The cerebrospinal fluid CD4/CD8 ratio and interleukin-6 and -10 levels in neurosarcoidosis: a multicenter, pragmatic, comparative study.

BACKGROUND AND PURPOSE: Neurosarcoidosis is a rare inflammatory disorder of unknown cause. The aim of this study was to evaluate the value of T/B lymphocyte population counts and the concentrations of the cytokines interleukin (IL) 6 and IL-10 in the cerebrospinal fluid (CSF) of neurosarcoidosis patients. METHODS: A retrospective study CSF biomarkers was conducted in patients with neurosarcoidosis who underwent CSF analysis between 2012 and 2017 as well as various control populations. RESULTS: Forty-three patients with neurosarcoidosis, 14 with multiple sclerosis (MS) and 48 with other inflammatory disorders were analyzed. The CSF IL-6 levels were higher in sarcoidosis patients than in MS patients (median 8 vs. 3 pg/ml, P = 0.006). The CSF CD4/CD8 ratio was higher in sarcoidosis patients than in MS patients and in patients with other inflammatory disorders (median 3.18 vs. 2.36 and 2.10, respectively, P = 0.008). The CSF IL-6 level was higher in patients with active neurosarcoidosis than in non-active neurosarcoidosis patients (median 13 vs. 3 pg/ml, P = 0.0005). In patients with neurosarcoidosis, a CSF IL-6 concentration >50 pg/ml was associated with a higher risk of relapse or progression-free survival (hazard ratio 3.60; 95% confidence interval 1.78-23.14). A refractory neurosarcoidosis patient was treated with an anti-IL-6 monoclonal antibody that produced a complete neurological response. CONCLUSIONS: The CSF CD4/CD8 ratio and IL-6 concentration are increased in neurosarcoidosis compared to MS and other inflammatory disorders. A CSF IL-6 concentration >50 pg/ml is associated with relapse or progression of neurosarcoidosis. IL-10 levels may be elevated in neurosarcoidosis.

[Induction of labor in women with previous caesarean delivery with balloon catheter: Is it worth it?] / Déclenchement par ballonnet en cas d'utérus cicatriciel et col défavorable : la tentative en vaut-elle la chandelle ?

OBJECTIF: Balloon catheters for labor induction at term after previous cesarean section is an alternative option to iterative cesarean section. The aim of this study was to analyze the maternal and neonatal outcomes of the trial of labor after cesarean (TOLAC) in women with unfavorable cervix and balloon catheter induction, 2 years after introduction of this process. METHODS: Unicentric observational study of women with term cephalic singleton, unfavorable cervix (simplified Bishop score<5) after TOLAC using double-balloon catheter. Were analyzed the mode of delivery and severe maternal (uterine rupture, post-partum hemorrhage, severe perineal tears) and neonatal (neonatal unit admission, APGAR<7 at 5minutes, pH<7.1) outcomes. Predictive factors for failed TOLAC were analyzed by using multivariate logistic regression. RESULTS: Between 2016-2017, 455 (75.4%) women had TOLAC, whose 59 (13%) women with balloon catheter. The overall vaginal delivery (VD) was 73.9%. After Balloon catheter, the VD rate was 50.8%, versus 79.1% after spontaneous labor, and 68.2% after alone oxytocin/artificial membrane rupture induction (P<0.05). Previous VD (aOR 0.176 CI-95% [0.048-0.651]) and prior sweeping membrane (aOR 0.161 CI-95% [0.034-0.761]) was protective for cesarean section after TOLAC. Severe maternal and neonatal morbidities were observed in 10 (17%) and 8 (13.6%) cases, respectively. CONCLUSION: Double-Balloon catheter is an option for unfavorable cervix and term induction after previous cesarean section. However, the TOLAC in women whose unfavorable cervix is not without maternal and neonatal risk, especially due to its failure.

Induction du travail après une version par manœuvres externes pour siège réussie : un sur-risque de césarienne?

OBJECTIVE: To assess the effect of successful external cephalic version (ECV) on the risk of caesarean section (CS) during attempted vaginal delivery after induction of labour. METHODS: A unicentric matched retrospective observational case-control cohort study with exposed and unexposed groups. All pregnant women who had an induction of labour after a successful external cephalic version (sECV) between 1998 and 2016 were included. A total of 88 cases were compared with 176 controls (spontaneous cephalic presentation), matching for the year of delivery, parity, gestational age, indication and mode of induction of labour. The main outcome measure was the risk of caesarean. A univariate analysis and a multivariate logistic regression analysis were performed. RESULTS: The caesarean section rate was significantly higher after sECV (22% versus 13.1%; p = 0.039) especially for postdate pregnancy (55% versus 8.2%; p <0.05). For the univariate analysis, age (31 years and 4 months versus 24 years and 6 months; p <0.01) and maximal speed of oxytocin infusion (72 ml/h versus 68 ml/h; p = 0.04) were higher in the case group. The multivariate analysis showed that the risk of caesarean section was significantly increased after an sECV (aOR 1.946; 95% CI 1.017-3.772) and after the use of prostaglandins for ripening (aOR 1.951; 95% CI 1.097-3.468), and decreased for multipara (aOR 0.208; 95% CI 0.114-0.377). CONCLUSION: Women who have a successful ECV are at increased risk of caesarean section after subsequent induction of labour.

Prognostic significance of morphotypes in canine lymphomas: A systematic review of literature.

Correlation between morphotypes and prognosis of canine lymphomas presented discordant results in literature, leading to some dilemma for application in clinical practice. The aim of this study was to present a systematic review of literature on the prognostic significance of morphotypes in canine lymphomas. Standardized Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria were applied. Retrospective and prospective studies were included. Level of evidence was determined for each study. Some acceptable evidence suggested a significant prognostic impact of morphotypes in canine lymphomas. However, the evidence is not sufficiently robust to determine with precision the most appropriate classification scheme. Updated Kiel and World Health Organization (WHO) classifications seem to remain the most appropriate classification systems with regards to the number of available studies and their levels of evidence. Limitations included lack of randomized control trial, and relative lack of prospective studies available. Current recommended classification of canine lymphoma is the systematic determination of morphotype in each new case. The Updated Kiel and the WHO classifications adapted to dog both remain the schemes with the most valuable interest. Prospective studies in larger population, and international consensus to define precisely each morphotype, are warranted, with application of standardized staging method and treatment.

Successful external cephalic version is an independent factor for caesarean section during trial of labor - a matched controlled study.

INTRODUCTION: To assess the mode of delivery and Caesarean Section (CS) rate after successful External Cephalic Version (ECV). MATERIAL AND METHODS: A matched case-control study. Data were gathered from a tertiary care university hospital register from 1996-2015. All pregnant women who delivered after successful External Cephalic Version (ECV). Among 643 women who attempted ECV, we identified 198 with successful ECVs and compared them with the next two women who presented for labor management with spontaneous cephalic presentation, matching for delivery date, maternal age, parity, body mass index, and delivery history using univariate and stepwise logistic regression. The main outcome measure was the risk of caesarean. RESULTS: The caesarean section rate was higher after successful ECV (respectively 20.7% versus 7.07%, P<0.05). Caesarean section for abnormal fetal head position (forehead, bregma, face) was higher after successful ECV (28.6% versus 0%). After adjustment for matching and confounding variables (variation of the caesarean section rate over the study period, gestational maternal complications, antepartum fetal complications, term of delivery, induction of labor, oxytocin use for dystocia, neonatal cephalic perimeter), a successful ECV increased the risk of caesarean section (adjusted OR 3.17, 95% CI 1.86-5.46). By stratifying on week, a trend for increased risk for caesarean section was observed at the week after ECV and at post term (28.6% before 37+6, 14.8% at 38+0-38+6, 13.8% at 39+0-39+6, 14.2% at 40+0-40+6 and 33.3% beyond 41+0 weeks' gestation, P=0.06). CONCLUSIONS: Women who have a successful ECV are at increased risk of caesarean section compared with women who experience spontaneous cephalic presentation.

Personalized thromboprophylaxis using a risk score for the management of pregnancies with high risk of thrombosis: a prospective clinical study.

Essentials Pregnancy is a risk factor for thrombosis. Management of thrombosis risk in pregnancy remains a challenge. Prophylaxis needs to be personalized. Our score may be a helpful tool for the management of pregnancies at high risk of thrombosis. SUMMARY: Background Patients with thrombophilia and/or a history of venous thromboembolism (VTE) are at risk of thrombosis during pregnancy. A risk score for pregnancies with an increased risk of VTE was previously described by our group (Lyon VTE score). Objectives The aim of this prospective study was to assess the efficacy and safety of our score-based prophylaxis strategy in 542 pregnancies managed between 2005 and 2015 in Lyon University Hospitals. Patients/Methods Of 445 patients included in the study, 36 had several pregnancies during the study period. Among these 445 patients, 279 had a personal history of VTE (62.7%), 299 patients (67.2%) had a thrombophilia marker, and 131 (29.4%) thrombophilic women had a personal history of VTE. During pregnancy, patients were assigned to one of three prophylaxis strategies according to the risk scoring system. Results In the antepartum period, low molecular weight heparin (LMWH) prophylaxis was prescribed to 64.5% of patients at high risk of VTE. Among them, 34.4% were treated in the third trimester only, and 30.1% were treated throughout pregnancy. During the postpartum period, all patients received LMWH for at least 6 weeks. Two antepartum-related VTEs (0.37%; one with a score of < 3 and the other with a score of > 6) and four postpartum-related VTEs (0.73%; three with scores of 3-5 and one with a score of > 6) occurred. No case of pulmonary embolism was observed during the study period. The rate of bleeding was 0.37%. No serious bleeding requiring transfusions or surgery occurred during the study period. Conclusion The use of a risk score may provide a rational decision process to implement safe and effective antepartum thromboprophylaxis in pregnant women at high risk of VTE.

[Cord accident after external cephalic version: Reality or mostly myth?] / Accident funiculaire après version par manœuvre externe : mythe ou réalité ?

OBJECTIVES: To study the occurrence of cords accident (nuchal cords, prolapse, and braces) after external cephalic version according to its failure or success. METHODS: Retrospective study between 1998-2015 comparing in the cord accident diagnosed at delivery (by midwife or doctors according to mode of delivery): Patients with attempt ECV: Group 1 cephalic presentation after successful ECV with trial of labor, and Group 2 failed ECV followed by elective cesarean or trial of labor. Patients with no attempt ECV Group 3 spontaneous cephalic presentation matching for delivery date, maternal age, parity, body mass index, and delivery history with group 1, Group 4 Breech presentation without attempt ECV with trial of labor. RESULTS: A total of 776 women with breech presentation were included (198 in group 1, 446 in group 2, 396 in group 3 and 118 in group 4). The prevalence of cord accident did not differ according to ECV attempt (17.08 % versus 18.9 %), to cephalic presentation (group 1: 24.7 % versus group 3: 25 %) and to breech presentation (group 2: 16.9 % versus group 4: 17.2 %). The trial of labor after failed ECV did not increase the risk of cord accident when compared with elective cesarean (17.4 % versus 16 %). A prolapse cord was only observed after trial of labor, i.e. in groups 1, 2 and 4 without difference (respectively 1, 0.8 and 1.7 %). In each group, the rate of cesarean was not different according to the presence of nuchal cord. CONCLUSION: Success or failed External cephalic version is not associated with an increased risk of cord accident.

Increasing screening frequency in men who have sex with men: impact of guidance on risk profiling on workload and earlier diagnosis of sexually transmitted infection and HIV.

Increasing screening frequency in men who have sex with men (MSM) engaging in high-risk behaviours can reduce prevalence of sexually transmitted infections (STIs). This evaluation investigated the impact of applying stricter screening guidelines for MSM on service workload and earlier STI diagnoses. A validated risk assessment tool (RAT) was distributed to MSM attending a level 3 sexual health service over three months. Australian screening guidelines were applied to the data to identify MSM requiring more frequent screening and data projected to the larger MSM population. The RAT identified a 2-5-fold increase in the number of STI and HIV screenings required based on six- and three-monthly screening intervals, respectively, in the MSM cohort. When screening intervals are reduced from three-monthly to six-monthly there is a potential loss of 66.7% of earlier HIV diagnoses. The use of RATs will increase workload in sexual health services, but potentially diagnose a large proportion of disease earlier.

Protection against the toxic effects of Loxosceles intermedia spider venom elicited by mimotope peptides.

The venom of Loxosceles intermedia (Li) spiders is responsible for cutaneous lesions and other clinical manifestations. We previously reported that the monoclonal antibody LimAb7 can neutralize the dermonecrotic activity of crude Li venom. In this study, we observed that this antibody recognizes several proteins from the venom dermonecrotic fraction (DNF), including LiD1. Identifying the epitope of such a neutralizing antibody could help designing immunogens for producing therapeutic sera or vaccination approaches. To this aim, two sets of 25- and 15-mer overlapping peptides that cover the complete amino acid sequence of LiD1 were synthesized using the SPOT technique. None of them was recognized by LimAb7, suggesting that the epitope is discontinuous. Then, the screening of four peptide phage-display libraries yielded four possible epitope mimics that, however, did not show any obvious similarity with the LiD1 sequence. These mimotopes, together with a 3D model of LiD1, were used to predict with the MIMOP bioinformatic tool the putative epitope region (residues C197, Y224, W225, T226, D228, K229, R230, T232 and Y248 of LiD1) recognized by LimAb7. This analysis and the results of alanine-scanning experiments highlighted a few residues (such as W225 and D228) that are found in the active site of different SMases D and that may be important for LiD1 enzymatic activity. Finally, the only mimotope NCNKNDHLFACW that interacts with LimAb7 by SPOT and its analog NSNKNDHLFASW were used as immunogens in rabbits. The resulting antibodies could neutralize some of the biological effects induced by crude Li venom, demonstrating a mimotope-induced protection against L. intermedia venom.

The accuracy of acquisition of an imageless computer-assisted system and its implication for knee arthroplasty.

The majority of the current computer-assisted systems (CAS) for knee prosthetic surgery require the acquisition of points using a tracker detected by an infrared camera. Two types of measurements are then essential: angles and distances. The goal of this study was to evaluate the accuracy of the data obtained during computer-assisted surgery using an in vitro protocol. Two models were developed to locate precisely both points (120 acquisitions) and distance measurements (144 acquisitions) and angles (170 acquisitions) with an image-free CAS using an infrared optical camera. For validation, a precise coordinate 3D measurement device was used to assess the accuracy of CAS acquisitions. The points, distances and angles had a mean error respectively of 0.638 mm (0.244 mm to 0.931 mm), 0.355 mm (0.001 mm to 1.338 mm) and 0.39° (0.06° to 0.69°). For all these acquisitions, the mean error was statistically less than 1mm or 1° (p<0.001). By using a 3D measurement system, it was possible to determine the accuracy of the data obtained with the navigation system. The precision assessed at less than 1mm or 1° corresponds with the accuracy needed in knee arthroplasty and with the use of CAS as a measurement tool. Variability in computer-assisted navigation may be more likely related to other aspects of the procedure such as bony landmark acquisition, tolerance of saw blades and cutting jigs than the accuracy of the imageless CAS itself.

A morphological study of 608 cases of canine malignant lymphoma in France with a focus on comparative similarities between canine and human lymphoma morphology.

This study reports cytomorphological, histomorphological, and immunological characterization of 608 biopsy cases of canine malignant lymphoma, with epidemiological and clinical data, collected from 7 French veterinary pathology laboratories. It compares morphological characteristics of malignant lymphoma in canines, per the updated Kiel classification system, with those reported in humans, per the World Health Organization (WHO) classification system. Of tumors described, 24.5% and 75.5% were classified as low- and high-grade malignant lymphomas, respectively. Presenting clinical signs included generalized or localized lymphadenopathy (82.4%) and extranodal diseases (17.6%) involving the skin (12.34%) and other sites (5.26%). Immunohistochemistry confirmed 63.8% B-cell (CD3-, CD79a+), 35.4% T-cell (CD3+, CD79a-), and 0.8% null-cell (CD3-, CD79a-) lymphomas. Most B-cell cases (38.49%) were of high-grade centroblastic polymorphic subtype; most T-cell cases (8.55%), high-grade pleomorphic mixed and large T-cell lymphoma subtypes. Some B-cell tumors showed morphologic characteristics consistent with follicular lymphomas and marginal zone lymphomas per the Revised European American Classification of Lymphoid Neoplasms and WHO canine classification systems and the WHO human classification system. Unusual high-grade B-cell subtypes included an atypical high-grade small B-cell lymphoma (0.66%), Burkitt-type B-cell lymphoma (1.64%), plasmacytoid lymphoma (0.99%), and mediastinal anaplastic large B-cell lymphoma (0.16%). Unusual T-cell subtypes included a previously undescribed high-grade canine immunoblastic T-cell type (1.15%), a rare low-grade prolymphocytic T-cell lymphoma (0.16%), and a recently described high-grade canine T-cell entity--aggressive granulocytic large-cell lymphoma (0.16%). Marginal zone lymphomas were common (10.86%); follicular lymphomas were rare (0.49%). Canine primary cutaneous malignant lymphoma subtypes were present (11.84%). There was no significant difference between B- and T-cell malignant lymphoma in regard to canine age and sex. A significant overrepresentation of Boxers (24.19%) was found for T-cell lymphomas.

Genetic and environmental risk indicators in canine non-Hodgkin's lymphomas: breed associations and geographic distribution of 608 cases diagnosed throughout France over 1 year.

BACKGROUND: The etiology of non-Hodgkin's lymphomas (NHL) is multifactorial. Environmental and genetic factors are frequently incriminated both in humans and dogs. OBJECTIVES: Our purpose was to study the geographic distribution of canine NHL (CNHL) in France and to evaluate genetic and environmental influences. ANIMALS: Six hundred and eight cases of CNHL, diagnosed throughout France over 1 year, were collected from 7 Veterinary Histopathologic Laboratories. METHODS: Retrospective study. Breeds affected by lymphomas were compared with the national population and associations between breed and immunophenotype were studied. The distribution of CNHL and canine T-cell NHL per 100,000 dogs per department was compared with the distribution of waste incinerators, polluted sites, and radioactive waste. RESULTS: The breeds significantly overrepresented among lymphoma cases were Boxer, Setter, and Cocker Spaniel (P < .001). There was a significant association between Boxer and T-cell NHL (P < .001), and between German Shepherd and Rottweiler and B-cell NHL (P < .01). The geographic distribution of CNHL and canine T-cell NHL indicated significant heterogeneity. Significant association between distributions of CNHL and waste incinerators (rho= 0.25, P < .05), polluted sites (rho= 0.36, P < .001), and radioactive waste (rho= 0.51, P < .001) was found. CONCLUSIONS AND CLINICAL IMPORTANCE: Influence of genetics in the development of CNHL was supported by the existence of an association between breed and immunophenotype. Waste incinerators, polluted sites, and radioactive waste could just be considered as risk indicators of CNHL, but not as risk factors. Case-control studies around critical sites are necessary to confirm the implication of those environmental factors in the development of CNHL.

Molecular cloning of a new member of the p53 family from the Pacific oyster Crassostrea gigas and seasonal pattern of its transcriptional expression level.

Like other sessile filter-feeding molluscs, oysters may be exposed in the natural environment to a variety of contaminants. Long-term exposure to pollutants may be one factor affecting prevalence of cancerous-like disorders, such as neoplasia. Environmentally induced alterations in p53 protein expression, in relation to leukemia, have been reported in various mollusc species inhabiting polluted water, suggesting that p53 proteins can also be used as a marker for environmental research. This work reports the cloning and sequencing of a p53-like cDNA in the mollusc bivalve Crassostreagigas. The deduced amino acid sequences of p53 shared a high degree of homology with the homologues from other mollusc species, including typical eukaryotic p53 signature sequences. We examined the p53 transcription expression pattern during the annual cycle in oyster gills and whole soft tissues in four locations along the French coasts. Real-time PCR analysis suggested that strong variations at p53 mRNA level are probably synchronized with the seasonal cycle at the four locations investigated.

Shell repair process in the green ormer Haliotis tuberculata: a histological and microstructural study.

In the present paper, juvenile and adult shells of the green ormer Haliotis tuberculata ('Oreille de Saint-Pierre') were perforated in a zone close to the shell edge and the shell repair process was followed at two levels: (1) by observing the histology of the calcifying mantle in the repair zone and (2) by analyzing with SEM the microstructure of the shell repair zone. Histological data clearly show the presence of calcium carbonate granules into the connective tissues, but not in the epithelial cells. This suggests that calcium carbonate granules are synthesized by sub-epithelial cells and actively transported through the epithelium to the repair zone, via a process which may be similar to that described by Mount et al. [Mount, A.S., Wheeler, A.P., Paradkar, R.P., Snider, D., 2004. Hemocyte-mediated shell mineralization in the eastern oyster. Science 304, 297-300]. Furthermore, SEM observations show that the repair zone exhibits different stratified microstructures (spherulitic, thin prismatic, blocklike, sub-nacreous, nacreous, foliated-like), some of which are not continuous (i.e. lenticular) along the repair zone. This suggests a complex secreting regime of the calcifying mantle and an elaborate geometry of the epithelium involved in shell repair.

Establishment of the European College of Veterinary Clinical Pathology (ECVCP) and the current status of veterinary clinical pathology in Europe.

After 5 years of development, the European College of Veterinary Clinical Pathology (ECVCP) was formally recognized and approved on July 4, 2007 by the European Board of Veterinary Specialisation (EBVS), the European regulatory body that oversees specialization in veterinary medicine and which has approved 23 colleges. The objectives, committees, basis for membership, constitution, bylaws, information brochure and certifying examination of the ECVCP have remained unchanged during this time except as directed by EBVS. The ECVCP declared full functionality based on the following criteria: 1) a critical mass of 65 members: 15 original diplomates approved by the EBVS to establish the ECVCP, 37 de facto diplomates, 7 diplomates certified by examination, and 5 elected honorary members; 2) the development and certification of training programs, laboratories, and qualified supervisors for residents; currently there are 18 resident training programs in Europe; 3) administration of 3 annual board-certifying examinations thus far, with an overall pass rate of 70%; 4) European consensus criteria for assessing the continuing education of specialists every 5 years; 5) organization of 8 annual scientific congresses and a joint journal (with the American Society for Veterinary Clinical Pathology) for communication of scientific research and information; the College also maintains a website, a joint listserv, and a newsletter; 6) collaboration in training and continuing education with relevant colleges in medicine and pathology; 7) development and strict adherence to a constitution and bylaws compliant with the EBVS; and 8) demonstration of compelling rationale, supporting data, and the support of members and other colleges for independence as a specialty college. Formal EBVS recognition of ECVCP as the regulatory body for the science and practice of veterinary clinical pathology in Europe will facilitate growth and development of the discipline and compliance of academic, commercial diagnostic, and industry laboratories in veterinary clinical pathology. Future needs are in developing sponsorship for resident positions, increasing employment opportunities, increasing compliance with laboratory, training, and continuing education standards, and advancing relevant science and technology.

Ability of a new oral nicotine substitute to reduce smoking urge in moderate smokers.

The aim of this study was to assess the effectiveness of a new nicotine lozenge ( Nicopass 1.5 mg) in reducing smoking urge after an overnight abstinence. Twenty-four moderate smokers participated in a randomized, double-blind, placebo-controlled, 2-period crossover trial. The results showed that 1.5 mg-nicotine lozenge is superior to placebo in reducing smoking urge (p = 0.0001). In addition, nicotine lozenge, but not placebo, significantly improved vigilance and psychomotor performances (p < 0.05) and displayed a cardiac chronotropic effect. Thus, the 1.5-mg nicotine lozenge appears as an effective aid to alleviate acute tobacco withdrawal symptoms in moderate smokers.