Shane A. Shapiro

A Prospective, Single-Blind, Placebo-Controlled Trial of Bone Marrow Aspirate Concentrate for Knee Osteoarthritis

Background: Bone marrow aspirate concentrate (BMAC) is increasingly used as a regenerative therapy for musculoskeletal pathological conditions despite limited evidence-based support. Hypothesis: BMAC will prove feasible, safe, and efficacious for the treatment of pain due to mild to moderate degenerative joint disease of the knee. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: In this prospective, single-blind, placebo-controlled trial, 25 patients with bilateral knee pain from bilateral osteoarthritis were randomized to receive BMAC into one knee and saline placebo into the other. Fifty-two milliliters of bone marrow was aspirated from the iliac crests and concentrated in an automated centrifuge. The resulting BMAC was combined with platelet-poor plasma for an injection into the arthritic knee and was compared with a saline injection into the contralateral knee, thereby utilizing each patient as his or her own control. Safety outcomes, pain relief, and function as measured by Osteoarthritis Research Society International (OARSI) measures and the visual analog scale (VAS) score were tracked initially at 1 week, 3 months, and 6 months after the procedure. Results: There were no serious adverse events from the BMAC procedure. OARSI Intermittent and Constant Osteoarthritis Pain and VAS pain scores in both knees decreased significantly from baseline at 1 week, 3 months, and 6 months (P ≤ .019 for all). Pain relief, although dramatic, did not differ significantly between treated knees (P > .09 for all). Conclusion: Early results show that BMAC is safe to use and is a reliable and viable cellular product. Study patients experienced a similar relief of pain in both BMAC- and saline-treated arthritic knees. Further study is required to determine the mechanisms of action, duration of efficacy, optimal frequency of treatments, and regenerative potential. Registration: ClinicalTrials.gov record 12-004459.

Subtalar Distraction Arthrodesis through a Posterior Approach

Background: Subtalar arthrodesis is a common procedure for treating subtalar arthrosis. An isolated lateral incision can be used as an approach to subtalar fusion alone. However, it can be a difficult approach for correction of varus or valgus hindfoot deformities through the subtalar joint; especially if it involves distraction to correct calcaneal alignment. Less commonly, two-incision or single-incision medial approaches also have been described, but distraction and angular correction can still be difficult. We present an alternative method, using a posterior Achilles tendon-splitting procedure, that gives excellent subtalar exposure and the ability to obtain distraction with angular correction and bone grafting. Materials and Methods: Six consecutive patients underwent subtalar fusion with a posterior approach. Both varus and valgus deformities secondary to trauma, tendon insufficiency, or congenital deformities were corrected. Distraction was accomplished with laminar spreaders, and fixation was obtained with two 7.3-mm partially threaded cannulated screws. All patients were followed until fusion, and clinical and radiographic results were recorded. No other concomitant procedures were performed. Results: Fusion was observed radiographically in all patients by 3 months postoperatively. No serious wound complications occurred. Correction to slightly valgus alignment (for varus deformity) or neutral alignment (for valgus deformity) was obtained without collapse of autologous bone graft. Talocalcaneal height and all angular measurements were significantly increased (all p < 0.05). Conclusion: The posterior approach for distraction arthrodesis is an alternative to the standard lateral approach technique. It allows safe exposure with the ability to distract while also correcting varus or valgus deformity of the subtalar joint.

Prevalence of hyponatremia, renal dysfunction, and other electrolyte abnormalities among runners before and after completing a marathon or half marathon.

Background: Prior reports on metabolic derangements observed in distance running frequently have small sample sizes, lack prerace laboratory measures, and report sodium as the sole measure. Hypothesis: Metabolic abnormalities—hyponatremia, hypokalemia, renal dysfunction, hemoconcentration—are frequent after completing a full or half marathon. Clinically significant changes occur in these laboratory values after race completion. Study Design: Observational, cross-sectional study. Methods: Consenting marathon and half marathon racers completed a survey as well as finger stick blood sampling on race day of the National Marathon to Fight Breast Cancer (Jacksonville, Florida, February 2008). Parallel blood measures were obtained before and after race completion (prerace, n = 161; postrace, n = 195). Results: The prevalence of prerace and postrace hyponatremia was 8 of 161 (5.0%) and 16 of 195 (8.2%), respectively. Hypokalemia was not present prerace but was present in 1 runner postrace (1 of 195). Renal dysfunction occurred prerace in 14 of 161 (8.7%) and postrace in 83 of 195 (42.6%). Among those with postrace renal dysfunction, 45.8% (38 of 83) were classified as moderate or severe. Hemoconcentration was present in 2 of 161 (1.2%) prerace and 6 of 195 (3.1%) postrace. The mean changes in laboratory values were (postrace minus prerace): sodium, 1.6 mmol/L; potassium, −0.2 mmol/L; blood urea nitrogen, 2.8 mg/dL; creatinine, 0.2 mg/dL; and hemoglobin, 0.3 g/dL for 149 pairs (except blood urea nitrogen, n = 147 pairs). Changes were significant for all comparisons (P < 0.01) except potassium (P = 0.08) and hemoglobin (P = 0.01). Conclusions: Metabolic abnormalities are common among endurance racers, and they may be present prerace, including hyponatremia. The clinical significance of these findings is unknown. Clinical relevance: It is unclear which runners are at risk for developing clinically important metabolic derangements. Participating in prolonged endurance exercise appears to be safe in the majority of racers.

Validity of the Posterior Tibial Edema Sign in Posterior Tibial Tendon Dysfunction

Background: Posterior tibial tendon dysfunction (PTTD) is a common malady leading to acquired flatfoot, which frequently causes foot and ankle pain and swelling. We hypothesized that patients with PTTD and pitting edema along the course of the posterior tibial tendon (PTT) would have evidence of fluid within the tendon sheath on MRI. We introduce and validate a novel, yet simple physical examination finding, the posterior tibial edema (PTE) sign, to help distinguish PTTD from other causes of foot and ankle pain and swelling. Patients and Methods: To determine an association between the PTE sign and changes to the PTT evident on MRI, we reviewed the medical records of patients with PTTD who underwent magnetic resonance imaging (MRI). Results: Of 186 patients identified with PTTD, 49 underwent MRI, and 42 (86%) demonstrated imaging characteristics consistent with tendonitis, tendinosis, or tenosynovitis. Presence or absence of increased posterior malleolar pitting edema agreed with presence or absence of these MRI findings in 43 patients (88%), making the clinical examination finding significantly predictive of MRI results (p = 0.01). The sensitivity of the test for PTE was 86%, with specificity of 100%. Conclusion: The PTE sign refers to pitting edema along the course of the PTT, not associated with acute trauma and not accompanied by other areas of edema. Physical examination signs that are highly sensitive and specific to the condition may help lower the cost of diagnosis by eliminating the need for expensive tests that are not always necessary.

Radiographic correlation of hallux MP fusion position and plate angle.

Background: This study assessed the variability of plate bend in regard to final metatarsophalangeal (MP) fusion angles and toe-to-floor distance. We hypothesized that the final MP angle, the angle of the proximal phalanx to the floor, and the weightbearing toe-to-floor distance would be dictated solely by the magnitude of the bend in the plate. Materials and Methods: This is a retrospective analysis of 35 sequential patients who underwent MP fusion with a low-contour titanium plate. Postoperative weightbearing radiographs were analyzed for plate angle, MP fusion angle, the angle of the proximal phalanx to the floor, and the weightbearing toe-to-floor distance. Results: We found statistical correlation between plate angle and MP angle and between plate angle and the angle of the proximal phalanx to the floor. However, there was low correlation between plate angle and with toe-to-floor distance. In addition, we noted many outliers, which resulted in higher or lower correlation of the MP angle to the expected plate angle and, thus, a relationship between angles that was far from linear. Conclusion: Care needs to be taken when relying solely on the bend in the plate to determine the final position of the toe in MP fusions. Although the association between plate bend and MP angle and proximal phalanx to floor angle was strong, the association between the bend in the plate and weight bearing toe-to-floor distance was variable. This could result in the toe hitting the shoe or the need to vault over the toe. Therefore, the surgeon must match the plate to each patients anatomy to ensure proper weight bearing toe-to-floor distance and not rely on plate angle exclusively. Level of Evidence: IV, Retrospective Case Series

Bone marrow aspiration for regenerative orthopedic intervention: technique with ultrasound guidance for needle placement

AIM We review relevant anatomy of the iliac crest, and describe an interventional technique to maximize harvesting of desired progenitor cells with ultrasound to guide safe trochar placement. MATERIALS & METHODS We validated the technique on both sides of the pelvis in four human cadavers. RESULTS Using ultrasound guidance, 32 BMA needles were placed in a safe zone along various portions of the iliac crest. CONCLUSION Ultrasound guidance can improve accuracy of bone marrow aspirations form the iliac crest. Mastery of this procedure will facilitate cell harvest and aid in patient safety when procuring mesenchymal stem cells from a bone marrow source.

Sonographic Appearance of the Median Nerve Following Revision Carpal Tunnel Surgery

The main objective of this pictorial essay is to illustrate the sonographic appearance of the postoperative carpal tunnel and median nerve. Carpal tunnel surgical treatment failures have been shown to occur in up to 19% of a large series requiring re-exploration. Surgical management options for recurrent carpal tunnel syndrome (CTS) include revision release, neurolysis, vein wrapping, and fat grafting procedures. While several descriptions of median nerve entrapment in CTS exist in the ultrasound literature, little is written regarding its postoperative appearance. We report the sonographic changes in the appearance of the median nerve and postoperative carpal tunnel.

Regenerative Medicine in the State of Florida: Letter Outlining the Florida Organization for Regenerative Medicine

Advances in regenerative medicine are generating transformative solutions to many of today’s incurable medical conditions. These advances have resulted from interdisciplinary efforts across the biological sciences, medicine, and engineering, changes in the regulatory environment—including the passage of the 21st Century Cures Act—and ongoing efforts to drive industry standardization. Increasingly, these advances have been catalyzed by regional initiatives around the U.S. and the world aimed at expediting the discovery, translation, and commercialization of transformative treatments. The proliferation of new models like the Centre for Commercialization of Regenerative Medicine (CCRM) in Canada, the California Institute for Regenerative Medicine (CIRM), and the Advanced Regenerative Manufacturing Institute (ARMI) in New Hampshire, among others, has inspired the creation of the Florida Organization for Regenerative Medicine (FORM), a nonprofit organization with a mission to facilitate translational research, commercialization, education, and therapeutic validation in the area of regenerative medicine with the ultimate aim of improving patient outcomes, creating high-quality jobs, and accelerating innovation through collaboration in the State of Florida and beyond. FORM is comprised ofmultiple strong and complementary clinical and research groups within Florida, including (from North to South) theMayo Clinic’s Center for RegenerativeMedicine; the University of Florida’s Center for Regenerative Medicine, which operates across the university and is based in the College of Medicine (CoM), and Institute for Cell and Tissue Science and Engineering (ICTSE) in the College of Engineering (CoE); Nova Southeastern University’s Cell Therapy Institute (CTI); Florida Atlantic University’s Center for Molecular Biology and Biotechnology (CMBB); and the University of Miami’s Diabetes Research Institute (DRI), Cell Transplant Center (CTC), and Interdisciplinary Stem Cell Institute (ISCI). Furthermore, FORM aims to convene nonprofit organizations and for-profit companies integral to the state’s regenerative medicine industry, including 42Bio, LLC, Akron Biotechnology, LLC, AxoGen, Corp, BioFlorida, Inc., Brammer Bio, LLC, CytoSen Therapeutics, Inc., Iovance Biotherapeutics, Inc., Lifelink Foundation, Inc., Leidos Health (subsidiary of Leidos, Inc.), Longeveron, LLC, RTI Surgical, Inc., and Vestion, Inc., among others. FORMaims to leverage state, federal, and philanthropic funding to foster strong and integrative collaboration among academic, government and private sectors in order to accelerate activities necessary to establish the State of Florida as one of the hubs of this nascent and important industry. These activities include supporting translational research, facilitating the commercialization of therapeutics and engineered tissues, creating and driving workforce development initiatives, and validating novel treatments to support the safe and efficacious uptake of regenerativemedicine. The State of Florida is home to various institutions and companies active in the regenerative medicine space. Given the strength of its research and clinical institutions, the dynamism of its industrial base, and its size and demographics, the state can and should be a key driver in the emergence of this new paradigm in human health. FORM endeavors to convene the state’s leading institutions and companies to drive economic growth, accelerate innovation, and improve patient outcomes through the development and commercialization of regenerative therapies.

Micro-fragmented adipose tissue for treatment of knee osteoarthritis with Baker's cyst: A case study

Adipose-derived therapies have increased in popularity for treatment of painful orthopaedic conditions, such as osteoarthritis. We report the passage of fat into a Baker’s cyst after injection of micro-fragmented adipose tissue in a patient with bilateral knee arthritis. Following fat grafting, the patient required drainage of fatty fluid from within the Baker’s cyst on multiple occasions. Approximately 3 months postprocedure, she began to notice an improvement in her knee pain with no further recurrence of pain or swelling from her Baker’s cyst.

Snapping Pes Anserinus and the Diagnostic Utility of Dynamic Ultrasound

Snapping pes anserinus syndrome is an often encountered cause of medial knee snapping. It results from impingement and translation of the gracilis tendon or semitendinosus tendon over the osseous structures of the knee during active flexion and extension. Ultrasonography is often the diagnostic imaging test of choice in cases of mechanical snapping. We report 2 cases of painful snapping pes anserinus and highlight the value of dynamic ultrasound in making an accurate diagnosis so as to direct care.