Prévention du métanome en Suisse: où en sommes-nous [Melanoma prevention in Switzerland: where do we stand?]

Over the last 50 years, skin cancer rates (particularly melanoma) have markedly increased in Caucasian populations. Switzerland, with some 1,600 cases of, and 220 deaths from, malignant melanoma per year has among the highest rates in Europe. This public health issue, affecting relatively young people, has led to primary and secondary nationwide prevention campaigns being carried out for nearly 20 years. Observed changes in sun protection knowledge and attitudes have yet to impact on incidence trend. Early detection has resulted in a large increase in rates of thin melanoma with little change in rates of thick melanoma. Mortality has levelled off and a recent decrease, especially in women, cannot be ruled out. The efficiency of prevention campaigns should soon become more blatant if current efforts persist.

The Role of Interleukin-2 in Memory CD8 Cell Differentiation

The current literature on the role of interleukin (IL)-2 in memory CD8(+) T-cell differentiation indicates a significant contribution of IL-2 during primary and also secondary expansion of CD8(+) T cells. IL-2 seems to be responsible for optimal expansion and generation of effector functions following primary antigenic challenge. As the magnitude of T-cell expansion determines the numbers of memory CD8(+) T cells surviving after pathogen elimination, these events influence memory cell generation. Moreover, during the contraction phase of an immune response where most antigen-specific CD8(+) T cells disappear by apoptosis, IL-2 signals are able to rescue CD8(+) T cells from cell death and provide a durable increase in memory CD8(+) T-cell counts. At the memory stage, CD8(+) T-cell frequencies can be boosted by administration of exogenous IL-2. Significantly, only CD8(+) T cells that have received IL-2 signals during initial priming are able to mediate efficient secondary expansion following renewed antigenic challenge. Thus, IL-2 signals during different phases of an immune response are key in optimizing CD8(+) T-cell functions, thereby affecting both primary and secondary responses of these T cells.

ICRC Factsheet, June 2010

Three Classes of Animals: 1. Pets are animals living with owners for purposes of love, affection, and company. 2. Emotional Support Animals provide some therapeutic benefit to person with mental or psychiatric disability, requiring no specific training. The mere presence of this animal mitigate the effects of the emotional or mental disability. 3. Service Animals are any animal individually trained to do work or perform tasks for the benefit of an individual with a physical, intellectual, and mental disability—IE guiding individuals with impaired vision, providing protection or rescue work, pulling a wheel chair, or fetching dropped items.

Early use of TIPS in patients with cirrhosis and variceal bleeding.

Background Patients with cirrhosis in ChildPugh class C or those in class B who have persistent bleeding at endoscopy are at high risk for treatment failure and a poor prognosis, even if they have undergone rescue treatment with a transjugular intrahepatic porto - systemic shunt (TIPS). This study evaluated the earlier use of TIPS in such patients. Methods We randomly assigned, within 24 hours after admission, a total of 63 patients with cirrhosis and acute variceal bleeding who had been treated with vasoactive drugs plus endoscopic therapy to treatment with a polytetrafluoroethylene-covered stent within 72 hours after randomization (early-TIPS group, 32 patients) or continuation of vasoactive-drug therapy, followed after 3 to 5 days by treatment with propranolol or nadolol and long-term endoscopic band ligation (EBL), with insertion of a TIPS if needed as rescue therapy (pharmacotherapyEBL group, 31 patients). Results During a median follow-up of 16 months, rebleeding or failure to control bleeding occurred in 14 patients in the pharmacotherapyEBL group as compared with 1 patient in the early-TIPS group (P=0.001). The 1-year actuarial probability of remaining free of this composite end point was 50% in the pharmacotherapyEBL group versus 97% in the early-TIPS group (P<0.001). Sixteen patients died (12 in the pharmacotherapyEBL group and 4 in the early-TIPS group, P=0.01). The 1-year actuarial survival was 61% in the pharmacotherapyEBL group versus 86% in the early-TIPS group (P<0.001). Seven patients in the pharmacotherapyEBL group received TIPS as rescue therapy, but four died. The number of days in the intensive care unit and the percentage of time in the hospital during follow-up were significantly higher in the pharmacotherapyEBL group than in the early-TIPS group. No significant diferences were observed between the two treatment groups with respect to serious adverse events. Conclusions In these patients with cirrhosis who were hospitalized for acute variceal bleeding and at high risk for treatment failure, the early use of TIPS was associated with signif icant reductions in treatment failure and in mortality. (Current Controlled Trials number, ISRCTN58150114.)

Nadolol plus isosorbide mononitrate alone or associated with band ligation in the prevention of recurrent bleeding: A multicenter randomized controlled trial.

Background and aims: Previous clinical trials suggest that adding non-selective beta-blockers improves the efficacy of endoscopic band ligation (EBL) in the prevention of recurrent bleeding, but no study has evaluated whether EBL improves the efficacy of beta-blockers + isosorbide-5-mononitrate. The present study was aimed at evaluating this issue in a multicentre randomised controlled trial (RCT) and to correlate changes in hepatic venous pressure gradient (HVPG) during treatment with clinical outcomes. Methods: 158 patients with cirrhosis, admitted because of variceal bleeding, were randomised to receive nadolol+isosorbide-5-mononitrate alone (Drug: n=78) or combined with EBL (Drug+EBL; n=80). HVPG measurements were performed at randomisation and after 4¿6 weeks on medical therapy. Results: Median follow-up was 15 months. One-year probability of recurrent bleeding was similar in both groups (33% vs 26%: p=0.3). There were no significant differences in survival or need of rescue shunts. Overall adverse events or those requiring hospital admission were significantly more frequent in the Drug+EBL group. Recurrent bleeding was significantly more frequent in HVPG non-responders than in responders (HVPG reduction ¿20% or ¿12 mm Hg). Among non-responders recurrent bleeding was similar in patients treated with Drugs or Drugs+EBL. Conclusions: Adding EBL to pharmacological treatment did not reduce recurrent bleeding, the need for rescue therapy, or mortality, and was associated with more adverse events. Furthermore, associating EBL to drug therapy did not reduce the high rebleeding risk of HVPG non-responders.

Accuracy of prehospital triage of trauma patients by emergency physicians: a retrospective study in western Switzerland.

OBJECTIVE: Accurate identification of major trauma patients in the prehospital setting positively affects survival and resource utilization. Triage algorithms using predictive criteria of injury severity have been identified in paramedic-based prehospital systems. Our rescue system is based on prehospital paramedics and emergency physicians. The aim of this study was to evaluate the accuracy of the prehospital triage performed by physicians and to identify the predictive factors leading to errors of triage.METHODS: Retrospective study of trauma patients triaged by physicians. Prehospital triage was analyzed using criteria defining major trauma victims (MTVs, Injury Severity Score >15, admission to ICU, need for immediate surgery and death within 48 h). Adequate triage was defined as MTVs oriented to the trauma centre or non-MTV (NMTV) oriented to regional hospitals.RESULTS: One thousand six hundred and eighti-five patients (blunt trauma 96%) were included (558 MTV and 1127 NMTV). Triage was adequate in 1455 patients (86.4%). Overtriage occurred in 171 cases (10.1%) and undertriage in 59 cases (3.5%). Sensitivity and specificity was 90 and 85%, respectively, whereas positive predictive value and negative predictive value were 75 and 94%, respectively. Using logistic regression analysis, significant (P<0.05) predictors of undertriage were head or thorax injuries (odds ratio >2.5). Predictors of overtriage were paediatric age group, pedestrian or 2 wheel-vehicle road traffic accidents (odds ratio >2.0).CONCLUSION: Physicians using clinical judgement provide effective prehospital triage of trauma patients. Only a few factors predicting errors in triage process were identified in this study.

Report on a special investigation of the City of Masonville for the period of March 18, 2002 to November 30, 2011

Report on a special investigation of the City of Masonville for the period of March 18, 2002 to November 30, 2011

Report on a special investigation of the City of Stockport for the period July 1, 2007 through October 31, 2011

Report on a special investigation of the City of Stockport for the period July 1, 2007 through October 31, 2011

Audit report on the City of Hastings, Iowa for the year ended June 30, 2011

Audit report on the City of Hastings, Iowa for the year ended June 30, 2011

Audit report on the City of Mystic, Iowa for the year ended June 30, 2011

Audit report on the City of Mystic, Iowa for the year ended June 30, 2011

Prevalence of Acute Coronary Syndrome in Patients Suspected for Pulmonary Embolism or Acute Aortic Syndromes: Rational for "Double" and "Triple" Rule-Out Concepts

PURPOSE To evaluate the prevalence of acute coronary syndrome (ACS) in patients presenting initially with atypical chest pain and suspected to have pulmonary embolism (PE) or acute aortic syndromes (AAS). To evaluate the overlap between ACS, PE and AAS in routine practice and determine how many patients could have benefit from a single CT protocol to rule out ACS at the same time as PE and AAS. METHOD AND MATERIALS Our electronic hospital database revealed 1122 consecutive patients who underwent a thoracic CT angiography for PE or AAS from 2004 to 2006 (mean age, 63±13 years). Patients without chest pain were excluded from this study. Thus, 447 patients presented with isolated atypical chest were included in the analysis. All patients who underwent a thoracic CT scan previously received standard clinical care and were initially considered as non ACS. The final diagnosis was obtained by the hospital stay report. RESULTS Among the 447 patients with atypical chest pain, 25 (5.5%) were finally found to have ACS: 19 patients (4.2%) were suspected for PE and 6 (1. 3%) were suspected for AAS. There were 90 patients diagnosed to have PE, 89 (98.8%) of them were suspected for PE while only 1 (1%) was suspected for AAS. Eleven patients diagnosed to have AAS, 9 (82%) of them were suspected for AAS while 2 (18%) were suspected for PE. CONCLUSION In clinical practice, the overlap between PE, AAS and ACS is limited which make the triple rule-out studies less recommended to be done at the time being because of the high dose radiation. A double rule-out investigation is suggested to be done for patients being evaluated for atypical chest pain and suspected of having AAS or PE because of a significant overlap between the two entities as well it doesn't implicate any increment in radiation dose. CLINICAL RELEVANCE/APPLICATION With 64-slice CT, coronary circulation and total chest can be evaluated at the same time offering new opportunitie for the evaluation of three major life-threatening conditions :ACS,PE and AAS.

Gene therapy regenerates protein expression in cone photoreceptors in Rpe65(R91W/R91W) mice.

Cone photoreceptors mediate visual acuity under daylight conditions, so loss of cone-mediated central vision of course dramatically affects the quality of life of patients suffering from retinal degeneration. Therefore, promoting cone survival has become the goal of many ocular therapies and defining the stage of degeneration that still allows cell rescue is of prime importance. Using the Rpe65(R91W/R91W) mouse, which carries a mutation in the Rpe65 gene leading to progressive photoreceptor degeneration in both patients and mice, we defined stages of retinal degeneration that still allow cone rescue. We evaluated the therapeutic window within which cones can be rescued, using a subretinal injection of a lentiviral vector driving expression of RPE65 in the Rpe65(R91W/R91W) mice. Surprisingly, when applied to adult mice (1 month) this treatment not only stalls or slows cone degeneration but, actually, induces cone-specific protein expression that was previously absent. Before the intervention only part of the cones (40% of the number found in wild-type animals) in the Rpe65(R91W/R91W) mice expressed cone transducin (GNAT2); this fraction increased to 64% after treatment. Correct S-opsin localization is also recovered in the transduced region. In consequence these results represent an extended therapeutic window compared to the Rpe65(-/-) mice, implying that patients suffering from missense mutations might also benefit from a prolonged therapeutic window. Moreover, cones are not only rescued during the course of the degeneration, but can actually recover their initial status, meaning that a proportion of altered cones in chromophore deficiency-related disease can be rehabilitated even though they are severely affected.

Canakinumab vs triamcinolone acetonide for treatment of acute flares and prevention of recurrent flares in "difficult to treat" gouty arthritis

Monosodium urate crystal deposition seen in gout stimulates IL-1 beta OR IL-1_; release. Canakinumab, a long-acting, fully human anti- IL-1 beta OR IL-1_; monoclonal antibody, effectively neutralizes IL-1 beta OR IL-1_;. Methods: This was an 8-week, dose-ranging, multi-center, blinded, doubledummy, active-controlled trial. Patients (aged 18-80 years) with an acute gout flare, refractory to or contraindicated to NSAlDs and/or colchicine, were randomized to one dose of canakinumab 10, 25, 50, 90, 150 mg s.c. or triamcinolone acetonide (TA) 40 mg i.m. Primary variable was assessed as pain intensity at 72 h post-dose (0-100 mm VAS). Secondary variables included pain intensity 24 and 48 h post-dose, time to 50% reduction in pain intensity, time to recurrence of gout flares up to 8 weeks post-dose, and rescue medication use. Results: 191/200 enrolled patients (canakinumab, n_143; TA, n_57) completed the study. Canakinumab showed significant dose-dependent pain reduction at 72 h. Canakinumab 150 mg showed superior pain relief versus TA starting from 24 h: estimated mean difference in pain intensity on VAS was -11.5 (24 h), -18.2 (48 h), and -19.2 (72 h) (all p_0.05). Canakinumab 150 mg provided a rapid onset of pain relief: median time to 50% reduction in pain was reached at 1 day with canakinumab 150 mg versus 2 days with TA (p_0.0006). At Week 8, recurrent flares occurred in 1 patient (3.7%) on canakinumab 150 mg versus 25 (44.6%) patients on TA (relative risk reduction, 94%; p_0.006). During 7 days post-dose, 6 patients (22.2%) on canakinumab 150 mg, and 31 patients (55.4%) on TA, took rescue medication. Time to first rescue medication was significantly longer with canakinumab 150 mg versus TA (hazard ratio, 0.36; p_0.02). Serious adverse events (canakinumab _lsqb_n_4_rsqb_ and TA _lsqb_n_1_rsqb_) were considered not treatment-related by investigators and no patient discontinued due to adverse events. Conclusions: Canakinumab 150 mg was well-tolerated, provided rapid and sustained pain relief in patients with acute gout flares, and significantly reduced the recurrent flare risk by 94% at 8-weeks post-dose compared with triamcinolone acetonide.

MAR-mediated integration of plasmid vectors for in vivo gene transfer and regulation.

BACKGROUND: The in vivo transfer of naked plasmid DNA into organs such as muscles is commonly used to assess the expression of prophylactic or therapeutic genes in animal disease models. RESULTS: In this study, we devised vectors allowing a tight regulation of transgene expression in mice from such non-viral vectors using a doxycycline-controlled network of activator and repressor proteins. Using these vectors, we demonstrate proper physiological response as consequence of the induced expression of two therapeutically relevant proteins, namely erythropoietin and utrophin. Kinetic studies showed that the induction of transgene expression was only transient, unless epigenetic regulatory elements termed Matrix Attachment Regions, or MAR, were inserted upstream of the regulated promoters. Using episomal plasmid rescue and quantitative PCR assays, we observed that similar amounts of plasmids remained in muscles after electrotransfer with or without MAR elements, but that a significant portion had integrated into the muscle fiber chromosomes. Interestingly, the MAR elements were found to promote plasmid genomic integration but to oppose silencing effects in vivo, thereby mediating long-term expression. CONCLUSIONS: This study thus elucidates some of the determinants of transient or sustained expression from the use of non-viral regulated vectors in vivo.