Nonhealing Foot Research Articles

Autologous G-CSF-Mobilized Peripheral Blood CD34+ Cell Therapy for Diabetic Patients with Chronic Nonhealing Ulcer

Recently, animal studies have demonstrated the efficacy of endothelial progenitor cell (EPC) therapy for diabetic wound healing. Based on these preclinical studies, we performed a prospective clinical trial phase I/IIa study of autologous G-CSF-mobilized peripheral blood (PB) CD34(+) cell transplantation for nonhealing diabetic foot patients. Diabetic patients with nonhealing foot ulcers were treated with 2 × 10(7) cells of G-CSF-mobilized PB CD34(+) cells as EPC-enriched population. Safety and efficacy (wound closure and vascular perfusion) were evaluated 12 weeks posttherapy and further followed for complete wound closure and recurrence. A total of five patients were enrolled. Although minor amputation and recurrence were seen in three out of five patients, no death, other serious adverse events, or major amputation was seen following transplantation. Complete wound closure was observed at an average of 18 weeks with increased vascular perfusion in all patients. The outcomes of this prospective clinical study indicate the safety and feasibility of CD34(+) cell therapy in patients with diabetic nonhealing wounds.

Towards Reaching the Target: Clinical Application of Mesenchymal Stem Cells for Diabetic Foot Ulcers

Mesenchymal stem cells (MSCs) hold great promise for therapeutic application in non-healing ulcers and tissue regeneration because of their multi-lineage differentiation potential. MSCs delivered may migrate to the sites of injury and improve wound healing by stimulating angiogenesis and promoting revascularization. The incidence of type 2 diabetes mellitus (T2DM) is increasing worldwide. It is associated with peripheral neuropathy and peripheral arterial occlusive disease (PAOD), which predispose patients to develop non-healing foot ulcers following minor trauma. A high rate of amputation exists among diabetic patients due to non-healing foot ulcers, which are a significant burden for the society despite new therapeutic protocols developed. In recent years, stem cell transplantation has been considered as a new therapeutic option for diabetic foot ulcers (DFUs). The regeneration potential of MSCs has been demonstrated in the experimental and clinical trials. Here we review the potential efficacy and systematic use of MSCs for the treatment of non-healing DFUs, current advances, MSC delivery systems, and possible options to enhance the therapeutic potential of stem cell for wound healing.

The Impact of Financial Barriers on Access to Care, Quality of Care and Vascular Morbidity Among Patients with Diabetes and Coronary Heart Disease

The prevalence and consequences of financial barriers to health care among patients with multiple chronic diseases are poorly understood. We sought to assess the prevalence of self-reported financial barriers to health care among individuals with diabetes and coronary heart disease (CHD) and to determine their association with access to care, quality of care and clinical outcomes. The 2007 Centers for Disease Control Behavioral Risk Factor Surveillance Survey. Diabetic patients with CHD. Financial barriers to health care were defined by a self-reported time in the past 12 months when the respondent needed to see a doctor but could not because of cost. The primary clinical outcome was vascular morbidity—a composite of stroke, retinopathy, nonhealing foot sores or bilateral foot amputations. Among the 11,274 diabetics with CHD, 1,541 (13.7 %) reported financial barriers to health care. Compared to individuals without financial barriers, those with financial barriers had significantly reduced rates of medical assessments within the past 2 years, hemoglobin (Hgb) A1C measurements in the past year, cholesterol measurements at any time, eye and foot examinations within the past year, diabetic education, antihypertensive treatment, aspirin use and a higher prevalence of vascular morbidity. In multivariable analyses, financial barriers to health care were independently associated with reduced odds of medical checkups (Odds Ratio [OR], 0.61; 95 % Confidence Intervals [CI], 0.55–0.67), Hgb A1C measurement (OR, 0.85; 95 % CI, 0.77–0.94), cholesterol measurement (OR, 0.76; 95 % CI, 0.67–0.86), eye (OR, 0.85; 95 % CI, 0.79–0.92) and foot (OR, 0.92; 95 % CI, 0.84–1.00) examinations, diabetic education (OR, 0.93; 95 % CI, 0.87–0.99), aspirin use (OR, 0.88; 95 % CI, 0.81–0.96) and increased odds of vascular morbidity (OR, 1.23; 95 % CI, 1.14–1.33). In diabetic adults with CHD, financial barriers to health care were associated with impaired access to medical care, inferior quality of care and greater vascular morbidity. Eliminating financial barriers and adherence to guideline-based recommendations may improve the health of individuals with multiple chronic diseases.

The Cost-effectiveness of Managing Non-healing Foot Wounds in Patients with Critical Limb Ischemia and End-Stage Renal Disease

The Cost-effectiveness of Managing Non-healing Foot Wounds in Patients with Critical Limb Ischemia and End-Stage Renal Disease

Prevention of diabetic foot ulceration: new evidences for an old problem

Diabetic patients have a 15 % lifetime risk of developing a foot ulcer and have a 15 % risk of developing a lower extremity amputation. Amputation is preceded by nonhealing foot wounds in 85 % of cases [1]. The ulcerated diabetic foot may be considered the complication of the peripheral neuropathy (PN) and/or peripheral arterial disease (PAD). Several studies showed that diabetic patients with PN are at risk of foot ulceration and indeed true neuropathic ulceration is found in almost 50 % of the patients with a new foot ulcer according to eurodiale [2]. Those with PAD are at risk of foot amputation and ischemic lesions are found in the other 50 % of patients with foot ulceration. However true ischemic ulcers are observed only in 15 % of cases. The remaining 35 % have both PAD and PN present at the same time: neuroischemic ulcers [2]. Many factors may be responsible of the appearance of an ulcer in those patients: intrinsic factors related to the progressive appearance of limited joint mobility, soft tissue stiffness, early and persistent windlass mechanism [3] presence of structural foot deformities as hammer toes, hallux valgus or pes cavus. Metatarsal heads are prominent. This results in increased pressure underneath the metatarsal heads, which will make the plantar forefoot more susceptible to breakdown, also because patients are unaware of this abnormal pressure because of the neuropathy. However, there are also other contributing factors leading to diabetic foot ulcer formation, such as arterial occlusive disease, foot trauma, history of previous amputations, and callus due to the increased plantar pressures caused by abnormal mechanical loading of the foot [4]. A sequence of

Foot Care

Foot Care

A cost-effectiveness analysis of infrainguinal bypass in the absence of great saphenous vein conduit

Good-quality great saphenous vein (GSV) is the preferred conduit for infrainguinal surgical revascularizations, but it is not available in all patients. We sought to identify the alternative conduit that would maximize cost-effectiveness in the context of infrapopliteal bypass for critical limb ischemia and nonhealing foot wounds. A Markov model was used to create a detailed simulation of 10-year outcomes in a hypothetical Edifoligide for the Prevention of Infrainguinal Vein Graft Failure (PREVENT) III-type patient cohort undergoing infrainguinal bypass for nonhealing foot wounds. The following management options were evaluated: (1) conservative therapy (local wound care, amputation as needed); (2) primary amputation; (3) bypass with autologous alternative vein (AAV), including arm or lesser saphenous vein; (4) bypass with GSV<3 mm in diameter; (5) bypass with polytetrafluoroethylene (PTFE); (6)cryopreserved venous allograft; and (7) cryopreserved arterial allograft. Estimates of 10-year total costs were incorporated into the model. Cost-effectiveness was measured in terms of incremental United States dollars per additional year of ambulation. Bypass with AAV had the highest effectiveness as measured in median years of ambulation. After primary amputation, bypass with PTFE had the lowest total costs. With incremental cost-effectiveness ratios of $5325 and $21,228, bypass with PTFE or AAV appeared to be cost-effective alternatives to conservative therapy for nonhealing ischemic wounds. Primary amputation, GSV<3 mm, and allograft options were dominated (ie, more costly and less effective). Primary amputation was weakly dominated. Bypass with PTFE or AAV appears to be a cost-effective option for the management of critical limb ischemia and nonhealing foot wounds when good-quality GSV is not available.

Abstract 18420: Regional Variations in Processes of Care and Vascular Morbidity in Diabetic Adults in the United States

Background : It is unclear whether geographic variation in processes of care and vascular morbidity exists among diabetics in the U.S. We sought to determine the extent of regional variations in processes of care and their association with vascular disease in a cohort of diabetic adults in the U.S. Methods and Results: The 2007 Centers for Disease Control Behavioral Risk Factor Surveillance Survey was utilized to identify a cohort of diabetic patients. Participant residence was classified based on four U.S. regions: (1) Northeast, (2) Midwest, (3) South, and (4) West. Demographic data, clinical history, processes of care (regular medical checkup, foot exam, eye exam, diabetic education, aspirin use, and antihypertensive use) and vascular morbidity for diabetics of each region were compared. Presence of vascular morbidity was based upon patient report of myocardial infarction, stroke, retinopathy, nonhealing foot sores or bilateral foot amputations. Among the 42,072 diabetics, 43.9% were from the South, while 18.7%, 18.7%, and 18.6% were from the Midwest, Northeast, and South respectively. Diabetics of each region differed significantly with respect to demographic characteristics, prior medical history, and processes of care. Vascular morbidity also differed among the regions such that the West had significantly lower rates of myocardial infarction, while the South had higher rates of stroke and diabetic retinopathy. On multivariate analysis, geographic region was found to be independently associated with processes of care. However, geographic region was not found to be independently predictive of vascular morbidity. Independent variables associated with vascular morbidity included older age (OR, 1.01; 95%CI, 1.01-1.02), male gender (OR, 1.55; 95%CI, 1.43-1.67), employment status, level of education, lower annual income, financial barriers to health care (OR, 1.48; 95%CI, 1.31-1.66), active smoking status (OR, 1.12; 95%CI, 1.03-1.23), hypertension (OR, 1.26; 95%CI, 1.16-1.37) and hypercholesterolemia (OR, 1.23; 95%CI, 1.14-1.34). Conclusion : Despite significant regional differences in process of care, no regional variations in vascular morbidity were observed in diabetic adults.

PERIPHERAL ARTERIAL DISEASE

Background: The increase in prevalence of type 2 diabetes and its complications is alarming. The incidence of diabetic footulcers due to peripheral arterial disease, which leads to foot amputations far too often, is unacceptably high especially in developing countries.This study has been conducted to find out frequency and degree of peripheral arterial disease in type 2 diabetics having foot ulcers at tertiarycare settings in Abbottabad. Methods: This was a prospective descriptive study-being conducted at Northern Institue of Medical Sciences(NIMS) and Ayub teaching hospital Abbottabad from August 2009 to June 2010. Type 2 diabetics with non-healing foot ulcers lasting longer thanten days, were selected for this study by non-probability purposive sampling method. All study subjects have undergone for palpation ofperipheral arterial pulses in the lower limbs. Ankle-brachial index (ABI) is the ratio of the systolic blood pressure at the ankle to that in the arm.Peripheral arterial disease (PAD) was considered to be present if ABI was less than 0.90. It was further graded as mild, moderate and severeaccording to ABI values between 0.70-0.90, 0.50-0.69 and less than 0.49 respectively, as per recommendations of American DiabetesAssociation. Results: A total of 83 type 2 diabetics with foot ulcers were enrolled during eleven months period of this study. The mean age ofstudy subjects was 53.68±9.51 years. There were 33 (39.75%) males and 50 (60.24%) females with M to F ratio of 1:1.51. Mean duration ofdiabetes was 13.67±5.80 years (ranging from 9-23 years). Majority 57 (68.67%) of our patients were obese having poor glycemic control.Peripheral arterial disease has been found in 35(42.16%) patients, out of them 18(51.42%) had mild PAD as their ABI values remained between0.70-0.90, 15(42.85%) had moderate PAD due to their ABI values between 0.50-0.69 and 2 (5.71%) had severe PAD as their ABI values liebelow 0.49. Conclusions: Ankle-brachial index is a non-invasive, inexpensive and office-based diagnostic tool for peripheral arterial diseasein type 2 diabetics having foot ulcers, Healthcare professionals must be trained about early referral and regular feet care of these patients.

New therapeutic efforts and upcoming developments in the field of diabetes medicine and endocrinology

I welcome the readers to the newest issue of Therapeutic Advances in Endocrinology and Metabolism. In this issue, two important therapeutic fields are addressed: In the diabetes area the pharmacologic improvement of insulin therapy and a specific cellular therapy for treating severe foot ulcers as a treatment option in complicated and therapy-resistant cases; in the field of specific endocrine and metabolic disorders, the pharmacologic treatment of the syndrome of inappropriate antidiuretic hormone (SIADH) which is also called the Schwartz-Bartter-Syndrome is extensively reviewed. It is a sobering statistic: in an online survey of 500 patients with types 1 and 2 diabetes mellitus, 57% reported intentionally omitting their insulin injections. From a patient’s perspective, avoiding hypoglycemia is a major concern and this is probably one of the main causes of non-adherence to this medication, resulting in poor glycemic control. A longer-acting basal insulin should, therefore, address this problem. The review by Ammar Wakil and Stephen Atkin in this issue looks at Degludec, a new long acting insulin with a longer half-life than others, a flat time-action profile (less likely to cause hypoglycemia) and less day-to-day variability, improving glycaemic control. Degludec is made by deleting a threonine residue from human insulin and adding an acyl side chain to a lysine residue, so that injection results in self-association and the formation of large soluble multi-hexamers – a subcutaneous depot. This promises better glycemic control compared with insulin glargine and patients have more choice as to the timing of their basal insulin dose. Lower limb amputations as a result of non-healing foot ulcers in diabetic patients are regrettable, especially because they might have been avoided with more consequent and earlier treatment of the disease. In a letter to the Editor from the group of Matthias Weck, an emerging cellular therapy using platelet-rich plasma gel is described, and seems to provide previously unavailable ulcer management options to avoid limb loss. Physicians haven’t had a specific therapy for hyponatremia until the recent arrival of vasopressin receptor antagonists, the vaptans. Peter Gross contributes to the issue with a comprehensive review focusing on SIADH, accounting for one third of hyponatremia and serving as a general model for the disease. Misdiagnosis is common, and the author discusses the importance of demonstrating reduced effective serum osmolality in a given hyponatremia to exclude the possibility of a normoosmolar or hyperosmolar hyponatremia. It must be considered that a common circumstance of hyperosmolar hyponatremia is hyperglycemia. The introduction of parenteral (conivaptan) and orally available (tolvaptan) renal V-2 vasopressin receptor antagonists – collectively called vaptans - for the specific, easily titratable treatment of SIADH has been considered a breakthrough. The author gives detailed practical expert advice on their therapeutic use.

ASSOCIATION OF FINANCIAL BARRIERS TO HEALTH CARE WITH ACCESS TO CARE, QUALITY OF CARE AND OUTCOMES IN DIABETICS WITH CORONARY ARTERY DISEASE

Abstract Category: 31. Quality of Care and Outcomes AssessmentPresentation Number: 1256-292Authors: Puja Parikh, Steven Leigh, Roopali Parikh, Hongdao Meng, Nicholas Sakellarios, David Brown, Stony Brook University Medical Center, Stony Brook, NY, USA Background: As the cost of health care in the United States increases, more patients experience difficulty paying their medical bills. We sought to describe the impact of financial barriers to health care on access to care, quality of care and vascular outcomes of diabetic patients with coronary artery disease (CAD).Methods: The 2007 Centers for Disease Control’s Behavioral Risk Factor Surveillance Survey was utilized to identify a cohort of 11,274 diabetics with CAD. Demographic data, clinical history, quality of care indices, and clinical outcomes were recorded in these patients. The primary outcome was a composite of major adverse vascular events (MAVE), defined by a history of stroke, retinopathy or diabetes-related ocular changes, bilateral foot amputations, and nonhealing foot sores.Results: Of 11,274 patients, 1,541 (14%) patients reported financial barriers to health care and 9,733 (86%) reported no such barriers. Patients with financial barriers were younger, more often female, less often with health insurance, and had higher rates of obesity, smoking, and hypercholesterolemia. They were also noted to have impaired access to care resulting in less frequent medical checkups, lower rates of annual cholesterol screening, HgbA1c screening, eye exams, foot exams, and diabetic education classes, and less aspirin and antihypertensive use. Patients with financial barriers experienced significantly higher MAVE rates (68% vs 55%, p<0.001). In multivariate analysis, financial barriers to care were an independent predictor of MAVE (OR 1.82, 95% CI 1.31-2.53). Financial barriers were also independently associated with indices of access to and quality of care including, medical checkup within the past two years (OR 0.33, 95% CI 0.26-0.42), annual cholesterol (OR 0.58, 95% CI 0.34-0.98) and HbA1c (OR 0.66, 95% CI 0.48-0.92) screening, annual eye (OR 0.75, 95% CI 0.61-0.92) and foot (OR 0.72, 95% CI 0.59-0.89) examinations, aspirin use (OR 0.65, 95% CI 0.48-0.89), and diabetic education (OR 0.77, 95% CI 0.63-0.93).Conclusions: Financial barriers to health care are independently associated with impaired access to care, poorer quality of care and worse clinical outcomes in diabetics with CAD.

Effectiveness and safety of elective surgical procedures to improve wound healing and reduce re‐ulceration in diabetic patients with foot ulcers

The objective is to evaluate the effectiveness and safety of surgical off-loading to heal diabetic foot ulcers and prevent ulcer recurrence. Usually, structural foot deformities such as hallux rigidus, hammertoe deformities and equinus of the ankle contribute to abnormal pressure and shear forces and non-healing foot ulcers. Elective surgery to remove the deformity and restore joint mobility has been shown to be safe and effective to improve wound healing of recalcitrant ulcer and to reduce the risk of re-ulceration. Unfortunately, there is very little high-level evidence to help guide patient selection or to compare clinical outcomes.

Split thickness skin grafts for the treatment of non-healing foot and leg ulcers in patients with diabetes: a retrospective review

We retrospectively reviewed 107 diabetic patients who received a split thickness skin graft (STSG) for treatment of a non-healing diabetic foot or leg ulcer to describe healing times based on patient characteristics, comorbidities or complications. The minimum follow-up was 6 months from the time of STSG application. The mean time to healing among all patients was 5.1 weeks (3 to 16 weeks). The mean healing time for patients with complications was 12.0 weeks (10 to 16 weeks) while the mean healing time for those without complications was 4.9 weeks (3 to 10 weeks). Overall complication rate was 2.8%. Patients with a STSG take of less than 95% had a mean healing time of 7.9 weeks compared to 4.8 weeks for those with a STSG take of 100% (p<0.001). The use of autologous STSG for treatment of non-healing diabetic foot and leg wounds is a viable method for soft tissue closure and may present a low complication rate and a satisfactory rate of healing.

MicroRNA and Mechanisms of Impaired Angiogenesis in Diabetes Mellitus

Diabetes mellitus impairs physiological angiogenesis, which may be manifested as nonhealing foot ulcers or refractory angina. Multiple molecular mechanisms have been proposed. Hyperglycemia induces the generation of reactive oxygen species that cause endothelial derangements,1 including the reduced synthesis2 and accelerated degradation3 of endothelium-derived nitric oxide (NO). The bioactivity of NO is critical for angiogenic processes such as the survival, proliferation, and migration of endothelial cells.4 The impairment in NO bioactivity may also explain in part the reduced expression of a major angiogenic cytokine, vascular endothelial growth factor (VEGF), in hyperglycemic states, because NO and VEGF have a reinforcing and reciprocal relationship.5 Glucose intolerance also reduces the number and function of bone marrow–derived endothelial progenitor cells,6 circulating cells that participate in the angiogenic response. In addition to generating reactive oxygen species, hyperglycemia may impair cytoprotective mechanisms against oxidative stress. In particular, the thioredoxins play a key role in angiogenic processes by maintaining endothelial redox homeostasis, with favorable effects on protein folding, activity of reductive and metabolic enzymes, energy utilization, and transcription factor activity.7 Emerging evidence indicates that hyperglycemia upsets this cytoprotective mechanism by increasing the expression of the endogenous inhibitor thioredoxin-interacting protein (TXNIP). Article see p 282 Is it possible that these and other disparate mechanisms for the impaired angiogenesis in diabetes mellitus have a common genomic basis? This question logically follows from the work of Caporali and colleagues in the current issue of Circulation .8 They have discovered a novel genomic mechanism for hyperglycemia-induced impairment of angiogenesis, ie, the increased expression of a specific microRNA (miRNA) that appears to orchestrate a pathophysiological response in diabetes mellitus. Accumulating data indicate that noncoding RNA plays a critical role in genomic regulation.9 One …

Relationship between ulcer healing after hyperbaric oxygen therapy and transcutaneous oximetry, toe blood pressure and ankle–brachial index in patients with diabetes and chronic foot ulcers

The randomised, double-blind, placebo-controlled Hyperbaric Oxygen Therapy (HBOT) in Diabetic Patients with Chronic Foot Ulcers (HODFU) study showed beneficial effect of HBOT. As this treatment is expensive and time-consuming, being able to select patients for therapy would be very useful. The aim of this study was to evaluate whether circulatory variables could help in predicting outcome of HBOT. All HODFU study participants who completed therapy, predefined as receiving at least 36 out of 40 scheduled HBOT/placebo sessions, were included in this study (n = 75). Baseline transcutaneous oximetry (TcPO₂), toe blood pressure (TBP) and ankle-brachial index (ABI) were measured. Ulcer healing rate was registered at the 9-month follow-up visit. An ulcer was considered healed when it was completely epithelialised and remained so at the 12-month follow-up. In the HBOT group TcPO₂ were significantly lower for patients whose ulcer did not heal as compared with those whose ulcers healed. A significantly increased healing frequency was seen with increasing TcPO(2) levels in the HBOT group (TcPO₂/healing rate: <25 mmHg/0%; 26-50 mmHg/50%; 51-75 mmHg/73%; and >75 mmHg/100%). No statistically significant relation between the level of TBP or ABI and healing frequency was seen. Our results indicate that TcPO₂ in contrast to ABI and TBP correlates to ulcer healing following HBOT. We suggest HBOT as a feasible adjunctive treatment modality in diabetic patients with chronic non-healing foot ulcers when basal TcPO₂ at the dorsum of the foot is above 25 mmHg. NCT00953186 Mrs Thelma Zoegas Foundation and Faculty of Medicine, Lund University.

71-Year-Old Man With Chronic Kidney Failure and Sudden Change of Mental Status

71-year-old man was admitted to the hospital for al- tered mental status. His wife reported that the patient had become progressively confused and had been having visual hallucinations, seeing people and animals that were not really there. These symptoms started about 2 weeks before admission as intermittent episodes. She could not identify any triggering events or temporal pattern for these episodes. In the past 2 days, the patient's symptoms had become more persistent. She added that he had become in- creasingly forgetful in the past year but had had no prob- lem performing simple tasks or taking care of himself. This type of confusion had never occurred previously. The patient had a 12-year history of type 2 diabetes, had undergone coronary artery bypass 3 years previously, had symptomatic peripheral vascular insufficiency, and had stage V chronic kidney disease primarily due to diabetic nephropathy. For the past 10 months, he had been undergo- ing hemodialysis 3 times weekly for 3.5 hours each time via a left arm arteriovenous fistula. He had last undergone dialysis 3 days previously and was due for his scheduled dialysis on the day of admission. Two months before admission, the patient developed critical lower limb ischemia and a nonhealing left foot ul- cer. Multiple vascular interventions failed to restore suffi- cient limb blood flow; a month later, the patient underwent a transmetatarsal amputation. Postoperatively, he devel- oped surgical wound infection, necessitating repeated de- bridement and intravenous vancomycin administration. The patient's medications included stable doses of as- pirin, atenolol, atorvastatin, calcium acetate, insulin, gaba-

71-Year-Old Man With Chronic Kidney Failure and Sudden Change of Mental Status

71-year-old man was admitted to the hospital for al- tered mental status. His wife reported that the patient had become progressively confused and had been having visual hallucinations, seeing people and animals that were not really there. These symptoms started about 2 weeks before admission as intermittent episodes. She could not identify any triggering events or temporal pattern for these episodes. In the past 2 days, the patient's symptoms had become more persistent. She added that he had become in- creasingly forgetful in the past year but had had no prob- lem performing simple tasks or taking care of himself. This type of confusion had never occurred previously. The patient had a 12-year history of type 2 diabetes, had undergone coronary artery bypass 3 years previously, had symptomatic peripheral vascular insufficiency, and had stage V chronic kidney disease primarily due to diabetic nephropathy. For the past 10 months, he had been undergo- ing hemodialysis 3 times weekly for 3.5 hours each time via a left arm arteriovenous fistula. He had last undergone dialysis 3 days previously and was due for his scheduled dialysis on the day of admission. Two months before admission, the patient developed critical lower limb ischemia and a nonhealing left foot ul- cer. Multiple vascular interventions failed to restore suffi- cient limb blood flow; a month later, the patient underwent a transmetatarsal amputation. Postoperatively, he devel- oped surgical wound infection, necessitating repeated de- bridement and intravenous vancomycin administration. The patient's medications included stable doses of as- pirin, atenolol, atorvastatin, calcium acetate, insulin, gaba-

Femoropopliteal prosthetic bypass graft infection due to Mycobacterium abscessus localized by FDG-PET/CT scan

A patient with postvascular graft placement presented with bacteremia but no localizing symptoms. Our standard infected graft workup of computed tomography (CT) scan, ultrasound scan, magnetic resonance imaging (MRI) scan, and additional laboratory tests did not localize the infection source. Nuclear medicine had three options including white blood cell (WBC) scan, gallium scan, and the fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET)/CT scan. FDG-PET/CT imaging alone demonstrated the location. We present an unusual case of Mycobacterium abscessus in a vascular graft not localized with CT scan, ultrasound scan, or MRI scan and could only be localized with FDG-PET/CT scan.

Identification of Fall Risk Factors in Older Adult Emergency Department Patients

Falls represent an increasingly frequent source of injury among older adults. Identification of fall risk factors in geriatric patients may permit the effective utilization of scarce preventative resources. The objective of this study was to identify independent risk factors associated with an increased 6-month fall risk in community-dwelling older adults discharged from the emergency department (ED). This was a prospective observational study with a convenience sampling of noninstitutionalized elders presenting to an urban teaching hospital ED who did not require hospital admission. Interviews were conducted to determine the presence of fall risk factors previously described in non-ED populations. Subjects were followed monthly for 6 months through postcard or telephone contact to identify subsequent falls. Univariate and Cox regression analysis were used to determine the association of risk factors with 6-month fall incidence. A total of 263 patients completed the survey, and 161 (61%) completed the entire 6 months of follow-up. Among the 263 enrolled, 39% reported a fall in the preceding year, including 15% with more than one fall and 22% with injurious falls. Among those completing the 6 months of follow-up, 14% reported at least one fall. Cox regression analysis identified four factors associated with falls during the 6-month follow-up: nonhealing foot sores (hazard ratio [HR] = 3.71, 95% confidence interval [CI] = 1.73 to 7.95), a prior fall history (HR = 2.62, 95% CI = 1.32 to 5.18), inability to cut one's own toenails (HR = 2.04, 95% CI = 1.04 to 4.01), and self-reported depression (HR = 1.72, 95% CI = 0.83 to 3.55). Falls, recurrent falls, and injurious falls in community-dwelling elder ED patients being evaluated for non-fall-related complaints occur at least as frequently as in previously described outpatient cohorts. Nonhealing foot sores, self-reported depression, not clipping one's own toenails, and previous falls are all associated with falls after ED discharge.

Inflammation and neuropeptides: the connection in diabetic wound healing

Abnormal wound healing is a major complication of both type 1 and type 2 diabetes, with nonhealing foot ulcerations leading in the worst cases to lower-limb amputation. Wound healing requires the integration of complex cellular and molecular events in successive phases of inflammation, cell proliferation, cell migration, angiogenesis and re-epithelialisation. A link between wound healing and the nervous system is clinically apparent as peripheral neuropathy is reported in 30-50% of diabetic patients and is the most common and sensitive predictor of foot ulceration. Indeed, a bidirectional connection between the nervous and the immune systems and its role in wound repair has emerged as one of the focal features of the wound-healing dogma. This review provides a broad overview of the mediators of this connection, which include neuropeptides and cytokines released from nerve fibres, immune cells and cutaneous cells. In-depth understanding of the signalling pathways in the neuroimmune axis in diabetic wound healing is vital to the development of successful wound-healing therapies.