Comprehensive review of the clinical application of autologous mesenchymal stem cells in the treatment of chronic wounds and diabetic bone healing.

Chronic ulcerations are a physical and financial burden to the health and economic establishment in the United States and Worldwide. Improvements in biotechnology and knowledge in stem cell applications have progressed and basic science results are making their way slowly into the clinical arena. Chronic wounds and diabetic bone healing are the key components in the limb salvage of the common diabetic foot. We have examined the current available literature and present the latest on stem cells applications as a novel clinical technique in the treatment of chronic wound and diabetic bone healing and their impact in the treatment paradigm of patients.

Stem cell applications in diabetic charcot foot and ankle reconstructive surgery .

 Bone regeneration and repair via mesenchymal stem cells (MSC) are intriguing and challenging thoughts today. Many have claimed that MSCs are powerful tools for bone regeneration due to their ability to differentiate into osteoblasts. Seeking all three essential bone growth properties for successful bone remodeling and repair-osteoinductive, osteoconductive, and osteogenic-has been a complex task; however, they are essential in difficult surgical situations with poor host bone tissue. Diabetic Charcot foot and ankle neuroarthropathy is challenging due to its inherent poor bone quality and patient's comorbidities. In this review of diabetic Charcot patients who underwent reconstructive surgery with and without MSC grafting, the radiographic healing time parameter was most striking between groups, 6.4 versus 9.2 weeks (P < 0.024). In both groups, there were non-unions, mal-unions, and/or delayed unions noted. Surgical application of MSC appears to be safe, and has the potential to be effective as an autograft substitute, but remains inconclusive. In these limb salvage situations, reconstructive surgeries create challenging environment for bone growth and healing. The ability to utilize the properties of MSCs to differentiate into the type of specialized cells is promising; however, it still does not support substituting autografts as the gold standard. .

Polyhexamethylene Biguanide (PHMB): An Addendum to Current Topical Antimicrobials.

Antimicrobials are routinely used in the treatment of chronic and problematic wounds. Despite the on-going increase in numbers and types of products, well-designed clinical trials that support their efficacy are limited. Antimicrobial products are applied with understanding of their mechanisms of action and role in wound repair. This manuscript reviews the major categories of products on the market, providing the clinician with information on the different types of products and their purported effect on wounds. A new product containing polyhexamethylene biguanide is described in greater detail with relevant case presentations and cost data. This new product does not appear to have any known cytotoxicity in the dressing configuration and may be applied to a wide range of wounds.

Infection-free Clinical Response Among Patients With Hidradenitis Suppurativa Who Were Treated With Adalimumab: Results from Two Phase 3 Studies.

OBJECTIVE: The objective of this study is to assess the rates of infection-free achievement of hidradenitis suppurativa clinical response (HiSCR) using integrated data from 2 phase 3, placebo-controlled trials, PIONEER I and II. MATERIALS AND METHODS: Analyses from the first 12 weeks of both studies were examined. Patients were randomized to receive adalimumab (ADA) or placebo, and they then were assessed in the clinic at weeks 0, 2, 4, 8, and 12. All reports of an adverse or serious adverse event and infection were classified as treatment-emergent adverse events (TEAEs). The HiSCR was evaluated as the primary endpoint; infection-free HiSCR was also evaluated. RESULTS: Treatment-emergent adverse events were observed in 55.4% of the ADA group and 64.4% of the placebo (P < .023). The rates of serious TEAEs and infection-related TEAEs were slightly less in the ADA group compared with the placebo group. A significantly higher percentage of ADA-treated patients achieved HiSCR at week 12 compared with placebo (P < .001). At each visit during the study's 12 weeks, a greater proportion of ADA-treated patients achieved infection-free HiSCR compared with patients treated with placebo (P < .001). Mean durations of HiSCR and infection-free HiSCR were significantly longer in ADA-treated patients when compared with placebo-treated patients (P < .001). CONCLUSIONS: Results of this integrated analysis indicate that patients with hidradenitis suppurativa who received a short duration of ADA treatment experienced better combined efficacy and similar safety compared with placebo. Further studies investigating longer ADA treatment may demonstrate further improvements in duration of infection-free clinical response.

Standardizing wound treatment procedures for advanced technologies.

New drugs and tissue replacements are currently being approved and integrated into treatment regimens for chronic wounds. This article focuses on a standardized procedure for the use of specific growth factor, a recombinant human platelet-derived growth factor (rhPDGF-BB) manufactured for topical administration. The recommendations made in this article may not reflect product recommendations made by the manufacturer of the drug. Clinicians must be able to support any off-label indication for use of a product.

Cellular senescence and matrix metalloproteinase activity in chronic wounds. Relevance to debridement and new technologies.

A prolonged inflammatory response may adversely affect wound closure. Delayed wound closure and extended exposure to chronic wound fluid may also affect cellular activity in a wound bed and result in cellular senescence. Prolonged inflammation and cellular senescence may adversely affect the efficacy of topically-applied biological agents, including growth factors. Appropriate wound bed preparation and debridement are necessary to improve clinical outcomes of new technologies.

Hallux, sesamoid, and first metatarsal injuries.

Hallux, sesamoid, and first metatarsal injuries are common foot injuries and have implications in the biomechanical functionality of the first ray and foot. They are essential for propulsion in normal gait. As part of the first ray, it is an important contributor to normal locomotion. Any structure disruption or injury can create angular changes or arthritis, which can have biomechanical implications, including pain, disability, compensation, swelling, and reduced range of motion.

Foot and ankle surgery: considerations for the geriatric patient.

The growing number of lower-extremity abnormalities that are seen in inpatient and outpatient settings has paralleled the increased number of elderly in the population. Foot and ankle deformities, disorders, and arthritis, which are not manifested until late in life, have become more common as more individuals attain longer lifespans. Although conservative therapies are a priority when addressing the geriatric population, surgical options may be overlooked secondary to a misunderstanding of their ability to overcome perioperative management. Advanced minimally invasive surgical procedures for the foot and ankle have decreased the complications associated with foot surgery, making surgical intervention a viable option for many of the elderly. The newer procedures do not, however, minimize strict perioperative management, including pharmacological and nutritional assessment, and cardiopulmonary precautions. Outpatient surgical intervention may effectively address many ongoing problems associated with pain, decreased ambulation, and decreased quality of life. Current techniques in joint reconstruction in the forefoot and midfoot allow weight bearing from the day of surgery. Most hindfoot and ankle surgeries now permit minimal bone resection and incision through arthroscopy, resulting in improved muscle and tendon repair and early weight bearing. The changes in surgical approaches for the geriatric foot have permitted more effective and rapid intervention in problems affecting ambulation and quality of life in our aged population.