Siponimod Inhibits the Formation of Meningeal Ectopic Lymphoid Tissue in Experimental Autoimmune Encephalomyelitis

Background and ObjectivesTo investigate whether the formation or retention of meningeal ectopic lymphoid tissue (mELT) can be inhibited by the sphingosine 1-phosphate receptor 1,5 modulator siponimod (BAF312) in a murine model of multiple sclerosis (MS).MethodsA murine spontaneous chronic experimental autoimmune encephalomyelitis (EAE) model, featuring meningeal inflammatory infiltrates resembling those in MS, was used. To prevent or treat EAE, siponimod was administered daily starting either before EAE onset or at peak of disease. The extent and cellular composition of mELT, the spinal cord parenchyma, and the spleen was assessed by histology and immunohistochemistry.ResultsSiponimod, when applied before disease onset, ameliorated EAE. This effect was also present, although less prominent, when treatment started at peak of disease. Treatment with siponimod resulted in a strong reduction of the extent of mELT in both treatment paradigms. Both B and T cells were diminished in the meningeal compartment.DiscussionBeneficial effects on the disease course correlated with a reduction in mELT, suggesting that inhibition of mELT may be an additional mechanism of action of siponimod in the treatment of EAE. Further studies are needed to establish causality and confirm this observation in MS

Anti-CD20 Depletes Meningeal B Cells but Does Not Halt the Formation of Meningeal Ectopic Lymphoid Tissue

Objective To investigate whether anti-CD20 B-cell-depleting monoclonal antibodies (alphaCD20 mAbs) inhibit the formation or retention of meningeal ectopic lymphoid tissue (mELT) in a murine model of multiple sclerosis (MS). Methods We used a spontaneous chronic experimental autoimmune encephalomyelitis (EAE) model of mice with mutant T-cell and B-cell receptors specific for myelin oligodendrocyte glycoprotein (MOG), which develop meningeal inflammatory infiltrates resembling those described in MS. alphaCD20 mAbs were administered in either a preventive or a treatment regimen. The extent and cellular composition of mELT was assessed by histology and immunohistochemistry. Results alphaCD20 mAb, applied in a paradigm to either prevent or treat EAE, did not alter the disease course in either condition. However, alphaCD20 mAb depleted virtually all B cells from the meningeal compartment but failed to prevent the formation of mELT altogether. Because of the absence of B cells, mELT was less densely populated with immune cells and the cellular composition was changed, with increased neutrophil granulocytes. Conclusions These results demonstrate that, in CNS autoimmune disease, meningeal inflammatory infiltrates may form and persist in the absence of B cells. Together with the finding that alphaCD20 mAb does not ameliorate spontaneous chronic EAE with mELT, our data suggest that mELT may have yet unknown capacities that are independent of B cells and contribute to CNS autoimmunity

Effect of total laparoscopic hysterectomy vs total abdominal hysterectomy on disease-free survival among women with stage I endometrial cancer: A randomized clinical trial

IMPORTANCE Current standard treatment for endometrial cancer involves removal of uterus, adnexa ± lymph nodes. Few randomized trials have compared disease-free survival outcomes for surgical approaches. OBJECTIVE To investigate whether total laparoscopic hysterectomy (TLH) is equivalent to total abdominal hysterectomy (TAH) in women with treatment-naive endometrial cancer. DESIGN, SETTING, AND PARTICIPANTS Multinational, randomized equivalence trial evaluating the laparoscopic approach to endometrial cancer (LACE). Between October 7, 2005 and June 30, 2010, 27 surgeons from 20 tertiary gynaecological cancer centres in Australia, New Zealand, and Hong Kong randomised 760 women with stage I endometrioid endometrial cancer to either TLH or TAH. Follow-up ended 3rd March 2016. INTERVENTIONS 353 patients were randomized to TAH, 407 to TLH. MAIN OUTCOMES AND MEASURES Analysis according to intention-to-treat assessed the primary outcome of disease-free survival (DFS, time interval between surgery and date of first recurrence including any new localized or distant endometrial cancer recurrence or any new cancers, at 4.5 years post-randomization). The pre-specified equivalence boundary was ∆=±7%. Among seven pre-specified secondary outcomes, disease recurrence and overall survival are reported. RESULTS Patients were followed for a median of 4.5 years. Of 760 patients who were randomized (mean age 63 years), 679 (89%) completed the trial. At 4.5 years follow-up, DFS was 81.3% in the TAH and 81.6% in the TLH group. Equivalence was established with a DFS rate difference of 0.3% (favoring TLH) [95% CI: -5.53% to 6.13], p for equivalence =0.007. There was no statistical difference in endometrial cancer recurrences between the two groups (TAH 28 of 353 (7.9%) and TLH 33 of 407 (8.1%), risk difference 0.2%, 95% CI: -3.7 to 4.0%, p=0.93) or in overall survival (TAH 24 of 353 (6.8%) and TLH 30 of 407 (7.4%), risk difference 0.6%, 95% CI: -3.0 to 4.2%, p=0.76). CONCLUSIONS AND RELEVANCE Among women with stage I endometrioid endometrial cancer, the use of TAH compared with TLH resulted in equivalent DFS at 4.5 years and no difference in overall survival was observed. These findings support the use of laparoscopic hysterectomy for stage 1 endometrial cancer

Exercise during chemotherapy for ovarian cancer (ECHO) trial : design and implementation of a randomised controlled trial

Introduction Epidemiological evidence supports an association between higher levels of physical activity and improved cancer survival. Trial evidence is now needed to demonstrate the effect of exercise in a clinical setting. The Exercise during CHemotherapy for Ovarian cancer (ECHO) trial is a phase III, randomised controlled trial, designed to determine the effect of exercise on progression-free survival and physical well-being for patients receiving first-line chemotherapy for ovarian cancer. Methods and analysis Participants (target sample size n=500) include women with newly diagnosed primary ovarian cancer, scheduled to receive first-line chemotherapy. Consenting participants are randomly allocated (1:1) to either the exercise intervention (plus usual care) or usual care alone, with stratification for recruitment site, age, stage of disease and chemotherapy delivery (neoadjuvant vs adjuvant). The exercise intervention involves individualised exercise prescription with a weekly target of 150 minutes of moderate-intensity, mixed-mode exercise (equivalent to 450 metabolic equivalent minutes per week), delivered for the duration of first-line chemotherapy through weekly telephone sessions with a trial-trained exercise professional. The primary outcomes are progression-free survival and physical well-being. Secondary outcomes include overall survival, physical function, body composition, quality of life, fatigue, sleep, lymphoedema, anxiety, depression, chemotherapy completion rate, chemotherapy-related adverse events, physical activity levels and healthcare usage. Ethics and dissemination Ethics approval for the ECHO trial (2019/ETH08923) was granted by the Sydney Local Health District Ethics Review Committee (Royal Prince Alfred Zone) on 21 November 2014. Subsequent approvals were granted for an additional 11 sites across Queensland, New South Wales, Victoria and the Australian Capital Territory. Findings from the ECHO trial are planned to be disseminated via peer-reviewed publications and international exercise and oncology conferences

Near-infrared spectra of Galactic stellar clusters detected on Spitzer/GLIMPSE images

We present near-infrared spectroscopic observations of massive stars in three stellar clusters located in the direction of the inner Galaxy. One of them, the Quartet, is a new discovery while the other two were previously reported as candidate clusters identified on mid-infrared Spitzer images (GLIMPSE20 and GLIMPSE13). Using medium-resolution (R=900-1320) H and K spectroscopy, we firmly establish the nature of the brightest stars in these clusters, yielding new identifications of an early WC and two Ofpe/WN9 stars in the Quartet and an early WC star in GLIMPSE20. We combine this information with the available photometric measurements from 2MASS, to estimate cluster masses, ages, and distances. The presence of several massive stars places the Quartet and GLIMPSE20 among the small sample of known Galactic stellar clusters with masses of a few 10^3 Msun, and ages from 3 to 8 Myr. We estimate a distance of about 3.5 kpc for Glimpse 20, and 6.0 kpc for Quartet. The large number of giant stars identified in GLIMPSE13 indicates that it is another massive (~ 6500 Msun) cluster, but older, with an age between 30 and 100 Myr, at a distance of about 3 kpc.Comment: aastex macro, 21 pages, 15 figures. ApJ, accepte

Is telemonitoring an option against shortage of physicians in rural regions? attitude towards telemedical devices in the North Rhine-Westphalian health survey, Germany

<p>Abstract</p> <p>Background</p> <p>General practitioners (GP) in rural areas of Germany are struggling to find successors for their private practices. Telemonitoring at home offers an option to support remaining GPs and specialists in ambulatory care.</p> <p>Methods</p> <p>We assessed the knowledge and attitude towards telemedicine in the population of North Rhine-Westphalia (NRW), Germany, in a population-based telephone survey.</p> <p>Results</p> <p>Out of 2,006 participants, 734 (36.6%) reported an awareness of telemedical devices. Only 37 participants (1.8%) have experience in using them. The majority of participants were in favour of using them in case of illness (72.2%). However, this approval declined with age. These findings were similar in rural and urban areas. Participants who were in favour of telemedicine (n = 1,480) strongly agreed that they would have to see their doctor less often, and that the doctor would recognize earlier relevant changes in their vital status. Participants who disliked to be monitored by telemedical devices preferred to receive immediate feedback from their physician. Especially, the elderly fear the loss of personal contact with their physician. They need the direct patient-physician communication.</p> <p>Conclusions</p> <p>The fear of being left alone with the technique needs to be compensated for today's elderly patients to enhance acceptance of home telemonitoring as support for remaining doctors either in the rural areas or cities.</p

Hessische Forschungsdateninfrastrukturen HeFDI

Das Projekt „Hessische Forschungsdateninfrastrukturen“ (HeFDI) setzt auf die kooperative Entwicklung einer gemeinsamen Forschungsdatenstrategie und den Aufbau vernetzter Services. Durch den Zusammenschluss von zehn hessischen Hochschulen baut der so entstandene Verbund auf Kooperation durch institutionelle Arbeitsteilung