Special Considerations in Podiatric Science: Translational Research, Cadavers, Gait Analysis, Dermatology, and Databases.

The objective of this article is to provide a brief overview of the critical analysis and design of unique and perhaps less common methodologies in podiatric science. These include basic science translational designs, cadaveric investigations, gait analyses, dermatologic studies, and database analysis. The relative advantages, disadvantages, and inherent limitations are reviewed with an intention to improve the interpretation of results and advance future foot and ankle scientific endeavors.

2023 International Consensus Meeting on musculoskeletal infection: Summary from the treatment workgroup and consensus on treatment in preclinical models.

In vitro and in vivo studies are critical for the preclinical efficacy assessment of novel therapies targeting musculoskeletal infections (MSKI). Many preclinical models have been developed and applied as a prelude to evaluating safety and efficacy in human clinical trials. In performing these studies, there is both a requirement for a robust assessment of efficacy, as well as a parallel responsibility to consider the burden on experimental animals used in such studies. Since MSKI is a broad term encompassing infections varying in pathogen, anatomical location, and implants used, there are also a wide range of animal models described modeling these disparate infections. Although some of these variations are required to adequately evaluate specific interventions, there would be enormous value in creating a unified and standardized criteria to animal testing in the treatment of MSKI. The Treatment Workgroup of the 2023 International Consensus Meeting on Musculoskeletal Infection was responsible for questions related to preclinical models for treatment of MSKI. The main objective was to review the literature related to priority questions and estimate consensus opinion after voting. This document presents that process and results for preclinical models related to (1) animal model considerations, (2) outcome measurements, and (3) imaging.

Racial and Ethnic Disparities in the Management of Diabetic Feet.

PURPOSE OF REVIEW: Diabetes mellitus is a chronic medical condition affecting many individuals worldwide and leads to billions of dollars spent within the healthcare system for its treatment and complications. Complications from diabetes include diabetic foot conditions that can have a devasting impact on quality of life. Diabetic foot ulcers and amputations occur in minority individuals at an increased rate compared to Caucasian individuals. This review provides an update examining the racial and ethnic disparities in the management of diabetic foot conditions and the differences in rates of amputation. RECENT FINDINGS: Current research continues to show a disparity as it relates to diabetic foot management. There are novel treatment options for diabetic foot ulcers that are currently being explored. However, there continues to be a lack in racial diversity in new treatment studies conducted in the USA. Individuals from racial and ethnic minority groups have diabetes at higher rates compared to Caucasian individuals, and are also more likely to develop diabetic foot ulcers and receive amputations. Over the last few years, more efforts have been made to improve health disparities. However, there needs to be an improvement in increasing racial diversity when investigating new therapies for diabetic foot ulcers.

Anatomy of the Deltoid-Spring Ligament Complex.

A thorough knowledge of the anatomy of the deltoid and spring ligament complex is important for treatment of deformities that impact the foot and ankle. Both ligaments are interconnected, and the study of their anatomic characteristics is better performed together than in isolation. The deltoid ligament is a group of ligaments that derives its origin from the medial malleolus, and the spring ligament complex consist of a group of ligaments that connects the navicular and the sustentaculum tali of the calcaneus. They both play an important role in stabilization of the medial ankle and medial column of the foot.

American College of Foot and Ankle Surgeons Clinical Consensus Statement: Appropriate Clinical Management of Adult-Acquired Flatfoot Deformity.

This clinical consensus statement of the American College of Foot and Ankle Surgeons focuses on the highly debated subject of the management of adult flatfoot (AAFD). In developing this statement, the AAFD consensus statement panel attempted to address the most relevant issues facing the foot and ankle surgeon today, using the best evidence-based literature available. The panel created and researched 16 statements and generated opinions on the appropriateness of the statements. The results of the research on this topic and the opinions of the panel are presented here.

Blockade of the OGF-OGFr pathway in diabetic bone.

Purpose: This research investigated the presence and integrity of the opioid growth factor (OGF)-opioid growth factor receptor (OGFr) regulatory pathway in type 1 diabetic (T1D) rats, and investigated whether modulation of this axis by naltrexone (NTX) altered the composition of normal bone or fractured femurs. Materials and Methods: Diabetes was induced by streptozotocin; controls rats received buffer. Hyperglycemic animals were subjected to femur osteotomy, with randomized cohorts receiving either topical NTX or sterile saline in calcium carbonate. In experiment 2, hyperglycemic rats were injected daily for 3 weeks with either 30 mg/kg NTX or sterile saline. Expression levels of OGF and OGFr were measured by immunohistochemistry, bone composition was assessed by histomorphometry, and bone integrity was evaluated by µCT and 3-point bending. Results: Relative to normoglycemic bones, OGF and OGFr expression levels were increased 95% and 84%, respectively, in T1D bone; serum levels of OGF in T1D rats were elevated 23%. Hyperglycemia decreased the strength (26%), osteocalcin expression (17%), and number of proliferative (Ki67+) cells (32%) in intact femur. Topical NTX treatment of fractured femurs reduced the percentage of granulation tissue and increased cartilage. Systemic NTX treatment of diabetic rats increased strength by 21% and energy absorbed by105% in bone relative to measurements in saline-treated diabetic rats. Conclusions: The OGF-OGFr pathway appears to be dysregulated in the bone of T1D rats. Topical NTX treatment of T1D fractured bone accelerated some aspects of delayed diabetic fracture repair, and systemic NTX protected against some elements of compromised bone composition.

Pigment epithelium-derived factor (PEDF) reduced expression and synthesis of SOST/sclerostin in bone explant cultures: implication of PEDF-osteocyte gene regulation in vivo.

Mutations in Serpinf1 gene which encodes pigment epithelium-derived factor (PEDF) lead to osteogenesis imperfecta type VI whose hallmark is defective matrix mineralization. We reported previously that PEDF reduced expression and synthesis of Sost/Sclerostin as well as other osteocytes genes encoding proteins that regulate matrix mineralization [1]. To determine whether PEDF had an effect on osteocyte gene expression in bone, we used bone explant cultures. First, osteocytes were isolated from surgical waste of bone fragments obtained from patients undergoing elective foot surgeries under approved IRB protocol by Penn State College of Medicine IRB committee. Primary osteocytes treated with PEDF reduced expression and synthesis of Sost/Sclerostin and matrix phosphoglycoprotein (MEPE) as well as dentin matrix protein (DMP-1). On the whole, PEDF reduced osteocyte protein synthesis by 50% and by 75% on mRNA levels. For bone explants, following collagenase digestion, bone fragments were incubated in alpha-MEM supplemented with 250 ng/ml of PEDF or BSA. After 7 days of incubation in a medium supplemented with PEDF, analysis of mRNA by PCR and protein by western blotting of encoded osteocyte proteins showed reduced Sclerostin synthesis by 39% and MEPE by 27% when compared to fragments incubated in medium supplemented with BSA. mRNA expression levels of osteocytes in bone fragments treated with PEDF were reduced by 50% for both SOST and MEPE when compared to BSA-treated bone fragments. Taken together, the data indicate that PEDF has an effect on osteocyte gene expression in bone and encourage further studies to examine effect of PEDF on bone formation indices in animal models and its effect on osteocyte gene expression in vivo following PEDF administration.

Topical Naltrexone Is a Safe and Effective Alternative to Standard Treatment of Diabetic Wounds.

Objective: Diabetes affects more than 29 million individuals in the United States, resulting in healthcare costs approaching $245 billion. Approximately 15% of these individuals will develop a chronic, non-healing foot ulcer (diabetic foot ulcer [DFU]) that, if untreated, may lead to amputation. The current treatments for DFU are expensive, have significant side-effects, and often result in non-compliance. A new topical treatment is described that accelerates cutaneous wound repair and is disease modifying by targeting underlying aberrant diabetic pathways. Approach: The efficacy of naltrexone (NTX), an opioid receptor antagonist, and Regranex® was compared in preclinical studies using type 1 diabetic rats. Dorsal cutaneous wounds were treated topically with 0.03% NTX, Regranex, or moisturizing cream alone. Wound closure, DNA synthesis, and cytokine production were monitored. Results: Wound closure rates with topical NTX in type 1 diabetic rats were comparable to Regranex. Topical NTX accelerated DNA synthesis, as measured by BrdU incorporation, increased mast cells, and enhanced expression of platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF), a marker for angiogenesis. Regranex had little effect on DNA synthesis, mast cells, and VEGF expression relative to vehicle-treated wounds, and it only temporarily increased PDGF expression. Fibroblast growth factor expression was not altered by either treatment. Innovation: Topical application of 0.03% NTX cream accelerates diabetic wound closure. Conclusion: Blockade of the opioid growth factor (OGF)-OGF receptor (OGFr) axis utilizing 0.03% NTX cream is comparable to standard care in preclinical studies, and it provides a safe, inexpensive, and effective alternative for treatment of diabetic wounds.

Effects of Medial Displacement Calcaneal Osteotomy and Calcaneal Z Osteotomy on Subtalar Joint Pressures: A Cadaveric Flatfoot Model.

Medial displacement calcaneal osteotomies have been shown to be successful in the surgical management of adult acquired flatfoot, in particular, stage 2 deformity. Classically, the medial displacement calcaneal osteotomy technique has been performed. However, a calcaneal Z osteotomy has been more recently described and applied in the surgical management of flatfoot deformity. Although the potential advantages of the calcaneal Z technique have been reported, data on its effect on the subtalar joint are lacking. A validated flatfoot model was induced in 8 cadaveric feet that had been randomly assigned to either medial displacement calcaneal osteotomy (n = 4) or calcaneal Z osteotomy (n = 4). The feet were loaded through the tibia with a constant ground reaction force of 400 N, with a simultaneous increase in the Achilles tendon force to 300 or 500 N. The subtalar joint pressures were recorded before and after osteotomy. We did not detect any statistically significant differences between the 2 techniques in terms of their effects on subtalar joint pressure.

Accelerating the pace of discovery in orthopaedic research: A vision toward team science.

The landscape of basic science in the United States and around the world is changing, and the field of orthopaedic research is positioned to lead by embracing a culture of collaborative, team science that reflects our field's interdisciplinary nature. In this article we hope to address some of the cultural challenges and programmatic barriers that impede a team science approach in the US and suggest opportunities for change. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1673-1679, 2016.

Nail and skin disorders of the foot.

Disorders of the dermis and the nails on the feet are common. Despite the simplicity of the skin and nail disorders of the foot, they can be debilitating and impact the patient's ability to ambulate and perform activities of daily living. Diagnosis in most cases is confirmed on physical examination alone. Diligent care of skin and nail disorders can prevent further pathology involving the deeper structures of the foot and allow the patient to fully participate in their usual activities.

Unilateral versus bilateral first ray surgery: a prospective study of 186 consecutive cases--patient satisfaction, cost to society, and complications.

Many studies have evaluated bilateral versus unilateral surgery in large joints, but limited research is available to compare outcomes of bilateral staged foot surgeries versus synchronous bilateral foot surgery. In total, 186 consecutive cases of first metatarsal-phalangeal (MTP) joint surgery were prospectively included in this study; 252 procedures were performed: 120 were unilateral or staged bilateral operations, and 66 were synchronous bilateral operations. Patients were evaluated at 6 and 12 weeks for specific early complications and surveyed about their return to work, activities of daily living, shoe gear requirements, satisfaction, and reasons for choosing staged or synchronous surgery. In addition, a cost analysis was performed on all surgical scenarios. Student t test showed no statistical significance between groups in all clinical settings to a 95% confidence level. Complication rates were similar and few in all situations. Patients were very satisfied when choosing bilateral synchronous surgery and would elect to repeat it the same way 97% of the time. The economic costs to the health system average 25% greater when patients undergoing first MTP joint surgery have the procedure performed one foot at a time. Combined with the time lost from work, this reveals a significant economic cost to both society and patient.

Extracorporeal shockwave therapy for interdigital neuroma: a randomized, placebo-controlled, double-blind trial.

BACKGROUND: We sought to evaluate the safety and effectiveness of extracorporeal shockwave therapy as a therapeutic treatment for destroying Morton's neuroma. METHODS: Twenty-five patients (25 feet) were included in the study. Indications for participation were more than 8 months of conservative care with a visual analog scale pain score of 4 or greater. The mean overall pain score on a modified visual analog scale was 6.9 preoperatively. RESULTS: Thirteen patients were randomized to the active group and 12 to the sham group. Two patients in the sham group were lost to follow-up. Post-treatment evaluations were performed at 1, 6, and 12 weeks by a blinded investigator (L.W.). The end point evaluation parameter was the reduction in visual analog scale score. The treatment group showed a significant difference before and after extracorporeal shockwave therapy (P < .0001). The sham group did not have a significant difference after 12 weeks (P = .1218). CONCLUSIONS: Extracorporeal shockwave therapy is a possible alternative to surgical excision for Morton's neuroma.

Revisional peripheral nerve surgery.

Peripheral nerve disorders are difficult to manage. In the surgical treatment of patients with peripheral nerve pathology, there are a multitude of factors that may alter the outcome of the patient's recovery and lead to incomplete recovery or possibly worsening of symptoms. The anatomy and function of the peripheral nerve is unique and the evaluation and management of these disorders must be approached in a manner different from musculoskeletal disorders. Many anatomic areas can tolerate scar tissue and adhesions, but in peripheral nerves, loss of the gliding functional and adherence to surrounding soft tissue structures is a common complication from over-zealous dissection and repeat peripheral nerve surgery without modification of technique. The approach to each patient must be thorough and individualized to treat their specific condition, and the surgeon must be aware that at times, the most appropriate treatment for the patient may not be medical but surgical management of the chronic pain condition.

Extracorporeal shockwave therapy for the treatment of Achilles tendinopathies: a prospective study.

BACKGROUND: Extracorporeal shockwave therapy has been shown to be effective in the treatment of chronic tendon pathology in the elbow, shoulder, and plantar fascia. This prospective study examines the efficacy of extracorporeal shockwave therapy in the treatment of chronic Achilles tendon disorders. METHODS: Twenty-three patients (23 feet) were treated with extracorporeal shockwave therapy for Achilles tendinosis, insertional tendonitis, or both. Indications for treatment were a minimum of 6 months of conservative care, and a visual analog pain score >5. The mean follow-up was 20 months (range, 4-35 months). RESULTS: Ninety-one percent (14 patients) were satisfied or very satisfied (23 patients) with treatment. Eighty-seven percent (20 patients) stated that extracorporeal shockwave therapy improved their condition, 13% (3 patients) said it did not affect the condition, and none stated that it made them worse. Eighty-seven percent (20 patients) stated they would have the procedure again if given the choice. Four months after extracorporeal shockwave therapy, the mean visual analog score for morning pain decreased from 7.0 to 2.3, and activity pain decreased from 8.1 to 3.1. CONCLUSION: High-power extracorporeal shockwave therapy is safe, noninvasive, and effective, and it has a role in the treatment of chronic Achilles tendinopathy.