Cardiac fibroblasts and myofibroblasts assemble and maintain extracellular matrix during normal development and following injury. Culture expansion of these cells yield a bioengineered matrix that ...could lead to intriguing therapeutic opportunities. For example, we reported that cultured rat cardiac fibroblasts form a matrix that can be used to delivery therapeutic stem cells. Furthermore, we reported that matrix derived from cultured human cardiac fibroblasts/myofibroblasts converted monocytes into macrophages that express interesting anti-inflammatory and pro-angiogenic properties. Expanding these matrix investigations require characterization of the source cells for quality control. In these efforts, we observed and herein report that Sushi Containing Domain 2 (SUSD2) is a novel and consistent marker for cultured human cardiac fibroblast and myofibroblasts.
•Cultured cardiac fibroblasts and myofibroblasts derived from normal human hearts express the novel marker SUSD2.•Under high density culture conditions, human cardiac myofibroblasts deposit a matrix scaffold rich in fibronectin.•Cultured dermal fibroblasts do not express SUSD2 and did not for form scaffolds in vitro.
•Critically ill pediatric allogeneic hematopoietic cell transplant (HCT) patients may benefit from early and aggressive interventions aimed at reversing the progression of multiorgan ...dysfunction.•Using a multicenter cohort of 936 critically ill pediatric allogeneic HCT patients across 77 intensive care units, this study identified that pre-HCT renal injury, pre-HCT cytomegalovirus seropositivity, acute myeloid leukemia, Both myeloid and myelogenous are acceptable post-HCT day, and a continuous metric of multiorgan dysfunction (the Pediatric Risk of Mortality 3 score) prognosticated pediatric intensive care unit mortality for the highest-risk patients.•A multivariable model using these components identified that patients in the top quartile of risk had 3 times greater mortality than other patients (35.1% versus 11.5%, P < .001).
Critically ill pediatric allogeneic hematopoietic cell transplant (HCT) patients may benefit from early and aggressive interventions aimed at reversing the progression of multiorgan dysfunction. Therefore, we evaluated 25 early risk factors for pediatric intensive care unit (PICU) mortality to improve mortality prognostication. We merged the Virtual Pediatric Systems and Center for International Blood and Marrow Transplant Research databases and analyzed 936 critically ill patients ≤21 years of age who had undergone allogeneic HCT and subsequently required PICU admission between January 1, 2009, and December 31, 2014. Of 1532 PICU admissions, the overall PICU mortality rate was 17.4% (95% confidence interval CI, 15.6% to 19.4%) but was significantly higher for patients requiring mechanical ventilation (44.0%), renal replacement therapy (56.1%), or extracorporeal life support (77.8%). Mortality estimates increased significantly the longer that patients remained in the PICU. Of 25 HCT- and PICU-specific characteristics available at or near the time of PICU admission, moderate/severe pre-HCT renal injury, pre-HCT recipient cytomegalovirus seropositivity, <100-day interval between HCT and PICU admission, HCT for underlying acute myeloid leukemia, and greater admission organ dysfunction as approximated by the Pediatric Risk of Mortality 3 score were each independently associated with PICU mortality. A multivariable model using these components identified that patients in the top quartile of risk had 3 times greater mortality than other patients (35.1% versus 11.5%, P < .001, classification accuracy 75.2%; 95% CI, 73.0% to 77.4%). These data improve our working knowledge of the factors influencing the progression of critical illness in pediatric allogeneic HCT patients. Future investigation aimed at mitigating the effect of these risk factors is warranted.
Highlights • Ten-year OS estimate for those who survived relapse-free ≥1 year after HCT was 87% • Thirty percent of survivors reported at least one late effect • Growth disturbance, cataracts, and ...hypothyroidism were the most commonly reported • TBI and chronic graft-versus-host-disease were associated with adverse outcomes • Efforts should focus on reducing relapse and late effects after HCT at young age
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