Defibrillator charging before rhythm analysis causes peri-shock pauses exceeding guideline recommended maximum 5 s : A randomized simulation trial.

INTRODUCTION: Charging defibrillators prior to analyzing heart rhythms may decrease the no-flow time during rhythm check pauses while resuscitating in cardiac arrest. Although this anticipatory method is already used in some centers little is known about its safety. This study was carried out to confirm the safety and feasibility of the anticipatory method. It was hypothesized that this anticipatory method results in shorter total no-flow times, while other parameters of defibrillation efficacy including defibrillator safety and minimization of peri-shock pauses are unchanged. METHODS: This manikin study assigned 243 medical students randomly to study groups, 121 to the anticipatory method and 122 to the recommended European Resuscitation Council (ERC) algorithm. Of these 237 students ultimately underwent training (112 anticipatory method vs. 125 ERC algorithm). Participants were assessed and video recorded during a simulated cardiac arrest scenario which included three different heart rhythms (ventricular fibrillation [VF], pulseless ventricular tachycardia [pVT], asystole) in randomized order. Video and software analyses were performed. Defibrillation safety was assessed using a 17-item checklist defined beforehand. RESULTS: A total of 203 simulated cardiac arrests (75 anticipatory method and 128 ERC 2010 algorithm) were analyzed. The anticipatory method did not significantly reduce no-flow time (25.8 s, standard deviation, SD 7.4 s vs. 27.4 s SD 8.4 s, p = 0.19); however, peri-shock pauses were significantly longer in the anticipatory group compared to the ERC 2010 group (9.5 s SD 2.8 s vs. 3.3 s SD 1.9 s, p < 0.001). No significant difference concerning defibrillation safety between the groups was observed according to the 17-item checklist (14.6 SD 1.6 vs. 15.0 SD 1.4, p = 0.07). CONCLUSION: Charging defibrillators before rhythm analysis did not decrease total no-flow time in simulated cardiac arrests but resulted in significantly longer peri-shock pauses exceeding 5 s. No significant differences in defibrillation safety were observed between the groups.

[Full-scale simulation in German medical schools and anesthesia residency programs : Status quo]. / Full-Scale-Simulation in der anästhesiologischen Lehre und Weiterbildung in Deutschland : Gegenwärtiger Stand.

BACKGROUND: Simulation has been increasingly used in medicine. In 2003 German university departments of anesthesiology were provided with a full-scale patient simulator, designated for use with medical students. Meanwhile simulation courses are also offered to physicians and nurses. Currently, the national model curriculum for residency programs in anesthesiology is being revised, possibly to include mandatory simulation training. OBJECTIVES: To assess the status quo of full-scale simulation training for medical school, residency and continuing medical education in German anesthesiology. METHODS: All 38 German university chairs for anesthesiology as well as five arbitrarily chosen non-university facilities were invited to complete an online questionnaire regarding their centers' infrastructure and courses held between 2010 and 2012. RESULTS: The overall return rate was 86 %. In university simulation centers seven non-student staff members, mainly physicians, were involved, adding up to a full-time equivalent of 1.2. All hours of work were paid by 61 % of the centers. The median center size was 100 m2 (range 20-500 m2), equipped with three patient simulators (1-32). Simulators of high or very high fidelity are available at 80 % of the centers. Scripted scenarios were used by 91 %, video debriefing by 69 %. Of the participating university centers, 97 % offered courses for medical students, 81 % for the department's employees, 43 % for other departments of their hospital, and 61 % for external participants. In 2012 the median center reached 46 % of eligible students (0-100), 39 % of the department's physicians (8-96) and 16 % of its nurses (0-56) once. For physicians and nurses from these departments that equals one simulation-based training every 2.6 and 6 years, respectively. 31 % made simulation training mandatory for their residents, 29 % for their nurses and 24 % for their attending physicians. The overall rates of staff ever exposed to simulation were 45 % of residents (8-90), and 30 % each of nurses (10-80) and attendings (0-100). Including external courses the average center trained 59 (4-271) professionals overall in 2012. No clear trend could be observed over the three years polled. The results for the non-university centers were comparable. CONCLUSIONS: Important first steps have been taken to implement full-scale simulation in Germany. In addition to programs for medical students courses for physicians and nurses are available today. To reach everyone clinically involved in German anesthesiology on a regular basis the current capacities need to be dramatically increased. The basis for that to happen will be new concepts for funding, possibly supported by external requirements such as the national model curriculum for residency in anesthesiology.

Predictive risk factors of serious infections in patients with rheumatoid arthritis treated with abatacept in common practice: results from the Orencia and Rheumatoid Arthritis (ORA) registry.

OBJECTIVES: Little data are available regarding the rate and predicting factors of serious infections in patients with rheumatoid arthritis (RA) treated with abatacept (ABA) in daily practice. We therefore addressed this issue using real-life data from the Orencia and Rheumatoid Arthritis (ORA) registry. METHODS: ORA is an independent 5-year prospective registry promoted by the French Society of Rheumatology that includes patients with RA treated with ABA. At baseline, 3 months, 6 months and every 6 months or at disease relapse, during 5 years, standardised information is prospectively collected by trained clinical nurses. A serious infection was defined as an infection occurring during treatment with ABA or during the 3 months following withdrawal of ABA without any initiation of a new biologic and requiring hospitalisation and/or intravenous antibiotics and/or resulting in death. RESULTS: Baseline characteristics and comorbidities: among the 976 patients included with a follow-up of at least 3 months (total follow-up of 1903 patient-years), 78 serious infections occurred in 69 patients (4.1/100 patient-years). Predicting factors of serious infections: on univariate analysis, an older age, history of previous serious or recurrent infections, diabetes and a lower number of previous anti-tumour necrosis factor were associated with a higher risk of serious infections. On multivariate analysis, only age (HR per 10-year increase 1.44, 95% CI 1.17 to 1.76, p=0.001) and history of previous serious or recurrent infections (HR 1.94, 95% CI 1.18 to 3.20, p=0.009) were significantly associated with a higher risk of serious infections. CONCLUSIONS: In common practice, patients treated with ABA had more comorbidities than in clinical trials and serious infections were slightly more frequently observed. In the ORA registry, predictive risk factors of serious infections include age and history of serious infections.

Effect of using a laryngeal tube on the no-flow time in a simulated, single-rescuer, basic life support setting with inexperienced users.

BACKGROUND: The laryngeal tube (LT) is a recommended alternative to endotracheal intubation during advanced life support (ALS). Its insertion is relatively simple; therefore, it may also serve as an alternative to bag mask ventilation (BMV) for untrained personnel performing basic life support (BLS). Data support the influence of LT on the no-flow time (NFT) compared with BMV during ALS in manikin studies. METHODS: We performed a manikin study to investigate the effect of using the LT for ventilation instead of BMV on the NFT during BLS in a prospective, randomized, single-rescuer study. All 209 participants were trained in BMV, but were inexperienced in using LT; each participant performed BLS during a 4-min time period. RESULTS: No significant difference in total NFT (LT: mean 81.1 ± 22.7 s; BMV: mean 83.2 ± 13.1 s, p = 0.414) was found; however, significant differences in the later periods of the scenario were identified. While ventilating with the LT, the proportion of chest compressions increased significantly from 67.2 to 73.2%, whereas the proportion of chest compressions increased only marginally when performing BMV. The quality of the chest compressions and the associated ventilation rate did not differ significantly. The mean tidal volume and mean minute volume were significantly lower when performing BMV. CONCLUSIONS: The NFT was significantly shorter in the later periods in a single-rescuer, cardiac arrest scenario when using an LT without previous training compared with BMV with previous training. A possible explanation for this result may be the complexity and workload of alternating tasks (e.g., time loss when reclining the head and positioning the mask for each ventilation during BMV).

[The basis for well-founded simulations]. / Grundlagen für ein fundiertes Simulationskonzept.

In medical education, simulation is gaining increasing importance for teaching a variety of subjects. A well-founded educational approach is necessary for effective use. In addition to material aspects, simulation environment, curriculum, learning environment, and methods of debriefing have to be considered. The role of a competent instructor should be emphasized and the importance of an elaborate change management process to implement a good concept should not be underestimated.

Calcifediol versus vitamin D3 effects on gait speed and trunk sway in young postmenopausal women: a double-blind randomized controlled trial.

UNLABELLED: In this double-blind RCT, 4-month treatment with calcifediol compared with vitamin D3 improved gait speed by 18% among young postmenopausal women. Consistently, change in 25(OH)D blood levels over time were significantly correlated with improvement in gait speed in these women. No effect could be demonstrated for trunk sway. INTRODUCTION: The aim of this study is to test the effect of calcifediol compared with vitamin D3 on gait speed and trunk sway. METHODS: Twenty healthy postmenopausal women with an average 25(OH)D level of 13.2 ng/ml (SD = ±3.9) and a mean age of 61.5 years (SD = ±7.2) were randomized to either 20 µg of calcifediol or 20 µg (800 IU) of vitamin D3 per day in a double-blind manner. At baseline and at 4 months of follow-up, the same physiotherapist blinded to treatment allocation tested 8-m gait speed and a body sway test battery (Sway star pitch and roll angle plus velocity while walking 8 m, and standing on both legs on a hard and soft surface). All analyses adjusted for baseline measurement, age, and body mass index. RESULTS: Mean 25(OH)D levels increased to 69.3 ng/ml (SD = ±9.5) in the calcifediol group and to 30.5 ng/ml (SD = ±5.0) in the vitamin D3 group (p < 0.0001). Women receiving calcifediol compared with vitamin D3 had an 18% greater improvement in gait speed at 4-month follow-up (p = 0.046) adjusting for baseline gait speed, age, and body mass index. Also, change in gait speed was significantly correlated with change in serum 25(OH)D concentrations (r = 0.5; p = 0.04). Across three tests of trunk sway, there were no consistent differences between groups and no significant correlation between change in 25(OH)D serum concentrations and change in trunk sway. CONCLUSIONS: Calcifediol improved gait speed in early postmenopausal women compared with vitamin D3 and change in 25(OH)D level was moderately correlated with improvement in gait speed. A benefit on trunk sway could not be demonstrated.

Drug rash with eosinophilia and systemic symptoms (DRESS) in patients receiving strontium ranelate.

UNLABELLED: We have reviewed 47 drug rash with eosinophilia and systemic symptoms (DRESS) cases associated to strontium ranelate reported up to March 2011 to the Marketing Holder. The main signs were skin rash, fever, face oedema hypereosinophilia and liver involvement. For ten patients, persistence of DRESS symptoms was reported at the latest news obtained, and DRESS was identified as the direct cause of death in one case. The maximum incidence of DRESS associated with strontium ranelate was 1/24,112 [95 % CI (1/14,859; 1/42,194)] newly treated patients in France. Because DRESS is a severe drug reaction, the occurrence of a rash in a patient treated with strontium ranelate should lead to prompt and permanent treatment discontinuation. INTRODUCTION: This study aims to describe cases of DRESS reported to the Marketing Authorisation Holder worldwide for patients receiving strontium ranelate by practitioner or by regulatory authorities. METHODS: Spontaneously reported hypersensitivity events from the strontium ranelate pharmacovigilance database since marketing authorisation (2004) to March 2011 were reviewed by an expert committee. Cases of DRESS were classified as established, probable, possible or no DRESS according to expert judgement. National incidences of DRESS were estimated in relation to the number of newly treated patients. RESULTS: Up to March 2011, 325 cases of strontium ranelate-induced hypersensitivity events were assessed from which 47 DRESS cases were confirmed. Mean age was 68.7 years and besides skin rash, the main signs and symptoms were hypereosinophilia, liver involvement, fever and face oedema. Median time to skin reaction was 33.5 days after treatment start. Most patients (62 %) recovered at the time of reporting or were recovering. For ten patients, persistence of DRESS symptoms was reported at the latest news obtained. Relapses were observed in a single case. The mortality rate was 8.5 %. The maximum incidence of DRESS associated with strontium ranelate was 1/24,112 [95 % CI (1/14,859; 1/42,194)] newly treated patients in France. CONCLUSION: DRESS is a well-identified and characterised adverse reaction to strontium ranelate. This risk should be integrated in the risk-benefit balance evaluation of patient treatment, and the occurrence of a rash should lead to prompt and permanent treatment discontinuation with careful follow-up.

Evidence of the contribution of the X chromosome to systemic sclerosis susceptibility: association with the functional IRAK1 196Phe/532Ser haplotype.

OBJECTIVE: Several autoimmune disorders, including systemic sclerosis (SSc), are characterized by a strong sex bias. To date, it is not known whether genes on the sex chromosomes influence SSc susceptibility. Recently, an IRAK1 haplotype that contains the 196Phe functional variant (rs1059702), located on Xq28, was found to confer susceptibility to systemic lupus erythematosus (SLE). This study was undertaken to test for an association between SSc and the IRAK1 SLE risk haplotype. METHODS: We tested for an association with the IRAK1 SLE risk haplotype in a discovery set of 849 SSc patients and 625 controls. IRAK1 rs1059702 was further genotyped in a replication set, which included Caucasian women from Italy (493 SSc patients and 509 controls) and Germany (466 SSc patients and 1,083 controls). RESULTS: An association between the IRAK1 haplotype and SSc was detected in the discovery set. In both the discovery and replication sets, the rs1059702 TT genotype was found to be associated with specific SSc subsets, highlighting a potential contribution to disease severity. A meta-analysis provided evidence of an association of both the T allele and TT genotype with the overall disease, with an odds ratio (OR) of 1.20 and 95% confidence interval (95% CI) of 1.06-1.35 for the T allele (P = 0.003) and an OR of 1.49 and 95% CI of 1.06-2.10 for the TT genotype (P = 0.023). However, the most notable associations were observed with the diffuse cutaneous, anti-topoisomerase I antibody positive, and SSc-related fibrosing alveolitis subsets (OR 2.35 [95% CI 1.51-3.66], P = 1.56 × 10(-4), OR 2.84 [95% CI 1.87-4.32], P = 1.07 × 10(-6), and OR 2.09 [95% CI 1.35-3.24], P = 9.05 × 10(-4), respectively). CONCLUSION: Our study provides the first evidence of an association between IRAK1 and SSc, demonstrating that a sex chromosome gene directly influences SSc susceptibility and its phenotypic heterogeneity.

Association of the CD226 Ser(307) variant with systemic sclerosis: evidence of a contribution of costimulation pathways in systemic sclerosis pathogenesis.

OBJECTIVE: The nonsynonymous polymorphism rs763361 of the CD226 gene, which encodes DNAX accessory molecule 1, which is involved in T cell costimulation pathways, has recently been identified as a genetic risk factor for autoimmunity. The purpose of this study was to test for association of the CD226 rs763361 polymorphism with systemic sclerosis (SSc) in European Caucasian populations. METHODS: CD226 rs763361 was genotyped in 3,632 individuals, consisting of a discovery sample (991 SSc patients and 1,008 controls) and a replication sample (999 SSc patients and 634 controls). All study subjects were of European Caucasian origin. Expression of CD226 was assessed on peripheral blood mononuclear cells obtained from 21 healthy donors genotyped for CD226 rs763361. RESULTS: The CD226 rs763361 T allele was found to be associated with SSc in both the discovery and the replication samples, showing the following results in the combined populations: odds ratio (OR) 1.22 (95% confidence interval [95% CI] 1.10-1.34), P = 5.69 × 10(-5) . The CD226 T allele was also associated with various SSc subsets, highlighting a potential contribution to disease severity. The most remarkable associations of the CD226 TT risk genotype were observed with the diffuse cutaneous SSc subtype, the anti-topoisomerase I antibody-positive, and SSc-related fibrosing alveolitis subsets: OR 1.86 (95% CI 1.42-2.43), P = 5.15 × 10(-6) , OR 1.82 (95% CI 1.38-2.40), P = 2.16 × 10(-5) , and OR 1.61 (95% CI 1.25-2.08), P = 2.73 × 10(-4) , respectively. CD226 expression was not significantly influenced by CD226 rs763361 genotypes whatever the T cell subtype investigated. CONCLUSION: Our results establish CD226 as a new SSc genetic susceptibility factor underlying the contribution of costimulation pathways in the pathogenesis of SSc. Further work is nevertheless needed to define the causal variant at the CD226 locus as well as the functional consequences.

Caries Detection on Intraoral Images Using Artificial Intelligence.

Although visual examination (VE) is the preferred method for caries detection, the analysis of intraoral digital photographs in machine-readable form can be considered equivalent to VE. While photographic images are rarely used in clinical practice for diagnostic purposes, they are the fundamental requirement for automated image analysis when using artificial intelligence (AI) methods. Considering that AI has not been used for automatic caries detection on intraoral images so far, this diagnostic study aimed to develop a deep learning approach with convolutional neural networks (CNNs) for caries detection and categorization (test method) and to compare the diagnostic performance with respect to expert standards. The study material consisted of 2,417 anonymized photographs from permanent teeth with 1,317 occlusal and 1,100 smooth surfaces. All the images were evaluated into the following categories: caries free, noncavitated caries lesion, or caries-related cavitation. Each expert diagnosis served as a reference standard for cyclic training and repeated evaluation of the AI methods. The CNN was trained using image augmentation and transfer learning. Before training, the entire image set was divided into a training and test set. Validation was conducted by selecting 25%, 50%, 75%, and 100% of the available images from the training set. The statistical analysis included calculations of the sensitivity (SE), specificity (SP), and area under the receiver operating characteristic (ROC) curve (AUC). The CNN was able to correctly detect caries in 92.5% of cases when all test images were considered (SE, 89.6; SP, 94.3; AUC, 0.964). If the threshold of caries-related cavitation was chosen, 93.3% of all tooth surfaces were correctly classified (SE, 95.7; SP, 81.5; AUC, 0.955). It can be concluded that it was possible to achieve more than 90% agreement in caries detection using the AI method with standardized, single-tooth photographs. Nevertheless, the current approach needs further improvement.

NLRP1 influences the systemic sclerosis phenotype: a new clue for the contribution of innate immunity in systemic sclerosis-related fibrosing alveolitis pathogenesis.

BACKGROUND: Recent evidence has highlighted a potential role of interleukin 1ß (IL-1ß) in systemic sclerosis (SSc). NLRP1 provides a scaffold for the assembly of the inflammasome that promotes the processing and maturation of pro-IL-1ß. In addition, NLRP1 variants were found to confer susceptibility to autoimmune disorders. OBJECTIVE: /st> To study a possible association of the NLRP1 rs6502867, rs2670660 and rs8182352, rs12150220 and rs4790797 with SSc in the European Caucasian population. METHODS: NLRP1 single nucleotide polymorphisms were genotyped in 3227 individuals comprising a discovery set (870 SSc patients and 962 controls) and a replication set including individuals from Germany (532 SSc patients and 324 controls) and Italy (527 SSc patients and 301 controls), all individuals being of European Caucasian origin. RESULTS: Conditional analyses revealed a significant association for the NLRP1 rs8182352 variant with both anti-topoisomerase-positive and SSc-related fibrosing alveolitis (FA) subsets under an additive model: p=0.0042, OR 1.23 (95% CI 1.07 to 1.41) and p=0.0065 OR 1.19 (95% CI 1.05 to 1.36), respectively. Logistic regression analysis showed an additive effect of IRF5 rs2004640, STAT4 rs7574865 and NLRP1 rs8182352 risk alleles on SSc-related FA. CONCLUSIONS: Our results establish NLRP1 as a new genetic susceptibility factor for SSc-related pulmonary fibrosis and anti-topoisomerase-positive SSc phenotypes. This provides new insights into the pathogenesis of SSc, underlining the potential role of innate immunity in particular in the FA-positive SSc subphenotype, which represents a severe subset of the disease.

Association of a KCNA5 gene polymorphism with systemic sclerosis-associated pulmonary arterial hypertension in the European Caucasian population.

OBJECTIVE: Pulmonary arterial hypertension (PAH) has emerged as a leading cause of death in systemic sclerosis (SSc). The genetic basis of PAH has been unraveled in recent years, with a major role played by transforming growth factor ß receptors; however, some other candidate genes have also been advocated, including potassium voltage-gated channel, shaker-related subfamily, member 5 (KCNA5). We undertook this study to determine whether KCNA5 polymorphisms confer susceptibility to SSc and its vascular phenotype, including PAH. METHODS: Four KCNA5 single-nucleotide polymorphisms (SNPs), rs10744676, rs1860420, rs3741930, and rs2284136, were genotyped in a discovery set of 638 SSc patients and 469 controls. In addition, rs10744676 was genotyped in an independent replication sample (938 SSc patients and 564 controls) and in a cohort of 168 patients with different PAH subtypes. RESULTS: The KCNA5 rs10744676 variant was found to be associated with SSc in the discovery sample, with an odds ratio (OR) of 0.62 (95% confidence interval [95% CI] 0.48-0.79, adjusted P = 0.0003) in comparison with controls (C allele frequency 11.4% versus 17.2%). When subphenotypes were investigated, an association was found solely for PAH associated with SSc (OR 0.31 [95% CI 0.13-0.71], adjusted P = 0.04). The other KCNA5 SNPs tested were not associated with any SSc subset. The above association with PAH associated with SSc was replicated in the second set. In the combined population, rs10744676 was strongly associated with PAH associated with SSc in comparison with controls (OR 0.36 [95% CI 0.21-0.63], P = 0.0002). In the independent cohort of patients with PAH, after investigating PAH subtypes, only rs10744676 showed an association with PAH associated with SSc. CONCLUSION: Our results provide the first evidence for an association between the KCNA5 rs10744676 variant and PAH associated with SSc.

Association of the TNFAIP3 rs5029939 variant with systemic sclerosis in the European Caucasian population.

BACKGROUND: TNFAIP3 encodes the ubiquitin-modifying enzyme, a key regulator of inflammatory signalling pathways. Convincing associations between TNFAIP3 variants and autoimmune diseases have been reported. OBJECTIVE: To investigate the association of TNFAIP3 polymorphisms with systemic sclerosis (SSc). METHODS: Three single nucleotide polymorphisms (SNPs) in a set of 1018 patients with SSc and 1012 controls of French Caucasian origin were genotyped. Two intergenic SNPs, rs10499194 and rs6920220, and one located in TNFAIP3 intron 2, rs5029939, were selected. The TNFAIP3 rs5029939 found to be associated with SSc in this first set was then genotyped in a second set of 465 patients with SSc and 182 controls from Germany and 184 patients with SSc and 124 controls from Italy. Pooled odd ratios were calculated by Mantel-Haenszel meta-analysis. RESULTS: The rs5029939 G allele was found to be significantly associated with SSc susceptibility (pooled OR=2.08 (95% CI 1.59 to 2.72); p=1.16×10⁻7), whereas the rs10499194 and rs6920220 variants displayed no association. Only one of the predicted haplotypes investigated in the French sample was significantly associated with SSc (p=8.91×10⁻8), and this haplotype was discriminating only in the presence of the rs5029939 risk allele, suggesting that this SNP tags the association signal. The strongest associations of rs5029939 with subphenotypes, having large magnitudes for complex genetic disorders, were observed for diffuse cutaneous SSc (pooled OR=2.71 (1.94 to 3.79), p=5.2×10⁻9), fibrosing alveolitis (pooled OR=2.26 (1.61 to 3.17), p=2.5×10⁻6) and pulmonary arterial hypertension (pooled OR=3.11 (1.86 to 5.17), p=1.3×10⁻5). CONCLUSION: These results suggest that TNFAIP3 is a genetic susceptibility factor for SSc.

Osteoporosis and venous thromboembolism: a retrospective cohort study in the UK General Practice Research Database.

UNLABELLED: In a retrospective cohort study using the General Practice Research Database (GPRD), there was a greater association of venous thromboembolism (VTE) in osteoporotic than in non-osteoporotic female patients. No greater association was shown in treated patients with strontium ranelate or alendronate compared to untreated osteoporotic female patients. INTRODUCTION: We explored the risk of VTE in usual practice in osteoporotic and non-osteoporotic women with and without anti-osteoporotic treatment. METHODS: A retrospective study was conducted using the GPRD in the UK. The cohorts consisted of untreated osteoporotic women (N = 11,546), osteoporotic women treated with alendronate (N = 20,084), or strontium ranelate (N = 2,408), and a sample of non-osteoporotic women (N = 115,009). Cohorts were compared using a Cox proportional hazards regression model. RESULTS: There was a significantly increased relative risk for VTE in untreated osteoporotic women versus non-osteoporotic women (annual incidence 5.6 and 3.2 per 1,000 patient-years, respectively; relative risk 1.75 [95% confidence interval (CI), 1.09-1.84]). Results were confirmed using adjusted models. The annual incidences of VTE in osteoporotic patients treated with strontium ranelate and alendronate were 7.0 and 7.2 per 1,000 patient-years, respectively, with no significant difference between untreated and treated patients whatever the treatment. Adjusted hazard ratios for treated versus untreated osteoporotic women were 1.09 (95% CI, 0.60-2.01) for strontium ranelate and 0.92 (95% CI, 0.63-1.33) for alendronate. CONCLUSION: This study shows a greater association of VTE in osteoporotic compared to non-osteoporotic patients, but does not show any greater association in treated patients with strontium ranelate or alendronate compared to untreated osteoporotic patients.

Rapid typing of the human neutrophil antigen 1a by the particle gel agglutination assay.

The human neutrophil antigen 1a (HNA-1a) plays a major role in immune neutropenias and transfusion-associated lung injury. In this study, we describe a simple and rapid particle gel agglutination assay (PaGIA) for HNA-1a phenotyping. A commercially available monoclonal antibody (MoAb) to HNA-1a was biotinylated and coupled onto superparamagnetic streptavidin particles. Diluted anticoagulated whole blood samples from healthy blood donors (n = 147) were incubated with MoAb-coated particles, washed, transferred into an ID-gel card, and, subsequently, centrifuged. HNA-1a-positive samples resulted in a visible agglutination of the particles on top of the gel column and could be evaluated macroscopically. The results obtained by the new test were identical with those obtained by the polymerase chain reaction-sequence-specific priming technique that was performed in parallel. Seventy-four (50.3%) of the 147 samples were found to be HNA-1a positive. The HNA-1a PaGIA is both simple and safe and can be implemented in various laboratory settings.

Crystal structure of a carbon monoxide dehydrogenase reveals a [Ni-4Fe-5S] cluster.

The homodimeric nickel-containing CO dehydrogenase from the anaerobic bacterium Carboxydothermus hydrogenoformans catalyzes the oxidation of CO to CO2. A crystal structure of the reduced enzyme has been solved at 1.6 angstrom resolution. This structure represents the prototype for Ni-containing CO dehydrogenases from anaerobic bacteria and archaea. It contains five metal clusters of which clusters B, B', and a subunit-bridging, surface-exposed cluster D are cubane-type [4Fe-4S] clusters. The active-site clusters C and C' are novel, asymmetric [Ni-4Fe-5S] clusters. Their integral Ni ion, which is the likely site of CO oxidation, is coordinated by four sulfur ligands with square planar geometry.

Association of hypoxia-inducible factor 1A (HIF1A) gene polymorphisms with systemic sclerosis in a French European Caucasian population.

OBJECTIVE: Systemic sclerosis (SSc) is a connective tissue disease characterized by generalized microangiopathy leading to chronic hypoxia. The aim of this study was to determine whether polymorphisms of the hypoxia-inducible factor 1A gene (HIF1A) affects susceptibility to SSc in a large French European Caucasian population. METHODS: A case-control study was performed in 659 SSc patients and 511 healthy matched controls. Three tag single nucleotide polymorphisms (SNPs) of the HIF1A gene (rs12434438 A/G, rs1957757 C/T, and rs11549465 C/T) were genotyped allowing whole gene coverage according to HapMap data. RESULTS: The frequency of genotypes carrying at least one G allele (A/G and/or GG) of the rs12434438 SNP was significantly higher in SSc patients than in controls [p(corr) = 0.018, odds ratio (OR) 1.44, 95% confidence interval (CI) 1.08-1.91]. Regarding SSc subgroup analyses, the heterozygous genotype A/G was associated with SSc (p(corr) = 0.012, OR 1.47, 95% CI 1.13-1.9), with the limited cutaneous form of SSc (p(corr) = 0.04, OR 1.43, 95% CI 1.08-1.91), and with positive anti-centromere antibodies (ACA; p(corr) = 0.016, OR 1.61, 95% CI 1.16-2.23). No association was detected for the remaining two HIF1A SNPs tested. Haplotype analyses did not detect any association with SSc. CONCLUSIONS: We observed an association between the HIF1A gene and SSc in a European Caucasian population, supporting a role for HIF1 in the pathophysiology of SSc.

Characterization of the immune response in the synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome.

OBJECTIVE: The aetiology of SAPHO (synovitis, acne, palmoplantar pustulosis, hyperostosis, osteitis) syndrome seems to involve genetic, infectious and immunological components. We examined innate and adaptive immune responses in SAPHO syndrome, as compared with PsA and RA. We also studied the effect of etanercept on immunological parameters. METHODS: We studied 29 patients with SAPHO syndrome, as well as 22 patients with RA, 21 patients with PsA and 15 healthy controls. Adaptive immune responses were investigated by assaying total serum immunoglobulins and several autoantibodies. Innate immunity was studied by quantifying blood PMN functions and plasma cytokine levels. PMN responses to Propionibacterium acnes were tested ex vivo. Eight patients who received etanercept for refractory rheumatic disorders were tested before and after 28 days of treatment. RESULTS: SAPHO syndrome was associated with elevated IL-8 and IL-18 plasma levels. IL-8 and TNF-alpha production by purified PMN was higher in the three patient groups than in the healthy controls, but the oxidative burst and IL-18 production were normal. No autoantibodies were detected in SAPHO patients. Induction of PMN IL-8 and TNF-alpha production by P. acnes was impaired in the SAPHO group as compared with the RA and PsA groups. After 28 days of etanercept therapy, PMN IL-8 and TNF-alpha production was down-regulated and TNF-alpha plasma levels were increased. CONCLUSIONS: These results support the view that the SAPHO syndrome may be triggered by an infectious state involving P. acnes, contributing to the strong humoral and cellular pro-inflammatory responses. Etanercept modulation of PMN activation status emphasizes these new immunological findings.

Late Steroid Withdrawal Following AB0-Incompatible Renal Transplantation.

BACKGROUND: Current evidence on steroid withdrawal following AB0-incompatible (AB0i) renal transplantation is low. We compared clinical outcomes of patients who agreed to late steroid withdrawal and patients who remained on steroid treatment. METHODS: Steroid withdrawal was carried out in 11 patients at ≥12 months after transplantation (group W). For comparison, we analyzed 19 patients who remained on triple immunosuppression including steroids (group M). Minimum follow-up was 24 months following transplantation and 12 months after steroid withdrawal. RESULTS: Baseline characteristics, including observation times, were not different between groups W and M. Graft survival was 100% in group W compared with 84% (16/19) in group M (P = .15). In group M, 1 patient experienced graft failure because of suspected antibody-mediated rejection (ABMR) following temporary cessation of mycophenolate treatment after a diagnosis of cryptococcal pneumonia. Two patients died with functioning graft because of sepsis. In group W, we observed 1 episode of ABMR following steroid withdrawal. At the end of follow-up, estimated glomerular filtration rates (eGFR) were 54 (19-91) versus 60 (15-85) mL/min/1.73 m2 in group W versus M, respectively (P = .67). CONCLUSIONS: Late steroid withdrawal following AB0i transplantation is feasible at a moderate risk of rejection. We recommend close monitoring of renal function and HLA antibodies during and after steroid withdrawal. On the other hand, the occurrence of severe infections causing death and graft loss in patients on triple maintenance immunosuppression including steroids should remind us to consider the overall immunosuppressive burden.

Visible spectroscopy diagnostics for tungsten source assessment in the WEST tokamak: First measurements.

The present work concerns the measurements obtained with the Tungsten (W) Environment in Steady-state Tokamak (WEST) visible spectroscopy system during the first experimental campaign. This system has been developed in the framework of the WEST project that equipped the existing Tore Supra device with a tungsten divertor in order to test actively cooled tungsten Plasma Facing Components (PFC) in view of preparing for ITER operation. The goal of this diagnostic is to measure the PFC sources and the deuterium recycling with spectral, spatial, and temporal resolution adapted to the predicted power deposition profiles on the objects observed. Three kinds of PFCs are monitored: the Ion Cyclotron Resonance Heating (ICRH) antenna and Low Hybrid Current Drive (LHCD) launcher W limiters; one of the 6 W inner bumpers; and the upper and lower W divertors. Large-aperture in-vessel actively cooled optical systems (f-number ∼ 3) were installed for each view and connected to optical fibres. A total of 240 optical fibers can be distributed on various detection systems including a fast response-time, multi-channel, filtered photodetector-based "Filterscope" system, developed by Oak Ridge National Laboratory (USA) as well as grating spectrometers optimized for multi-sightline analysis. The first WEST experimental campaign conducted in 2017 has been dedicated to plasma start-up development during which the visible spectroscopy system has provided crucial information related to the impurity content first and then impurity sources. The diagnostic setup for that first experimental campaign was limited to the inner bumper and outer limiters but was sufficient to demonstrate that the optical setup was in accordance with the specifications. The radiance calibration procedure allowed us to estimate fluxes from the main limiter of about 8 × 1018 atoms/(s m2) and to show a first W source radial profile along the outboard limiter.