papillary muscles in vitro at calcium concentrations of 0.5 and 1 mM under low (isotony) and high (isometry) loads. Protamine induced a negative inotropic effect that was less pronounced at calcium 0.5 mM (active force at protamine 300 microg/mL, 84 +/- 20 vs 57 +/- 15% of baseline, P: < 0.05); whereas at calcium 1 mM there was a marked contracture of the muscle. For the smallest concentrations of protamine and at calcium 0.5 mM, we observed a moderate positive inotropic effect that was suppressed by nifedipine. Protamine induced a negative lusitropic effect under low load and decreased postrest potentiation, suggesting an impairment in the functions of the sarcoplasmic reticulum. Heparin was able to inhibit and reverse the negative inotropic effect of protamine. The negative inotropic effect of protamine is enhanced by an increase in extracellular calcium concentration. This negative inotropic effect is probably related to calcium overload and impairment in sarcoplasmic reticulum functions, and heparin can block these effects., Implications: The negative inotropic effect of protamine is enhanced by an increase in extracellular calcium concentration. This negative inotropic effect is probably related to calcium overload and impairment in sarcoplasmic reticulum functions, and heparin can block these effects.

Despite the use of highly sensitive molecular tools, such as polymerase chain reaction, for the detection of Mycobacterium tuberculosis, ocular tuberculosis remains a subject of controversy. The diagnosis is often presumptive in the absence of ocular biopsies. Choroiditis is the most common ocular manifestation in patients with pulmonary and systemic tuberculosis. Indocyanine green angiography seems to be an interesting method to determine choroidal involvement. PCR technology is proposed to evaluate the presence of the tubercule bacillus DNA in ocular fluids and tissues when conventional microbiologic methods fail to confirm a bacterial etiology. Most of the presumed cases of ocular tuberculosis should be treated with associations of antituberculous drug, especially when a systemic steroid regimen is required.

Electrophysiological and biochemical approaches were used to assess possible changes in central 5-HT neurotransmission in mice that had been subjected to chronic ultramild stress for 8 weeks. This treatment produced a significant decrease in the potency of the 5-HT1A agonist ipsapirone to inhibit the electrical activity of serotoninergic neurons in the dorsal raphe nucleus, without modifying 5-HT1A receptor binding in various brain areas. These data demonstrate that chronic ultramild stress triggers a long term and durable functional desensitization of somatodendritic 5-HT1A autoreceptors in mice.

Recent developments in microsporidiosis research include the increased utilization of molecular techniques for the investigation of clinical specimens as well as for epidemiological and phylogenetic studies. Special attention is given to studies reporting severe disseminated microsporidioses involving most organs in AIDS patients, and the increased number of HIV-seronegative and immunocompetent individuals with microsporidiosis. The potential efficacy of fumagillin (Sanofi Recherche, Gentilly, France) in infections caused by Enterocytozoon bieneusi, and the remission of intestinal microsporidiosis in HIV infected patients with antiretroviral therapy are also highlighted.