Search

Background As lenalidomide becomes increasingly established for upfront treatment of multiple myeloma, patients refractory to this drug represent a population with an unmet need. The combination of pomalidomide, bortezomib, and dexamethasone has shown promising results in phase 1/2 trials of patients with relapsed or refractory multiple myeloma. We aimed to assess the efficacy and safety of this triplet regimen in patients with relapsed or refractory multiple myeloma who previously received lenalidomide. Methods We did a randomised, open-label, phase 3 trial at 133 hospitals and research centres in 21 countries. We enrolled patients (aged >= 18 years) with a diagnosis of multiple myeloma and measurable disease, an Eastern Cooperative Oncology Group performance status of 0-2, who received one to three previous regimens, including a lenalidomide-containing regimen for at least two consecutive cycles. We randomly assigned patients (1:1) to bortezomib and dexamethasone with or without pomalidomide using a permutated blocked design in blocks of four, stratified according to age, number of previous regimens, and concentration of beta(2) microglobulin at screening. Bortezomib (1.3 mg/m(2)) was administered intravenously until protocol amendment 1 then either intravenously or subcutaneously on days 1,4, 8, and 11 for the first eight cycles and subsequently on days 1 and 8. Dexamethasone (20 mg [10 mg if age >75 years]) was administered orally on the same days as bortezomib and the day after. Patients allocated pomalidomide received 4 mg orally on days 1-14. Treatment cycles were every 21 days. The primary endpoint was progression-free survival in the intention-to-treat population, as assessed by an independent review committee. Safety was assessed in all patients who received at least one dose of study medication. This trial is registered at ClinicalTrials.gov, number NCT01734928; patients are no longer being enrolled. Findings Between Jan 7, 2013, and May 15,2017,559 patients were enrolled. 281 patients were assigned pomalidomide, bortezomib, and dexamethasone and 278 were allocated bortezomib and dexamethasone. Median follow-up was 15.9 months (IQR 9.9-21.7). Pomalidomide, bortezomib, and dexamethasone significantly improved progression-free survival compared with bortezomib and dexamethasone (median 11.20 months [95% CI 9.66-13-73] vs 7.10 months [5.88-8-48]; hazard ratio 0.61, 95% CI 0.49-0-77; p

Background and aims Clinicopathological characteristics of gastric cancer (GC) are changing, especially in the West with a decreasing incidence of distal, intestinal-type tumours and the corresponding increasing proportion of tumours with Laurén diffuse or WHO poorly cohesive (PC) including signet ring cell (SRC) histology. To accurately assess the behaviour and the prognosis of these GC subtypes, the standardization of pathological definitions is needed. Methods A multidisciplinary expert team belonging to the European Chapter of International Gastric Cancer Association (IGCA) identified 11 topics on pathological classifications used for PC and SRC GC. The topics were debated during a dedicated Workshop held in Verona in March 2017. Then, through a Delphi method, consensus statements for each topic were elaborated. Results A consensus was reached on the need to classify gastric carcinoma according to the most recent edition of the WHO classification which is currently WHO 2010. Moreover, to standardize the definition of SRC carcinomas, the proposal that only WHO PC carcinomas with more than 90% poorly cohesive cells having signet ring cell morphology have to be classified as SRC carcinomas was made. All other PC non-SRC types have to be further subdivided into PC carcinomas with SRC component ( 10% SRCs) and PC carcinomas not otherwise specified (

Background: Cancer in older patient favours the development of frailty: feeling of exhaustion, loss of weight, decreased muscle strength, slow gait speed, and low physical activity. Objectives: To evaluate the efficacy of adapted physical activity phone advices in limiting the cancer-induced loss of autonomy and frailty phenotype development. Design: Multicenter randomized controlled trial. Setting: Patients (>70y) undergoing curative treatment for cancer (n=400) will be recruited from 12 centres. Intervention: The intervention consists in phoned personalized physical activity advices related to strength, aerobic, balance, proprioception, and flexibility. The contacts are performed twice a month during six months and then monthly until 1 year. The intervention complements the PNNS booklet advices (National Nutritional Health Program). The trial compares "individualized phone advices + PNNS" to "usual care + PNNS". Measurements: Functional, cognitive, clinical and self-reported data are assessed before treatment and at 3, 6, 12, 18, and 24 month follow-up. The primary outcome is the proportion of subjects with a one-year decreased SPPB (Short Physical Performance Battery) score of one point or more, as compared to baseline. The secondary outcomes include quality of life items, rate of hospitalizations, institutionalizations, mortality, Fried phenotype at 1 and 2 years, and the SPPB score at 2 years. Discussion: This large trial will provide clinical data of the effects of an exercise advices intervention in older patients during cancer therapy on function and cognition evolution, and quality of life. The possibilities of minimizing the development of frailty phenotype due to these advices will be explored.

Introduction EURECCA (EUropean REgistration of Cancer CAre) is a network aiming to improve cancer care by auditing outcome. EURECCA initiated an international survey to share and compare patient outcome for oesophagogastric cancer. The present study assessed how a uniform dataset could be introduced for oesophagogastric cancer in Europe. Methods Participating countries presented data using common data items describing patients', disease, strategies, and outcome characteristics. Patients treated with curative surgery for squamous cell carcinoma (SCC) or adenocarcinoma (ACA) were included. Results United Kingdom, the Netherlands, France, Spain and Ireland participated. There were differences in data source ranging from national registries to large collaborative groups. 4668 oesophagogastric cancer cases over a 12 months period were included. The predominant histological type was ACA. Disease stage tended to be earlier in France and Ireland. In oesophageal and junctional cancers neoadjuvant chemoradiotherapy was preferred in the Netherlands and Ireland contrasting with chemotherapy in the UK and France. All countries used perioperative chemotherapy in gastric cancer but 1/3 of patients received this treatment. The mean R0 resection rate was 86% for oesophageal and junctional resections and 88% for gastric resections. Postoperative mortality varied from 1% to 7%. Conclusion This European survey shown that implementing a uniform treatment and outcome data format of oesophagogastric cancer is feasible. It identified differences in disease presentation, treatment approaches and outcome, which need to be investigated, especially by increasing the number of participating countries. Future comparisons will facilitate developments in treatment for the benefit of patient outcomes.

Objective: To examine variables associated with bone mineral density (BMD) in patients with rheumatoid arthritis (RA). Methods: We investigated 373 patients with low to moderately active RA. Patients with low disease activity were recruited from a cohort of patients in clinical remission. Patients with moderately active disease were included in a trial comparing the effects of long term high intensity exercise programme and conventional physical therapy. Demographic and clinical data were collected. Bone mineral density (BMD) was measured by means of dual x ray absorptiometry (DXA). Associations between demographic and clinical measurements on the one hand and BMD on the other were investigated in regression analyses. Results: The patient group consisted of middle aged, mainly female, patients. The median (interquartile range) disease duration was 7 (4 to 13) years, the mean disease activity score (standard deviation) was 3.2 (1.4). Of the group, 66% was rheumatoid factor positive, and 83% (n = 304) had never used corticosteroids. The median Larsen score of hands and feet was 27 (5 to 61). Greater age and low body mass index were related to low BMD at the hip and spine. High Larsen score for hands and feet was significantly associated with low BMD at the hip. The use of corticosteroids was not independently associated with BMD. The results of the multiple regression analyses also applied to the subgroup of corticosteroid naive patients. Conclusion: BMD data of patients with low to moderately active RA demonstrated an association between high radiological RA damage and low BMD at the hip, which suggests an association between the severity of RA and the risk of generalised bone loss, which also occurred in corticosteroid naive patients.

Identity development is a highly salient task for adolescents, especially those from immigrant backgrounds, yet longitudinal research that tracks simultaneous change in ethnic identity and American identity over time has been limited. With a focus on 177 Asian American adolescents recruited from an emerging immigrant community, in the current study, we used hierarchical linear modeling and found that ethnic identity tends to remain fairly stable across the 4 years of high school, whereas American identity increases over time. When ethnic identity and American identity were examined simultaneously, consistent with existing research, ethnic identity was positively associated with positive relationships, high self-esteem, academic motivation, and lower levels of depression over time. Although American identity was not significantly associated with depression, positive links with relationships, self-esteem, and academic motivation were found. Both identities were interactively associated with academic motivation. Acculturative implications and the importance of considering the dual construction of ethnic identity and American identity in light of adolescent adjustment are discussed.

The 1st St. Gallen EORTC Gastrointestinal Cancer Conference 2012 Expert Panel clearly differentiated treatment and staging recommendations for the various gastroesophageal cancers. For locally advanced gastric cancer (>= PT3N+), the preferred treatment modality was pre- and postoperative chemotherapy. The majority of panel members would also treat T2N+ or even T2N0 tumours with a similar approach mainly because pretherapeutic staging was considered highly unreliable. It was agreed that adenocarcinoma of the gastroesophageal junction (AEG) is classified best according to Siewert et al. Preoperative radiochemotherapy (RCT) is the preferred treatment for AEG type I and II tumours. For AEG type III, i.e. tumours which may be considered as gastric cancer, perioperative chemotherapy is the majority approach. For resectable squamous cell cancer of the oesophagus a clear majority recommended radiochemotherapy followed by surgery as optimal approach, irrespective of tumour size. In contrast, definitive RCT was judged appropriate for advanced tumours with extended lymph node involvement (N2) or for cancers of the upper oesophagus. Additional recommendations are presented on the use of endosonography, PET-CT scan and laparoscopy for staging and on the preferred approach to surgery. (c) 2012 Elsevier Ltd. All rights reserved.

We consider the problem −Δu=|u|p−1u+λu in Ω with\(\frac{{\partial u}}{{\partial n}} = 0\) on δΩ, where Ω is a bounded domain inRN,p=(N+2)/(N−2) is the critical Sobolev exponent,n the outward pointing normal and λ a constant. Our main result is that if Ω is a ball inRN, then for every λ∈R the problem admits infinitely many solutions. Next we prove that for every bounded domain Ω inR3, symmetric with respect to a plane, there exists a constant μ>0 such that for every λ

Background Bone loss is a well-known side effect of glucocorticoid (GC) therapy, but its extent has been poorly quantified. Objectives To investigate GC-induced bone loss in patients with chronic inflammatory diseases (low dose) or transplants (high dose) through a meta-analysis of cohorts. Methods Data sources: A search of published studies in PubMed (1995 – 2012), Cochrane databases (1995 – 2012), EMBASE (1995 – 2012), and bibliographic references extending and expanding a previous systematic review on chronic disease [1] up to 2012. Study selection Prospective studies were included of patients receiving GC who underwent at least two bone mineral density (BMD) measurements by dual x-ray absorptiometry over a period of at least 8 months. Only supplementation with calcium and/or Vitamin D3 was allowed. Cohorts studying patients using bisphosphonates or other anti-osteoporotic drugs or diseases associated with influence on bone loss were excluded. Primary outcome was the one-year change in lumbar spine BMD; secondary outcome the change in femoral neck BMD. Where applicable, data was linearly extrapolated or interpolated to estimate bone loss at one year, but only in the chronic inflammatory diseases group. In the transplantation group the last observation (no earlier than at 8 months) was carried forward Data extraction and synthesis Of 5602 titles, 285 articles remained. In these, 44 articles with 51 relevant study arms studied chronic inflammatory diseases group (N=1565). Likewise 21 articles with 24 study arms were included in the transplantation group (N=679). GC dose is expressed as prednisolone equivalents. Review Manager v 5.1 calculated weighted means (inverse variance method); strong heterogeneity required application of the random effects model Results In the chronic inflammatory diseases group (both starters and chronic users) the mean daily dose of GC was 8,8 mg (range 1.2 – 16.4). Bone loss at the lumbar spine was -1.8% [95%CI: -2.2; -1.3]; see graph. Only 39 cohorts (N=1255) also measured femoral neck; in these bone loss was -1.5% [-2.1; -0.9] in the lumbar spine, and -1.3% [-1.8; -0.8] in the femoral neck. In the transplantation group (almost all starters) the mean daily dose of GC was 20.4 mg (range 7.7 – 52.7). Bone loss at the lumbar spine was -4.9%[-6.6; -3.1]. Only 18 cohorts (N=551) also measured femoral neck; in these bone loss was -4.1% [-6.0; -2.2] in the lumbar spine, and -3 [-4.8; -1.3] in the femoral neck. The graph depicts individual studies, weighted mean and 95%CI. Conclusions This meta-analysis provides definitive data on one-year bone loss across a range of diseases and GC doses. It shows GC treatment at the high doses used in transplantation patients leads to considerable bone loss, especially in the lumbar spine. In contrast, bone loss is limited during GC treatment at the lower doses used in chronic inflammatory disease. Existing guidelines should be updated to reflect this data. References Lodder MC, et al. Ann Rheum Dis 2003;62 (suppl 1):94. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5036

One of the main challenges in ultrafast material science is to trigger phase transitions with short pulses of light. Here we show how strain waves, launched by electronic and structural precursor phenomena, determine a coherent macroscopic transformation pathway for the semiconducting-to-metal transition in bistable Ti3O5 nanocrystals. Employing femtosecond powder X-ray diffraction, we measure the lattice deformation in the phase transition as a function of time. We monitor the early intra-cell distortion around the light absorbing metal dimer and the long range deformations governed by acoustic waves propagating from the laser-exposed Ti3O5 surface. We developed a simplified elastic model demonstrating that picosecond switching in nanocrystals happens concomitantly with the propagating acoustic wavefront, several decades faster than thermal processes governed by heat diffusion. Ultrafast control of materials draws interest. Here, the authors extend X-ray powder diffraction to the femtosecond timescale to follow the photo-induced semiconductor to metal transition in titanium pentaoxide, observing a phase front that moves at the speed of sound and proposing a little explored mechanism.