Sheldon S. Lin

Plantar forefoot ulceration with equinus deformity of the ankle in diabetic patients : The effect of tendo-Achilles lengthening and total contact casting

Between 1993 and 1995, 93 neuropathic diabetes mellitus patients with foot ulcers underwent a total contact cast (TCC) protocol. A randomly chosen group of 21 patients (Group I) demonstrated ulcer healing in a mean time of 43.5 days. Despite 9 weeks of TCC, 15 patients (Group II) with forefoot ulcers failed to heal. Physical examination of Group I revealed plantarflexion/dorsiflexion range of motion of the ankle of 33.8 degrees / 1.9 degrees compared to 32.3 degrees / -10.5 degrees of Group II, demonstrating an ankle equinus deformity and limited joint motion. Group II patients underwent a correction of the equinus deformity with percutaneous tendo-Achilles lengthening (TAL), followed by a TCC. All but one ulcer (93.3%) healed within 39.4 days. Four (19.0%) ulcers recurred (at the same site) in Group I, compared to none in Group II at the latest follow up of 17.3 months. Surgical correction with percutaneous TAL and TCC results in healing of forefoot ulcer and helps prevent ulcer recurrence.

The effects of blood glucose control upon fracture healing in the BB Wistar rat with diabetes mellitus

Several clinical series, analyzing fracture healing in patients with diabetes mellitus (DM), demonstrated significant incidence of delayed union, non‐union, and pseudarthrosis. In this study, analysis was performed to evaluate the effects of blood glucose (BG) control on fracture healing in the DM BB Wistar rat, a rat strain that represents a close homology to Type I DM in man. Our study showed decreased cell proliferation at the fracture site as well as decreased mechanical stiffness and bony content in the poorly controlled DM rats. To determine the effect of BG control, DM rats were treated with insulin sufficient to maintain physiologic BG levels throughout the course of the study. Values of cellular proliferation, biomechanical properties and callus bone content in tightly controlled DM animals were not significantly different from values of non‐DM control values. This study suggests that insulin treatment with resultant improved BG control will ameliorate the impaired early and late parameters of DM fracture healing.

COMPLICATIONS OF ANKLE FRACTURES IN DIABETIC PATIENTS

Ankle fracture in patients with DM mandates a stepwise protocol to minimize the potential complications of delayed fracture healing, wound complications, and development of Charcot arthropathy. For nondisplaced ankle fracture, a nonoperative approach with increased duration of immobilization seems successful based on experience of the limited series. A displaced ankle fracture in a patient with DM requires a surgical intervention. The authors advocate tight glucose control in both groups to improve the fracture milieu and to ameliorate the potential complications. Appropriate stable fixation with adequate length of immobilization is crucial for successful fracture resolution.

Chlorhexidine provides superior skin decontamination in foot and ankle surgery: a prospective randomized study.

Feet are prone to bacterial contamination. We hypothesized that chlorhexidine scrub and isopropyl alcohol paint provide superior local flora reduction than povidone-iodine scrub and paint. Patients with intact, uninfected skin having clean elective foot and ankle surgery were prospectively enrolled and randomly assigned to skin preparation with povidone-iodine (Group 1) or chlorhexidine scrub and isopropyl alcohol paint (Group 2). Culture swabs (aerobic, anaerobic, acid fast, fungus, and routine antibiotic sensitivity) were taken from all web spaces, nail folds, toe surfaces, and proposed surgical incision sites. One-hundred twenty-seven patients were enrolled (mean age, 46 years; range, 16–85 years). Sixty-seven patients were assigned to Group 1; 60 patients were assigned to Group 2. In Group 1, 53 of 67 patients (79%) had positive cultures; in Group 2, 23 of 60 patients (38%) had positive cultures. These data indicate that chlorhexidine and alcohol provide better reduction in bacterial carriage than povidone-iodine. Based on these data, we recommended chlorhexidine as the surgical preparatory agent for the foot and ankle. Level of Evidence: Therapeutic study, Level I-1a (significant difference). See the Guidelines for Authors for a complete description of levels of evidence.

Decreased platelet derived growth factor expression during fracture healing in diabetic animals.

Animal model experiments have suggested that diabetes inhibits cell proliferation during fracture healing. Immunohistochemical analysis of proliferating cell nuclear antigen revealed significant reductions in cellular proliferation rates in the fracture callus of spontaneously diabetic BB Wistar rats as compared with healthy BB Wistar rats. Because platelet derived growth factor is associated with the early stage of fracture healing, it was hypothesized that diabetes causes decreased platelet derived growth factor expression during the early phase of fracture healing with a concomitant decrease in cell proliferation. Midshaft femur fractures were created in healthy and spontaneously diabetic BB Wistar rats and analyzed at Days 2, 4, and 7 after fracture for expression of platelet derived growth factor. Immunohistochemistry showed decreased localization of platelet derived growth factor in early diabetic fracture callus compared with healthy controls. Platelet derived growth factor messenger ribonucleic acid levels, as determined by reverse transcription and polymerase chain reaction, also were decreased in early diabetic fractures compared with healthy controls. Therefore the decreased cell proliferation rates associated with diabetic fracture healing are consistent with decreased platelet derived growth factor levels and suggest a causal relationship. These results suggest that diabetes is affecting the early phase of fracture healing by inhibiting cell proliferation through decreasing expression of platelet derived growth factor.

Low-intensity pulsed ultrasound increases the fracture callus strength in diabetic BB Wistar rats but does not affect cellular proliferation

Type I diabetes mellitus (DM) is associated with impaired fracture healing. Specifically, DM affects multiple phases of fracture healing including early cellular proliferation and late phases resulting in inferior biomechanical properties. Recent studies demonstrated the utility of pulsed low‐intensity ultrasound (US) to facilitate fracture healing. The current study evaluated the effects of daily application of US on mid‐diaphyseal femoral fractures in DM and non‐DM BB Wistar rats. Immunohistochemical staining for PCNA was used to evaluate cellular proliferation at 2, 4, and 7 days post‐fracture. In concordance with previous findings, DM fracture callus demonstrated decreased cellular proliferation. Importantly, the application of US did not significantly alter the proliferation in either DM or control groups. However, mechanical testing revealed significantly greater torque to failure and stiffness in US‐treated DM versus non‐US‐treated DM groups at six weeks post‐fracture. Despite the inability of US to affect the early proliferative phase of fracture healing, its application clearly results in improved mechanical properties during the late phases of healing. These findings suggest a potential role of US as an adjunct for DM fracture treatment.

Recombinant Human Platelet-Derived Growth Factor-BB and Beta-Tricalcium Phosphate (rhPDGF-BB/β-TCP): An Alternative to Autogenous Bone Graft

BACKGROUND Joint arthrodesis employing autogenous bone graft (autograft) remains a mainstay in the treatment of many foot and ankle problems. However, graft harvest can lead to perioperative morbidity and increased cost. We tested the hypothesis that purified recombinant human platelet-derived growth factor-BB (rhPDGF-BB) homodimer combined with an osteoconductive matrix (beta-tricalcium phosphate [β-TCP]) would be a safe and effective alternative to autograft. METHODS A total of 434 patients were enrolled in thirty-seven clinical sites across North America in a prospective, randomized (2:1), controlled, non-inferiority clinical trial to compare the safety and efficacy of the combination rhPDGF-BB and β-TCP with those of autograft in patients requiring hindfoot or ankle arthrodesis. Radiographic, clinical, functional, and quality-of-life end points were assessed through fifty-two weeks postoperatively. RESULTS Two hundred and sixty patients (394 joints) underwent arthrodesis with use of rhPDGF-BB/β-TCP. One hundred and thirty-seven patients (203 joints) underwent arthrodesis with use of autograft. With regard to the primary end point, 159 patients (61.2% [262 joints (66.5%)]) in the rhPDGF-BB/β-TCP group and eighty-five patients (62.0% [127 joints (62.6%)]) in the autograft group were fused as determined by computed tomography at six months (p < 0.05). Clinically, 224 patients (86.2%) [348 joints (88.3%)]) in the rhPDGF-BB/β-TCP group were considered healed at fifty-two weeks, compared with 120 patients (87.6% [177 joints (87.2%)] in the autograft group (p = 0.008). Overall, fourteen of sixteen secondary end points at twenty-four weeks and fifteen of sixteen secondary end points at fifty-two weeks demonstrated statistical non-inferiority between the groups, and patients in the rhPDGF-BB/β-TCP group were found to have less pain and an improved safety profile. CONCLUSIONS In patients requiring hindfoot or ankle arthrodesis, treatment with rhPDGF-BB/β-TCP resulted in comparable fusion rates, less pain, and fewer side effects as compared with treatment with autograft.

In Vivo Kinematics of the Salto Total Ankle Prosthesis

Background: Recent technological advancements in total ankle arthroplasty (TAA) have included the introduction of the mobile bearing concept. This bearing has several advantages, but researchers have questioned whether or not increased mobility sacrifices joint stability or durability of the implant. The present study evaluated the kinematics of this type of prosthesis implanted in patients. Materials and Methods: Fluoroscopy and 3D-to-2D registration techniques were used to determine the in vivo kinematics for 20 TAA subjects performing two activities: gait and step-up. The motion of the prostheses was described in terms of clinical rotations and as rotation about the helical (screw) axis. Then, the anterior-posterior translation and axial rotation of the mobile bearing insert were determined. Results: Among the clinical rotations, the dorsi-/plantarflexion was the most dominant, revealing the greatest pattern change and the largest magnitude. During gait, the orientation of the prosthetic components changed smoothly from plantarflexion to dorsiflexion. The average range of this motion was 9.2 degrees. For step-up activity, the range was 8.0 degrees. However, between 33% and 66% of stance phase, the talar components orientation changed from dorsiflexion to plantarflexion. The average absolute range of anterior-posterior translation of the mobile bearing insert was 1.5 mm and 2.3 mm for gait and step-up, respectively. Conclusion: These measured translations were relatively small and may suggest that the rotational portion of the motion was more dominant than translational and provided sufficient mobility. Level of Evidence: IV, Retrospective Case Series

Mesenchymal stem cells accelerate bone allograft incorporation in the presence of diabetes mellitus

Allograft (Allo) incorporation in the presence of a systemic disease like diabetes mellitus (DM) is becoming a major issue in the orthopedic community. Mesenchymal stem cells (MSC) are multipotent stem cells that may be derived from adult, whole bone marrow and have been shown to induce bone formation in segmental defects when combined with the appropriate carrier/scaffold. The objectives of this study were to analyze the effect of DM upon Allo incorporation in a segmental rat femoral defect and to also investigate MSC augmentation of Allo incorporation. Segmental (5 mm) femoral defects were created in non‐DM and DM rats and treated with Allo containing demineralized bone matrix (DBM) or DBM with MSC augmentation. Histological scoring at 4 weeks demonstrated less mature bone in the DM/DBM group compared to its non‐DM counterpart (p < 0.001). However, there was significantly more mature bone in the DM/MSC group when compared to the DM/DBM group at both 4 and 8 weeks (p < 0.001 and p = 0.004). Furthermore, significantly more bone formation was observed in the DM/MSC group compared to the DM/DBM group at the 4‐week time point (p < 0.001). The results of this study suggest that MSC are a potential adjunct for bone regeneration when implanted in an orthotopic site in the presence of DM.

The effects of low-intensity pulsed ultrasound upon diabetic fracture healing

In the United States, over 17 million people are diagnosed with type 1 diabetes mellitus (DM) with its inherent morbidity of delayed bone healing and nonunion. Recent studies demonstrate the utility of pulsed low‐intensity ultrasound (LIPUS) to facilitate fracture healing. The current study evaluated the effects of daily application of LIPUS on mid‐diaphyseal femoral fracture growth factor expression, cartilage formation, and neovascularization in DM and non‐DM BB Wistar rats. Polymerase chain reaction (PCR) and ELISA assays were used to measure and quantify growth factor expression. Histomorphometry assessed cartilage formation while immunohistochemical staining for PECAM evaluated neovascularization at the fracture site. In accordance with previous studies, LIPUS was shown to increase growth factor expression and cartilage formation. Our study also demonstrated an increase in fracture callus neovascularization with the addition of LIPUS. The DM group showed impaired growth factor expression, cartilage formation, and neovascularization. However, the addition of LIPUS significantly increased all parameters so that the DM group resembled that of the non‐DM group. These findings suggest a potential role of LIPUS as an adjunct for DM fracture treatment.