Increased Risk of Nonunion and Charcot Arthropathy After Ankle Fracture in People With Diabetes.

The aim of this study was to evaluate the frequency of complications after an ankle fracture in patients with and without diabetes and to evaluate risk factors for nonunion. We conducted a retrospective study of 439 patients with ankle fractures (31.7% had diabetes) and followed them for 1 year or until the fracture healed. The fracture severity and determination of nonunion and Charcot arthropathy were determined from independent evaluation of radiographs by 2 members of the research team. Nonunion was defined as a fracture that did not heal within 6 months of the fracture. The majority of patients were women (67% in each group). The risk of complications was significantly higher in patients with diabetes compared with those without diabetes. The odds ratio (OR) and 95% confidence interval (CI) for nonunion was 6.5 (3.4 to 12.8); for Charcot arthropathy, 7.6 (2.3 to 21.0); for wounds, 1.8 (1.1 to 2.9); for infection, 2.8 (1.4 to 5.7); and for amputation, 6.6 (0.98 to 80.0). In the logistical regression analysis, 6 factors were associated with fracture nonunion: dialysis (7.7; 1.7 to 35.2), diabetes (3.3; 1.5 to 7.4), fracture severity (bi- and trimalleolar fractures) (4.9; 1.4 to 18.0), beta blockers (2.5; 1.1 to 5.4), steroids (3.1; 1.2 to 7.7), and infection (3.7; 1.2 to 11.3). The results of the study demonstrate the increased risk of complications after an ankle fracture among patients with diabetes, dialysis, or open fractures and those using steroids and beta blockers. Further work is needed to identify areas for risk reduction.

Type 2 Diabetes and Metformin Influence on Fracture Healing in an Experimental Rat Model.

Persons with diabetes have a greater incidence of fractures compared with persons without diabetes. However, very little published information is available concerning the deleterious effect of late-stage diabetes on osseous structure and bone healing. The purpose of the present study was to evaluate the role of diabetes on fracture healing in a rat femur repair model. Thirty-six lean and diabetic Zucker rats were subdivided into 3 groups: (1) 12 lean rats as the control group; (2) 12 diabetic rats without blood glucose control (DM group); and (3) 12 diabetic rats treated with 300 mg/kg metformin to reduce the blood glucose levels (DM + Met group). Radiographs were taken every week to determine the incidence of bone repair and delayed union. All the rats were killed at 6 weeks after surgery. In both the sham-operated and the fractured and repaired femurs, significant decreases in the fracture-load/weight and marginal decreases in the fracture-load between the lean and DM groups were found. Metformin treatment significantly reduced the blood glucose and body weight 12 days postoperatively. Furthermore, a decrease in the fracture-load and fracture-load/weight in the repaired femurs was found in the DM + Met group. Diabetes impairs bone fracture healing. Metformin treatment reduces the blood glucose and body weight but had an adverse effect on fracture repair in diabetic rats. Further investigations are needed to reveal the mechanisms responsible for the effects of type 2 diabetes mellitus on bone and bone quality and the effect of medications such as metformin might have in diabetic bone in the presence of neuropathy and vascular disease.

Amputations and foot-related hospitalisations disproportionately affect dialysis patients.

Patients with diabetes have increased risk for foot ulcers, amputations and hospitalisations. We evaluated a closed cohort of patients with diabetes and established risk factors in two high risk groups: (i) dialysis patients and (ii) patients with previous foot ulceration. We used claims data for diabetes (ICD-9 250.X), ulceration (ICD-9 707·10, 707·14 and 707·15) and dialysis (CPT 90935-90937) from the Scott and White Health Plan to identify 150 consecutive patients with diabetes on dialysis (dialysis group) and 150 patients with a history of foot ulceration (ulcer history group). We verified these diagnoses by manually reviewing corresponding electronic medical records. Each patient was provided 30 months follow-up period. The incidence of foot ulcers was the same in dialysis patients and patients with an ulcer history (210 per 1000 person-years). The amputation incidence rate was higher in dialysis patients (58·0 versus 13·3, P < 0·001). Hospital admission was common in both study groups. The incidence of hospitalisation was higher in the ulcer history group (477·3 versus 381·3, P < 0·001); however, there were more foot-related hospital admissions in the dialysis group (32·9% versus 14·0%, P < 0·001) during the 30-month evaluation period. The incidence of ulcers, amputations and all-cause hospitalisations is high in persons with diabetes and a history of foot ulceration or on dialysis treatment; however, those on dialysis treatment have disproportionately higher rates of foot-related hospitalisations. Intervention strategies to reduce the burden of diabetic foot disease must target dialysis patients as a high-risk group.

The MLH1 D132H variant is associated with susceptibility to sporadic colorectal cancer.

Most susceptibility to colorectal cancer (CRC) is not accounted for by known risk factors. Because MLH1, MSH2 and MSH6 mutations underlie high-penetrance CRC susceptibility in hereditary nonpolyposis colon cancer (HNPCC), we hypothesized that attenuated alleles might also underlie susceptibility to sporadic CRC. We looked for gene variants associated with HNPCC in Israeli probands with familial CRC unstratified with respect to the microsatellite instability (MSI) phenotype. Association studies identified a new MLH1 variant (415G-->C, resulting in the amino acid substitution D132H) in approximately 1.3% of Israeli individuals with CRC self-described as Jewish, Christian and Muslim. MLH1 415C confers clinically significant susceptibility to CRC. In contrast to classic HNPCC, CRCs associated with MLH1 415C usually do not have the MSI defect, which is important for clinical mutation screening. Structural and functional analyses showed that the normal ATPase function of MLH1 is attenuated, but not eliminated, by the MLH1 415G-->C mutation. The new MLH1 variant confers a high risk of CRC and identifies a previously unrecognized mechanism in microsatellite-stable tumors. These studies suggest that variants of mismatch repair proteins with attenuated function may account for a higher proportion of susceptibility to sporadic microsatellite-stable CRC than previously assumed.

Incidence of Complications and Risk Factors for Nonunion After Ankle Fracture in Diabetes Mellitus.

BACKGROUND: To evaluate complications and risk factors for nonunion in patients with diabetes after ankle fracture. METHODS: We conducted a retrospective study of 139 patients with diabetes and ankle fractures followed for 1 year. We evaluated the incidence of wounds, infections, nonunions, Charcot's arthropathy, and amputations. We determined Fracture severity (unimalleolar, bimalleolar, trimalleolar), nonunion, and Charcot's arthropathy from radiographs. Nonunion was defined as a fracture that did not heal within 6 months of fracture. Analysis of variance was used to compare continuous variables, and χ2 tests to compare dichotomous variables, with α = 0.05. Logistic regression was performed with a binary variable representing nonunions as the dependent variable. RESULTS: Complications were common: nonunion (24.5%), Charcot's arthropathy (7.9%), wounds (5.2%), wound site infection (17.3%), and leg amputation (2.2%). Patients with nonunions were more likely to be male (55.9% versus 29.5%; P = .005), have sensory neuropathy (76.5% versus 32.4%; P < .001), have end-stage renal disease (17.6% versus 2.9%; P < .001), and use insulin (73.5% versus 40.1%; P < .001), ß-blockers (58.8% versus 39.0%; P = .049), and corticosteroids (26.5% versus 9.5%; P = .02). Among patients with nonunion, there was an increased risk of wounds (odds ratio [OR], 3.3; 95% confidence interval [CI], 1.46-7.73), infection (OR, 2.04; 95% CI, 0.72-5.61), amputation (OR, 7.74; 95% CI, 1.01-100.23), and long-term bracing (OR, 9.51; 95% CI, 3.8-23.8). In the logistic regression analysis, four factors were associated with fracture nonunion: dialysis (OR, 7.7; 95% CI, 1.7-35.2), insulin use (OR, 3.3; 95% CI, 1.5-7.4), corticosteroid use (OR, 4.9; 95% CI, 1.4-18.0), and ankle fracture severity (bimalleolar or trimalleolar fracture) (OR, 2.5; 95% CI, 1.1-5.4). CONCLUSIONS: These results demonstrate risk factors for nonunions: dialysis, insulin use, and fracture severity after ankle fracture in patients with diabetes.

Does the Start of Dialysis Initiate a Period of Increased Risk of Ulceration or Amputation?

BACKGROUND: Dialysis therapy is associated with an increased incidence of lower-extremity wounds and amputations. We compared the incidence of foot ulcers and amputations before and after the start of dialysis. METHODS: We evaluated 150 consecutive diabetic patients receiving dialysis and compared the incidence of foot complications 30 months before and after initiation of hemodialysis. We used claims data for diabetes, ulceration, and dialysis and abstracted medical records to verify diagnoses and dates of ulcers and amputations. We compared initial and cumulative ulcer/amputation incidence to account for multiple events in the same person over time. We used the same formula to determine the incidence rate difference and 95% confidence intervals (CIs) to compare new ulcers and amputations during the study. RESULTS: There was no significant difference in the incidence of first foot ulcers before (91.7 per 1,000 patient-years; 95% CI, 73.7-112.3 per 1,000 patient-years) and after (82.7; 95% CI, 65.7-102.3) the start of hemodialysis. The incidence of cumulative ulcers was significantly higher before (304.0 per 1,000 patient-years; 95% CI, 270.8-340.2) compared with after (210.7 per 1,000 patient-years; 95% CI, 183.0-240.9) dialysis. There was no difference in the incidence of first amputation before (29.3 per 1,000 patient-years; 95% CI, 1 9.4-41.7 per 1,000 patient-years) and after (37.3 per 1,000 patient-years; 95% CI, 19.4-41.7 per 1,000 patient-years) dialysis or in the cumulative incidence of amputations before (61.3 per 1,000 patient-years; 95% CI, 46.7-8.4 per 1,000 patient-years) and after (58.7 per 1,000 patient-years; 95% CI, 44.5-75.5 per 1,000 patient-years) dialysis. CONCLUSIONS: There was no increase in the incidence of ulcers or amputations after beginning hemodialysis.

Syme ankle disarticulation in patients with diabetes.

BACKGROUND: Syme ankle disarticulation is an amputation level that minimizes disability and preserves function, but it has been used sparingly in patients with diabetes mellitus. Surgeons have avoided this level because of the perceived high risk for wound failure, wound infection, or migration of the heel pad, which makes prosthesis use difficult. METHODS: Ninety-seven adult patients with diabetes mellitus who underwent Syme ankle disarticulation because of a neuropathic foot with an infection or gangrene, or both, during an eleven-year period were studied retrospectively. Selection of the amputation level was made on the basis of clinical examination and an assessment of the wound-healing parameters, i.e., vascular inflow, tissue nutrition, and immunocompetence. The average age of the patients was 53.2 +/- 17.5 years. RESULTS: Eighty-two patients (84.5%) ultimately achieved wound-healing. When threshold levels for vascular inflow (ultrasound Doppler ischemic index of 0.5 or transcutaneous partial pressure of oxygen between 20 and 30 mm Hg) and tissue nutrition (serum albumin of 2.5 g/dL) were met, an overall success rate of 88% was achieved. Total lymphocyte count (an absolute lymphocyte count of 1500) and the smoking of cigarettes during the study period did not appear to impact wound-healing rates. The overall infection rate was 23%, and it was three times greater in smokers. Most infections were managed with local wound care and antibiotic therapy. At a minimum follow-up of two years, all but two patients were able to walk with a prosthesis. Thirty of the ninety-seven patients died at an average of 57.1 months following surgery. CONCLUSIONS: The results of this retrospective review support the value of Syme ankle disarticulation in diabetic patients with infection or gangrene. This function-sparing amputation can be successfully performed with a reasonable risk. Patients managed with a Syme ankle disarticulation appeared to remain able to walk better and to survive longer than similar patients who had a transtibial amputation and served as historical controls. In diabetic patients with dysvascular disease who have adequate vascular inflow to support wound-healing (an ultrasound Doppler ischemic index of 0.5 or a transcutaneous partial pressure of oxygen between 20 and 30 mm Hg), the threshold for the wound-healing parameter of serum albumin appears to be as low as 2.5 g/dL.

The role of surgical off-loading to prevent recurrent ulcerations.

Foot ulcerations in patients with diabetes are common. Most ulcers heal with conservative treatment, but recurrence is common. The pathway of ulcer development includes neuropathy, deformity, and trauma. The first attempt to avoid recurrence is by the use of shoes and insoles. When shoes and insoles fail, surgical correction of deformity leading to the ulcer can be attempted. This article reviews the most common procedures performed to heal ulcers or avoid recurrence.

Fracture healing and biomarker expression in a diabetic Zucker rat model.

BACKGROUND: Persons with diabetes have a higher incidence of fractures compared with persons without diabetes. However, there is little published information concerning the deleterious effect of late-stage diabetes on fracture healing. There are no studies using animal models that evaluate the effect of advanced diabetes on fracture healing. The purpose of our study was to evaluate cytokine expression, specifically macrophage inflammatory protein 1 (MIP-1) and vascular endothelial growth factor, in fracture healing in a type 2 diabetes rat model. METHODS: We evaluated biomarker expression after femur fracture using a rat model. The two groups consisted of 24 Zucker diabetic rats (study group) and 12 Zucker lean rats (control group). An independent reviewer was used to assess delayed union. We evaluated serum samples 2, 4, 7, and 14 days after surgery for MIP-1, vascular endothelial growth factor, leptin, and other cytokine levels. RESULTS: At 3 weeks, Kaplan-Meier estimates showed that 45.8% of femur fractures in Zucker diabetic rats had healed, whereas 81.8% of those in Zucker lean rats had healed (P = .02). A logistic regression model to predict fast healing that included the three cytokines and diabetes status showed that the only factor achieving significance was MIP-1α. Vascular endothelial growth factor was the only biomarker to show significance compared with delayed healing. CONCLUSIONS: These results confirm significant differences in biomarker expression between diabetic and nondiabetic rats during bone healing. The key factors for bone healing may appear early in the healing process, whereas differences in diabetes versus nondiabetes are seen later in the healing process. Increased levels of MIP-1α were associated with the likelihood of delayed healing.

Risk factors for methicillin-resistant Staphylococcus aureus in diabetic foot infections.

OBJECTIVE: The purpose of this study was to evaluate risk factors for methicillin-resistant Staphylococcus aureus (MRSA) in patients hospitalized for diabetic foot infections. METHODS: We reviewed hospital admissions for foot infections in patients with diabetes which had nasal swabs, and anaerobic and aerobic tissue cultures at the time of admission. Data collected included patient characteristics and medical history to determine risk factors for developing an MRSA infection in the foot. RESULTS: The prevalence of MRSA in these infections was 29.8%. Risk factors for MRSA diabetic foot infections were history of MRSA foot infection, MRSA nasal colonization, and multidrug-resistant organisms (p<0.05). Positive predictive value (PPV) and negative predictive value (NPV) of nasal colonization with MRSA to identify MRSA diabetic foot infections were 66.7% and 80.0% (sensitivity 41%, specificity 90%). Admission from a nursing home was not a significant risk factor. CONCLUSION: Positive nasal swabs are not predictive of the infecting agent; however, a negative nasal swab rules out MRSA as the infecting agent in foot wounds with 90% accuracy.

Controlled side-by-side assembly of gold nanorods and dye molecules into polymer-wrapped SERRS-active clusters.

The controlled side-by-side assembly of gold nanorods in solution together with Raman reporter dye molecules to create small SERRS-active clusters stabilised by a surrounding polymer layer is demonstrated. This promising new class of nanotags offers several advantages over spherical nanoparticles for bioimaging and is of potential importance for a wide range of plasmon-enhanced spectroscopies and can also serve as building blocks for more complex solution-phase nanostructures.

The economics of limb salvage in diabetes.

BACKGROUND: Limb salvage requires early prevention therapy, knowledgeable use of wound care technology, and active management of peripheral vascular disease. This field has changed considerably over the past decade, with new advanced wound healing products and minimally invasive surgery for peripheral vascular disease. Treatment can be very costly in terms of medical and human resources. Evaluation of the clinical and economic impact of medical care is becoming more important as the population with diabetes and the need to contain the cost of health care simultaneously increase. The aim of this study was to review the economic impact of prevention therapies, wound care, and peripheral vascular disease interventions to prevent major lower extremity amputations. METHODS: The authors reviewed the economic impact of prevention therapy, wound care, and peripheral vascular disease interventions to prevent lower extremity amputations. RESULTS: Length of stay in the hospital and intensive care drive the cost of treatment. Surgical intervention and complications for foot ulcers, amputations, and peripheral vascular disease are significant factors in the cost of limb salvage. CONCLUSIONS: Not surprisingly, prevention and evidenced-based treatments are the most cost-effective way of reducing the use of medical resources and improving and prolonging productive lifestyles. Future prospective studies need to be conducted to more accurately understand the financial impact of limb salvage.

Safety and effectiveness of flexor tenotomies to heal toe ulcers in persons with diabetes.

AIM: To evaluate the effectiveness and safety of percutaneous tenotomy of the flexor digitorum longus to heal neuropathic ulcers on the tip of the toe. METHODS: We retrospectively reviewed a cohort of 48 patients with 58 tenotomy procedures with diabetes related neuropathy and ulceration at the tip of the toe. Subjects were treated with tenotomy of the flexor digitorum longus. We then evaluated healing of the ulceration and any adverse events including recurrence, infection, healing failure, and amputation. RESULTS: 98.3% of the ulcerations healed. Mean ulcer healing time was 40+/-52 days. 12.1% had a recurrence of ulceration at the same site. Mean time to recurrence was 13.9 months. Five percent had post-operative soft tissue infection. Two patients had amputation of the digit; both had pre-existing osteomyelitis. Mean follow up was 28 months. CONCLUSION: Flexor tenotomy is a safe, simple procedure, which can enhance patients' healing potential with very little risk.

Impact of chronic kidney disease on survival after amputation in individuals with diabetes.

OBJECTIVE: To identify factors that influence survival after diabetes-related amputations. RESEARCH DESIGN AND METHODS: We abstracted medical records of 1,043 hospitalized subjects with diabetes and a lower-extremity amputation from 1 January to 31 December 1993 in six metropolitan statistical areas in south Texas. We identified mortality in the 10-year period after amputation from death certificate data. Diabetes was verified using World Health Organization criteria. Amputations were identified by ICD-9-CM codes 84.11-84.18 and categorized as foot, below-knee amputation, and above-knee amputation and verified by reviewing medical records. We evaluated three levels of renal function: chronic kidney disease (CKD), hemodialysis, and no renal disease. We defined CKD based on a glomerular filtration rate<60 ml/min and hemodialysis from Current Procedural Terminology (CPT) codes (90921, 90925, 90935, and 90937). We used χ2 for trend and Cox regression analysis to evaluate risk factors for survival after amputation. RESULTS: Patients with CKD and dialysis had more below-knee amputations and above-knee amputations than patients with no renal disease (P<0.01). Survival was significantly higher in patients with no renal impairment (P<0.01). The Cox regression indicated a 290% increase in hazard for death for dialysis treatment (hazard ratio [HR] 3.9, 95% CI 3.07-5.0) and a 46% increase for CKD (HR 1.46, 95% CI 1.21-1.77). Subjects with an above-knee amputation had a 167% increase in hazard (HR 2.67, 95% CI 2.14-3.34), and below-knee amputation patients had a 67% increase in hazard for death. CONCLUSIONS: Survival after amputation is lower in diabetic patients with CKD, dialysis, and high-level amputations.

Diabetic foot prevention: a neglected opportunity in high-risk patients.

OBJECTIVE: To evaluate the frequency of foot prevention strategies among high-risk patients with diabetes. RESEARCH DESIGN AND METHODS: Electronic medical records were used to identify 150 patients on dialysis and 150 patients with previous foot ulceration or amputation with 30 months follow-up to determine the frequency with which patients received education, podiatry care, and therapeutic shoes and insoles as prevention services. RESULTS: Few patients had formal education (1.3%), therapeutic shoes/insoles (7%), or preventative podiatric care (30%). The ulcer incidence density was the same in both groups (210 per 1,000 person-years). In contrast, the amputation incidence density was higher in the dialysis group compared with the ulcer group (58.7 vs. 13.1 per 1,000 person-years, P < 0.001). Patients on dialysis were younger and more likely to be of non-Hispanic white descent (P = 0.006) than patients with a previous history of ulcer or amputation. CONCLUSIONS: Prevention services are infrequently provided to high-risk patients.

The reliability and validity of the Q-angle: a systematic review.

The quadriceps or Q-angle is an index of the vector for the combined pull of the extensor mechanisms and the patellar tendon. It is used as an indicator for patellofemoral joint dysfunction. The purpose of this article is to systematically review and appraise the literature to determine the reliability and validity of this test. An electronic database search was performed accessing AMED, British Nursing Index, CINAHL, the Cochrane database, EMBASE, ovid Medline, Physiotherapy Evidence Database (PEDro), PsycINFO, Pubmed and Zetoc to April 2008. All English language, human subject, clinical trials, assessing the inter- or intra-tester reliability, or the criterion validity, were included. The Critical Appraisal Skills Programme appraisal tool was used to establish the methodological quality of each study. Ten articles including 569 control and 179 patellofemoral disorder knees were reviewed. The findings suggest that there is considerable disagreement on the reliability and validity of the clinical Q-angle measurement. This may be due to a lack of standardisation in the measurement procedure. Further study is advocated to re-evaluate this topic using well-designed, and sufficiently large observational studies of specific patellofemoral dysfunction populations.

The physiotherapy management of muscle haematomas.

Muscle haematomas may present in athletes following a muscle tear or contusion injury. The objective of this literature review was to examine the literature pertaining to the physiotherapeutic management of muscle haematomas. An electronic literature search was performed of the databases AMED, Cinahl, Embase, PEDro and Ovid Medline from their inception to April 2006. Human and animal subject, clinical trials, written in English, which could assist in the assessment of this topic, were included. Seventeen (of 7794) papers met the inclusion criteria and were reviewed. The review concluded that few clinical trials have been published assessing the efficacy of these strategies. Furthermore, since numerous methodological weaknesses plagued the limited evidence-base, it was not possible to support or refute the application of different physiotherapy modalities, for the treatment of muscle haematomas. Further study is recommended to identify the best therapeutic interventions to treat muscle haematomas.