MIJ821 (onfasprodil) in healthy volunteers: First-in-human, randomized, placebo-controlled study (single ascending dose and repeated intravenous dose).

This single-center study administered MIJ821 (onfasprodil) as an intravenous infusion to healthy volunteers and included two parts: a single ascending dose study (Part 1) and a repeated intravenous dose study (Part 2). Primary objective was to evaluate the safety and tolerability of single ascending intravenous doses infused over a 40-min period and of two repeated doses (1 week apart) of MIJ821 in healthy volunteers. Secondary objectives were to assess the pharmacokinetics of MIJ821 after intravenous infusion in Part 1 and Part 2 of the study. Overall, 43 subjects in Part 1 and 12 subjects in Part 2 were randomized in the study. Median age in Part 1 and Part 2 was 45.0 and 43.5 years, respectively, with the majority being Caucasian (Part 1: 84%; Part 2: 92%). 19 subjects (44.2%) in Part 1 and 8 subjects (66.7%) in Part 2 experienced at least one adverse event (AE). Following single dose in Part 1 and Part 2, the AUCinf values of MIJ821 increased in a dose-proportional manner across the dose range 0.016-0.48 mg/kg and the Cmax values in a slight overproportional manner across the dose range 0.048-0.48 mg/kg. At the highest dose of 0.48 mg/kg, the geometric mean AUCinf was 708 h ng/mL and the geometric mean Cmax was 462 ng/mL. Inspection of 1-h post-dose resting electroencephalography activity across cohorts showed a relationship to administered dose, providing exploratory evidence of distal target engagement. In conclusion, MIJ821 showed a good safety and tolerability profile in healthy volunteers. Dissociative AEs were mild, transient, and dose-dependent.

Treatment of Insertional Achilles Tendinosis With Polyurethane Urea-Based Matrix Augmentation.

INTRODUCTION: Surgical treatment for insertional Achilles tendinosis (IAT) sometimes requires tendon repair augmentation. The purpose of this study is to evaluate the efficacy of polycaprolactone-based polyurethane urea (PUUR) matrix augmentation in the treatment of IAT. METHODS: A retrospective review was performed in surgically treated IAT. Repairs were augmented with a PUUR matrix. Factors evaluated included date of full weightbearing, patient satisfaction, Visual Analog Scale (VAS) pain score, strength, and ankle motion. The Wilcoxon signed-rank test was used to compare baseline and final follow-up VAS scores. RESULTS: A total of 18 cases were included in the study. The mean patient age was 54.61 ± 8.25 (40-75) years with a mean follow-up of 163.61 ± 57.81 (92-314) days. Patient satisfaction was obtained on 15 of 18 patients, with 14 patients satisfied with their outcome. Mean VAS for pain significantly decreased from 6.19 ± 1.97 (2.5-9) to 0.83 ± 1.54 (0-5) postoperatively, which was statistically significant (P < .01). CONCLUSION: Achilles tendon augmentation with the PUUR matrix is a viable option in the treatment of IAT. Its use in this condition has minimal morbidity and can be an alternative to other forms of augmentation. LEVELS OF EVIDENCE: Level IV: Retrospective case series.

Thumb volar plate reconstruction utilizing extensor pollicis brevis autograft: evaluation of a new technique.

BACKGROUND: Sagittal plane instability of the thumb metacarpophalangeal joint is a difficult problem with numerous surgical techniques described. The purpose of the study is to demonstrate a technique in which a distally based extensor pollicis brevis tendon autograft is utilized to reconstruct the deficient volar plate. METHODS: This is a retrospective case series of four patients who were followed a minimum of 2 years after this procedure. Patient demographics, return to work status, and objective outcomes are reported. RESULTS: This technique compared favorably to those previously described, in terms of technical ease, functional results, and patient satisfaction. Each patient returned to his previous activity level and was maintained on active duty in his current military occupational specialty. None required a permanent profile to limit the physical demands of his job. CONCLUSIONS: Preliminary data suggests this technique is anatomically sound, technically less demanding, and requires minimal surgical dissection compared to previously described procedures.

Acute complications associated with removal of flexible intramedullary femoral rods placed for pediatric femoral shaft fractures.

BACKGROUND: The American Academy of Orthopaedic Surgeons position statement on the treatment of pediatric femoral shaft fractures could not comment on the safety of flexible intramedullary (IM) rod removal because of a lack of published evidence. This study reviews the acute complications of flexible IM rod removal from pediatric patients treated for femoral shaft fractures. METHODS: A retrospective clinical and radiographic analysis at a single institution over a 5-year period. Demographic and radiographic parameters were analyzed to determine their influence on intraoperative and immediate postoperative complications. RESULTS: One hundred sixty-three subjects (133 males, 30 females), mean age of 9.3±2.8 years (range, 2.7 to 14.8 y) and mean weight of 34.4±15.3 kg (range, 14.0 to 139.0 kg), underwent femoral flexible IM rod removal a mean 12.4±10.8 months (range, 2.4 to 63.8 mo) after placement with mean operative time of 51.1±22.3 minutes (range, 10 to 131 min). One hundred fifty-one subjects (92.6%) had stainless-steel Ender rods and the remaining nails were titanium. There were no significant demographic, intraoperative, or radiographic differences comparing subjects with Ender versus titanium rods. Indications for rod removal were pain at insertion site, family request, or surgeon's recommendation. There were 4 (2.5%) minor intraoperative difficulties, including the inability to remove 1 of 2 rods secondary to IM migration (n=1) and complete bone overgrowth at insertion site resulting in prolonged extraction time (n=3). Three of the 4 subjects had the rods placed >60 months before removal. Immediately postoperative (n=134), there were 4 (3.0%) complications, including superficial wound infection (n=3, 2.2%) and knee contracture (n=1, 0.8%). Subjects were released to full activities at a mean 4.7±1.8 weeks postoperatively with no known postoperative fractures. CONCLUSIONS: The rate of intraoperative and immediate postoperative complications is low. Neither patient demographics, fracture characteristics, nor operative technique influenced the complication rate. Intraoperative difficulties may be minimized with removal of rods before signs of overgrowth. LEVELS OF EVIDENCE: Level IV, intervention case series.

Novel technique for passing tendon grafts through bone tunnels.

Anatomic reconstruction in orthopedic surgery often requires the passage of soft tissue through bone tunnels. Difficulties may arise due to anatomic constraints surrounding the bone tunnels or the graft size. The authors present a novel technique for passing tendon grafts through bone tunnels that is simple, readily available, effective, and comparatively inexpensive.

Common bacterial dermatoses: protecting competitive athletes.

Athletes competing in a wide variety of sports are at risk of contracting and spreading bacterial skin infections. Bacteria proliferate in environments of wet, macerated skin that is repeatedly abraded against competing athletes, equipment, clothing, or objects in the field of play. Common infections include impetigo, folliculitis, furunculosis, pitted keratolysis, and otitis externa. Diagnosis and treatment are often straightforward and vary little from care for nonathletes. However, knowledge of preventive strategies and return-to-play criteria, as outlined by the National Collegiate Athletic Association, are paramount for clinicians who care for competitive athletes.

Thrombocytopenia in pregnancy.

BACKGROUND: Thrombocytopenia, defined as a platelet count of less than 150,000/microL, has been more commonly diagnosed in pregnant women in the last 20 years because platelet counts are included with the automated blood cell counters. Evaluation and treatment of this condition can be expensive and invasive and can result in an adverse outcome. METHODS: MEDLINE was searched from 1980 to present using the key words. "thrombocytopenia," "pregnancy," and "platelet." Case reports were excluded from literature review. RESULTS AND CONCLUSIONS: Thrombocytopenia is the second most common hematologic abnormality during pregnancy and is usually a benign condition. Some patients, however, will have chronic medical disorders or pregnancy-induced conditions that require further evaluation and therapy. Even with its wide differential diagnosis, the cause of thrombocytopenia during pregnancy can usually be determined with a thorough history, physical examination, and directed laboratory studies. The challenge to the clinician is to weigh the risks of maternal and fetal bleeding complications against the benefits of diagnostic tests and interventions.