Suchergebnisse

OBJECTIVE: Patients using U-500 regular insulin are severely insulin resistant, requiring high doses of insulin. It has been observed that a patient's insulin requirements may dramatically decrease during hospitalization. This study sought to systematically investigate this phenomenon. METHODS: We performed a retrospective chart review of patients with U-500 insulin outpatient regimens who were admitted to the San Antonio Military Medical Center over a 5-year period. Each patient's outpatient total daily dose (TDD) of insulin was compared to the average inpatient TDD. The outpatient estimated average glucose (eAG) was calculated from the glycated hemoglobin (HbA1c) and compared to the average inpatient glucose. RESULTS: There were 27 patients with a total of 62 separate admissions. The average age was 64.4 years, with a mean body mass index of 38.9 kg/m CONCLUSION: U-500 insulin is prone to errors in the hospital setting, so conversion to U-100 insulin is a preferred option. Despite a significant reduction in insulin TDD, these patients had clinically similar glucose levels. Therefore, patients taking U-500 insulin as an outpatient can be converted to a U-100 basal-bolus regimen with at least a 50% reduction of their outpatient TDD. ABBREVIATIONS: BG = blood glucose eAG = estimated average glucose HbA1c = glycated hemoglobin NPO = nil per os SPSS = Statistical Package for the Social Sciences TDD = total daily dose.

Orlova, Bellin, Mummery, and colleagues combined three hiPSC-derived cardiac cell types in 3D microtissues. Cardiomyocytes matured structurally and functionally. Replacing healthy hiPSC-cardiac fibroblasts with patient fibroblasts recapitulated aspects of arrhythmogenic cardiomyopathy. Single-cell transcriptomics, electrophysiology, metabolomics, and ultrastructural analysis revealed roles for CX43 gap junctions and cAMP signaling in the tri-cell-type dialog.Cardiomyocytes (CMs) from human induced pluripotent stem cells (hiPSCs) are functionally immature, but this is improved by incorporation into engineered tissues or forced contraction. Here, we showed that tri-cellular combinations of hiPSC-derived CMs, cardiac fibroblasts (CFs), and cardiac endothelial cells also enhance maturation in easily constructed, scaffold-free, three-dimensional microtissues (MTs). hiPSC-CMs in MTs with CFs showed improved sarcomeric structures with T-tubules, enhanced contractility, and mitochondrial respiration and were electrophysiologically more mature than MTs without CFs. Interactions mediating maturation included coupling between hiPSC-CMs and CFs through connexin 43 (CX43) gap junctions and increased intracellular cyclic AMP (cAMP). Scaled production of thousands of hiPSC-MTs was highly reproducible across lines and differentiated cell batches. MTs containing healthy-control hiPSC-CMs but hiPSC-CFs from patients with arrhythmogenic cardiomyopathy strikingly recapitulated features of the disease. Our MT model is thus a simple and versatile platform for modeling multicellular cardiac diseases that will facilitate industry and academic engagement in high-throughput molecular screening. ; European Research Council (ERCAdG 323182 STEMCARDIOVASC); European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 602423; European Union's Horizon 2020 Research and Innovation Programme under grant agreement no. 668724; Netherlands Organ-on-Chip Initiative, an NWO Gravitation project funded by the Ministry of Education, Culture and Science of the government of the Netherlands; Transnational Research Project on Cardiovascular Diseases (JTC2016_FP-40-021 ACMHF); the Netherlands Organisation for Health Research and Development ZonMW (MKMD project no. 114022504);