Objective The devastating effect of traumatic brain injury (TBI) is exacerbated by an acute secondary neuroinflammatory response, clinically manifest as elevated intracranial pressure (ICP) due to cerebral edema. The treatment effect of cell based therapies in the acute post-TBI period has not been clinically studied although preclinical data demonstrate that bone marrow derived mononuclear cell (BMMNC) infusion downregulates the inflammatory response. Our study evaluates whether pediatric TBI patients receiving intravenous, autologous BMMNCs within 48 hours of injury experienced a reduction in therapeutic intensity directed towards managing elevated ICP relative to matched controls. Design The study was a retrospective cohort design comparing pediatric patients in a Phase I clinical trial treated with intravenous autologous BMMNCs (n=10) to a control group of age and severity matched children (n=19). Setting The study setting was at Children's Memorial Hermann Hospital, an American College of Surgeons Level 1 Pediatric Trauma Center and teaching hospital for the University of Texas Health Science Center at Houston from 2000-2008. Patients Study patients were 5-14 years with post resuscitation Glasgow Coma Scale scores of 5-8. Interventions The treatment group received 6 million autologous BMMNC/kg body weight intravenously within 48 hours of injury. The control group was treated in an identical fashion, per standard of care, guided by our TBI management protocol, derived from American Association of Neurological Surgeons guidelines. Measurements The primary measure was the Pediatric Intensity Level of Therapy (PILOT) scale, used to quantify treatment of elevated ICP. Secondary measures included the Pediatric Logistic Organ Dysfunction (PELOD) score and days of ICP monitoring as a surrogate for length of neurointensive care. Main Results A repeated measure mixed model with marginal linear predictions identified a significant reduction in the PILOT score beginning at 24 hours post treatment through week one (P<0.05). This divergence was also reflected in the PELOD score following the first week. The duration of ICP monitoring was 8.2±1.3 days in the treated group, and 15.6±3.5 days (p=0.03) in the time matched control group. Conclusions Intravenous autologous BMMNC therapy is associated with lower treatment intensity required to manage ICP, associated severity of organ injury, and duration of neurointensive care following severe TBI. This may corroborate preclinical data that autologous BMMNC therapy attenuates the effects of inflammation in the early post TBI period.
Burn injuries are a pervasive clinical problem. Extensive thermal trauma can be life-threatening or result in long-lasting complications, generating a significant impact on quality of life for patients as well as a cost burden to the healthcare system. The importance of addressing global or systemic issues such as resuscitation and management of inhalation injuries is not disputed but is beyond the scope of this review, which focuses on cutaneous pathophysiologic mechanisms for current treatments, both in the acute and long-term settings. Pathophysiological mechanisms of burn progression and wound healing are mediated by highly complex cascades of cellular and biochemical events, which become dysregulated in slow-healing wounds such as burns. Burns can result in fibroproliferative scarring, skin contractures, or chronic wounds that take weeks or months to heal. Burn injuries are highly individualized owing to wound-specific differences such as burn depth and surface area, in addition to patient-specific factors including genetics, immune competency, and age. Other extrinsic complications such as microbial infection can complicate wound healing, resulting in prolonged inflammation and delayed re-epithelialization. Although mortality is decreasing with advancements in burn care, morbidity from postburn deformities continues to be a challenge. Optimizing specialized acute care and late burn outcome intervention on a patient-by-patient basis is critical for successful management of burn wounds and the associated pathological scar outcome. Understanding the fundamentals of integument physiology and the cellular processes involved in wound healing is essential for designing effective treatment strategies for burn wound care as well as development of future therapies. Published 2018. Compr Physiol 8:371-405, 2018.
Optimal treatment of full-thickness skin injuries requires dermal and epidermal replacement. To spare donor dermis, dermal substitutes can be used ahead of split-thickness skin graft (STSG) application. However, this two-stage procedure requires an additional general anaesthetic, often prolongs hospitalisation, and increases outpatient services. Although a few case series have described successful single-stage reconstructions, with application of both STSG and dermal substitute at
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