Notes

Organisational models throughout major medical care to deal with long-term problems: A scoping assessment.
Patient-reported outcomes among survivors of pediatric hematopoietic stem cell transplant (HSCT) are understudied. We compared symptom prevalence, health-related quality of life (HRQOL), and risk factors in adult survivors of childhood hematologic malignancies treated with HSCT to those treated with conventional therapy and non-cancer controls. Survivors of childhood hematologic malignancies (HSCT N=112 [70% allogeneic, 30% autologous]; conventionally-treated N=1,106) and non-cancer controls (N=242) from the St. Jude Lifetime Cohort Study completed surveys assessing 10 symptom domains, and SF-36 HRQOL summary scores. Chronic health conditions (CHCs) were validated by clinical assessment. Multivariable logistic regression reveals that compared to non-cancer controls, HSCT survivors endorsed a significantly higher symptom prevalence in sensation (OR=4.7, 95% CI=2.6-8.4), motor/movement (OR=4.3, 95% CI=1.6-11.0), pulmonary (OR=4.6, 95% CI=1.8-11.8) and memory domains (OR=4.8, 95% CI=2.5-9.2), and poorer physical HRQOL (OR=6.9, 95% CI=2.8-17.0). HSCT and conventionally-treated survivors had a similar prevalence of all symptom domains and HRQOL (P's>0.05); however, HSCT survivors had a significantly higher cumulative prevalence for specific symptoms double vision (P=0.04), very dry eyes (P less then 0.0001), and trouble seeing when wearing glasses (P less then 0.0001). Occurrence of organ-specific CHCs, instead of transplant receipt, was significantly associated with a higher prevalence of all symptom domains (P's less then 0.05) in adult survivors of childhood cancer, except for pain and anxiety domains. This study found that patient-reported outcomes were equally impaired between HSCT and conventionally-treated survivors, but poorer in both groups compared to non-cancer controls. Poor patient-reported outcomes in all survivors of childhood hematologic malignancies correlated with the presence of CHCs, whether treated with conventional therapy or HSCT. Copyright © 2020 American Society of Hematology.AIMS Uromodulin is produced exclusively in the kidney and secreted into both urine and blood. Serum levels of uromodulin are correlated with kidney function and reduced in chronic kidney disease (CKD) patients, but physiological functions of serum uromodulin are still elusive. The present study investigated the role of uromodulin in medial vascular calcification, a key factor associated with cardiovascular events and mortality in CKD patients. METHODS AND RESULTS Experiments were performed in primary human (HAoSMCs) and mouse (MOVAS) aortic smooth muscle cells, cholecalciferol overload and subtotal nephrectomy mouse models and serum from CKD patients. In three independent cohorts of CKD patients, serum uromodulin concentrations were inversely correlated with serum calcification propensity. Uromodulin supplementation reduced phosphate-induced osteo-/chondrogenic transdifferentiation and calcification of HAoSMCs. In human serum, pro-inflammatory cytokines TNFα and IL-1β co-immunoprecipitated with uromodulin. Urively in the kidney and secreted into urine and blood. While multiple functions of urinary uromodulin have been established, the physiological functions of circulating uromodulin are still elusive. In chronic kidney disease, serum uromodulin concentrations were inversely correlated with serum calcification propensity, a marker for adverse cardiovascular outcomes. ARC155858 Uromodulin ameliorated vascular calcification in vitro and in mice with cholecalciferol overload, but not during renal failure in mice. Uromodulin carbamylation abolished its anti-calcific effects. These data suggest an important role of uromodulin in vascular homeostasis and provide a novel link between reduced kidney function and vascular pathology. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions please email [email protected]  Indexed effective orifice area (EOAi) charts are used to determine the likelihood of prosthesis-patient mismatch (PPM) after aortic valve replacement (AVR). The aim of this study is to validate whether these EOAi charts, based on echocardiographic normal reference values, can accurately predict PPM. METHODS AND RESULTS  In the PERIcardial SurGical AOrtic Valve ReplacemeNt (PERIGON) Pivotal Trial, 986 patients with aortic valve stenosis/regurgitation underwent AVR with an Avalus valve. Patients were randomly split (5050) into training and test sets. The mean measured EOAs for each valve size from the training set were used to create an Avalus EOAi chart. This chart was subsequently used to predict PPM in the test set and measures of diagnostic accuracy (sensitivity, specificity, and negative and positive predictive value) were assessed. PPM was defined by an EOAi ≤0.85 cm2/m2, and severe PPM was defined as EOAi ≤0.65 cm2/m2. The reference values obtained from the training set ranged from 1.27 cm2 for size 19 mm up to 1.81 cm2 for size 27 mm. The test set had an incidence of 66% of PPM and 24% of severe PPM. The EOAi chart inaccurately predicted PPM in 30% of patients and severe PPM in 22% of patients. For the prediction of PPM, the sensitivity was 87% and the specificity 37%. For the prediction of severe PPM, the sensitivity was 13% and the specificity 98%. CONCLUSION  The use of echocardiographic normal reference values for EOAi charts to predict PPM is unreliable due to the large proportion of misclassifications. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.INTRODUCTION siRNA-based targeting of PCSK9 represents a novel therapeutic approach that may provide a convenient, infrequent and safe dosing schedule to robustly lower LDL-C. Given the long duration of action, however, establishing safety in particular with respect to immunogenicity is of paramount importance. In earlier clinical studies of other RNA-targeted treatment approaches (antisense oligonucleotide therapy) immunological and haematological adverse-effects, in particular thrombocytopenia and pro-inflammatory effects, have been reported. Here, we present the pre-specified safety analysis from ORION-1 evaluating platelets, immune cells, immunological markers, antidrug antibodies and clinical immunogenicity adverse events under PCSK9 siRNA treatment with inclisiran. METHODS AND RESULTS The pre-specified safety analysis from ORION-1 was performed in 6 different inclisiran dosing regimens in patients at high risk of cardiovascular disease with elevated LDL-C levels. Patients received either a single-dose (SD 200mg, n = 60; 300mg, n = 62 or 500mg, n = 66) or double-dose starting regimen (DD 100mg, n = 62; 200mg, n = 63; or 300mg, n = 61 on days 1 and 90) of inclisiran or placebo (single-dose n = 65; double-dose n = 62).
Homepage: https://www.selleckchem.com/products/ar-c155858.html