Summary Background & aims Cancer cachexia is multifactorial and should be targeted using a multimodal form of intervention. The purpose of the present trial was to test the effects of a combined ...nutrition and physical exercise program on cancer patients with metastatic or locally advanced tumors of the gastrointestinal and lung tracts. Methods Patients were randomized into two groups: One group received a minimum of three standardized individual nutritional counselling sessions and participated in a 60-min exercise program twice a week. The second group received their usual care. The intervention spanned a period of three months. Quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire version 3.0), physical performance (hand-grip strength, 6-min walk test, timed sit-to-stand test and 1 repetition maximum leg press), nutritional status (body weight, bioelectrical impedance analysis), dietary intake (three-day dietary record) and clinical data (unexpected hospital days, performance status) were tested at baseline and after three and six months. Results In total, 18 women and 40 men (mean age 63, range 32–81) with metastatic or locally advanced tumors of the gastrointestinal ( n = 38) and lung ( n = 20) tracts were included. Median adherence to the supervised exercise program was 75%. The median number of individual nutritional counselling sessions was 3.0 (range 0–7 sessions). Post intervention, no difference in global health status/quality of life (overall QoL) was observed. Intervention was superior to UC for the patient-rated symptom scale regarding nausea and vomiting ( p = 0.023) and protein intake ( p = 0.01). No statistical differences were observed for energy intake, nutritional status and physical performance. Conclusions The results show good adherence to a combined nutrition and exercise program. The multimodal intervention did not improve overall QoL, but contributed to an adequate protein intake and to the general well-being of the patient by reducing nausea and vomiting.
The European Society for Medical Oncology (ESMO) consensus conference on mature B cell lymphomas and chronic lymphocytic leukaemia (CLL) was held on 20 June 2015 in Lugano, Switzerland, and included ...a multidisciplinary panel of 25 leading experts. The aim of the conference was to develop recommendations on critical subjects difficult to consider in detail in the ESMO Clinical Practice Guidelines. The following areas were identified: (1) the elderly patient, (2) prognostic factors suitable for clinical use, and (3) the ‘ultra-high-risk’ group. Before the conference, the expert panel was divided into three working groups; each group focused on one of these areas in order to address clinically-relevant questions relating to that topic. All relevant scientific literature, as identified by the experts, was reviewed in advance. During the consensus conference, each working group developed recommendations to address each of the four questions assigned to their group. These recommendations were presented to the entire panel and a consensus was reached. This consensus, which was further developed in continuous post-meeting discussions, formed the basis of three manuscripts, each covering one of the three key areas identified. This manuscript presents the consensus recommendations regarding the clinical management of elderly patients diagnosed with malignant lymphoma. Four clinically-relevant topics identified by the panel were: 1) how to define patient fitness, 2) assessing quality of life, 3) diagnostic work-up and 4) clinical management of elderly patients with lymphoma. Each of these key topics is addressed in the context of five different lymphoma entities, namely: CLL, follicular lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma and diffuse large B-cell lymphoma. Results, including a summary of evidence supporting each recommendation, are detailed in this manuscript.
The SAKK 35/10 phase 2 trial, developed by the Swiss Group for Clinical Cancer Research and the Nordic Lymphoma Group, compared the activity of rituximab vs rituximab plus lenalidomide in untreated ...follicular lymphoma patients in need of systemic therapy. Patients were randomized to rituximab (375 mg/m2 IV on day 1 of weeks 1-4 and repeated during weeks 12-15 in responding patients) or rituximab (same schedule) in combination with lenalidomide (15 mg orally daily for 18 weeks). Primary end point was complete response (CR)/unconfirmed CR (CRu) rate at 6 months. In total, 77 patients were allocated to rituximab monotherapy and 77 to the combination (47% poor-risk Follicular Lymphoma International Prognostic Index score in each arm). A significantly higher CR/CRu rate at 6 months was documented in the combination arm by the investigators (36%; 95% confidence interval CI, 26%-48% vs 25%; 95% CI, 16%-36%) and confirmed by an independent response review of computed tomography scans only (61%; 95% CI, 49%-72% vs 36%; 95% CI, 26%-48%). After a median follow-up of 4 years, significantly higher 30-month CR/CRu rates and longer progression-free survival (PFS) and time to next treatment (TTNT) were observed for the combination. Overall survival (OS) rates were similar in both arms (≥90%). Toxicity grade ≥3 was more common in the combination arm (56% vs 22% of patients), mainly represented by neutropenia (23% vs 7%). Addition of lenalidomide to rituximab significantly improved CR/CRu rates, PFS, and TTNT, with expected higher, but manageable toxicity. The excellent OS in both arms suggests that chemotherapy-free strategies should be further explored. This trial was registered at www.clinicaltrials.gov as #NCT01307605.
•Compared with rituximab only, a short rituximab-lenalidomide regimen improved CR rate and PFS in untreated symptomatic follicular lymphomas.•Excellent OS in both arms suggests that chemotherapy-free strategies should be further explored in follicular lymphoma.
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Pore-spanning membranes (PSMs) composed of supported membrane parts as well as freestanding membrane parts are shown to be very versatile to investigate SNARE-mediated fusion on the single-particle ...level. They provide a planar geometry readily accessible by confocal fluorescence microscopy, which enabled us for the first time, to our knowledge, to investigate the fusion of individual natural secretory granules (i.e., chromaffin granules (CGs)) on the single-particle level by two-color fluorescence microscopy in a time-resolved manner. The t-SNARE acceptor complex ΔN49 was reconstituted into PSMs containing 2 mol % 1,2-dipalmitoyl-sn-glycero-3-phosphatidylinositol-4,5-bisphosphate and Atto488-1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine, and CGs were fluorescently labeled with 2-((1E,3E)-5-((Z)-3,3-dimethyl-1-octadecylindolin-2-ylidene)penta-1,3-dien-1-yl)-3,3-dimethyl-1-octadecyl-3H-indol-1-ium perchlorate. We compared the dynamics of docked and hemifused CGs as well as their fusion efficacy and kinetics with the results obtained for synthetic synaptobrevin 2-doped vesicles fusing with PSMs of the same composition. Whereas the synthetic vesicles were fully immobile on supported PSMs, docked as well as hemifused CGs were mobile on both PSM parts, which suggests that this system resembles more closely the natural situation. The fusion process of CGs proceeded through three-dimensional post-lipid-mixing structures, which were readily resolved on the gold-covered pore rims of the PSMs and which are discussed in the context of intermediate states observed in live cells.
Hairy cell leukemia (HCL) remains an incurable disease. However, first-line treatment with either intravenous or subcutaneous cladribine generally leads to long-lasting remissions. Although there are ...excellent long-term data for intravenous application, similar data regarding subcutaneous administration are lacking. We therefore analyzed the long-term outcome of 3 prospective multicenter clinical trials on subcutaneous cladribine performed by the Swiss Group for Clinical Cancer Research (SAKK), which recruited 221 patients with classical HCL between 1993 and 2005. Median overall survival from start of treatment was not reached. Pretreatment anemia, higher Eastern Cooperative Oncology Group score, and higher age were associated with poorer overall survival in multivariable analysis, whereas early progression at 24 and 36 months had no significant impact on overall survival. Second-line treatment was necessary in 53 (23.7%) patients after a median of 5 (range, 0.2-20.4) years, and first retreatment was mainly monotherapy with cladribine (66%) or rituximab (15.1%) or a combination of these drugs (15.1%). A total of 44 (19.9%) patients developed second primary malignancies with a median time to occurrence of 5.7 (range, 0.01-17.5) years. Second primary malignancies were the main cause for death (14; 27.5%). Compared with a matched normal Swiss population, the incidence of second primary malignancies was not increased. However, survival of patients with HCL was slightly inferior by comparison (P = .036). In conclusion, the outcome of HCL patients treated with subcutaneous cladribine is excellent, and in most patients, 1 cycle of subcutaneous cladribine is sufficient for long-term disease control.
•Subcutaneous cladribine shows excellent long-term survival in patients with hairy cell leukemia; progression of disease at 24 or 36 months is not prognostic.•Secondary primary malignancies are the main cause of death but are not significantly increased compared with the normal population.
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To determine the frequency and clinical relevance of acquired von Willebrand syndrome (aVWS) due to antiepileptic therapy by valproic acid, we investigated 50 consecutive children in three ...neuropediatric institutions. Coagulation factors were determined in local laboratories before and three times after starting therapy with valproic acid. Parameters of von Willebrand factor (VWF) were additionally investigated in a reference laboratory including multimeric analysis. Significant changes in the coagulation system were found concerning fibrinogen (decreased from 287 +/- 70 mg/dl to 222 +/- 67 mg/dl; p < 0.001) and platelet count. Changes of VWF parameters were also found but no patient developed laboratory defined aVWS. We conclude that the bleeding tendency observed in some children undergoing antiepileptic therapy with valproic acid is not due to aVWS.
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The Routledge Handbook of Ecolinguistics is the first comprehensive exploration into the field of ecolinguistics, also known as language ecology. Organized into three sections that treat the ...different topic areas of ecolinguistics, the Handbook begins with chapters on language diversity, language minorities, and language endangerment, with authors providing insight into the link between the loss of languages and the loss of species. It continues with an overview of the role of language and discourse in describing, concealing, and helping to solve environmental problems. With discussions on new orientations and topics for further exploration in the field, chapters in the last section show ecolinguistics as a pacesetter into a new scientific age. This Handbook is an excellent resource for students and researchers interested in language and the environment, language contact and beyond.ii
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