Lysosomal dysfunction in diabetic cardiomyopathy.

Diabetes is a major risk factor for a variety of cardiovascular complications, while diabetic cardiomyopathy, a disease specific to the myocardium independent of vascular lesions, is an important causative factor for increased risk of heart failure and mortality in diabetic populations. Lysosomes have long been recognized as intracellular trash bags and recycling facilities. However, recent studies have revealed that lysosomes are sophisticated signaling hubs that play remarkably diverse roles in adapting cell metabolism to an ever-changing environment. Despite advances in our understanding of the physiological roles of lysosomes, the events leading to lysosomal dysfunction and how they relate to the overall pathophysiology of the diabetic heart remain unclear and are under intense investigation. In this review, we summarize recent advances regarding lysosomal injury and its roles in diabetic cardiomyopathy.

Ligament Insufficiency with Flatfoot: Spring Ligament and Deltoid Ligament.

The objective of this article was to review the deltoid ligament and spring ligament specifically as they pertain to ligament insufficiency and adult-acquired flatfoot deformity. Discussion includes the normal and abnormal biomechanical forces that extend through these ligaments in normal and flatfoot deformity. Current literature related to spring ligament repair as part of the flatfoot deformity reconstruction is also reviewed.

Metformin Inhibits Autophagy, Mitophagy and Antagonizes Doxorubicin-Induced Cardiomyocyte Death.

The antidiabetic drug metformin has been shown to reduce cardiac injury under various pathological conditions, including anticancer drug doxorubicin (DOX)-induced cardiotoxicity, which makes metformin a prime candidate for repurposing. However, the mechanisms that mediate the cardioprotective effects of metformin remain highly controversial. In this study, we tested a prevailing hypothesis that metformin activates autophagy/mitophagy to reduce DOX cardiotoxicity. FVB/N mice and H9C2 cardiac myoblasts were treated with metformin, respectively. Autophagy/mitophagy was determined by Western blot analysis of microtubule-associated protein light chain 3, form-II (LC3-II), a well-established marker of autophagic vesicles. Although metformin had minimal effects on basal LC3-II levels, it significantly inhibited the accumulation of LC3-II levels by the lysosomal protease inhibitors pepstatin A and E64d in both total cell lysates and mitochondrial fractions. Also, dual fluorescent autophagy/mitophagy reporters demonstrated that metformin slowed the degradation rate of autophagic cargos or mitochondrial fragments in the lysosomes. These surprising results suggest that metformin inhibits rather than stimulates autophagy/mitophagy, sharply contrasting the popular belief. In addition, metformin diminished DOX-induced autophagy/mitophagy as well as cardiomyocyte death. Together, these results suggest that the cardioprotective effects of metformin against DOX cardiotoxicity may be mediated by its ability to inhibit autophagy and mitophagy, although the underlying molecular mechanisms remain to be determined.

Evaluation of the Relationship Between Aspects of Medical Complexity and Work Relative Value Units (wRVUs) for Foot and Ankle Surgical Procedures.

Work relative value units (wRVUs) have been assigned to current procedural terminology codes in an effort to help establish physician compensation. However, the ability of these to accurately and efficiently capture the time, technical, and perioperative managerial aspects required of various procedures has recently been called into question for several surgical subspecialties. Therefore, the objective of this investigation was to evaluate various measures of medical complexity against wRVUs for foot and ankle surgical procedures. The 2018 American College of Surgeons National Surgical Quality Improvement Program database was utilized to identify and extract data related to the perioperative medical complexity of 16 foot and ankle surgical current procedural terminology codes. We observed a "weak" positive relationship between wRVUs and operation time as defined by a correlation coefficient of 0.234 (p < .001). Other variables associated with medical complexity in the perioperative period were found to significantly vary between wRVUs categories, but these differences were neither consistently nor directly associated with assigned relative values. We conclude that wRVUs might not always represent an efficient means for determining compensation for foot and ankle surgical procedures.

Soft Tissue Reconstruction with Diabetic Foot Tissue Loss.

Although substantial advances have been made in treatment of diabetic foot disease with respect to patient education, preventative measures, early intervention, and prophylactic procedures, most surgical interventions for this condition are reactionary. Patients still primarily present to emergency departments with acute infections and tissue necrosis. The surgical intervention for this results in soft tissue deficit, often with partial foot amputation, through excisional debridement of pathologic tissue. Minimizing this initial soft tissue loss, with subsequent reconstruction of the defect, forms the focus of this article with a detailed anatomic assessment of structures at risk in the forefoot, midfoot and rearfoot.

Early Weightbearing After Arthrodesis of the First Metatarsal-Medial Cuneiform Joint: A Systematic Review of the Incidence of Nonunion.

Arthrodesis of the first metatarsal-medial cuneiform articulation is a reliable and effective surgery for correction of hallux abducto valgus deformity. However, one potential relative contraindication to the procedure is the extended period of non-weightbearing immobilization that is typically associated with the postoperative course. The objective of this investigation was to perform a systematic review of the incidence of nonunion after early weightbearing in patients who underwent arthrodesis of the first metatarsal-medial cuneiform articulation for correction of a hallux abducto valgus deformity. We performed a review of electronic databases with the inclusion criteria of retrospective case series, retrospective clinical cohort analyses, and prospective clinical trials with 15 or more participants; a mean follow-up period ≥12 months; a postoperative early weightbearing protocol (defined as ≤2 weeks); a clear description of the fixation construct; and a reported incidence rate of nonunion. Eight studies met our inclusion criteria, with a total of 443 arthrodeses analyzed. Of these, 16 (3.61%) were described as developing a nonunion. This would likely be considered an acceptable rate of nonunion when considering this procedure and might indicate that the Lapidus procedure does not always require an extended period of postoperative non-weightbearing immobilization.

Early Weight-Bearing After Arthrodesis of the First Metatarsal-Phalangeal Joint: A Systematic Review of the Incidence of Non-Union.

Arthrodesis of the first metatarsal-phalangeal joint is a reliable procedure for correction of both hallux limitus/rigidus and severe hallux abducto valgus deformities. However, 1 potential contraindication to the procedure is the extended period of non-weight-bearing immobilization that is typically associated with the postoperative course. The objective of this investigation was to perform a systematic review of the incidence of non-union after early weight bearing in patients who underwent arthrodesis of the first metatarsal-phalangeal joint. We performed a review of electronic databases with the inclusion criteria of retrospective case series, retrospective clinical cohort analyses, and prospective clinical trials with n ≥ 15 feet, a mean follow-up of ≥12 months, a defined postoperative early weight-bearing protocol (defined as ≤2 weeks), a clear description of the fixation construct, a reported incidence rate of non-union, and patients who underwent primary surgery for hallux abducto valgus or hallux limitus/rigidus deformities. Seventeen studies met our inclusion criteria, with a total of 898 feet analyzed. Of these, 57 (6.35%) were described as developing a non-union. This would likely be considered an acceptable crude, heterogeneous incidence of non-union when considering this procedure. It might also indicate that arthrodesis of the first metatarsal-phalangeal joint does not always require an extended period of non-weight-bearing postoperative immobilization.

Effect of Obesity on Total Ankle Arthroplasty: A Systematic Review of Postoperative Complications Requiring Surgical Revision.

Total ankle arthroplasty has become an increasingly used alternative to ankle arthrodesis for the treatment of end-stage ankle arthritis. However, despite progressive technological advances and the advent of multiple commercial implant systems, some concern remains for the relatively high complication and failure rates. The objective of the present investigation was to perform a systematic review of the incidence of complications in obese patients undergoing total ankle arthroplasty. We performed a review of electronic databases with the inclusion criteria of retrospective case series, retrospective clinical cohort analyses, and prospective clinical trials with ≥15 total participants, a mean follow-up period of ≥12 months, ≥1 defined cohort with a body mass index of ≥30 kg/m2, and a reported incidence rate of complications requiring revisional surgery at the final follow-up point. Four studies met our inclusion criteria, with a total of 400 implants analyzed. Of these, ≥71 (17.8%) developed a complication requiring a revisional surgical procedure. The most commonly reported surgeries were revision of the metallic components and ankle gutter debridement. It is our hope that our investigation will allow foot and ankle surgeons to more effectively communicate the perioperative risk to their patients during the education and consent process.

Demographic description of the presentation and treatment of lower extremity skin and soft tissue infections secondary to skin popping in intravenous drug abusers.

Skin popping refers to the act of subcutaneous injection of intravenous drugs, a practice that often results in the development of cellulitis and the formation of soft tissue abscesses. Although the foot and ankle represent common injection sites, few data have described the presentation and natural history of this pathologic entity. The objective of the present study was to retrospectively assess the descriptive demographic data of a patient cohort admitted for lower extremity skin and soft tissue infection caused by intravenous drug abuse. Fifty skin popping lesions in 49 patients were identified during a 733-day data collection period (August 1, 2010 to August 31, 2012) that had been treated by the in-patient podiatric surgical service for lower extremity infection caused by intravenous drug abuse at an urban, level-one trauma center. With respect to patient race, our hospital has a typical in-patient census of 55% black patients and 25% white patients. The present patient cohort consisted of 12% black patients and 65% white patients. The mean length of stay was 5.71 ± 3.56 days, and 42 patients (85.71%) underwent some form of surgical debridement, with 31 (63.27%) having undergone a formal procedure in the operating room. Six patients (12.24%) left the hospital against medical advice or refused intervention at some definitive point of care, and 36 (73.47%) did not return for scheduled outpatient follow-up visits. Three cases (6%) resulted in minor amputation. The microbiologic culture data and common antibiotic prescriptions used in the diagnosis and treatment, respectively, of these patients have been summarized. We hope these original descriptive data can be used by other physicians treating patients at similar urban practices to improve the care of these sometimes difficult-to-treat patients and better serve this population as a whole.

Can foot and ankle surgeons accurately estimate patient body mass index?

The body mass index (BMI) is an objective patient finding that has been established to have a negative effect on the development and outcomes of podiatric pathologic entities and interventions. The objective of the present investigation was to assess the ability of podiatric physicians to estimate the patient BMI from clinical and radiographic observation. For the clinical estimation of the patient BMI, podiatric specialists across 3 levels of experience (i.e., students, residents, and practicing clinicians) performed 294 estimations on 72 patients in 3 clinical situations (standing, sitting in a treatment chair, and lying in a hospital bed). It was more common to inaccurately estimate the patient BMI (77.9%) than it was to correctly estimate it (22.1%), with underestimations being the most common error (48.3%). The estimations were particularly inaccurate when the patients were in the common clinical situation of sitting in a treatment chair or lying in a hospital bed and with patients actually classified as obese. For the radiographic estimation of patient BMI, 150 consecutive lateral ankle radiographs were analyzed, with the ratio of the overlying soft tissue diameter to the underlying bone diameter calculated and compared. Positive, but weak, relationships were observed with these ratios. From these data, we have concluded that podiatric practitioners should perform an actual calculation of the patient BMI during the patient examination and medical decision-making process to fully appreciate the potential risks inherent to the treatment of obese patients.