Previous microvascular decompression decreases the chances of pain free in patients treated with Gamma Knife radiosurgery for TIC

Object: The authors sought to establish whether the safety-efficacy of Gamma Knife radiosurgery (GKRS) as a second treatment for intractable trigeminal neuralgia (ITN) are influenced by prior microvascular decompression (MVD) which remains, for some of the authors, the reference technique. Methods: Between July 1992 and November 2010, 737 patients have been operated with GKRS for ITN and prospectively evaluated in Timone University Hospital in Marseille, France. Among these, 54 patients had a previous MVD history. Radiosurgery using a Gamma Knife (model B or C or Perfexion) was performed relying on both MR and CT targeting. A single 4 mm isocenter was positioned in the cisternal portion of the trigeminal nerve at a median distance of 7.6 mm (range 3.9- 11.9) anteriorly to the emergence of the nerve (retrogasserian target). A median maximum dose of 85 Gy (range 70-90) was delivered. Are further analyzed only 45 patients with previous MVD and a follow-up longer than one year (the patients with megadolichobasilar artery compression and multiple sclerosis were excluded). Results: The median age in this series was 56.75 years (range 28.09-82.39). The median follow-up period was 39.48 months (range 14.10-144.65). All the patients had a past history of surgery, with at least one previous failed MVD, but also a radiofrequency lesion (RFL) in 16 (35.6%) patients, balloon microcompression in 7 (15.6%) patients and glycerol rhizotomy in 1 case (2.2%). Thirty-five patients (77.8%) were initially pain free in a median time of 14 days (range 0, 180). Patients from this group had less probability of being pain free compared to our global population of essential trigeminal neuralgia without previous MVD history (p=0.010, hazard ratio of 0.64). Their probability of remaining pain free at 3, 5, 7 and 10 years was 66.5%, 59.1%, 59.1% and 44.3%, respectively. Twelve patients (34.3%) initially pain free experienced a recurrence with a median delay of 31.21 months (range 3.40-89.93). The hypoesthesia actuarial rate at 1 year was 9.1% and remained stable till 12 years with a median delay of onset of 8 months (range 8-8). Conclusions: Retrogasserian GKRS proofed to be safe and effective on the long-term basis even after failed previous MVD. Even if the initial result of pain free was of only 77.8%, the toxicity was low with only 9.1% hypoesthesia. No patient reported a bothersome hypoesthesia. The probability of maintaining pain relief in long-term was of 44.3% at 10 years.

Diet and breeding success of long-eared owls in a semi-arid environment

Only a few studies, and mostly in temperate climates in Europe, have examined the breeding and diet of long-eared owls (Asia otus) compared to studies of cavity-breeding owls, possibly because of the difficulties in reaching the nests of the former. Here we studied a population of long-eared owls, monitoring the diet of breeding owls and that of owls at a communal roost, every two to three months during 2006 -2009, in a semi-arid region in Israel. It was found that the studied owls produced more young than in most countries in Europe. Diet was not associated with breeding parameters of the owls, whereas laying date was negatively correlated with both clutch size and number of nestlings. We found that more social voles (Microtus socialis) and fewer birds and house mice (Mus musculus) made up the diet at nests than that of adults at the roosts. The diet and breeding of long-eared owls in Israel differ from that in Europe, with birds and mice comprising an important part of the diet, in addition to voles.

Equipes de psychiatrie mobiles pour les trois âges de la vie: l'expérience lausannoise [Psychiatric mobile teams for the three ages of live: the Lausanne experience]

Des équipes mobiles de psychiatrie ont été développées dans les trois âges pour répondre aux besoins de personnes qui devraient bénéficier d'une évaluation ou de soins spécialisés, lorsque ceux-ci doivent avoir lieu à domicile. Pour arriver à ce but, les équipes tissent de forts liens de partenariat dans le réseau, que ce soit avec les proches ou avec les professionnels impliqués. Les principes généraux d'intervention sont semblables entre les âges : une population cible définie, une intervention à domicile au bénéfice également des proches et des soins de proximité, des équipes pluridisciplinaires avec une charge de cas limitée pour garantir leur disponibilité. Les spécificités de chaque âge seront analysées. Mobile teams have been developed for the three ages to meet the needs of people who should receive--but do not access to--a psychiatric assessment or to specialized care. To achieve this goal, the teams built a strong partnership within the social network, both with relatives and professionals involved. The general principles of intervention are similar between the ages: a focused target population, assertive outreach which benefits also relatives and carers, multidisciplinary teams with a limited caseload to ensure availability. The specificities of each age will be analyzed

Investigations on hydrogen isotope ratios of endogenous urinary steroids: reference-population-based thresholds and proof-of-concept.

Carbon isotope ratio (CIR) analysis has been routinely and successfully used in sports drug testing for many years to uncover the misuse of endogenous steroids. One limitation of the method is the availability of steroid preparations exhibiting CIRs equal to endogenous steroids. To overcome this problem, hydrogen isotope ratios (HIR) of endogenous urinary steroids were investigated as a potential complement; results obtained from a reference population of 67 individuals are presented herein. An established sample preparation method was modified and improved to enable separate measurements of each analyte of interest where possible. From the fraction of glucuronidated steroids; pregnanediol, 16-androstenol, 11-ketoetiocholanolone, androsterone (A), etiocholanolone (E), dehydroepiandrosterone (D), 5α- and 5β-androstanediol, testosterone and epitestosterone were included. In addition, sulfate conjugates of A, E, D, epiandrosterone and 17α- and 17β-androstenediol were considered and analyzed after acidic solvolysis. The obtained results enabled the calculation of the first reference-population-based thresholds for HIR of urinary steroids that can readily be applied to routine doping control samples. Proof-of-concept was accomplished by investigating urine specimens collected after a single oral application of testosterone-undecanoate. The HIR of most testosterone metabolites were found to be significantly influenced by the exogenous steroid beyond the established threshold values. Additionally, one regular doping control sample with an extraordinary testosterone/epitestosterone ratio of 100 without suspicious CIR was subjected to the complementary methodology of HIR analysis. The HIR data eventually provided evidence for the exogenous origin of urinary testosterone metabolites. Despite further investigations on HIR being advisable to corroborate the presented reference-population-based thresholds, the developed method proved to be a new tool supporting modern sports drug testing procedures.

Target blood pressure attainment with antihypertensive therapy in Swiss primary care.

Introduction: The control of high blood pressure (BP) remains insufficient in developed as well as in developing countries. We conducted a cross-sectional survey to investigate the management of hypertension and the achievement of target BPs in a large population of hypertensive patients treated by Swiss primary care physicians. Methods. Data from 4594 hypertensive patients were collected and assessed for demographic data, mode of treatment and BP achievements for the overall population and for high-risk patients such as diabetics and patients with impaired renal function (CKD patients). Furthermore, we analysed the achieved BP in patients receiving single pill combinations or dual free combinations for the three most commonly prescribed substances. Results. In this large patient population, 84% of patients were receiving an antihypertensive treatment of which 54% showed BP control (< 140/90 mmHg or < 130/80 mmHg for diabetics and patients with CKD). Considering the higher BP target in the elderly, 60.6% of treated patients were on target. In contrast, 28.8% of treated diabetics and 29.7% of patients with impaired renal function met BP goals. Diuretics and blockers of the renin-angiotensin system were the most commonly prescribed substances. High-risk patients and patients at advanced age (≥ 80 years) received dual free combination more frequently than younger patients. The use of diuretics was particularly high because of the prescription of single pill formulations. Differences in the pattern of drug prescription were found according to the linguistic areas. Conclusion. The control of hypertension in the Swiss hypertensive population is relatively high but still insufficient particularly among high cardiovascular risk patients such as diabetics and patients with impaired renal function. A further improvement of BP control could perhaps be achieved with a greater use of single pill combinations particularly in patients with complicated hypertension.

Prevalence of Inflammatory Bowel Disease in the Canton of Vaud (Switzerland): A population-based cohort study

Background and aims: Because of the changing epidemiology of Inflammatory Bowel Diseases 0131)), we set out to characterize the population-based prevalence of Crohn's Disease (CD) and Ulcerative Colitis (UC) in a defined population of Switzerland. Methods: Adult IBD patients were identified by a cross-matched review of histological, hospital and gastroenterologist files throughout a geographical defined population (Canton of Vaud). Demographic factors statistically significantly associated with prevalence were evaluated using a stepwise Poisson regression analysis. Results were compared to IBD prevalence rates in other population-based studies and time trends were performed, based on a systematic literature review. Results: Age and sex-adjusted prevalence rates were 205.7 IBD (100.7 CD and 105.0 UC) cases per 105 inhabitants. Among 1016 IBD patients (519 CD and 497 UC), females outnumbered mates in CD (p < 0.001), but mates were more represented in elderly UC patients (p = 0.008). Thus, being a mate was statistically associated with UC (Relative Risk (RR) 1.25; p = 0.013), whereas being a female was associated with CD (RR 1.27; p = 0.007). Living in an urban zone was associated with both CD and UC (RR 1.49; p < 0.001, 1.63; p < 0.001, respectively). From 1960 to 2005, increases in UC and CD prevalences of 2.4% (95%CI, 2.1%-2.8%; p < 0.001) and 3.6% (95%CI, 3.1%-4.1%; p < 0.001) per annum were found in industrialised countries.

Prospective monitoring of a CD4+ CD25high CD45RO+ CD127high T-cell population after first kidney transplantation following thymoglobulin or basiliximab induction

Background: Recent data have suggested that a population of CD4+ CD25high T cells, phenotypically characterized by the expression of CD45RO and CD127, is significantly expanded in stable liver and kidney transplant recipients and represents alloreactive T cells. Induction therapies may have an impact on this alloreactive T cell population. In this study, we prospectively analyzed CD4+ CD25high CD45RO+ CD127high T cells after induction with either thymoglobulin or basiliximab. Patients and methods: A total of twenty-seven kidney transplant recipients were prospectively enrolled; 14 received thymoglobulin induction followed by a 4-day course of steroids with tacrolimus and mycophenolate mofetil («thymo group»), and 13 received basiliximab induction followed by standard triple immunosuppression (tacrolimus, mycophenolate mofetil and prednisone) («BSX group»). Phenotypical analysis by flow cytometry of the expression of CD25, CD45RO and CD127 on peripheral CD4+ T cells was performed at 0, 3 and 6 months after transplantation. Twenty-four healthy subjects (HS) were studied as controls. Results: There were no differences in baseline characteristics between the groups; at 6 months, patient survival (100%), graft survival (100%), serum creatinine (thymo group versus BSX group: 129 versus 125 micromol/l) and acute rejection (2/14 versus 2/13) were not significantly different. Thymo induction produced a prolonged CD4 T cell depletion. As compared to pre-transplantation values, an expansion of the alloreactive T cell population was observed at 3 months in both thymo (mean: from 6.38% to 14.72%) and BSX (mean: from 8.01% to 18.42%) groups. At 6 months, the alloreactive T cell population remained significantly expanded in the thymo group (16.92 ± 2.87%) whereas it tended to decrease in the BSX group (10.22 ± 1.38%). Conclusion: Overall, our results indicate that the expansion of alloreactive T cells occurs rapidly after transplantation in patients receiving either thymo or BSX induction. Whether differences at later timepoints or whether different IS regimens may modify this alloreactive population remains to be studied.

Incidence of bullous pemphigoid and pemphigus in Switzerland: a 2-year prospective study.

BACKGROUND: Bullous pemphigoid (BP), pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are autoimmune bullous diseases characterized by the presence of tissue-bound and circulating autoantibodies directed against disease-specific target antigens of the skin. Although rare, these diseases run a chronic course and are associated with significant morbidity and mortality. There are few prospective data on gender- and age-specific incidence of these disorders. OBJECTIVES: Our aims were: (i) to evaluate the incidence of BP and PV/PF in Swiss patients, as the primary endpoint; and (ii) to assess the profile of the patients, particularly for comorbidities and medications, as the secondary endpoint. METHODS: The protocol of the study was distributed to all dermatology clinics, immunopathology laboratories and practising dermatologists in Switzerland. All newly diagnosed cases of BP and pemphigus occurring between 1 January 2001 and 31 December 2002 were collected. In total, 168 patients (73 men and 95 women) with these autoimmune bullous diseases, with a diagnosis based on clinical, histological and immunopathological criteria, were finally included. RESULTS: BP showed a mean incidence of 12.1 new cases per million people per year. Its incidence increased significantly after the age of 70 years, with a maximal value after the age of 90 years. The female/male ratio was 1.3. The age-standardized incidence of BP using the European population as reference was, however, lower, with 6.8 new cases per million people per year, reflecting the ageing of the Swiss population. In contrast, both PV and PF were less frequent. Their combined mean incidence was 0.6 new cases per million people per year. CONCLUSIONS; This is the first comprehensive prospective study analysing the incidence of autoimmune bullous diseases in an entire country. Our patient cohort is large enough to establish BP as the most frequent autoimmune bullous disease. Its incidence rate appears higher compared with other previous studies, most likely because of the demographic characteristics of the Swiss population. Nevertheless, based on its potentially misleading presentations, it is possible that the real incidence rate of BP is still underestimated. Based on its significant incidence in the elderly population, BP should deserve more public health concern.

Prevalence of Joint Hypermobility and Joint Hypermobility Syndrome in a Swiss population with Chronic Low Back Pain

Objective¦Joint hypermobility (JH) and Joint Hypermobility Syndrome (JHS) are often underdiagnosed¦and were never specifically assessed in a selected population of chronic low back pain¦(LBP). This study aimed to assess JH and JHS among a population with chronic LBP using the¦Beighton and the Brigthon criteria.¦Methods¦We conducted a retrospective cross-sectional study based on a prospective data base¦among 143 patients with non-specific chronic LBP. Patients were seen by the same rheumatologist,¦who looked for JH and JHS and took their medical history. Data were analysed using logistic¦regression.¦Results¦We found a JH prevalence of 33,3% (CI 95% 22.0-44.6) among women and 21,4% (11.7-¦31.2) among men, and for JHS, of 37,9% (26.0-49.8) among women and 30,9% (19.7-42.0) among¦men. JH was less frequent among people older than fifty (P < 0.02). JHS was more prevalent among¦Swiss individuals (P < 0.01) and among individuals having a non-manual job (P<0.03) compared to¦there opposites. Patients having an important limitation for daily living activities were four times¦more likely to have JHS. Degenerative spinal disorders were negatively associated with JH (OR¦0.31 (0.13-0.73) and JHS (OR 0.31 (0.14-0.68).¦Conclusion¦A high prevalence of joint hypermobility was found in our population. JHS should be¦part of differential diagnosis in individuals with chronic non-specific LBP.

Expression quantitative trait locus mapping across water availability environments reveals contrasting associations with genomic features in Arabidopsis.

The regulation of gene expression is crucial for an organism's development and response to stress, and an understanding of the evolution of gene expression is of fundamental importance to basic and applied biology. To improve this understanding, we conducted expression quantitative trait locus (eQTL) mapping in the Tsu-1 (Tsushima, Japan) × Kas-1 (Kashmir, India) recombinant inbred line population of Arabidopsis thaliana across soil drying treatments. We then used genome resequencing data to evaluate whether genomic features (promoter polymorphism, recombination rate, gene length, and gene density) are associated with genes responding to the environment (E) or with genes with genetic variation (G) in gene expression in the form of eQTLs. We identified thousands of genes that responded to soil drying and hundreds of main-effect eQTLs. However, we identified very few statistically significant eQTLs that interacted with the soil drying treatment (GxE eQTL). Analysis of genome resequencing data revealed associations of several genomic features with G and E genes. In general, E genes had lower promoter diversity and local recombination rates. By contrast, genes with eQTLs (G) had significantly greater promoter diversity and were located in genomic regions with higher recombination. These results suggest that genomic architecture may play an important a role in the evolution of gene expression.

Lack of EGFR-activating mutations in European patients with triple-negative breast cancer could emphasise geographic and ethnic variations in breast cancer mutation profiles.

INTRODUCTION: Triple-negative breast cancers (TNBCs) are characterised by lack of expression of hormone receptors and epidermal growth factor receptor 2 (HER-2). As they frequently express epidermal growth factor receptors (EGFRs), anti-EGFR therapies are currently assessed for this breast cancer subtype as an alternative to treatments that target HER-2 or hormone receptors. Recently, EGFR-activating mutations have been reported in TNBC specimens in an East Asian population. Because variations in the frequency of EGFR-activating mutations in East Asians and other patients with lung cancer have been described, we evaluated the EGFR mutational profile in tumour samples from European patients with TNBC. METHODS: We selected from a DNA tumour bank 229 DNA samples isolated from frozen, histologically proven and macrodissected invasive TNBC specimens from European patients. PCR and high-resolution melting (HRM) analyses were used to detect mutations in exons 19 and 21 of EGFR. The results were then confirmed by bidirectional sequencing of all samples. RESULTS: HRM analysis allowed the detection of three EGFR exon 21 mutations, but no exon 19 mutations. There was 100% concordance between the HRM and sequencing results. The three patients with EGFR exon 21 abnormal HRM profiles harboured the rare R836R SNP, but no EGFR-activating mutation was identified. CONCLUSIONS: This study highlights variations in the prevalence of EGFR mutations in TNBC. These variations have crucial implications for the design of clinical trials involving anti-EGFR treatments in TNBC and for identifying the potential target population.

The role of focal therapy in the management of localised prostate cancer: a systematic review.

CONTEXT: The incidence of localised prostate cancer is increasing worldwide. In light of recent evidence, current, radical, whole-gland treatments for organ-confined disease have being questioned with respect to their side effects, cancer control, and cost. Focal therapy may be an effective alternative strategy. OBJECTIVE: To systematically review the existing literature on baseline characteristics of the target population; preoperative evaluation to localise disease; and perioperative, functional, and disease control outcomes following focal therapy. EVIDENCE ACQUISITION: Medline (through PubMed), Embase, Web of Science, and Cochrane Review databases were searched from inception to 31 October 2012. In addition, registered but not yet published trials were retrieved. Studies evaluating tissue-preserving therapies in men with biopsy-proven prostate cancer in the primary or salvage setting were included. EVIDENCE SYNTHESIS: A total of 2350 cases were treated to date across 30 studies. Most studies were retrospective with variable standards of reporting, although there was an increasing number of prospective registered trials. Focal therapy was mainly delivered to men with low and intermediate disease, although some high-risk cases were treated that had known, unilateral, significant cancer. In most of the cases, biopsy findings were correlated to specific preoperative imaging, such as multiparametric magnetic resonance imaging or Doppler ultrasound to determine eligibility. Follow-up varied between 0 and 11.1 yr. In treatment-naïve prostates, pad-free continence ranged from 95% to 100%, erectile function ranged from 54% to 100%, and absence of clinically significant cancer ranged from 83% to 100%. In focal salvage cases for radiotherapy failure, the same outcomes were achieved in 87.2-100%, 29-40%, and 92% of cases, respectively. Biochemical disease-free survival was reported using a number of definitions that were not validated in the focal-therapy setting. CONCLUSIONS: Our systematic review highlights that, when focal therapy is delivered with intention to treat, the perioperative, functional, and disease control outcomes are encouraging within a short- to medium-term follow-up. Focal therapy is a strategy by which the overtreatment burden of the current prostate cancer pathway could be reduced, but robust comparative effectiveness studies are now required.

Efficacy and Safety of Certolizumab Pegol in an Unselected Crohn's Disease Population: 26 Week Data of the FACTS II Survey.

BACKGROUND: Certolizumab pegol (Cimzia, CZP) was approved for the treatment of Crohn's disease (CD) patients in 2007 in Switzerland as first country worldwide. This prospective phase IV study aimed to evaluate the efficacy and safety of CZP over 26 weeks in a multicenter cohort of practice-based patients. METHODS: Evaluation questionnaires at baseline, week 6 and 26 were completed by gastroenterologists in hospitals and private practices. RESULTS: Sixty patients (38F/22M) were included, 53% had complicated disease (stricturing or penetrating), 45% had undergone prior CD related surgery. All patients had prior exposure to systemic steroids, 96% to immunomodulators, 73% to infliximab, and 43% to adalimumab. A significant decrease of Harvey Bradshaw Index (HBI) was observed under CZP therapy (12.24.9 at week 0 vs 6.34.7 at week 6 and 6.75.3 at week 26, both P <0.001). Response and remission rates were 70% and 40% (week 6) and 67% and 36% respectively (week 26). The complete perianal fistula closure rate was 36% at week 6 and 55% at week 26. The frequency of adverse drug reactions attributed to CZP was 5%. CZP was continued in 88% of patients beyond week 6 and in 67% beyond week 26. CONCLUSIONS: In a population of CD patients with predominantly complicated disease behaviour, CZP proved to be effective in induction and maintenance of response and remission. This series provides the first evidence of CZP's effectiveness in perianal fistulizing CD in clinical practice.

Identification of ectodysplasin target genes reveals the involvement of chemokines in hair development.

Ectodysplasin (Eda), a member of the tumor necrosis factor (Tnf) family, regulates skin appendage morphogenesis via its receptor Edar and transcription factor NF-κB. In humans, inactivating mutations in the Eda pathway components lead to hypohidrotic ectodermal dysplasia (HED), a syndrome characterized by sparse hair, tooth abnormalities, and defects in several cutaneous glands. A corresponding phenotype is observed in Eda-null mice, where failure in the initiation of the first wave of hair follicle development is a hallmark of HED pathogenesis. In an attempt to discover immediate target genes of the Eda/NF-κB pathway, we performed microarray profiling of genes differentially expressed in embryonic skin explants after a short exposure to recombinant Fc-Eda protein. Upregulated genes included components of the Wnt, fibroblast growth factor, transforming growth factor-β, Tnf, and epidermal growth factor families, indicating that Eda modulates multiple signaling pathways implicated in skin appendage development. Surprisingly, we identified two ligands of the chemokine receptor cxcR3, cxcl10 and cxcl11, as new hair-specific transcriptional targets of Eda. Deficiency in cxcR3 resulted in decreased primary hair follicle density but otherwise normal hair development, indicating that chemokine signaling influences the patterning of primary hair placodes only.

CleanEx: a database of heterogeneous gene expression data based on a consistent gene nomenclature.

The main goal of CleanEx is to provide access to public gene expression data via unique gene names. A second objective is to represent heterogeneous expression data produced by different technologies in a way that facilitates joint analysis and cross-data set comparisons. A consistent and up-to-date gene nomenclature is achieved by associating each single experiment with a permanent target identifier consisting of a physical description of the targeted RNA population or the hybridization reagent used. These targets are then mapped at regular intervals to the growing and evolving catalogues of human genes and genes from model organisms. The completely automatic mapping procedure relies partly on external genome information resources such as UniGene and RefSeq. The central part of CleanEx is a weekly built gene index containing cross-references to all public expression data already incorporated into the system. In addition, the expression target database of CleanEx provides gene mapping and quality control information for various types of experimental resource, such as cDNA clones or Affymetrix probe sets. The web-based query interfaces offer access to individual entries via text string searches or quantitative expression criteria. CleanEx is accessible at: http://www.cleanex.isb-sib.ch/.