Because respiratory dysfunction after hematopoietic stem cell transplantation is a manifestation of a continuum of dysfunction temporarily induced by the transplant process, a proactive rather than reactive approach might prevent or attenuate its progression to acute respiratory distress syndrome. Organ dysfunction in this population results from cytokine-driven processes, of which the first manifestation includes fluid accumulation. We describe a multistep protocol that first targets fluid balance control, both through restriction of intake and through augmentation of output using dopamine and furosemide infusions. If these steps fail to stem the tide of water accumulation, we advocate the relatively early use of continuous renal replacement therapy, its use triggered by a continued increase in body weight (>10% above baseline), an increasing c-reactive protein level, and an increasing oxygen need. Renal function parameters do not figure in this protocol. We recommend continuous renal replacement therapy at 35 mL/kg/h (2,000 mL/1.73 m(2)/h), a dose that allows adequate flexibility in fluid management and that may provide effective clearance of proinflammatory (and anti-inflammatory) mediators that drive the evolving dysfunction. Proactive intervention improves the clinical status such that the transition to mechanical ventilation may proceed smoothly or in some cases even may be avoided altogether.
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http://dx.doi.org/10.1016/j.semnephrol.2008.05.008 | DOI Listing |
Am J Hosp Palliat Care
January 2025
Department of Pediatrics, University of Chicago, Comer Children's Hospital, Chicago, IL, USA.
Pediatric neuro-oncology patients have one of the highest mortality rates among all children with cancer. Our study examines the potential relationship between palliative care consultation and intensity of in-hospital care and determines if racial and ethnic differences are associated with palliative care consultations during their terminal admission. Retrospective observational study using the Pediatric Health Information System (PHIS) database with data from U.
View Article and Find Full Text PDFNeuro Oncol
January 2025
Department of Medicine, Division of Experimental Medicine, McGill University.
Background: Glioblastoma is an aggressive brain cancer with a 5-year survival rate of 5-10%. Current therapeutic options are limited, due in part to drug exclusion by the blood-brain barrier, restricting access of targeted drugs to the tumor. The receptor for the type 1 insulin-like growth factor (IGF-1R) was identified as a therapeutic target in glioblastoma.
View Article and Find Full Text PDFSci Transl Med
January 2025
Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA.
Tissue-specific T cell immune responses play a critical role in maintaining organ health but can also drive immune pathology during both autoimmunity and alloimmunity. The mechanisms controlling intratissue T cell programming remain unclear. Here, we leveraged a nonhuman primate model of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation to probe the biological underpinnings of tissue-specific alloimmune disease using a comprehensive systems immunology approach including multiparameter flow cytometry, population-based transcriptional profiling, and multiplexed single-cell RNA sequencing and TCR sequencing.
View Article and Find Full Text PDFSci Transl Med
January 2025
Graduate Program in Human Genetics, University of Miami Miller School of Medicine, 1501 NW 10th Avenue (M-860), Miami, FL 33136, USA.
Primary mitochondrial disorders are most often caused by deleterious mutations in the mitochondrial DNA (mtDNA). Here, we used a mitochondrial DddA-derived cytosine base editor (DdCBE) to introduce a compensatory edit in a mouse model that carries the pathological mutation in the mitochondrial transfer RNA (tRNA) alanine (mt-tRNA) gene. Because the original m.
View Article and Find Full Text PDFSci Adv
January 2025
Division of Regenerative Medicine, Hartman Institute for Therapeutic Organ Regeneration, Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
Tissue-specific endothelial cells (ECs) are critical for the homeostasis of pancreatic islets and most other tissues. In vitro recapitulation of islet biology and therapeutic islet transplantation both require adequate vascularization, which remains a challenge. Using human reprogrammed vascular ECs (R-VECs), human islets were functionally vascularized in vitro, demonstrating responsive, dynamic glucose-stimulated insulin secretion and Ca influx.
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