Raj Mani

Guidelines for the treatment of arterial insufficiency ulcers

1. Co-chaired panel 2. University of Utah, Salt Lake City, UT 3. University of Texas, San Antonio, TX 4. Sinai Hospital/Johns Hopkins Medical Institutions, Baltimore, MD 5. GKT School of Medicine, King’s College, London, UK 6. University of Texas Health Science Center at Houston, TX 7. Sequoia Hospital, Redwood City, CA 8. Maricopa Medical Center, Phoenix, AZ 9. Tufts-New England Medical Center, Boston, MA 10. Southampton University Hospitals Trust NHS, Southampton, UK 11. Penrose–St. Francis Health Services, Colorado Springs, CO 12. Beverly Surgical Associates, Beverly, MA 13. Saint Francis Memorial Hospital, San Francisco, CA 14. Northbay Center for Wound Care, Vacaville, CA, and 15. University of California, San Francisco, CA

A Review of the Clinical Significance of Tissue Hypoxia Measurements in Lower Extremity Wound Management

The aim of this paper is to review techniques that are currently available to measure tissue hypoxia in order to benefit the management of wounds. Direct measurement of tissue partial oxygen pressure (PO2) is invasive and therefore unappealing in clinical practice. Several techniques (PET scans, MRI derived techniques) are primarily applicable to research rather than clinical applications. Imaging techniques (duplex ultrasonography, arteriography, MRI techniques) are recommended only as part of the workup for revascularisation. Techniques that assess local perfusion include clearance methods, transcutaneous O2 and CO 2 pressure measurement, and laser Doppler flowmetry and imaging. These techniques permit interpretation of altered perfusion states. Each technique offers subtly different information concerning microvascular function. All these techniques require strict protocols to derive reliable data. The potential of the promising near infrared reflectance spectroscopy (NIRS) technique is yet to be determined.

A Review of the Microcirculation in Skin in Patients With Chronic Venous Insufficiency: The Problem and the Evidence Available for Therapeutic Options:

Impairment of the cutaneous microcirculation is a major predisposing factor in inflammation and ulceration in patients with chronic venous insufficiency (CVI). Increase of capillary filtration rate predisposes to the formation of edema. Local lymphedema is a complication of CVI, often underdiagnosed. This review is focused on CVI but excludes the complication of ulceration. Treatment of microcirculatory dysfunction can be done by pharmacologic intervention or compression therapy or using a combination of both. This review is focused on drugs that have been evaluated by randomized prospective controlled trials. The following compounds are discussed: horse chestnut seed extracts, flavonoids, red vine leaves extracts, total triterpenic fraction of Centella asiatica (L), prociadins, calcium dobesilate, and pentoxifylline. The microcirculatory effects of compression therapy using bandages or stockings are also reviewed. The major microcirculatory effects that have been shown are the reduction of capillary filtration rate and improvements in levels of transcutaneous partial pressures of oxygen and carbon dioxide (TcPO2 and TcPCO2). Available data suggest that a combination of pharmacologic and compression therapy may have some additive effects.

Science of measurements in wound healing

Wounds that are slow to heal are poorly understood. Clinicians and researchers have attempted to predict treatment outcomes from simple physical measurements without, as yet, understanding the pathogenesis or the role of complications on chronic wounds. Laboratory studies on tissues from biopsies and wound fluids are essential. These must be associated with carefully conducted physiological measurements before, the significance of measurements in wound healing is established.

Optimizing Technology Use for Chronic Lower-Extremity Wound Healing: A Consensus Document.

Innovations in technology are used in managing chronic wounds. Despite the wide range of technologies available, healing of chronic wounds remains variable. In this paper, the authors offer an evidence based approach to the use of technology for diagnosis and management based on the concept of standardised care.

Advances in Infections and Wound Healing for the Diabetic Foot The Die Is Cast

The diabetic foot remains a considerable health burden worldwide, calling for improvement in diagnosis and management. Especially, infections and wound healing pose a challenge for the clinician. The present special issue presents advances achieved in these areas. Management of diabetic foot infections requires appropriate cultures to guide antibiotic treatment. Ideally, tissue cultures should be used, although swabs are generally easier to obtain and are still widely used. Demetriou et al have examined the diagnostic performance of swabs versus tissue cultures in 50 diabetic patients (28 with neuropathic and 22 with neuroischemic foot ulcer). All subjects presented with clinically infected foot ulcers. It was found that swabs yielded excellent sensitivity (100%) and negative predictive value (100%), both for confirmation of infection and for identification of true pathogens, whereas their corresponding specificities (14% to 40%) and positive predictive values (54% to 88.5%) were less satisfactory. Thus, negative swab cultures emerged as very reliable in ruling out infection, and similarly, the absence of a microorganism could virtually exclude its role as a pathogen. These diagnostic patterns were seen in neuropathic as well as neuroischemic foot ulcers. The authors have presented a clear and original viewpoint, as well as a novel distinction between neuropathic and neuroischemic ulcers, and so this study appears to have useful clinical implications. However, further experience in larger patient series is desirable. Patients with diabetic foot osteomyelitis need appropriate diagnosis and follow-up. Michail et al have looked at the performance of serum inflammatory markers (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], white blood cells [WBC], and procalcitonin [PCT]) for the diagnosis and follow-up of such patients. For the diagnosis of osteomyelitis, CRP (cut-off > 14 mg/L) yielded 85% sensitivity and 83% specificity. The corresponding values for ESR (cutoff >67 mm/h) were 84% and 75%, for WBC (cutoff >14 × 10/L) were 75% and 79%, and for PCT (cutoff >0.30 ng/mL) were 81% and 71%. All these markers were reduced following initiation of antibiotic treatment. Importantly, WBC, CRP, and PCT soon reverted to near-normal. Conversely, ESR elevation persisted for 3 months in patients with osteomyelitis, distinguishing them from those with simple soft tissue infection. Thus, ESR was identified as the best marker to monitor the response to therapy in patients with osteomyelitis. The strengths of this study include its clear message, the enrolment of an adequate patient series (n = 61), and the 3-month follow-up. Given the clinical conundrum of distinguishing osteomyelitis from soft tissue infection and, worse still, of deciding on the length of optimal antibiotic treatment in the individual patient, the data of Michail et al appear promising for the foot clinic. A less well-known aspect of diabetic foot infections is the role of local cytokines and proteases in the course of infection and in response to treatment. In a small case series of 8 patients, with methicillin-resistant Staphylococcus aureus (MRSA) foot infection, Ambrosch et al have examined the effect of daptomycin therapy (4-6 mg/kg body weight per day) on wound secretion of pro-inflammatory interleukin-6 (IL-6), matrix metalloproteinase-9 (MMP-9), and metallopeptidase inhibitor-1 (TIMP-1). Daptomycin was administered for a maximum of 14 days. A reduction of IL-6 as early as after 3 treatment days was shown, followed by a reduction of MMP-9 and an increase of TIMP-1 after 14 days, in parallel with a reduction of ulcer dimensions. MRSA was finally eradicated in all patients. Thus, daptomycin led to a cascade of favorable molecular changes, namely reduction of pro-inflammatory IL-6 and MMP-9 with an increase of anti-protease activity. Such actions were reflected in reduction of wound size and microbiolgical eradication. Despite the pilot design, this work opens new perspectives for the study of foot infections at the molecular level, which is becoming an evolving field. Equally interesting is the role of MRSA genetic factors in foot infection with this pathogen. Wang et al have examined risk and genetic factors in 429 patients 490507 IJLXXX10.1177/1534734613490507The International Journal of Lower Extremity WoundsPapanas and Mani research-article2013

Some Effects of Sustained Compression On Ulcerated Tissues

Sustained leg compression is the first line of treatment for patients with chronic venous ulcers. The success rates of this treatment vary, and the mode(s) of action are not well understood. In this study, tissue oxygen tension (TcPO2), surface pH, and reactive hyperemia measure ments were made to observe changes associated with sustained compression in patients with chronic venous ulcers. Patients with chronic venous ulcers (n = 20, 13 F, 7 M, median age 65.5 years, median ulcer size 13.9 cm2) were assigned to the same treatment, wound dressings, and 4-layer bandaging during a 24-week period. Duplex ultrasound, venous refilling time, skin tissue oxygen, and ulcer surface pH were measured at defined time points. Ulcer areas were calcu lated from contour traces done at regular dressing changes. The difference between ulcer surface pH and control values measured proximally on the same leg diminished with healing (p = 0.02), which occurred despite the evidence of deep venous reflux. Ulcers with smaller initial areas healed quicker (p=0.003). A greater likelihood of healing was observed in women (p = 0.017). Sustained compression may potentiate healing by acting on the microcirculation in ulcerated tissues.

A Systematic Review and Meta-Analysis of Nutritional Supplementation in Chronic Lower Extremity Wounds

A systematic review and meta-analyses of nutritional supplementation to treat chronic lower extremity wounds was done in order to test the premise that impaired nutrition is implicated in healing. The databases of Ovid MEDLINE, Ovid EMBASE, Cochrane Library, and EBSCO CINAHL (1972-October 2014) were searched systematically. Only randomized controlled trials in adults with chronic lower extremity wounds were included. Both topical and systemic routes of supplementing nutrition were considered. The primary outcome was wound healing. Study characteristics, outcomes, and risk of bias were extracted by trained researchers and confirmed by the principal investigator. Twenty-three of 278 (8.3%) retrieved articles met the inclusion criteria and were selected. Most of the studies were of unclear or low risk. Overall, nutritional supplementation was favorable (risk ratio [RR] = 1.44, 95% confidence interval [CI] = 1.25-1.66). The systemic route was marginally better than the topical one (RR = 1.51, 95% CI = 1.36-1.67; RR = 1.14, 95% CI = 0.96-1.36, respectively). For venous ulcers, the data showed nutritional supplementation to be significantly beneficial compared to placebo (RR = 1.44, 95% CI = 1.31-1.59). Similar data were found for diabetic foot and sickle cell ulcers (RR = 1.17, 95% CI = 0.93-1.47; RR = 1.56, 95% CI = 0.94-2.60, respectively). These data permit the inferences that nutritional supplementation in the populations studied showed significant benefits in the healing of venous ulcers and tendency (nonsignificant trends) in the healing of diabetic and sickle cell ulcers.

How to Cope With the Increasing Burden of the Diabetic Foot “Better Three Hours Too Soon Than a Minute Too Late”

The diabetic foot continues to be an inexorable menace, both for the individual patient and for the health system. Certainly, considerable progress has been achieved during the past 30 years, but the rising prevalence of diabetes mellitus and prolonged patient survival have created the need for efficacious and readily available foot care for a larger number of patients. In Western societies, these patients now increasingly present with ischemia due to peripheral arterial disease, requiring timely successful revascularization. The latter needs to be routinely incorporated into the rapid evaluation and management of both patient and foot pathology. In this setting, Manu et al., in the current issue of the journal, describes the transformation of the multidisciplinary diabetic foot clinic to a day unit, in an endeavor to address the increased therapeutic demands and to improve outcomes. The reorganized foot clinic can now offer sameday investigation of new and/or deteriorating foot lesions with results of these investigations immediately available: this is essential to avoid catastrophes. Thus, urgent sameday treatment can be offered with casting for neuropathic ulcers and Charcot osteoarthropathy, aggressive infection control with parenteral antibiotic administration via peripherally inserted central catheters, and Duplex arterial imaging for early revascularization. Impressively, such treatment can be offered on an open-access basis, not only allowing patients to freely visit the clinic when they notice a new/worsening foot problem but also accepting new patients self-presenting for foot-related pathology. In the vast majority of cases, no hospital admission was required, despite the huge increase in the number of patients examined, as compared to when the foot clinic was inaugurated more than 30 years ago. As might be anticipated, the center’s approach led to high patient satisfaction and high attendance rates. What are the clinical implications of these new data? In the face of the large patient numbers and the complexities of their foot lesions, treatment should be promptly offered. The therapeutic strategy should include same-day evaluation of infection and ischemia and, ideally, urgent initiation of treatment including revascularization. If practiced vigorously by engaged personnel, this can not only avoid delays in management but also reduce hospital admissions, thereby lowering cost and reducing complications. This modern scheme is one step further than the classical diabetic foot clinics, which years ago revolutionized foot care, leading to reduced amputations. At the same time, urgent patient referral and even emergency self-referral should be facilitated and encouraged. We believe that smooth liaison between primary health care and hospital-based clinics can and will promote timely expert referrals. Indeed, widespread awareness of the diabetic foot and its alarming signs throughout all health care levels can help patients’ access to expert teams when needed and avoid sinister outcomes. An example of promoting knowledge is training of medical students, nurses and others in recognition of peripheral arterial disease and in accurate measurement of Ankle-Brachial Index: we argue that such a skill, based as it is on simple, reliable technology, may be transferred to practitioners within the primary/community setting. These steps will help not only in Western societies with traditionally high levels of investments in health care but also in emerging countries, such as China, India, and the Middle East, where diabetes and its complications are growing faster by comparison. In conclusion, this new study has shown that urgent same-day multi-expert patient evaluation and treatment can avoid unnecessary delays and hospital admissions, thereby improving care of the diabetic foot. The example set by the team at King’s College Hospital now needs to be followed and further improved. Indeed, when treating the diabetic foot, one should act, like the Shakespearean character, “Better three hours too soon than a minute too late.” 548167 IJLXXX10.1177/1534734614548167The International Journal of Lower Extremity Wounds 13(3)Papanas and Mani editorial2014

Prevalence of deep venous incompetence and microvascular abnormalities in patients with diabetes mellitus.

The involvement of venous disease in the diabetic neuropathic foot is widely accepted. This article reports the result of prevalence of venous incompetence, impaired calf vein hemodynamics, and loss of microvascular control in the skin over the dorsum of the foot in an effort to document whether increased retrograde pressure caused by venous incompetence or loss of sympathetic regulation of the microcirculation is present in the diabetic patient who is at risk of foot disease. It was found that 64% and 70.7% of diabetic patients had deep venous incompetence in their right and left legs, respectively, which was statistically significantly greater than what was found in a previous report on the general population (P < .05); 42.7% and 49.3% of patients had a reduced venous refilling time in the right and left legs, respectively, and 30.7% and 33.3% of patients had loss of the arteriovenous response in the right and left legs. Some previous reports have suggested evidence of hemodynamic and morphological changes in patients with diabetic foot disease. The outstanding contribution of this report is the finding of venous incompetence in patients with diabetes but not foot disease. Because some 15% of the population with diabetes develop foot complications, the reported observations offer hope of alleviating symptoms if not preventing ulcers.