Longer survival for patients with alternative lengthening of telomeres (ALT) glioblastoma multiforme is due to a less aggressive phenotype and not to improved response to adjuvant therapy

Introduction: The Alternative Lengthening of Telomeres (ALT) mechanism is a significant prognostic factor for longer survival in patients with GBM, irrespective of age. The reasons for this are unknown. We considered two possibilities; firstly that ALT identifies a subset of less aggressive GBMs, or alternatively, a group of tumours that respond more favourably to adjuvant therapy. Methods: ALT was determined by staining for ALT Associated PML Bodies (APBs) in archival tissue in a retrospective analysis of 573 GBM patients. IDH1 mutation was determined by immunohistochemistry in a subset of these. Results: We identified the presence of the telomerase-independent ALT in 15% of GBM patients and found that it correlated with survival (22% of ALT patients survive more than 2 years compared to 9% for non-ALT). This survival advantage was independent of surgery type (biopsy or full resection) and treatment (radiotherapy and chemotherapy). Interestingly ALT conferred a significant survival advantage for patients who only received surgery (13.3 months compared to 5.5 months) (19% vs 1% .2 year survival). This survival benefit was also observed in GBM patients who received surgery and radiotherapy (18.5% vs 2.4%. 2 year survival), but less so for chemotherapy (21% vs 17% . 2 year survival). For the ALT patients the fraction surviving more than 2 years did not improve significantly with adjuvant therapy. IDH1 mutation also associated with ALT. Conclusions: These data indicate ALT+ tumours are biologically distinct and associated with improved patient survival, probably due to less aggressive/invasive growth. However they respond poorly to current adjuvant treatment and therefore new therapies are urgently needed for this group.

Mélanome: une nouvette ère thérapeutique [Melanoma: a new therapeutic era].

Melanoma is the cancer with the fastest incidence increase in Switzerland. 30% of the cases arise before the age of 50 years. Once metastatic, the median survival under current systemic therapies is about 8 months, with less than 5% of patients alive at 5 years. Many efforts in the understanding of cellular biology, intracellular signaling pathways, as well as the role of cellular immunity have been made in the recent years. This has resulted in the development of novel and very promising therapies. In this review, we will cover the results obtained with targeted therapies such as "tyrosin kinase inhibitors" (TKI), as well as those obtained with a monoclonal antibody directed against the CTLA-4 receptor of lymphocytes.

Lymphatic vascular morphogenesis in development, physiology, and disease.

The lymphatic vasculature constitutes a highly specialized part of the vascular system that is essential for the maintenance of interstitial fluid balance, uptake of dietary fat, and immune response. Recently, there has been an increased awareness of the importance of lymphatic vessels in many common pathological conditions, such as tumor cell dissemination and chronic inflammation. Studies of embryonic development and genetically engineered animal models coupled with the discovery of mutations underlying human lymphedema syndromes have contributed to our understanding of mechanisms regulating normal and pathological lymphatic morphogenesis. It is now crucial to use this knowledge for the development of novel therapies for human diseases.

Aromatherapy with ylang ylang for anxiety and self-esteem: a pilot study

Objective: To verify if the use of ylang ylang essential oil by cutaneous application or inhalation alters the anxiety and self-esteem perception and physiological parameters as blood pressure and temperature. Method : A pilot study with 34 professionals from a nursing group randomized in three groups: one received the ylang ylang essential oil by cutaneous application, the second received through inhalation and the third (placebo) received the ylang ylang essence through cutaneous application. The assessment was done by an Anxiety Inventory (IDATE) and the Dela Coleta self-esteem scale, applied on baseline, after 30, 60 and 90 days and after 15 days post-intervention (follow up). Results : In the pre and post-intervention intergroup analysis, there was a significant difference in self-esteem for the three groups (p values: G1=0.014; G2=0.016; G3=0.038). There were no differences in the analysis between groups for anxiety or for physiological parameters. Conclusion : It was found significant alterations only to the intergroup perception of self-esteem for the three groups.


Prevalence of comedications and effect of potential drug-drug interactions in the Swiss HIV Cohort Study.

BACKGROUND: Potential drug-drug interactions (PDDIs) might expand with new combination antiretroviral therapies (ART) and polypharmacy related to increasing age and comorbidities. We investigated the prevalence of comedications and PDDIs within a large HIV cohort, and their effect on ART efficacy and tolerability. METHODS: All medications were prospectively recorded in 1,497 ART-treated patients and screened for PDDIs using a customized version of the Liverpool drug interactions database. RESULTS: Overall, 68% (1,013/1,497) of patients had a comedication and 40% (599/1,497) had > or = 1 PDDI. Among patients with comedication, 2% (21/1,013) had red-flag interactions (contraindicated) and 59% (597/1,013) had orange-flag interactions (potential dose adjustment and/or close monitoring required). The latter involved mainly central nervous system drugs (49%), cardiovascular drugs (34%) and methadone (19%). In the multivariate analysis, factors associated with having a comedication were advanced age, female gender, obesity and HCV infection. Independent risk factors for PDDIs were regimens combining protease inhibitors and non-nucleoside reverse transcriptase inhibitors (odds ratio [OR] 3.06, 95% confidence interval [CI] 1.44-6.48), > or = 2 comedications (OR 1.89, 95% CI 1.32-2.70), current illicit drug use (OR 2.00, 95% CI 1.29-3.10) and patients with HCV infection (OR 1.74, 95% CI 1.19-2.56). Viral response was similar in patients with and without PDDIs (84.5% versus 86.4%; P=0.386). During follow-up, ART was modified in 134 patients with comedication regardless of the presence of PDDIs (P=0.524). CONCLUSIONS: PDDIs increase with complex ART and comorbidities. No adverse effect was noted on ART efficacy or tolerability; however, most PDDIs affected comedication but were manageable through dose adjustment or monitoring.

Occupational low back pain in nursing workers: massage versus pain

Objective: To assess the efficacy of massage for decreasing occupational low back pain in workers of a Nursing team in an Emergency Room. Method: A randomized controlled trial, using a socio-demographic/morbidity questionnaire and a Pain Numeric Scale. Forty-five subjects were randomly allocated for intervention (G1 – Massage by acupressure), placebo group (G2 – application of Garlium Arseneid Laser 904nm turned off) and control (G3 – no intervention). Results: The main triggering factor, as well as the worsening of pain, was the patient manipulation, both with a prevalence of 34.9%. The main treatment for low back pain before this research was the use of medication, with a prevalence of 44.2%. In accordance with a variance analysis, only G1 presented a significant statistical difference, with a better result after 12 sessions. Massage presented an enormous effect (d = 4.59), corresponding to 86% of reduction in the pain level. Conclusion: Massage was effective to decrease occupational low back pain of those Nursing workers.


Rehabilitation outcomes for orthopaedic trauma individuals as measured by the INTERMED.

PURPOSE: Bio-psychosocial characteristics of patients after orthopaedic traumas may be a strong predictor of poor outcome. The objective of this prospective study was to assess whether the INTERMED, a measure of bio-psychosocial complexity, identifies complex inpatients during rehabilitation including vocational aspects with a poor outcome 1 year after discharge. METHOD: At entry, the INTERMED scores of 118 inpatients were used to assign patients to the high or low complexity group. A questionnaire evaluated 1 year after discharge whether patients: (1) returned to work, (2) still have therapies, (3) take psychoactive drugs, (4) take medication against pain and (5) were satisfied with vocational therapy. Univariate logistic regressions identified which variables predict INTERMED case complexity during hospitalisation as well as predictors (i.e. INTERMED case complexity, French as preferred language, duration of the disability, accident at work, work qualification, severity of the injury, psychiatric co-morbidities, pain) of the five measured outcomes 1 year after discharge. RESULTS: During hospitalisation, the high complexity group was associated with a high prevalence of psychiatric co-morbidities, a higher level of pain and a weaker perception of treatment effects. One year after discharge, the INTERMED was the sole variable to predict all outcomes. CONCLUSION: The INTERMED identifies complex patients during vocational rehabilitation after orthopaedic trauma and is a good predictor of poor outcome 1 year after discharge.

Contributions of auriculotherapy in smoking cessation: a pilot study

Objective To evaluate the contribution of auriculotherapy in smoking cessation. Method Double-blind randomized controlled trial, conducted with 30 smokers allocated into two groups: Experimental Group (21 participants received 10 sessions of auriculotherapy at specific points for smoking) and Control Group (nine participants received auriculotherapy in points that have no effect on the focus of research). Results Auriculotherapy contributed in reducing the number of cigarettes smoked in 61.9% of participants (p=0.002), in reducing the difficult to abstain from smoking in places where it is forbidden by 38% (p=0.050) and in not smoking when ill 23.8% (p=0.025). Conclusion Given the efficacy only in terms of reducing the number of cigarettes smoked and other parameters, we suggest that future studies consider the use of auriculotherapy combined with other treatment methods, in order to achieve better results in cessation/abstinence.

Role of T-cell-mediated inflammation in psoriasis: pathogenesis and targeted therapy

Psoriasis is one of the most common chronic, inflammatory, T-cell-mediated autoimmune diseases. Over the past decade, increased knowledge of disease pathogenesis has fundamentally changed psoriasis treatment, with the introduction of biologics, and this has led to a multitude of improved selective targets providing potential therapeutic options. Indeed, numerous pathogenesis-based treatments are currently in development, as psoriasis has also become increasingly relevant for proof-of-concept studies. The purpose of this review was to summarize current knowledge of psoriasis immunopathogenesis, focusing on the T-cell-mediated immune response and its initiation. The authors describe recent advances in psoriasis treatment and discuss pathogenesis-based therapies that are currently in development or which could be envisioned for the future. Although current biologics are well tolerated, several issues such as long-term efficacy, long-term safety, and high costs keep driving the search for new and better therapies. With further advances in understanding disease pathogenesis, more genomic data from psoriasis patients becoming available, and potentially the identification of autoantigens in psoriasis, current research should lead to the development of a growing arsenal of improved targeted treatments and to further breakthrough immunotherapies.

European French-speaking study from the GEMO group on bone metastases management: a special focus on external beam radiotherapy practice survey.

This study seeks to perform a survey of patterns of practice among the different physicians involved in the bone metastases management, with special focus on external beam radiotherapy (EBRT).A questionnaire about bone metastases based on clinical cases and supplemented with general questions, including medical therapies, EBRT and metabolic radiotherapy strategies, surgery, and supportive care approaches, was sent to 4,706 French-speaking physicians in Belgium, France, Luxemburg, and Switzerland.Overall, 644 questionnaires were analyzed. Twenty-eight percent concerned the radiotherapy approach and were judged adequate to respond to the part dedicated to EBRT. Sixty-nine percent of physicians used a total dose irradiation of 30 Gy delivered in ten fractions. A large majority (75%) used two opposed fields prescribed at mid-depth (30%), or with non-equally weighted fields (45%). Seventy percent irradiated also above and below the concerned vertebra. A dosimetry planning treatment was done in 85% and high-energy megavoltage photons were used in 42%. Moreover, 54% physicians used short course radiotherapy in routine.Radiotherapy remains the mainstay of treatment of bone metastases, but there is substantial heterogeneity in clinical practice. Guidelines and treatment protocols are required to improve the treatment quality.

Predictors of Weight Change in Sedentary Smokers Receiving a Standard Smoking Cessation Intervention.

INTRODUCTION: Quitting smoking is associated with weight gain, which may threaten motivation to engage or sustain a quit attempt. The pattern of weight gained by smokers treated according to smoking cessation guidelines has been poorly described. We aimed to determine the weight gained after smoking cessation and its predictors, by smokers receiving individual counseling and nicotine replacement therapies for smoking cessation. METHODS: We performed an ancillary analysis of a randomized controlled trial assessing moderate physical activity as an aid for smoking cessation in addition to standard treatment in sedentary adult smokers. We used mixed longitudinal models to describe the evolution of weight over time, thus allowing us to take every participant into account. We also fitted a model to assess the effect of smoking status and reported use of nicotine replacement therapy at each time point. We adjusted for intervention group, sex, age, nicotine dependence, and education. RESULTS: In the whole cohort, weight increased in the first 3 months, and stabilized afterwards. Mean 1-year weight gain was 3.3kg for women and 3.9kg for men (p = .002). Higher nicotine dependence and male sex were associated with more weight gained during abstinence. Age over median was associated with continuing weight gain during relapse. There was a nonsignificant trend toward slower weight gain with use of nicotine replacement therapies. CONCLUSION: Sedentary smokers receiving a standard smoking cessation intervention experience a moderate weight gain, limited to the first 3 months. Older age, male sex, and higher nicotine dependence are predictors of weight gain.

Acquired form of angioedema of the head and neck related to a deficiency in c1-inhibitor: a case report with a review of the literature.

Angioedema related to a deficiency in the C1-inhibitor protein is characterized by its lack of response to therapies including antihistamine, steroids, and epinephrine. In the case of laryngeal edema, mortality rate is approximately 30 percent. The first case of the acquired form of angioedema related to a deficiency in C1-inhibitor was published in 1972. In our paper, we present a case of an acquired form of angioedema of the oropharyngeal region secondary to the simultaneous occurrence of two causative factors: neutralization of C1-inhibitor by an autoantibody and the use of an angiotensin convertin enzyme inhibitor.

Massage with aromatherapy: effectiveness on anxiety of users with personality disorders in psychiatric hospitalization

OBJECTIVE To investigate the effectiveness of aromatherapy massage using the essential oils (0.5%) of Lavandula angustifolia and Pelargonium graveolens for anxiety reduction in patients with personality disorders during psychiatric hospitalization. METHOD Uncontrolled clinical trial with 50 subjects submitted to six massages with aromatherapy, performed on alternate days, on the cervical and the posterior thoracic regions. Vital data (heart and respiratory rate) were collected before and after each session and an anxiety scale (Trait Anxiety Inventory-State) was applied at the beginning and end of the intervention. The results were statistically analyzed with the chi square test and paired t test. RESULTS There was a statistically significant decrease (p < 0.001) of the heart and respiratory mean rates after each intervention session, as well as in the inventory score. CONCLUSION Aromatherapy has demonstrated effectiveness in anxiety relief, considering the decrease of heart and respiratory rates in patients diagnosed with personality disorders during psychiatric hospitalization.

The sign of the Cross of Andreas in the iris and Diabetes Mellitus: a longitudinal study

OBJECTIVETo compare the development of diabetes mellitus in subjects with and without the sign of the Cross of Andreas in the iris over a period of four years.METHODA prospective, descriptive study of quantitative approach. This cohort study had 91 patients without the disease, with and without the signal. The monitoring was conducted by means of the records in medical charts.RESULTSAt the end of the research, 28.2% of the group with the sign of the Cross of Andreas was diagnosed with diabetes and 56.5% had two or more episodes of impaired glucose tolerance. In the group without the sign, 4.4% was diagnosed with the disease and 24.5% had two or more episodes of glucose intolerance. There was a statistically significant difference between the groups regarding the development of the disease and glucose intolerance.CONCLUSIONThe group with the Cross of Andreas developed more glucose intolerance and diabetes than the group without the sign.

Trabecular bone score: a noninvasive analytical method based upon the DXA image.

The trabecular bone score (TBS) is a gray-level textural metric that can be extracted from the two-dimensional lumbar spine dual-energy X-ray absorptiometry (DXA) image. TBS is related to bone microarchitecture and provides skeletal information that is not captured from the standard bone mineral density (BMD) measurement. Based on experimental variograms of the projected DXA image, TBS has the potential to discern differences between DXA scans that show similar BMD measurements. An elevated TBS value correlates with better skeletal microstructure; a low TBS value correlates with weaker skeletal microstructure. Lumbar spine TBS has been evaluated in cross-sectional and longitudinal studies. The following conclusions are based upon publications reviewed in this article: 1) TBS gives lower values in postmenopausal women and in men with previous fragility fractures than their nonfractured counterparts; 2) TBS is complementary to data available by lumbar spine DXA measurements; 3) TBS results are lower in women who have sustained a fragility fracture but in whom DXA does not indicate osteoporosis or even osteopenia; 4) TBS predicts fracture risk as well as lumbar spine BMD measurements in postmenopausal women; 5) efficacious therapies for osteoporosis differ in the extent to which they influence the TBS; 6) TBS is associated with fracture risk in individuals with conditions related to reduced bone mass or bone quality. Based on these data, lumbar spine TBS holds promise as an emerging technology that could well become a valuable clinical tool in the diagnosis of osteoporosis and in fracture risk assessment.