Chronic wounds arising from orthopedic surgery present a major clinical challenge. Osteomyelitis may develop from polymicrobial infection, which can be unresponsive to treatment and lead to amputation. Topical negative pressure (TNP) is an effective treatment in wound management and is now used worldwide. Activated protein C (APC) is an anticoagulant with cytoprotective and healing properties. The aim of this study was to determine whether combined treatment of TNP and APC was tolerated and was efficacious for treatment of difficult-to-treat wounds. Four patients who presented to Royal North Shore Hospital with wounds that were not responsive to conventional therapy were studied. All cases showed a marked reduction in wound size and depth within 1 week of starting treatment and progressively improved over time. There was a remarkable increase in the volume of granulation tissue. After treatment, wounds either completely closed or provided sufficient granulation tissue to allow split-thickness skin grafting. The treatment was well tolerated, and the patients were able to be managed on out-patient basis. Long-term follow-up suggested that this treatment prevented osteomyelitis. This innovative treatment is very promising and may significantly increase quality of care for patients with recalcitrant orthopedic wounds. A randomized, placebo-controlled double blind trial is required to further determine the efficacy of APC plus TNP.

Burns are debilitating, life threatening, and difficult to assess and manage. Recent advances in assessment and management have occurred since a comprehensive review of the care of patients with severe burns was last published, which may influence research and clinical practice. Recent Advances: Recent advances have occurred in the understanding of burn pathophysiology, which has led to the identification of potential biomarkers of burn severity, such as protein C. There is new evidence about the potential superiority of natural colloids over crystalloids during fluid resuscitation, and new evidence about components of initial and perioperative management, including an improved understanding of pain following burns. Critical Issues: The limitations of the clinical examination highlight the need for imaging and biomarkers to assist in estimations of burn severity. Fluid resuscitation reduces mortality, although there is conjecture over the ideal method. The subsequent perioperative period is associated with significant morbidity and the evidence for preventing and treating pain, infection, and fluid overload while maximizing wound healing potential is described. Future Directions: Promising developments are ongoing in imaging technology, histopathology, biomarkers, and wound healing adjuncts such as hyperbaric oxygen therapy, topical negative pressure therapy, stem cell treatments, and skin substitutes. The greatest benefit from further research on management of patients with burns would most likely be derived from the elucidation of optimal fluid resuscitation protocols, pain management protocols, and surgical techniques from randomized controlled trials.

Pressure ulcers present a major clinical challenge, are physically debilitating and place the patient at risk of serious comorbidities such as septic shock. Recombinant human activated protein C (APC) is an anticoagulant with anti-inflammatory, cytoprotective and angiogenic effects that promote rapid wound healing. Topical negative pressure wound therapy (TNP) has become widely used as a treatment modality in wounds although its efficacy has not been proven through randomised controlled trials. The aim of this study was to determine the preliminary efficacy and safety of treatment with APC for severe chronic pressure sores with and without TNP. This case presentation describes the history, management and outcome of two patients each with a severe chronic non-healing pressure ulcer that had failed to respond to conventional therapy. TNP was added to conservative management of both ulcers with no improvement seen. Then local application of small doses of APC was added to TNP and with conservative management, resulted in significant clinical improvement and rapid healing of both ulcers, displaying rapid growth of vascular granulation tissue with subsequent epithelialisation. Patients tolerated the treatment well and improvements suggested by long-term follow-up were provided. Randomised placebo-controlled double blind trials are needed to quantify the efficacy, safety, cost-effectiveness, optimal dose and quality of life changes seen from treatment with APC.

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