Michael S. Brogan

Analysis of the proteomic profile of chronic pressure ulcers

Analysis of the proteomic profile of pressure ulcers over time is a critical step in the identification of biomarkers of healing or nonhealing in pressure ulcers. The wound fluid from 32 subjects with 42 pressure ulcers was evaluated over 6 weeks at 15 time points. Samples specific to both the interior and the periphery of the wound bed were collected. Antibody screening arrays, isobaric tags for relative and absolute quantitation with mass spectrometry and multiplexed microarrays were used to characterize wound fluid and results were correlated with clinical outcome. Twenty‐one proteins were found to distinguish between healed and chronic wounds and 19 proteins were differentially expressed between the interior and periphery of wounds. Four proteins, pyruvate kinase isozymes M1/M2, profilin‐1, Ig lambda‐1 chain C regions, and Ig gamma‐1 chain C region, were present in lower levels for periphery samples when compared to interior samples and six proteins, keratin, type II cytoskeletal 6A (KRT6A), keratin, type I cytoskeletal 14, S100 calcium binding proteins A7, alpha‐1‐antitrypsin precursor, hemoglobin subunit alpha, and hemoglobin subunit beta, were present in higher levels in periphery samples when compared with interior samples. S100 calcium binding protein A6, S100 calcium binding protein A7, and soluble receptor for advanced glycation end‐products had higher levels in the periphery of chronic wounds vs. the interior in planar arrays. A significant temporal trend was noted for monokine induced by gamma interferon (MIG), synonomous with chemokine (C‐X‐C motif) ligand 9 (CXCL9), which increased as wounds healed and remained nearly constant for ulcers that were not approaching closure.

Dry needling versus acupuncture: the ongoing debate

Although Western medical acupuncture (WMA) is commonly practised in the UK, a particular approach called dry needling (DN) is becoming increasingly popular in other countries. The legitimacy of the use of DN by conventional non-physician healthcare professionals is questioned by acupuncturists. This article describes the ongoing debate over the practice of DN between physical therapists and acupuncturists, with a particular emphasis on the USA. DN and acupuncture share many similarities but may differ in certain aspects. Currently, little information is available from the literature regarding the relationship between the two needling techniques. Through reviewing their origins, theory, and practice, we found that DN and acupuncture overlap in terms of needling technique with solid filiform needles as well as some fundamental theories. Both WMA and DN are based on modern biomedical understandings of the human body, although DN arguably represents only one subcategory of WMA. The increasing volume of research into needling therapy explains its growing popularity in the musculoskeletal field including sports medicine. To resolve the debate over DN practice, we call for the establishment of a regulatory body to accredit DN courses and a formal, comprehensive educational component and training for healthcare professionals who are not physicians or acupuncturists. Because of the close relationship between DN and acupuncture, collaboration rather than dispute between acupuncturists and other healthcare professionals should be encouraged with respect to education, research, and practice for the benefit of patients with musculoskeletal conditions who require needling therapy.

Low-Voltage Direct Current as a Fungicidal Agent for Treating Onychomycosis

Onychomycosis, most commonly caused by two species of dermatophyte fungi--Trichophyton rubrum and Trichophyton mentagrophytes--is primarily treated with regimens of topical and systemic antifungal medications. This study was undertaken to evaluate in vitro the efficacy of low-voltage direct current as an antifungal agent for treating onychomycosis. Agar plate cultures of T rubrum and T mentagrophytes were subjected to low-voltage direct current electrostimulation, and antifungal effects were observed as zones in the agar around the electrodes lacking fungal growth. Zones devoid of fungal growth were observed for T rubrum and T mentagrophytes around anodes and cathodes in a dose-dependent manner in the current range of 500 microA to 3 mA. Low-voltage direct current electrostimulation has great clinical potential for the treatment of onychomycosis and perhaps other superficial maladies of fungal etiology.

Analysis of pressure ulcer wound fluid using two‐dimensional electrophoresis

The incidence rate of pressure ulcers in the USA ranges from 0·4% to 38% in acute care settings and from 2·2% to 23·9% in long‐term care settings, and their treatment costs are in the billions of dollars yearly. The proteome of wound fluid may contain early indicators or biomarkers associated with healing in pressure ulcers that would enable treatment regimes to be optimised for each individual. Wound fluid was collected from the interior and periphery of 19 chronic pressure ulcers at 15 time points during 42 days for an analysis of protein expression. Proteins were fractionated using two‐dimensional polyacrylamide gel electrophoresis. A comparison of the spot distributions indicates a biochemical difference between the interior and the periphery of wounds. Pressure ulcers that healed show a greater number of spots for interior and peripheral locations combined over time when compared with wounds that did not heal. Using this technique, protein S100A9 was identified as a potential biomarker of wound healing. The identification of differences within the proteome of healing versus non healing pressure ulcers could have great significance in the use of current treatments, as well as the development of new therapeutic interventions.

Chronic and non-healing wounds: The story of vascular endothelial growth factor

The pathophysiology of the chronicity and non-healing status of wounds remains unknown. This paper presents the following hypothesis: abnormal patterns of vascular endothelial growth factor receptors (VEGFRs) are the culprits of wound chronicity and non-healing. More specifically, for patients with poor circulation, the decreased VEGFR-2 level is the cause of poor wound healing; for patients with non-compromised circulation, for example, patients with concurrent chronic wounds and active autoimmune diseases, the increased VEGFR-1 level is related to the non-healing status of wounds. The hypothesis is supported by the following facts. VEGFR-1 is the main contributor for inflammation and VEGFR-2 facilitates angiogenesis; soluble VEGFR-1 (sVEGFR-1) inactivates both VEGFR-1 and VEGFR-2. Patients with auto-immune disease have abnormally increased VEGFR-1 and decreased sVEGFR. Wounds in patients with active autoimmune diseases have poor response to electric stimulation which facilitates chronic wound healing in patients without active autoimmune diseases via increasing vascular endothelial growth factor (VEGF) secretion. Patients with chronic wounds (including diabetic foot ulcers and venous leg ulcers) but no active autoimmune diseases have decreased VEGFR-2 levels. We thus believe that abnormal patterns of VEGFRs are the culprits of wound chronicity and non-healing. For wounds with compromised circulation, VEGFR-2 decrease contributes to its chronicity; whereas for wounds with non-compromised circulation, VEGFR-1 increase is the leading cause of the non-healing status of chronic wounds. Treatments and research in wound care should be tailored to target these changes based on circulation status of wounds. Complete elucidation of changes of VEGFRs in chronic and non-healing wounds will enhance our understandings in tissue healing and thus better our selection of appropriate treatments for chronic and non-healing wounds.

The wound healing trajectory and predictors with combined electric stimulation and conventional care: one outpatient wound care clinic's experience

Electric stimulation (E‐stim) has been found to be an effective treatment in improving wound healing rates. However, the wound healing trajectory and its related predictors for complete wound closure (CWC) have not been reported with E‐stim treatment.