Pediatric medulloblastomas are the most frequently diagnosed embryonal tumors of the central nervous system. Current therapies cause severe neurological and cognitive side effects including secondary malignancies. Cellular immunotherapy might be key to improve survival and to avoid morbidity. Efficient killing of tumor cells using immunotherapy requires to overcome cancer-associated strategies to evade cytotoxic immune responses. Here, we examined the immune response and immune evasion strategies in pediatric medulloblastomas. Cytotoxic T-cells, infiltrating medulloblastomas with variable activation status, showed no correlation with overall survival of the patients. We found limited numbers of PD1+ T-cells and complete absence of PD-L1 on medulloblastomas. Medulloblastomas downregulated immune recognition molecules MHC-I and CD1 d. Intriguingly, expression of granzyme inhibitors SERPINB1 and SERPINB4 was acquired in 23% and 50% of the tumors, respectively. Concluding, pediatric medulloblastomas exploit multiple immune evasion strategies to overcome immune surveillance. Absence of PD-L1 expression in medulloblastoma suggest limited or no added value for immunotherapy with PD1/PD-L1 blockers.

GrB, but not GrK and GrM, is increased in the serum and kidney of patients with SLE and correlates with measures of poor prognosis in LN. These data suggest that GrB may contribute to the pathogenesis of SLE/LN, which indicates the possibility that GrB might be used as a biomarker and/or a therapeutic target.

Background Cardiac tamponade may present with very different signs and clinical consequences in patients who are supported with venoarterial extracorporeal membrane oxygenation. Failure to recognize cardiac tamponade in this setting can cause failure to wean from venoarterial extracorporeal membrane oxygenation, and even lead to death. Case presentation We present a 44-year-old Caucasian female in whom cardiac tamponade manifested as venoarterial extracorporeal membrane oxygenation weaning failure. After discovering the contribution of cardiac tamponade, it was possible to wean the patient from venoarterial extracorporeal membrane oxygenation support. No clear signs of cardiac tamponade had existed beforehand. Conclusions The diagnosis of cardiac tamponade can be very challenging in venoarterial extracorporeal membrane oxygenation supported patients due to (patho)physiological particularities related to the parallel blood flow.

ObjectiveTo develop and validate a symptom-based prediction rule for early recognition of acute coronary syndrome (ACS) in patients with acute chest discomfort who call out-of-hours services for primary care (OHS-PC).DesignCross-sectional study. A diagnostic prediction rule was developed with multivariable regression analyses. All models were validated with internal-external cross validation within seven OHS-PC locations. Both age and sex were analysed as statistical interaction terms, applying for age non-linear effects.SettingSeven OHS-PC in the Netherlands.Participants2192 patients who called OHS-PC for acute chest discomfort (pain, pressure, tightness or discomfort) between 2014 and 2017. Backed up recordings of telephone triage conversations were analysed.Primary and secondary outcomes measuresDiagnosis of ACS retrieved from the patient’s medical records in general practice, including hospital specialists discharge letters. Performance of the prediction rules was calculated with the c-statistic and the final model was chosen based on net benefit analyses.ResultsAmong the 2192 patients who called the OHS-PC with acute chest discomfort, 8.3% females and 15.3% males had an ACS. The final diagnostic model included seven predictors (sex, age, acute onset of chest pain lasting less than 12 hours, a pressing/heavy character of the pain, radiation of the pain, sweating and calling at night). It had an adjusted c-statistic of 0.77 (95% CI 0.74 to 0.79) with good calibration.ConclusionThe final prediction model for ACS has good discrimination and calibration and shows promise for replacing the existing telephone triage rules for patients with acute chest discomfort in general practice and OHS-PC.Trial registration numberNTR7331.