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Purpose This retrospective study evaluates the effectiveness and safety of the Angio-Seal closure device in superficial femoral artery (SFA) antegrade punctures compared to common femoral artery (CFA) antegrade punctures. Methods Over a period of 46 months from January 2012, consecutive patients who underwent antegrade CFA or SFA punctures using Angio-Seal as a closure device in a single centre were studied. Patients were identified by reading all the individual reports on our radiology system for all patients who underwent any angiographic examination during the study period, and their individual case notes were subsequently reviewed. A retrospective analysis of prospectively collected data on patients' demographics, type of intervention, clinical indication, Angio-Seal size, haemostasis status and complications was performed. Results Overall, 194 patients (mean (s.d.) age 74(12) years, 123(44%) males) underwent CFA or SFA antegrade punctures. A total of 228 (CFA group, n = 70, SFA group, n = 158) antegrade punctures were performed. Clinical characteristics of the two groups were comparable. Angio-Seal size 6F was deployed in 69(99%) antegrade CFA punctures and 155(98%) antegrade SFA punctures (P = 1.000). Haemostasis was achieved in 65(93%) antegrade CFA punctures compared to 156(99%) antegrade SFA punctures (P = 0.030). Conclusion Angio-Seal closure device is safe and effective method of haemostasis both in antegrade SFA and CFA punctures with no significant complications or delayed discharge.

Cellular therapies with CD4+ T regulatory cells (Tregs) hold promise of efficacious treatment for the variety of autoimmune and allergic diseases as well as posttransplant complications. Nevertheless, current manufacturing of Tregs as a cellular medicinal product varies between different laboratories, which in turn hampers precise comparisons of the results between the studies performed. While the number of clinical trials testing Tregs is already substantial, it seems to be crucial to provide some standardized characteristics of Treg products in order to minimize the problem. We have previously developed reporting guidelines called minimum information about tolerogenic antigen-presenting cells, which allows the comparison between different preparations of tolerance-inducing antigen-presenting cells. Having this experience, here we describe another minimum information about Tregs (MITREG). It is important to note that MITREG does not dictate how investigators should generate or characterize Tregs, but it does require investigators to report their Treg data in a consistent and transparent manner. We hope this will, therefore, be a useful tool facilitating standardized reporting on the manufacturing of Tregs, either for research purposes or for clinical application. This way MITREG might also be an important step toward more standardized and reproducible testing of the Tregs preparations in clinical applications. This work was supported by a grant from the European Cooperation in Science and Technology (COST) for the AFACTT project (Action to Focus and Accelerate Cell-based Tolerance-inducing Therapies; BM1305). COST is part of the EU Framework Programme Horizon 2020. peer-reviewed

Eligibility for anti-tumour necrosis factor (TNF) therapy in most European countries is restricted to severe, active rheumatoid arthritis (RA). The DAS28 score is a marker of disease severity and incorporates one of two inflammatory markers, erythrocyte sedimentation rate (ESR) or C-reactive protein. We aimed to determine the relation between genetic variants known to affect ESR and levels of ESR in patients with active RA. DNA samples were genotyped for four single-nucleotide polymorphisms (SNPs) rs7527798 (CR1L), rs6691117 (CR1), rs10903129 (TMEM57) and rs1043879 (C1orf63). The association between SNPs and baseline ESR, baseline DAS28-ESR, and change in DAS28-ESR was evaluated. Baseline ESR was significantly associated with CR1 rs6691117 genotype (P=0.01). No correlation was identified between baseline DAS28-ESR or change in DAS28-ESR. In conclusion, genetic variation in the gene encoding CR1 may alter ESR levels but not DAS28-ESR, indicating no adjustment for CR1 genotype is required in the assessment of patients with severe active RA.

Appendicitis is a common cause of acute abdominal pain in children and is treated by an open or laparoscopic appendicectomy. Well documented post-operative complications include wound infection, intra-abdominal collection, and adhesional bowel obstruction. We present the rare case of right sacro-iliitis and iliac bone osteomyelitis in a 13 year old boy following an open appendicectomy for a perforated appendicitis.

Approximately 30% of rheumatoid arthritis (RA) patients fail to respond to anti-tumour necrosis factor (anti-TNF) treatment;1 hence, the ability to predict which patients will respond to treatment would represent a major clinical advance. Vitamin D has been implicated in many autoimmune diseases including RA; in addition, vitamin D has been shown to induce TNFα production by some immune cells leading to the hypothesis that vitamin D levels may influence anti-TNF treatment response.2 ,3 Several studies have now confirmed the association of genetic variants within four vitamin D metabolism genes ( GC, DHCR7/NADSYN1, CYP2R1, CYP24A1 ) with circulating vitamin D levels in healthy controls.4 ,5 In addition, single nucleotide polymorphisms (SNPs) in these genes have also been associated with autoimmune diseases.6 The association of the same variants in the same genes that control circulating levels of vitamin D with response to anti-TNF treatment provides an unbiased test of the hypothesis that vitamin D levels are important in response to these therapies (Mendelian randomisation).7 We, therefore, investigated the effect of vitamin D on response to anti-TNF therapy, testing six SNPs previously associated with circulating levels of vitamin D4 ,5 for association with response to anti-TNF therapy in RA patients from the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGSS) cohort (table 1), which includes patients recruited across the UK.8 SNPs were selected to capture by linkage disequilibrium (LD) (r2>0.8) 94.26% of SNPs previously associated with vitamin D levels in two previous studies.4 ,5 Multivariate linear and logistic regression was used to assess the effects of each SNP on treatment response measured by absolute change in Disease Activity Score in 28 joints (DAS28) over 6 months9 (n=1396) or in poor (n=237) versus good (n=322) responders according to European League …

Introduction In many European countries, restrictions exist around the prescription of anti-tumor necrosis factor (anti-TNF) treatments for rheumatoid arthritis (RA). Eligibility and response to treatment is assessed by using the disease activity score 28 (DAS28) algorithm, which incorporates one of two inflammatory markers, erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP). Although DAS28-CRP provides a more reliable measure of disease activity, functional variants exist within the CRP gene that affect basal CRP production. Therefore, we aimed to determine the relation between functional genetic variants at the CRP gene locus and levels of serum CRP in RA patients, and whether these variants, alone or in combination, are correlated with DAS28-CRP and change in DAS28-CRP after anti-TNF treatment. Methods DNA samples from the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGSS) were genotyped for rs1205, rs1800947, and rs3091244 by using either TaqMan or the Sequenom MassARRAY iPLEX system. Estimated haplotypes were constructed for each sample by using the expectation maximization algorithm implemented in the haplo.stats package within the R statistical program. CRP values were log transformed, and the association between single nucleotide polymorphisms (SNPs), haplotypes of SNPs and baseline CRP, baseline DAS28-CRP, and change in DAS28-CRP were evaluated by using linear regression in STATA v.10. Results Baseline CRP measurements were available for 599 samples with 442 also having data 6 months after treatment with an anti-TNF. For these 442 samples, the study had > 80% power to detect a clinically meaningful difference of 0.6 DAS28 Units for an allele frequency of 5%. Estimated haplotype frequencies corresponded with previous frequencies reported in the literature. Overall, no significant association was observed between any of the markers investigated and baseline CRP levels. Further, CRP haplotypes did not correlate with baseline CRP (P = 0.593), baseline DAS28-CRP (P = 0.540), or change in DAS28-CRP after treatment with an anti-TNF over a 6-month period (P = 0.302). Conclusions Although CRP genotype may influence baseline CRP levels, in patients with very active disease, no such association was found. This suggests that genetic variation at the CRP locus does not influence DAS28-CRP, which may continue to be used in determining eligibility for and response to anti-TNF treatment, without adjusting for CRP genotype.

We have developed a noninvasive ultrasound tech nique that may be used to differentiate complete and incomplete acute tears of the anterior talofibular liga ment. Direct visualization of the ligament will demon strate the lesion in most cases and can be supple mented by an anterior drawer test with the ligament under direct vision. Seventeen athletes involved in sports and work that put high-demand pressure on their ankles underwent ultrasonic examination of their acute lateral ankle ligament injuries before surgical explora tion. Fourteen scans demonstrating a complete lesion of the anterior talofibular ligament were confirmed at operation. Three scans were equivocal; two of these patients had incomplete lesions of their anterior talo fibular ligaments and one patient had a complete tear that was not detected. We have found that the dynamic ultrasound test is a simple and reliable examination. We suggest that this technique is indicated where the extent of an acute lateral ligament injury requires further defi nition. Ankle ultrasonography may reduce the need for ankle arthrography.

Auditory responses, including the well-characterized auditory brainstem response, have been used extensively in clinical investigations. Evoked responses have not been adequately developed to investigate the vestibular system. The purpose of this study is to describe a new method for the evaluation of short-latency vestibular evoked potentials in human subjects. Standard ABR equipment is used, with a customized solid-state modification of the triggering mechanism. Signal averaging is used to record responses to multiple linear decelerations. Results indicate the presence of a short-latency wave, which is absent in vestibular-deficient subjects. The literature is reviewed and illustrative cases are presented. We believe vestibular evoked potentials are a promising new modality in investigation of vestibular physiology.

On national security issues, expect major fights on marginal issues, and marginal fights on the major ones.

It has been 35 years, more than a generation, since the first nuclear explosion was released over the New Mexico desert. The most we can say is that mankind has continued to survive the increasingly ominous chain of moves and counter-moves that have flowed from that war-born measure. But at what cost?The whole world is increasingly afflicted by the threat of nuclear war. An insane and ever-intensifying arms race has bred violence in every lesser form, carried hunger and disease in its train as needed resources were devoted elsewhere, and has deepened the insecurity even of those who were arming themselves to the teeth. Are we condemned to a race in which the only conceivable end is assured mutual destruction today or tomorrow?As Americans enter the decade of the 1980s, they may expect to spend over one trillion dollars in the first five years on their defense. In the name of national security, the U.S. Congress has permitted the military a stranglehold on an immense sector of government expenditure.In thi...