Anti-tumor necrosis factor drug survival in axial spondyloarthritis is independent of the classification criteria.

To compare the impact of meeting specific classification criteria [modified New York (mNY), European Spondyloarthropathy Study Group (ESSG), and Assessment of SpondyloArthritis international Society (ASAS) criteria] on anti-tumor necrosis factor (anti-TNF) drug retention, and to determine predictive factors of better drug survival. All patients fulfilling the ESSG criteria for axial spondyloarthritis (SpA) with available data on the axial ASAS and mNY criteria, and who had received at least one anti-TNF treatment were retrospectively retrieved in a single academic institution in Switzerland. Drug retention was computed using survival analysis (Kaplan-Meier), adjusted for potential confounders. Of the 137 patients classified as having axial SpA using the ESSG criteria, 112 also met the ASAS axial SpA criteria, and 77 fulfilled the mNY criteria. Drug retention rates at 12 and 24 months for the first biologic therapy were not significantly different between the diagnostic groups. Only the small ASAS non-classified axial SpA group (25 patients) showed a nonsignificant trend toward shorter drug survival. Elevated CRP level, but not the presence of bone marrow edema on magnetic resonance imaging (MRI) scans, was associated with significantly better drug retention (OR 7.9, ICR 4-14). In this cohort, anti-TNF drug survival was independent of the classification criteria. Elevated CRP level, but not positive MRI, was associated with better drug retention.

Les thromboses veineuses mésentériques : facteurs associés à une évolution chronique et prévalence et importance clinique dans la Swiss Inflammatory Bowel Disease Cohort

Ce projet de thèse consiste en deux travaux sur le thème commun des thromboses veineuses mésentériques. Dans le premier travail, préliminaire au deuxième, nous avons décrit les signes d'évolution chronique des thromboses veineuses mésentériques. Les signes aigus sont bien connus et bien décrits (défaut de remplissage intra-luminal) contrairement aux signes chroniques dont la description manquait dans la littérature. Nous avons de plus cherché quels étaient les facteurs prédicateurs pour une évolution chronique. Pour se faire, nous avons sélectionné un collectif de patients avec un diagnostic de thromboses veineuses mésentériques aiguës et avons revu tous les scanners abdominaux en phase veineuse de ces patients à la recherche des signes d'évolution des thromboses. Cette étude a permis de mettre en évidence que les signes d'évolution chronique des thromboses veineuses mésentériques sont la sténose ou l'obstruction complète de la veine thrombosée et le développement d'un réseau de collatérales permettant de contourner la veine thrombosée. D'autre part, nous avons mis en évidence que la plupart des cas de thrombose veineuse mésentérique présente une évolution chronique, indépendamment de si le patient a reçu un traitement anticoagulant. Les thromboses étendues, situées dans des veines de petit calibre, auquel s'associe une infiltration de la graisse mésentérique au moment du diagnostic sont des facteurs favorisants pour une évolution chronique. La seconde étude a été réalisée grâce et avec la collaboration de la « Swiss Inflammatory Bowel Disease Cohort study » (SIBDCS). Les patients atteints de maladie inflammatoire chronique de l'intestin (MICI) présentent un risque augmenté de complications thromboemboliques, principalement de thrombose veineuse périphérique et d'embolie pulmonaire mais également de thrombose veineuse mésentérique. La littérature à ce sujet est pauvre et la prévalence de cette complication n'est pas connue dans cette population. Les buts de cette étude étaient donc d'évaluer la prévalence des thromboses veineuses mésentériques chez les patients atteints de MICI et de corréler leur survenue avec l'évolution clinique des patients. Parmi les patients inclus dans la SIBDCS, suivis au CHUV, nous avons revu tous les scanners abdominaux réalisés en phase veineuse à la recherche de signes (aigus ou chroniques) de thrombose veineuse mésentérique. Nous avons ainsi créé deux groupes de patients : les patients avec ou sans thrombose veineuse mésentérique. Ces deux collectifs ont ensuite été corrélés à la présence de signes radiologiques d'activité de la maladie inflammatoire de l'intestin et à la survenue aux complications liées à la MICI. Ainsi, nous avons mis en évidence que les thromboses veineuses mésentériques sont fréquentes chez les patients atteints de MICI, soit près de 30% chez les patients atteints de maladie de Crohn et 20% chez les patients atteints de RCUH. D'autre part, dans le groupe de patients atteints de maladie de Crohn, nous avons trouvé une association entre la survenue de thrombose veineuse mésentérique et une évolution de la maladie de Crohn plus sévère (plus de signes d'activité radiologique) et plus compliquée (plus de sténose et de nécessité de recours à la chirurgie). Ces deux articles ont été publiés dans l'American Journal of Roentgenology au mois de juillet 2014 dans la rubrique Gastrointestinal imaging.

Clinical and biological determinants of kidney outcomes in a population-based cohort study

BACKGROUND/AIMS: Prospective studies on factors associated with adverse kidney outcomes in European general populations are scant. Also, few studies consider the potential confounding effect of baseline kidney function. METHODS: We used baseline (2003-2006) and 5-year follow-up data of adults from the general population to evaluate the effect of baseline kidney function and proteinuria on the association of clinical, biological (e.g. uric acid, homocysteine, cytokines), and socioeconomic factors with change in kidney function, rapid decline in kidney function, and incidence of chronic kidney disease (CKD). Estimated glomerular filtration rate (eGFR) and urinary albuminuria-to-creatinine ratio (UACR) were collected. Kidney outcomes were modeled using multivariable regressions. RESULTS: A total of 4,441 subjects were included in the analysis. Among participants without CKD at baseline, 11.4% presented rapid decline in eGFR and/or incident CKD. After adjustment for baseline eGFR and log UACR, only age (Odds Ratio; 1.25 [95%CI 1.18-1.33]), diabetes (OR 1.48 [1.03-2.13]), education (OR middle vs. high 1.51 [1.08-2.11]) and log ultrasensitive CRP (OR 1.16 [1.05-1.22]) were associated with rapid decline in eGFR or incident CKD. Baseline log UACR (OR 1.18 [1.06-1.32]) but not eGFR was associated with rapid decline in eGFR and/or incident CKD. CONCLUSION: In addition to age and diabetes, education and CRP levels are associated with adverse kidney outcomes independently of baseline kidney function.

Protein interaction data curation: the International Molecular Exchange (IMEx) consortium.

The International Molecular Exchange (IMEx) consortium is an international collaboration between major public interaction data providers to share literature-curation efforts and make a nonredundant set of protein interactions available in a single search interface on a common website (http://www.imexconsortium.org/). Common curation rules have been developed, and a central registry is used to manage the selection of articles to enter into the dataset. We discuss the advantages of such a service to the user, our quality-control measures and our data-distribution practices.

Connective tissue growth factor, steatosis and fibrosis in patients with chronic hepatitis C.

BACKGROUND/AIM: Both steatosis and insulin resistance have been linked to accelerated fibrosis in chronic hepatitis C. Connective tissue growth factor (CTGF) plays a major role in extracellular matrix production in fibrotic disorders including cirrhosis, and its expression is stimulated in vitro by insulin and glucose. We hypothesized that CTGF may link steatosis, insulin resistance and fibrosis. METHODS: We included 153 chronic hepatitis C patients enrolled in the Swiss Hepatitis C Cohort Study and for whom a liver biopsy and plasma samples were available. CTGF expression was assessed quantitatively by immunohistochemistry. In 94 patients (57 with genotypes non-3), plasma levels of glucose, insulin and leptin were also measured. CTGF synthesis was investigated by immunoblotting on LX-2 stellate cells. RESULTS: Connective tissue growth factor expression was higher in patients with steatosis (P=0.039) and in patients with fibrosis (P=0.008) than those without these features. CTGF levels were neither associated with insulinaemia or with glycaemia, nor with inflammation. By multiple regression analysis, CTGF levels were independently associated with steatosis, a past history of alcohol abuse, plasma leptin and HCV RNA levels; when only patients with genotypes non-3 were considered, CTGF levels were independently associated with a past history of alcohol abuse, plasma leptin levels and steatosis. Leptin stimulated CTGF synthesis in LX-2 cells. CONCLUSIONS: In patients with chronic hepatitis C and steatosis, CTGF may promote fibrosis independently of inflammation. CTGF may link steatosis and fibrosis via increased leptin levels.

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

A cohort-based analysis of the evolution of lifetime prevalence of recourse to prostitution by men in the general population of Switzerland, 1987-2000

Background: Despite their relevance to the prevention of sexually transmitted infections, there are few data on the frequency of recourse to prostitution in the male population in Switzerland. Using data gathered for the evaluation of the Swiss AIDS prevention strategy, we analysed net aggregate change and cohort-based change in lifetime prevalence of recourse to prostitution. Methods: Seven repeated cross-sectional telephone surveys of the general population aged 17-45 years (17-30 years only for the 1987 and 1988 surveys) were undertaken from 1987 to 2000 providing information on sexual behaviour including men's recourse to prostitution (total n¼9318). Age categories were: 17-20, 21-25, 26-30, 31-35, 36-40 and 41-45 years. Prevalence at 17-30 years was available in all surveys and prevalence at 41-45 was available for 1989-2000, though not for the same cohorts. Intra-cohort increase in prevalence over 10 years was analysed using truncated information for cohorts aged 21-25 and 26-30 years in 1987 and 1990. Population estimates were computed with 95% confidence intervals (CI). Results: No net change occurred in the 17-45 years male population prevalence between 1989 (17.6%, CI ¼ 15.4; 20.0) and 2000 (17.7%, CI ¼ 15.6; 20.0). The median starting prevalence of recourse to prostitution at age 17-20 was 4.8% (in 1989, CI ¼ 2.0; 9.7) and the range was from 1.8 (in 1994) to 10.4% (in 1990). The median ending prevalence at age 41-45 was 21.9% (in 1994, CI 16.7; 27.9) and the range was from 17.9 (in 2000) to 26.1% (in 1992). No clear trend was observed in either starting or ending prevalence. Intra-cohort evolution of the 1997 and 1990 cohorts was very similar. Conclusions: Based on available data, there was no net (aggregate) change in the prevalence of recourse to prostitution by males in Switzerland between 1989 and 2000. Within the time frame available, intra-cohort evolution was also very similar.

The Visual Dysphagia Questionnaire: Piloting a New Tool for Assessing Food Consistency-Dependent Dysphagia in Eosinophilic Esophagitis

Background and Aims: The international EEsAI study group is currently developing the first activity index specific for Eosinophilic Esophagitis (EoE). None of the existing dysphagia questionnaires takes into account the consistency of the ingested food that considerably impacts the symptom presentation. Goal: To develop an EoE-specific questionnaire assessing dysphagia associated with different food consistencies. Methods: Based on patient chart reviews, an expert panel (EEsAI study group) identified internationally standardized food prototypes typically associated with EoE-related dysphagia. Food consistencies were correlated with EoE-related dysphagia, also considering potential food avoidance. This Visual Dysphagia Questionnaire (VDQ) was then tested, as a pilot, in 10 EoE patients. Results: The following 9 food consistency prototypes were identified: water, soft foods (pudding, jelly), grits, toast bread, French fries, dry rice, ground meat, raw fibrous foods (eg. apple, carrot), solid meat. Dysphagia was ranked on a 5-point Likert scale (0=no difficulties, 5=very severe difficulties, food will not pass). Severity of dysphagia in the 10 EoE patients was related to the eosinophil load and presence of esophageal strictures. Conclusions: The VDQ will be the first EoE-specific tool for assessing dysphagia related to internationally defined food consistencies. It performed well in a pilot study and will now be further evaluated in a cohort study including 100 adult and 100 pediatric EoE patients.

Objectifying psychomental stress in the workplace--an example.

BACKGROUND: Psychomental stress is a major source of illness and reduced productivity. Data objectifying physiological stress responses are scarce. We studied salivary cortisol levels in a highly stressful environment, the pediatric critical care unit. The aim was to identify targets for organizational changes, to implement these changes and to assess their impact on cortisol levels. DESIGN: Repeated measurements observational cohort study (before and after intervention). SUBJECTS: 84 nurses working in two independent teams (A and B) in a 19 bed pediatric intensive care unit. Between study periods team A experienced a major exchange of experienced staff while the turnover rate in team B remained average. MEASUREMENTS AND INTERVENTIONS: Salivary cortisol samples were collected every 2 h and after stressful events. Nurses in study period I showed elevated cortisol levels at the beginning of the late shift, interpreted as an anticipatory stress reaction. To ease conditions during the early part of the late shift (conflicting tasks, noise and crowding), we postponed the afternoon ward round, limited non-urgent procedures and introduced a change in visiting hours. The early shift, which was not affected by the intervention, served as control. MAIN RESULTS: Both crude and adjusted analysis revealed a decrease of cortisol levels at the beginning of the late shift in team B (p = 0.0009), but not in team A (p = 0.464). The control situation showed no difference between teams and study periods. INTERPRETATION: We demonstrated reduced cortisol secretions in one team following organizational changes, which was probably overridden by the disruption of social coherence in the second team.