Can the trabecular bone score be considered as a major clinical risk factor of osteoporotic fractures? A meta-like analysis.

To have an added value over BMD, a CRF of osteoporotic fracture must be predictable of the fracture, independent of BMD, reversible and quantifiable. Many major recognized CRF exist. Out of these factors many of them are indirect factor of bone quality. TBS predicts fracture independently of BMD as demonstrated from previous studies. The aim of the study is to verify if TBS can be considered as a major CRF of osteoporotic fracture. Existing validated datasets of Caucasian women were analyzed. These datasets stem from different studies performed by the authors of this report or provided to our group. However, the level of evidence of these studies will vary. Thus, the different datasets were weighted differently according to their design. This meta-like analysis involves more than 32000 women (≥50years) with 2000 osteoporotic fractures from two prospective studies (OFELY&MANITOBA) and 7 cross-sectional studies. Weighted relative risk (RR) for TBS was expressed for each decrease of one standard deviation as well as per tertile difference (TBS=1.300 and 1.200) and compared with those obtained for the major CRF included in FRAX®. Overall TBS RR obtained (adjusted for age) was 1.79 [95%CI-1.37-2.37]. For all women combined, RR for fracture for the lowest compared with the middle TBS tertile was 1.55[1.46-1.68] and for the lowest compared with the highest TBS tertile was 2.8[2.70-3.00]. TBS is comparable to most of the major CRF and thus could be used as one of them. Further studies have to be conducted to confirm these first findings.

Sentinel lymph node involvement and a high Breslow index are independent factors of risk for early relapse of melanoma.

AIM: The clinical relevance of sentinel lymph node (SLN) analysis was evaluated prospectively and compared with other known risk factors of relapse in early stage melanoma. METHODS: Surgery was guided by lymphoscintigraphy, blue dye and gamma probe detection. SLN were analysed by haematoxylin eosin (HE) histochemistry and multimarker immunohistochemistry (IHC). Disease free survival (DFS) was evaluated with Kaplan-Meier plots according to different parameters and Cox analyses of variance. RESULTS: From 210 patients a total of 381 SLN were excised. Lymphoscintigraphy identified all excised SLN with only 2 false positive lymphatic lakes. Fifty patients (24%) had tumour positive SLN. With a mean follow-up of 31.3 months, 29 tumour recurrences were observed, 19 (38%) in 50 SLN positive and 10 (6%) in 160 SLN negative patients. Strong predictive factors for early relapse (p < 0.0005) were SLN positivity and a high Breslow index. CONCLUSION: SLN tumour positivity is an independent factor of high risk for early relapse with a higher power of discrimination than the Breslow index.

Withdrawal, "serosorting" and "strategic positioning": use of risk reduction strategies with casual sex partners in men who have sex with men (MSM) in Switzerland, 2007

Introduction: 1) Withdrawal before ejaculation, "serosorting" (to choose a partner of same serostatus) and "strategic positioning" (only insertive vs. only receptive role in anal sex according to serostatus) are known to be used by MSM as alternatives to condom use. 2) Despite their questionable levels of effectiveness they are collectively labelled as "risk reduction strategies" (RRS). Objectives: The aim of this study is to estimate the prevalence and factors related to RRS in men who report unprotected anal intercourse (UAI) with occasional partners in the last 12 months. Methods: 1) In 2007, a module on RRS was included in a repeated national survey conducted among readers of gay newspapers, members of gay organizations and visitors of gay websites (N=2953). 2) Using an anonymous self-completed questionnaire, participants were asked whether, with the aim of avoiding HIV infection, RRS were used with occasional partners. Analysis: 1) Prevalences were calculated in participants who reported UAI with occasional partners in the last 12 months (n=416). 2) A logistic regression was performed, using "at least one RRS" as dependent variable. Number of partners in the last 12 months, HIV-status and usual socio-demographic characteristics were used as independent factors. Result : 1) 70% (292/416) of the participants reporting UAI used at least one RRS when they had unprotected sex with casual partners in the last 12 months (Table 1). 2) Withrawal before ejaculation was the most frequently reported strategy, followed by serosorting and strategic positioning (Table 1). 3) Participants who reported at least one RRS were more likely to be over 30 years and to belong to a gay organisation. HIV-positive and non-tested participants were less likely to report RRS than HIV-negative participants (Table 2). Conclusions: 1) The majority of MSM who reported UAI in the last 12 months tried to reduce risk of HIV transmission by using specific strategies (withdrawal, serosorting, strategic positioning). It is not known, however, to what extent the use of these strategies was systematic. 2) It is necessary to provide MSM with balanced information on these strategies and their respective level of effectiveness. 3) It is important to monitor the use of RRS in HIV behavioural surveillance surveys in MSM.

Maturation of marginal zone and follicular B cells requires B cell activating factor of the tumor necrosis factor family and is independent of B cell maturation antigen.

B cells undergo a complex series of maturation and selection steps in the bone marrow and spleen during differentiation into mature immune effector cells. The tumor necrosis factor (TNF) family member B cell activating factor of the TNF family (BAFF) (BLyS/TALL-1) plays an important role in B cell homeostasis. BAFF and its close homologue a proliferation-inducing ligand (APRIL) have both been shown to interact with at least two receptors, B cell maturation antigen (BCMA) and transmembrane activator and cyclophilin ligand interactor (TACI), however their relative contribution in transducing BAFF signals in vivo remains unclear. To functionally inactivate both BAFF and APRIL, mice transgenic for a soluble form of TACI were generated. They display a developmental block of B cell maturation in the periphery, leading to a severe depletion of marginal zone and follicular B2 B cells, but not of peritoneal B1 B cells. In contrast, mice transgenic for a soluble form of BCMA, which binds APRIL, have no detectable B cell phenotype. This demonstrates a crucial role for BAFF in B cell maturation and strongly suggests that it signals via a BCMA-independent pathway and in an APRIL-dispensable way.

The social transition of risk factors for cardiovascular disease in the African region: evidence from three cross-sectional surveys in the Seychelles.

OBJECTIVES: To examine the association between socioeconomic status (SES) and several cardiovascular disease risk factors (CVRFs) and to assess whether this association has changed over a 15-year observation period. METHODS: Three independent population-based surveys of CVRFs were conducted in representative samples of all adults aged 25-64 years in the Seychelles, a small island state located east to Kenya, in 1989 (N=1081), 1994 (N=1067) and 2004 (N=1255). RESULTS: Among men, current smoking and heavy drinking were more prevalent in the low versus the high SES group, and obesity was less prevalent. The socioeconomic gradient in diabetes reversed over the study period from lower prevalence in the low versus the high SES group to higher prevalence in the low SES group. Hypercholesterolemia was less prevalent in the low versus the high SES group in 1989 but the prevalence was similar in the two groups in 2004. Hypertension showed no consistent socioeconomic pattern. Among women, the SES gradient in smoking tended to reverse over time from lower prevalence in the low SES group to lower prevalence in the high SES group. Obesity and diabetes were more common in the low versus the high SES group over the study period. Heavy drinking, hypertension and hypercholesterolemia were not socially patterned among women. CONCLUSION: The prevalence of several CVRFs was higher in low versus high SES groups in a rapidly developing country in the African region, and an increase of the burden of these CVRFs in the most disadvantaged groups of the population was observed over the 15 years study period.

Systematic evaluation of risk factors for diagnostic delay in inflammatory bowel disease.

The diagnosis of inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), continues to present difficulties due to unspecific symptoms and limited test accuracies. We aimed to determine the diagnostic delay (time from first symptoms to IBD diagnosis) and to identify associated risk factors. A total of 1591 IBD patients (932 CD, 625 UC, 34 indeterminate colitis) from the Swiss IBD cohort study (SIBDCS) were evaluated. The SIBDCS collects data on a large sample of IBD patients from hospitals and private practice across Switzerland through physician and patient questionnaires. The primary outcome measure was diagnostic delay. Diagnostic delay in CD patients was significantly longer compared to UC patients (median 9 versus 4 months, P < 0.001). Seventy-five percent of CD patients were diagnosed within 24 months compared to 12 months for UC and 6 months for IC patients. Multivariate logistic regression identified age <40 years at diagnosis (odds ratio [OR] 2.15, P = 0.010) and ileal disease (OR 1.69, P = 0.025) as independent risk factors for long diagnostic delay in CD (>24 months). In UC patients, nonsteroidal antiinflammatory drug (NSAID intake (OR 1.75, P = 0.093) and male gender (OR 0.59, P = 0.079) were associated with long diagnostic delay (>12 months). Whereas the median delay for diagnosing CD, UC, and IC seems to be acceptable, there exists a long delay in a considerable proportion of CD patients. More public awareness work needs to be done in order to reduce patient and doctor delays in this target population.

Systematic evaluation of risk factors for diagnostic delay in inflammatory bowel

Aim: The diagnosis of inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), continues to present difficulties due to unspecific symptoms and limited test accuracies. We aimed to determine the diagnostic delay (time from first symptoms to IBD diagnosis) and to identify associated risk factors in a national cohort in Switzerland.¦Materials and Methods: A total of 1,591 IBD patients (932 CD, 625 UC, 34 indeterminate colitis) from the Swiss IBD cohort study (SIBDCS) were evaluated. The SIBDCS collects data on a large sample of IBD patients from hospitals and private practice across Switzerland through physician and patient questionnaires. The primary outcome measure was the diagnostic delay.¦Results: Diagnostic delay in CD patients was significantly longer compared to UC patients (median 9 vs. 4 months, P < 0.001). Seventy-five percent of CD patients were diagnosed within 24 months compared to 12 months for UC and 6 months for IC patients. Multivariate logistic regression identified age <40 years at diagnosis (OR 2.15, P = 0.010) and ileal disease (OR 1.69, P = 0.025) as independent risk factors for long diagnostic delay in CD (>24 months). A trend for long diagnostic delay (>12 months) was associated with NSAID intake (OR 1.75, P = 0.093) and male gender (OR 0.59, P = 0.079) in UC patients.¦Conclusions: Whereas the median delay for diagnosing CD, UC, and IC seems to be acceptable, there exists a long delay in a considerable proportion of CD patients. More public awareness work needs to be done in order to reduce patient's and doctor's delay in this target population.

Prospective evaluation of risk of vertebral fractures using quantitative ultrasound measurements and bone mineral density in a population-based sample of postmenopausal women: results of the Basel Osteoporosis Study.

OBJECTIVE: Prospective studies have shown that quantitative ultrasound (QUS) techniques predict the risk of fracture of the proximal femur with similar standardised risk ratios to dual-energy x-ray absorptiometry (DXA). Few studies have investigated these devices for the prediction of vertebral fractures. The Basel Osteoporosis Study (BOS) is a population-based prospective study to assess the performance of QUS devices and DXA in predicting incident vertebral fractures. METHODS: 432 women aged 60-80 years were followed-up for 3 years. Incident vertebral fractures were assessed radiologically. Bone measurements using DXA (spine and hip) and QUS measurements (calcaneus and proximal phalanges) were performed. Measurements were assessed for their value in predicting incident vertebral fractures using logistic regression. RESULTS: QUS measurements at the calcaneus and DXA measurements discriminated between women with and without incident vertebral fracture, (20% height reduction). The relative risks (RRs) for vertebral fracture, adjusted for age, were 2.3 for the Stiffness Index (SI) and 2.8 for the Quantitative Ultrasound Index (QUI) at the calcaneus and 2.0 for bone mineral density at the lumbar spine. The predictive value (AUC (95% CI)) of QUS measurements at the calcaneus remained highly significant (0.70 for SI, 0.72 for the QUI, and 0.67 for DXA at the lumbar spine) even after adjustment for other confounding variables. CONCLUSIONS: QUS of the calcaneus and bone mineral density measurements were shown to be significant predictors of incident vertebral fracture. The RRs for QUS measurements at the calcaneus are of similar magnitude as for DXA measurements.

Systematic review and meta-analysis of risk factors for survival after lung metastasectomy in colorectal cancer patients

Objective: Resection of lung metastases (LM) from colorectal cancer (CRC)¦is increasingly performed with a curative intent.Most series report small groups¦of patients, and it is currently not possible to identify those CRC patients who¦may benefit the most of surgical management. It is clinically relevant to assess¦risk factors for prolonged survival after this type of procedures.¦Methods: A meta analysis of 24 series published between 2000 and 2011¦which focused on surgical management of LM from CRC and included more¦than 40 patients each, with or without prior resection of in transit liver¦metastases. Random effects were calculated for five variables considered as¦potential prognostic factors.¦Results: A total of 2815 patients who underwent surgery with a curative¦intent were considered in this analysis. Four parameters were associated with¦a decreased survival: 1) a short disease-free interval between primary tumor¦resection and development of LM (HR = 1·59, 95% CI 1·27-1·98); 2) multiple¦LM (HR = 2·04, 95%CI 1·72-2·41); 3) positive hilar/mediastinal lymph nodes¦(HR = 1·65, 95% CI 1·35-2·02); and 4) a high prethoracotomy CEA value (HR¦=1·91, 95% CI 1·57-2·32). By comparison, a history of resected liver metastases¦(HR = 1·36, 95% CI 0·92-2·03) did not achieve statistical significance.¦Conclusion: Risk factors for poor clinical outcome after surgery for lung¦metastases in CRC patients include: 1) synchronous lung metastases; 2) high¦pre-thoracotomy CEA; 3) hilar nodes involvement; and 4) multiple pulmonary¦lesions.

Clustering of risk behaviors with cigarette consumption: a population-based survey.

OBJECTIVE: This study assessed clustering of multiple risk behaviors (i.e., low leisure-time physical activity, low fruits/vegetables intake, and high alcohol consumption) with level of cigarette consumption. METHODS: Data from the 2002 Swiss Health Survey, a population-based cross-sectional telephone survey assessing health and self-reported risk behaviors, were used. 18,005 subjects (8052 men and 9953 women) aged 25 years old or more participated. RESULTS: Smokers more frequently had low leisure time physical activity, low fruits/vegetables intake, and high alcohol consumption than non- and ex-smokers. Frequency of each risk behavior increased steadily with cigarette consumption. Clustering of risk behaviors increased with cigarette consumption in both men and women. For men, the odds ratios of multiple (> or =2) risk behaviors other than smoking, adjusted for age, nationality, and educational level, were 1.14 (95% confidence interval: 0.97, 1.33) for ex-smokers, 1.24 (0.93, 1.64) for light smokers (1-9 cigarettes/day), 1.72 (1.36, 2.17) for moderate smokers (10-19 cigarettes/day), and 3.07 (2.59, 3.64) for heavy smokers (> or =20 cigarettes/day) versus non-smokers. Similar odds ratios were found for women for corresponding groups, i.e., 1.01 (0.86, 1.19), 1.26 (1.00, 1.58), 1.62 (1.33, 1.98), and 2.75 (2.30, 3.29). CONCLUSIONS: Counseling and intervention with smokers should take into account the strong clustering of risk behaviors with level of cigarette consumption.

Sentinel lymph node involvement and a high Breslow index are independent factors of risk for early relapse of melanoma

Rapport de synthèse : Le ganglion sentinelle (GS) se défini comme le premier ganglion de la chaîne ganglionnaire qui draine le territoire anatomique où siège une tumeur et, par conséquent, celui ayant le plus de possibilités de recevoir des métastases. La combinaison des deux techniques de détection du GS existantes, lymphoscintigraphie et coloration, permettent de déceler le GS dans 95-100% des cas. Le taux d'attente métastatique du GS varie entre 16 et 21 % des patients. Dans 50 à 87% des cas, le GS est le seul site de métastase et la probabilité de trouver des micro-métastases dans des ganglions appartenant aux relais supérieurs sans atteinte du GS est estimée à moins de 2%. Ces chiffres relèvent l'importance de la détection du GS. L'emploi de cette technique offre de nombreux avantages par rapport à la lymphadénéctomie élective que nous décrirons. Selon Rousseau et al., il existe une probable association entre le statut du GS et la survie de la maladie. Cette interprétation et celles d'autres auteurs soulignent la pertinence clinique du statut du GS dans le mélanome. En ce qui concerne la survie sans maladie (DFS) et la survie globale (OS), aucune différence significative n'a été observée entre les patients ayant subi une résection complète immédiate des ganglions lymphatiques et ceux qui d'abord ont subi une résection chirurgicale et analyse du GS secondaire, suivies par une dissection élective en cas de positivité. L'objectif de cette étude prospective était d'évaluer la pertinence de la positivité tumorale du GS dans l'évaluation des risques de rechute du mélanome. Cette étude a confirmé l'intérêt de la scintigraphie des ganglions lymphatiques (associée à la technique de coloration par bleu et celle de détection par sonde portable) dans l'identification du GS comme approche thérapeutique au stade précoce du mélanome. Elle a montré, en autre, que le statut du GS et l'indice de Breslow sont des facteurs de risque indépendants importants de rechute chez des patients atteints d'un mélanome au stade précoce. La combinaison de ces deux paramètres a permis de créer des groupes de patients à risque de rechute différents qui pourraient conduire à l'adaptation des protocoles de thérapie en fonction de ces risques.

Unique and conserved functions of B cell-activating factor of the TNF family (BAFF) in the chicken.

The chicken represents the best-characterized animal model for B cell development in the so-called gut-associated lymphoid tissue (GALT) and the molecular processes leading to B cell receptor diversification in this species are well investigated. However, the mechanisms regulating B cell development and homeostasis in GALT species are largely unknown. Here we investigate the role played by the avian homologue of B cell-activating factor of the tumor necrosis factor family (BAFF). Flow cytometric analysis showed that the receptor for chicken B cell-activating factor of the tumor necrosis factor family (chBAFF) is expressed by mature and immature B cells. Unlike murine and human BAFF, chBAFF is primarily produced by B cells both in peripheral lymphoid organs and in the bursa of Fabricius, the chicken's unique primary lymphoid organ. In vitro and in vivo studies revealed that chBAFF is required for mature B cell survival. In addition, in vivo neutralization with a decoy receptor led to a reduction of the size and number of B cell follicles in the bursa, demonstrating that, in contrast to humans and mice, in chickens BAFF is also required for the development of immature B cells. Collectively, we show that chBAFF has phylogenetically conserved functions in mature B cell homeostasis but displays unique and thus far unknown properties in the regulation of B cell development in birds.