Mediamusic (E-Journal)
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Endothelium-derived stromal cells contribute to hematopoietic bone marrow niche formation
No full textBone marrow stromal cells (BMSCs) play pivotal roles in tissue maintenance and regeneration. Their origins, however, remain incompletely understood. Here we identify rare LNGFR(+) cells in human fetal and regenerative bone marrow that co-express endothelial and stromal markers. This endothelial subpopulation displays transcriptional reprogramming consistent with endothelial-to-mesenchymal transition (EndoMT) and can generate multipotent stromal cells that reconstitute the bone marrow (BM) niche upon transplantation. Single-cell transcriptomics and lineage tracing in mice confirm robust and sustained contributions of EndoMT to bone precursor and hematopoietic niche pools. Interleukin-33 (IL-33) is overexpressed in subsets of EndoMT cells and drives this conversion process through ST2 receptor signaling. These data reveal generation of tissue-forming BMSCs from mouse and human endothelial cells and may be instructive for approaches to human tissue regeneration.</p
Switch-maintenance gemcitabine after first-line chemotherapy in patients with malignant mesothelioma (NVALT19):an investigator-initiated, randomised, open-label, phase 2 trial
No full textBackground Almost all patients with malignant mesothelioma eventually have disease progression after first-line therapy. Previous studies have investigated maintenance therapy, but none has shown a great effect. We aimed to assess the efficacy and safety of switch-maintenance gemcitabine in patients with malignant mesothelioma without disease progression after first-line chemotherapy.Methods We did a randomised, open-label, phase 2 trial in 18 hospitals in the Netherlands (NVALT19). We recruited patients aged older than 18 years with unresectable malignant mesothelioma with no evidence of disease progression after at least four cycles of first-line chemotherapy (with platinum and pemetrexed), who had a WHO performance status of 0-2, adequate organ function, and measurable or evaluable disease. Exclusion criteria were active uncontrolled infection or severe cardiac dysfunction, serious disabling conditions, symptomatic CNS metastases, radiotherapy within 2 weeks before enrolment, and concomitant use of any other drugs under investigation. Patients were randomly assigned (1:1), using the minimisation method, to maintenance intravenous gemcitabine (1250 mg/m(2) on days 1 and 8, in cycles of 21 days) plus supportive care, or to best supportive care alone, until disease progression, unacceptable toxicity, serious intercurrent illness, patient request for discontinuation, or need for any other anticancer agent, except for palliative radiotherapy. A CT scan of the thorax or abdomen (or both) and pulmonary function tests were done at baseline and repeated every 6 weeks. The primary outcome was progression-free survival in the intention-to-treat population. Safety was analysed in all participants who received one or more doses of the study drug or had at least one visit for supportive care. Recruitment is now closed; treatment and follow-up are ongoing. This study is registered with the Netherlands Trial Registry, NTR4132/NL3847.Findings Between March 20, 2014, and Feb 27, 2019, 130 patients were enrolled and randomly assigned to gemcitabine plus supportive care (65 patients [50%]) or supportive care alone (65 patients [50%]). No patients were lost to follow-up; median follow-up was 36.5 months (95% CI 34.2 to not reached), and one patient in the supportive care group withdrew consent. Progression-free survival was significantly longer in the gemcitabine group (median 6.2 months [95% CI 4.6-8.7]) than in the supportive care group (3.2 months [2.8-4.1]; hazard ratio [HR] 0.48 [95% CI 0.33-0.71]; p=0.0002). The benefit was confirmed by masked independent central review (HR 0.49 [0.33-0.72]; p=0.0002). Grade 3-4 adverse events occurred in 33 ( 52%) of 64 patients in the gemcitabine group and in ten (16%) of 62 patients in the supportive care group. The most frequent adverse events were anaemia, neutropenia, fatigue or asthenia, pain, and infection in the gemcitabine group, and pain, infection, and cough or dyspnoea in the supportive care group. One patient (2%) in the gemcitabine group died, due to a treatment-related infection.Interpretation Switch-maintenance gemcitabine, after first-line chemotherapy, significantly prolonged progression-free survival compared with best supportive care alone, among patients with malignant mesothelioma. This study confirms the activity of gemcitabine in treating malignant mesothelioma.</p
Reduction of anti-K-mediated hemolytic disease of newborns after the introduction of a matched transfusion policy:A nation-wide policy change evaluation study in the Netherlands
No full textBackground: During pregnancy, maternal red blood cell (RBC) antibodies can lead to life-threatening fetal hemolysis and anemia. Women can become immunized by a pregnancy or an unmatched transfusion. Our aim was to quantify the effect of a nationwide K-matched transfusion policy for women of childbearing age potential to prevent K-immunization in pregnancy.Study Design and Methods: In this nation-wide policy change evaluation study we determined the occurrence of RBC antibodies before and after introduction of a K-matched transfusion policy and evaluated the cause K alloimmunization 10 years after introduction of this measure. K-matched transfusion for females under 45 years of age is advised in the Dutch transfusion guideline since 2004. We used laboratory data from pregnancies with RBC antibodies identified in the period 1999-2018 obtained as part of a population-based screening program in the Netherlands.Results: Tests of 36 286 pregnancies produced a positive antibody screening result which concerned anti-K in 1550 pregnancies. The occurrence of anti-K decreased from 67.9 to 20.2 per 100 000 pregnancies. The relative risk reduction was 0.70 which largely exceeded the relative risk reduction of 0.27 for antibodies against RBC antigens for which no preventive matching is required. The number of pregnancies at risk for anti-K-mediated disease decreased from 9.7 to 4.2 per 100 000 pregnancies.Conclusions: A K-matched transfusion policy is associated with a major decrease in a number of pregnant women with anti-K and pregnancies at risk for anti-K-mediated disease. A relatively simple measure is now shown to impact prevention of hemolytic disease in the fetus and newborn.</p
New Results on Stabilization of Port-Hamiltonian Systems via PID Passivity-Based Control
No full textIn this article, we present some new results for the design of PID passivity-based controllers (PBCs) for the regulation of port-Hamiltonian (pH) systems. The main contributions of this article are: (i) new algebraic conditions for the explicit solution of the partial differential equation required in this design; (ii) revealing the deleterious impact of the dissipation obstacle that limits the application of the standard PID-PBC to systems without pervasive dissipation; (iii) the proposal of a new PID-PBC which is generated by two passive outputs, one with relative degree zero and the other with relative degree one. The first output ensures that the PID-PBC is not hindered by the dissipation obstacle, while the relative degree of the second passive output allows the inclusion of a derivative term. Making the procedure more constructive and removing the requirement on the dissipation significantly extends the realm of application of PID-PBC. Moreover, allowing the possibility of adding a derivative term to the control, enhances its transient performance.</p
A new tool to assess Clinical Diversity In Meta‐analyses (CDIM) of interventions
No full textOBJECTIVE: To develop and validate Clinical Diversity In Meta-analyses (CDIM), a new tool for assessing clinical diversity between trials in meta-analyses of interventions.STUDY DESIGN AND SETTING: The development of CDIM was based on consensus work informed by empirical literature and expertise. We drafted the CDIM tool, refined it, and validated CDIM for interrater scale reliability and agreement in three groups.RESULTS: CDIM measures clinical diversity on a scale that includes four domains with 11 items overall: setting (time of conduct/country development status/units type); population (age, sex, patient inclusion criteria/baseline disease severity, comorbidities); interventions (intervention intensity/strength/duration of intervention, timing, control intervention, cointerventions); and outcome (definition of outcome, timing of outcome assessment). The CDIM is completed in two steps: first two authors independently assess clinical diversity in the four domains. Second, after agreeing upon scores of individual items a consensus score is achieved. Interrater scale reliability and agreement ranged from moderate to almost perfect depending on the type of raters.CONCLUSION: CDIM is the first tool developed for assessing clinical diversity in meta-analyses of interventions. We found CDIM to be a reliable tool for assessing clinical diversity among trials in meta-analysis.</p
Ex Situ Dual Hypothermic Oxygenated Machine Perfusion for Human Split Liver Transplantation
No full textLiver splitting allows the opportunity to share a deceased graft between 2 recipients but remains underutilized. We hypothesized that liver splitting during continuous dual hypothermic oxygenated machine perfusion (DHOPE) is feasible, with shortened total cold ischemia times and improved logistics. Here, we describe a left lateral segment (LLS) and extended right lobe (ERL) liver split procedure during continuous DHOPE preservation with subsequent transplantation at 2 different centers.Methods: After transport using static cold storage, a 51-year-old brain death donor liver underwent end-ischemic DHOPE. During DHOPE, the donor liver was maintained <10 °C and oxygenated with a Po2 of >106 kPa. An ex situ ERL/LLS split was performed with continuing DHOPE throughout the procedure to avoid additional ischemia time.Results: Total cold ischemia times for the LLS and ERL were 205 minutes and 468 minutes, respectively. Both partial grafts were successfully transplanted at 2 different transplant centers. Peak aspartate aminotransferase and alanine aminotransferase were 172 IU/L and 107 IU/L for the LLS graft, and 839 IU/L and 502 IU/L for the ERL graft, respectively. The recipient of the LLS experienced an episode of acute cellular rejection. The ERL transplantation was complicated by severe acute pancreatitis with jejunum perforation requiring percutaneous drainage and acute cellular rejection. No device-related adverse events were observed.Conclusions: Liver splitting during continuous DHOPE preservation is feasible, has the potential to substantially shorten cold ischemia time and may optimize transplant logistics. Therefore liver splitting with DHOPE can potentially improve utilization of split liver transplantation.</p
Endoscopic closure of a postoperative rectal anastomotic leakage with hemoclips:a case report
No full textTime, tone and the brain: Behavioral and neurophysiological studies on time reference and grammatical tone in Akan
No full textLanguages of the world have several ways of expressing time reference. Many languages such as those in the Indo-European group express time reference through tense. Asian languages such as Chinese express time reference through aspectual adverbs, while Akan (spoken in Ghana) does so through grammatical tone. The goal of this dissertation was to investigate grammatical tone and time reference processing in Akan brain damaged speakers with and without aphasia, as well as healthy Akan speakers. Using behavioral and neurophysiological methods, the results of this project showed that grammatical tone processing is problematic for individuals with brain damage. However, the problems with grammatical tone processing, particularly in individuals with brain damage leading to agrammatic aphasia, was largely driven by past time reference deficit, and not grammatical tone per se. That is, individuals with agrammatic aphasia showed more difficulties in processing past verbs than the non-past verbs. This is because past time reference requires extra processing load compared to the non-past time reference. The dissociation between the past and non-past processing was also confirmed by the electrophysiological brain response of the healthy Akan speakers. The conclusion is that regardless of how time reference is expressed, whether through affixes (in Indo-European languages), aspectual adverbs (in Chinese) or tone (in Akan), the processing of past and non-past time reference show different underlying neural processes. Therefore, the findings of this project highlight the need for cross-linguistic studies, especially in understudied languages, in order to test and broaden the already existing neuro-linguistic theories
Organization and activities of school health services among EU countries
No full textBACKGROUND: School health services (SHS) can be defined as health services provided to enrol pupils by health professionals and/or allied professions. The aim of this study was to explore the current state of the governance, organization and workforce of SHS and their provision of preventive activities in European countries.METHODS: Observational study. Data were collected as part of the Horizon 2020-funded project 'Models of Child Health Appraised'. Only 1 expert from each of the 30 included European countries answered a closed-items questionnaire during the years 2017 and 2018.RESULTS: All countries (except Spain and the Czech Republic, which do not have formal SHS) provided school-based individual screening and health-enhancing measures. The majority performed height, weight, vision and hearing checks; some integrated other assessments of limited evidence-based effectiveness. Most countries also delivered health education and promotion activities in areas, such as sexual health, substance use and healthy nutrition. Almost all countries seemed to suffer from a shortage of school health professionals; moreover, many of these professionals had no specific training in the area of school health and prevention.CONCLUSIONS: Many EU countries need better administrative and legal support. They should promote evidence-based screening procedures and should hire and train more school health professionals. Overall, they need to adapt to the evolving health priorities of pupils, adopt a more holistic paradigm and extend their activities beyond traditional screening or vaccination procedures.</p