Stephan Coerper

A new wound-based severity score for diabetic foot ulcers: A prospective analysis of 1,000 patients.

OBJECTIVE—Several well-accepted classification systems are available for diabetic foot ulcers. However, there are only a few and scientifically not validated severity scores. The aim of this study was to establish a new wound-based clinical scoring system for diabetic foot ulcers suitable for daily clinical practice anticipating chances for healing and risk of amputation. RESEARCH DESIGN AND METHODS—Four clinically defined parameters, namely palpable pedal pulses, probing to bone, ulcer location, and presence of multiple ulcerations, were prospectively assessed in 1,000 consecutive patients. In the next step, a new diabetic ulcer severity score (DUSS) was created from these parameters. Palpable pedal pulses were categorized by the absence (scored as 1) or presence (scored as 0) of pedal pulses, while probing to bone was defined as yes (scored as 1) or no (scored as 0). The site of ulceration was defined as toe (scored as 0) or foot (scored as 1) ulcer. Patients with multiple ulcerations were graded as 1 compared with those with single ulcers (scored as 0). The DUSS was calculated by adding these separate gradings to a theoretical maximum of 4. Wounds were followed-up for 365 days or until healing or amputation if earlier. Probability of healing and risk of amputation were calculated by the Kaplan-Meier method. RESULTS—Uni- and multivariate analyses showed a significantly higher probability of healing for patients with palpable pulses, no probing to bone, toe ulcers, and absence of multiple ulcerations. When patients were divided into subgroups with the same DUSS, we found significantly different probabilities for healing. We showed a decreasing probability of healing for ulcers with a high DUSS, concurrent with increasing amputation rates. An increase in the DUSS by one score point reduced the chance for healing by 35%. Similarly, the higher the ulcer score, the larger the initial wound area, the longer the wound history, and the more likely the need for surgery or hospitalization. CONCLUSIONS—The DUSS categorizes different ulcers into subgroups with specific severity and similar clinical outcome. Using this score, the probabilities for healing, amputation, need for surgery, and hospitalization are predictable with high accuracy. This might be useful for the anticipation of health care costs and for comparison of subgroups of patients in clinical studies.

The mast cell‐nerve axis in wound healing: a hypothesis

Beyond their classic roles in allergic reactions and defence against parasites, mast cells can now be viewed as key players in regulating connective tissue homeostasis. There is good evidence that mast cells are in close morphological and functional contact with the peripheral nervous system. Although substantial differences exist between mast cells of different tissues and different species, they produce a wide range of agents, including cytokines, growth factors, and other regulatory molecules, and they respond to an equally wide range of substances, including neuropeptides. At our current level of understanding wound healing, inflammation plays a central role in this process, with macrophages being central protagonists at the cellular level. There is now increasing evidence that mast cells are also involved in wound healing, in health and disease. They produce and secrete histamine, heparin, and multifunctional cytokines and growth factors, which represent important agents in the wound‐healing process. Reviewing the recent literature supporting this hypothesis, we also outline the clinical importance of this work to help close the gap between basic research and clinical application.

Fifty percent area reduction after 4 weeks of treatment is a reliable indicator for healing : analysis of a single-center cohort of 704 diabetic patients

INTRODUCTION The aim of the study was to investigate whether an area reduction greater than 50% within the first 4 weeks of treatment is associated with a higher long-term probability of healing. PATIENTS AND METHODS We treated diabetic foot ulcers according to a comprehensive interdisciplinary wound care protocol. Follow-up was documented through a special wound documentation system. Data were entered into SPSS for statistical analysis to calculate the probability of healing according to the Kaplan-Meier method. Results were expressed as median (minimum-maximum), and the percentage of area reduction (PA) was defined as [(area(4 weeks)/area(baseline))x100)/area(baseline). Patients were divided into responders when PA reached at least 50% and nonresponders when PA was less than 50%. Healing was defined as PA=100%. RESULTS In total, 704 patients were included into the analysis. Median time of follow-up was 71 (2-365) days. Wound duration was 31 (1-4018) days, and the initial wound size was calculated to be 1.18 (0.1-99) cm(2). In 27.8%, there was a positive probing to bone; in 64.5%, both pedal pulses were not palpable. Major amputation rate was 2.8% and minor amputation rate was 10.2%. The overall probability of healing was 35% after 12 weeks, 41% after 16 weeks, and 73% after 1 year. The surrogate visit (4 weeks) was performed after a median of 27 (14-42) days without a difference between responders and nonresponders. There were 334 (47%) responders and 370 (53%) nonresponders. Responders had a significantly higher probability of healing compared with nonresponders (12 weeks: 52.3% vs. 18.4%, P=.0001; 16 weeks: 46.7% vs. 26.5%, P=.0001; 1 year: 82.5% vs. 64.9%, P=.0001). CONCLUSIONS The calculation of the percentage of area reduction after 4 weeks of treatment is a valid tool to estimate the probability of healing. In clinical practice, a reevaluation of the treatment schedule is recommended for wounds that do not reach 50% area reduction within the first 4 weeks of therapy.

Comparison of inflammatory and systemic sources of growth factors in acute and chronic human wounds

Inflammatory cells are generally assumed to be the primary source of most growth factors/cytokines that participate in wound healing. Correspondingly, most attempts to enhance wound healing have been directed at the wound itself. However, certain key factors such as insulin‐like growth factor‐I (IGF‐I) and related proteins are present in blood in sufficient quantities to suggest significant contributions from outside the wound. Because little is known of the dynamics of IGF family members in wounds, particularly in human wounds, we serially measured the mRNAs and proteins of the IGF family in fluid and tissues taken from acute as well as chronically inflamed human wounds and compared them to their corresponding concentrations in blood. We also measured transforming growth factor‐β1 and ‐β3, vascular endothelial growth factor, interleukin‐1β, matrix metalloproteinases and selected isomers/receptors, all of which are associated with inflammation. All IGF proteins reached their highest concentrations immediately after injury. No difference between IGF‐I mRNA expression between acute and inflamed wounds was found. As a group, IGF‐related proteins, in contrast to transforming growth factor‐β, vascular endothelial growth factor, and interleukin‐1β, are highly correlated to and are generally below their concentrations in blood and are not elevated by inflammation. The IGF family therefore appears to enter wounds, even inflamed wounds, mainly from blood. If blood IGF‐I is low, wound levels are lower. This data suggests that healing impairment due to IGF‐I deficiency can be readily detected and is, at least in part, easily and safely correctable. (WOUND REP REG 2003;11:253–260)

Haemodialysis is associated with changes in cutaneous microcirculation in diabetes mellitus.

Aims  To examine the cutaneous microcirculation on the dorsum of the foot before, during and after haemodialysis in diabetic and non‐diabetic patients.

M.A.I.D.: a prognostic score estimating probability of healing in chronic lower extremity wounds.

Objective:To evaluate a wound-based prognostic score for chronic lower extremity wounds suitable for daily routine use capable of predicting long-term healing. Summary Background Data:The main obstacle in the treatment of chronic wounds is to estimate long-term clinical outcome. For diabetic foot ulcers, several ulcer, and nonulcer-related risk factors associated with impaired healing have been described in the past. Methods:A new chronic lower extremity ulcer score (M.A.I.D.) was created out of 4 clinically defined parameters, namely palpable pedal pulses (I), wound area (A), ulcer duration (D), and presence of multiple ulcerations (M). Palpable pedal pulses were categorized by the absence (scored as 1) or presence (scored as 0) of pedal pulses, while wounds >4 cm2 were scored as 1 and wounds ≤4 cm2 as 0. Ulcers lasting more than 130 days were categorized as 1 and wounds with a duration of <130 days as 0. Patients with multiple ulcerations were graded as 1 (=1) compared with those with single ulcers (=0). M.A.I.D. was calculated by adding these separate scores to a theoretical maximum of 4. Results:Two thousand nineteen consecutive patients with 4004 wounds were included. When patients were divided into subgroups with the same M.A.I.D., we showed a decreasing probability of healing for ulcers with higher M.A.I.D. scores. An increase in the M.A.I.D. by 1 score-point reduced the chance for healing by 37%. Similarly, the higher the ulcer score, the larger the initial wound area, the longer the wound history, and the more likely the occurrence of soft-tissue infection during follow-up. Conclusions:This new chronic lower extremity ulcer score is capable of anticipating long-term probability of healing by combining 4 clinically assessable parameters. However, adequate and standardized wound care is an indispensable prerequisite for M.A.I.D. to be a valid diagnostic tool in daily clinical routine.

Experimental ischemic wounds: correlation of cell proliferation and insulin-like growth factor I expression and its modification by different local IGF-I release systems.

We investigated cell proliferation and local insulin‐like growth factor‐I (IGF‐I) expression in ischemic wounds after topical application of IGF‐I through different delivery systems. IGF‐I dressings were fabricated from an IGF‐I containing polyvinyl alcohol film placed on a standard hydrogel dressing. In vitro, the release of IGF‐I from this dressing was assessed by enzyme‐linked immunosorbent assay. For animal experiments, a standardized ischemic skin flap containing a full‐thickness wound was created on the back of male Sprague‐Dawley rats. An identical wound outside the flap served as control. We initially investigated intracutaneous pO2 (ptiO2), cell proliferation, and local IGF‐I expression. In a second setting, wounds were treated either with IGF‐I dissolved in methylcellulose gel or with an IGF‐I dressing, and ulcer size and cell proliferation were assessed. In vitro, approximately 60% of IGF‐I was released from the IGF‐I dressing, compared to a 97% release from methylcellulose gel. In vivo, ischemic wounds showed less cell proliferation and decreased IGF‐I expression than nonischemic wounds. A lower local ptiO2 correlated with larger wound size, less cell proliferation, and decreased IGF‐I expression. Ulcer size was reduced after treatment with either IGF‐I dressing or methylcellulose gel. However, cell proliferation only increased after treatment with IGF‐I dressing, but not after methylcellulose gel treatment. We conclude that IGF‐I expression is decreased in ischemic wounds and correlates with low cell proliferation. This can be reversed by local IGF‐I application, but the efficacy of treatment depends on the delivery system.

Everolimus interferes with the inflammatory phase of healing in experimental colonic anastomoses.

BACKGROUND Delayed wound healing is a serious side effect of mTOR inhibitor-based immunosuppression after solid organ transplantation. The aim of this study was to test the hypothesis that the mTOR inhibitor everolimus interferes with the inflammatory phase of healing in experimental colonic anastomoses. MATERIALS AND METHODS Thirty male Sprague-Dawley rats received a colonic anastomosis. Then, animals were randomized to three groups of daily treatment with either vehicle or everolimus in two different dosages (1.0mg/kg or 3.0mg/kg). After 7 d, rats were sacrificed, and mechanical, histologic, and biochemical parameters of intestinal healing were assessed. RESULTS Anastomotic bursting pressure was significantly decreased by everolimus in both dosages, whereas hydroxyproline content was reduced only by the high everolimus dosage. Everolimus diminished cellular proliferation and new vessel growth. Furthermore, both quantity as well as quality of newly synthesized collagen fibers in the anastomotic granulation tissue was reduced. On the other hand, myeloperoxidase-positive (MPO) cells and interleukin-6 (IL-6) concentrations were increased, as was the activity of matrix-metalloproteinases MMP-2 and MMP-9. CONCLUSION Everolimus interferes with the inflammatory phase of healing. However, it remains unclear whether this phenomenon is involved in everolimus impairment of experimental anastomotic repair.

The impact of a micro-lightguide spectrophotometer on the intraoperative assessment of hepatic microcirculation : A pilot study

INTRODUCTION The intraoperative measurement of the peripheral microperfusion after liver transplantation is connected with quite an effort and a continuous evaluation in the postoperative follow up is not possible till now. PATIENTS AND METHODS Before mobilization of the liver during surgical intervention the following parameters were measured on the surface of the right (segment 7/8) and the left (segment 2/3) liver lobe with a probe, combining laser-Doppler-flowmetry and tissue-spectrometry: the oxygen saturation (SO2), the relative capillary hemoglobin concentration (rHB), the blood flow (flow) and the blood flow velocity (velo). In addition the peripheral oxygen saturation (SPO2), the central venous pressure (ZVP), the positive endexspiratory pressure (PEEP) and the hemoglobin (HB) were documented. RESULTS 9 patients (median age 75 years) were included in the study. SPO2, ZVP, PEEP and HB were regular. The parameters SO2, rHB, flow and velo showed no significant changes between the right and the left liver lobe. CONCLUSIONS The O2C-method allows a reproducible intraoperative evaluation of the hepatic microcirculation.

Die chirurgische Wundsprechstunde Ein interdisziplinäres, diagnostisches und therapeutisches Konzept für chronische Wunden

Summary. In Germany there is no standardized wound care for patients with chronic wounds in specialized centers. We have established a wound care unit for the past 6 years. The principal concept of therapy was characterized by standardized local surgery, moist wound dressings and concomitant treatment of the underlying disease. We performed local therapy, coordinated the interdisciplinary treatment and developed a new wound documentation system for quality control. We established a close network, integrating general practitioners and home care organizations to realize a mainly outpatient treatment supported by short hospital therapy. Exclusive outpatient treatment was performed in 42 % of all patients. According to our prospective data, we achieved an improvement in wound care: 69 % of the wounds resistant to therapy for a mean of 30 months healed within 12 months after therapy according to our protocol. Our data strongly supported the importance of local surgery: neither wound depth nor wound infection had any influence on the healing rate, presumably due to radical excisional debridement of necrotic tissue. The presented data justify on medical and economic grounds the establishment of such wound care centers in Germany.Zusammenfassung. Für Patienten mit chronischen Wunden fehlen in Deutschland standardisierte Therapiekonzepte in zentralen Behandlungszentren. Wir haben vor 6 Jahren ein solches Zentrum eingerichtet, wobei die lokalchirurgische Sanierung, feuchte Wundbehandlung und begleitende Therapie der Grunderkrankung im Mittelpunkt des standardisierten Behandlungskonzeptes steht. In dieser Wundsprechstunde wurde die lokale Wundbehandlung und die Koordination der einzelnen interdisziplinären Behandlungsschritte vorgenommen. Ein spezielles Wunddokumentationssystem diente zur Qualitätssicherung. Die Einbeziehung der Hausärzte und ambulanten Pflegedienste führte zu einer Erweiterung der Infrastruktur und ermöglichte eine kontrollierte Vernetzung der stationären und ambulanten Behandlung, wodurch 42 % der Patienten ausschließlich ambulant behandelt werden konnten. Nach den vorgestellten Daten konnte eine verbesserte Patientenversorgung erreicht werden: 69 % der Wunden, die zuvor 30 Monate erfolglos behandelt wurden, waren nach unserem Protokoll innerhalb von 12 Monaten abgeheilt. Die Analyse der Daten unterstreicht den Stellenwert der lokalchirurgischen Sanierung, wonach weder die Wundtiefe noch die Wundinfektion einen Einfluß auf die Heilungsraten hat, vermutlich durch die radikale Entfernung der Nekrosen. Nach den vorgestellten Daten rechtfertigen medizinische, soziale und wirtschaftliche Gründe die Einrichtung einer interdisziplinär organisierten Wundsprechstunde, die zwischenzeitlich in Deutschland Modellcharakter aufweist.