Larson, A. Noelle

Purpose Tarsal coalitions are congenital fusions of two or more tarsal bones and can lead to foot pain and stiffness. Few studies examine the long-term reoperation rates following paediatric tarsal coalition surgery. Methods A population-based database, linking medical records at all medical centres to capture the entire medical history of the full population of a Midwest county, was used to identify tarsal coalitions in children between 1966 and 2018. Records were reviewed for clinical data, surgical records and followed up to identify any subsequent surgical interventions. Results A total of 58 patients (85 coalitions) were identified; 46 calcaneonavicular (CN) coalitions, 30 talocalcaneal (TC) coalitions and nine other coalitions (seven talonavicular, one naviculocuboid, one naviculocuneiform). In all, 46 coalitions were treated surgically (43 coalition resections, three arthrodeses) and 39 were treated nonoperatively. Patients treated surgically were less likely to report ongoing symptoms at final follow-up compared with patients managed nonoperatively (33% versus 67%; p = 0.0017). With a median 14.4 years (interquartile range 9.3 to 19.7) follow-up, there was an overall re-operation rate of 8.7% (4/46). Differences in reoperation rates by initial surgery (resection versus arthrodesis; p = 0.2936), coalition type (CN versus TC versus Other; p = 0.6487) or composition (osseous versus fibrocartilaginous; p = 0.29) did not reach statistical significance. Conclusion This is the first population-based study demonstrating the durability of surgical management of tarsal coalitions in a paediatric population. At final follow-up, patients treated surgically are less likely to report persistent symptoms compared with patients managed nonoperatively. Long-term reoperation rates appear to be low (8.7%). Level of evidence III

Background: Tarsal coalitions are an important reason for foot pain in children. Early estimates placed the prevalence at up to 2%, while more recent data suggest that it is as high as 11% to 13%. To our knowledge, there have been no population-based studies to determine the true incidence of symptomatic tarsal coalitions in a pediatric population. Methods: A population-based database was used to identify all new diagnoses of symptomatic tarsal coalitions in children 18 years old or younger between 1966 and 2018. Patient records were reviewed for clinical data, and comparisons were made between the types and characteristics of the coalitions identified to determine differences in the affected populations. The annual age-specific, sex-specific, and type-specific incidence rates were estimated. Results: During the study period, 58 patients with a total of 79 symptomatic tarsal coalitions were identified (annual incidence = 3.5 per 100,000 children). There were 43 calcaneonavicular (CN) coalitions (annual incidence = 1.9 per 100,000 children), 27 talocalcaneal (TC) coalitions (annual incidence = 1.2 per 100,000 children), as well as 9 other coalitions (7 talonavicular, 1 naviculocuboid, and 1 naviculocuneiform) (annual incidence = 0.4 per 100,000 children). The overall incidence peaked between the ages of 10 and 14 years for both boys and girls (8.1 per 100,000 and 7.4 per 100,000 children, respectively). Statistical differences were identified between the types of tarsal coalitions. TC coalitions present at an older age relative to CN and other coalitions (mean,13.9, 12.7, and 11.4 years, respectively; p = 0.02). While CN and TC coalitions were similar in composition (23% and 30%, respectively, were osseous as opposed to fibrocartilaginous), other coalitions were more likely to be osseous (78%) (p = 0.0035). Other coalitions were also less likely to require surgery than CN and TC coalitions (11%, 74%, and 56%, respectively; p = 0.0015). Conclusions: This population-based study demonstrates differences in the clinical presentation of tarsal coalitions and provides an estimate of the true incidence of symptomatic tarsal coalitions in a pediatric population.

Skeletal development is controlled by epigenetic mechanisms that regulate chromatin compaction and suppress access to gene regulatory sequences. Post‐translational modifications in the N‐termini of histone 3 (H3), including tri‐methylated H3 lysine 9 (H3K9Me3) or lysine 27 (H3K27Me3) represent repressive chromatin marks that are recognized by a family of heterochromatin‐associated Chromobox (Cbx) proteins (i.e., Cbx1 to Cbx8). We show using RNA‐seq analysis that each of these Cbx isoforms is actively expressed in bone and osteoblasts with variable expression of distinct members (between 1 and 100 reads per million). The most prominently expressed Cbx member is Cbx3, which encodes a member of the heterochromatin protein 1 (HP1) family that interacts with H3K9me3. Cbx3 is known to be important for normal development while promoting neurogenesis, as well as renal and smooth muscle development. Therefore, we postulated that CBx3 may perform a similar role in osteoblastogenesis. We tested this hypothesis by both transient and stable knock‐down of Cbx3 by respectively siRNA or shRNA. RNA interference in MC3T3 osteoblasts effectively decreases Cbx3 mRNA levels by 2 to 5 fold, while increasing expression of bone‐related markers by RT‐qPCR (e.g., Alpl/alkaline phosphatase, Ibsp/bone sialoprotein, Bglap/osteocalcin, and Col1a1/Collagen Type I α1 chain). In addition, Cbx3 depletion increases mineral deposition as measured by Alizarin Red staining. Thus, Cbx3 normally appears to suppress osteoblastic differentiation, unlike its essential function in the neuronal differentiation. Because Cbx3 recognizes H3K9me3, we examined whether Cbx3 controls the levels of this histone mark. Loss of Cbx3 did not affect total H3K9me3 levels unless Cbx1 and Cbx5 were simultaneously depleted by siRNA. We propose that Cbx3 may suppress osteoblastogenesis by controlling select loci with H3K9me3 marks.

Background: Annual rankings by US News and World Report are a widely utilized metric by both health care leaders and patients. One longstanding measure is time to treatment of femur shaft fractures. Hospitals able to provide at least 80% of pediatric patients with an operating room start time within 18 hours of admission to the emergency department score better as part of the overall pediatric orthopaedic ranking. Therefore, it is important to determine whether the 18-hour treatment time for pediatric femur shaft fractures is a clinically meaningful metric. Methods: A retrospective review of clinical outcomes of 174 pediatric patients (aged below 16 y) with isolated femur shaft fractures (Injury Severity Score=9) was conducted from 1997 to 2017 at a single level I pediatric trauma center. The 2 comparison groups were patients receiving fracture reduction within 18 hours of emergency department admission (N=87) or >18 hours (N=87). Results: Patient, injury, and surgical characteristics were similar between the 2 groups. Both groups had a similar mean age (treatment <18 h=7.5 y; treatment >18 h=8.1 y). Patients who received treatment within 18 hours were more often immobilized postoperatively (70.1% vs. 53.5%; P=0.0362) and had a shorter median hospital length of stay (2 vs. 3 d; P=0.0047). There were no statistically significant differences in any outcomes including surgical site infection, time to weight-bearing (treatment <18 h mean=48.1 d vs. 52.5 d), time to complete radiographic fracture healing (treatment <18 h mean=258.9 d vs. 232.0 d), decreased range of motion, genu varus/valgus, limb length discrepancy, loss of reduction, or persistent pain. Conclusions: Treatment of pediatric femur shaft fractures within 18 hours does not impact clinical outcomes. National quality measures should therefore use evidence-based metrics to help improve the standard of care. Level of Evidence: Therapeutic level III.

Objective. Osteochondral allograft (OCA) transplantation has demonstrated good long-term outcomes in treatment of cartilage defects. Viability, a key factor in clinical success, decreases with peri-implantation storage at 4°C during pathogen testing, matching logistics, and transportation. Modern, physiologic storage conditions may improve viability and enhance outcomes. Design. Osteochondral specimens from total knee arthroplasty patients (6 males, 5 females, age 56.4 ± 2.2 years) were stored in media and incubated at normoxia (21% O 2 ) at 22°C or 37°C, and hypoxia (2% O 2 ) at 37°C. Histology, live-dead staining, and quantitative polymerase chain reaction (qPCR) was performed 24 hours after harvest and following 7 days of incubation. Tissue architecture, cell viability, and gene expression were analyzed. Results. No significant viability or gene expression deterioration of cartilage was observed 1-week postincubation at 37°C, with or without hypoxia. Baseline viable cell density (VCD) was 94.0% ± 2.7% at day 1. At day 7, VCD was 95.1% (37°C) with normoxic storage and 92.2% (37°C) with hypoxic storage ( P ≥ 0.27). Day 7 VCD (22°C) incubation was significantly lower than both the baseline and 37°C storage values (65.6%; P < 0.01). COL1A1, COL1A2, and ACAN qPCR expression was unchanged from baseline ( P < 0.05) for all storage conditions at day 7, while CD163 expression, indicative of inflammatory macrophages and monocytes, was significantly lower in the 37°C groups ( P < 0.01). Conclusion. Physiologic storage at 37°C demonstrates improved chondrocyte viability and metabolism, and maintained collagen expression compared with storage at 22°C. These novel findings guide development of a method to optimize short-term fresh OCA storage, which may lead to improved clinical results.

Background: The purpose of the present study was to identify trends in management and to compare the outcomes and complications following nonoperative and operative management (including external fixation, closed reduction and percutaneous pinning, and open reduction and internal fixation) for distal radial fractures in patients ≥65 years of age. Methods: We performed a retrospective analysis, with use of the OptumLabs Data Warehouse database, of patients ≥65 years of age who had been managed for a distal radial fracture between 2009 and 2014 (as indicated by diagnosis codes according to the International Classification of Diseases, Ninth Revision, Clinical Modification). Ninety-day and 1-year complication rates per 1,000 fractures were analyzed overall and by treatment modality. Results: Thirteen thousand, seven hundred and thirteen distal radial fractures were analyzed. The overall 90-day complication rate was 36.5 per 1,000 fractures, and the 1-year upper-extremity-specific complication rate was 236.2 and 307.5 per 1,000 fractures for nonoperative and operative management, respectively. Overall, post-injury stiffness was the most common 1-year upper-extremity-specific complication (incidence, 11.5%). There was no significant difference between operative and nonoperative management in terms of 90-day complication rates. However, operative management had a higher 1-year complication rate than nonoperative management (307.5 versus 236.2 per 1,000 fractures). Overall, the 5 most common upper-extremity-specific complications following operative treatment of distal radial fracture were stiffness (16.0%), chronic regional pain syndrome (9.9%), median neuropathy (8.0%), implant-related complications (3.8%), and tendon-related complications (2.8%). Stiffness was significantly more frequent following operative management (16.0% versus 9.8%; p < 0.01). Conclusions: Operative management of a distal radial fracture should be carefully considered when discussing treatment options with patients ≥65 years of age. Level of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

OBJECTIVEThe authors sought to assess whether Hounsfield units (HU) increase following teriparatide treatment and to compare HU increases with changes in bone mineral density (BMD) as measured by dual-energy x-ray absorptiometry (DEXA).METHODSA retrospective chart review was performed from 1997 to 2018 across all campuses at our institution. The authors identified patients who had been treated with at least 6 months of teriparatide and compared HU and BMD as measured on DEXA scans before and after treatment.RESULTSFifty-two patients were identified for analysis (46 women and 6 men, average age 67 years) who underwent an average of 20.9 ± 6.5 months of teriparatide therapy. The mean ± standard deviation HU increase throughout the lumbar spine (L1–4) was from 109.8 ± 53 to 133.9 ± 61 HU (+22%, 95% CI 1.2–46, p value = 0.039). Based on DEXA results, lumbar spine BMD increased from 0.85 to 0.93 g/cm2 (+9%, p value = 0.044). Lumbar spine T-scores improved from −2.4 ± 1.5 to −1.7 ± 1.5 (p value = 0.03). Average femoral neck T-scores improved from −2.5 ± 1.1 to −2.3 ± 1.0 (p value = 0.31).CONCLUSIONSTeriparatide treatment increased both HU and BMD on DEXA in the lumbar spine, without a change in femoral BMD. The 22% improvement in HU surpassed the 9% improvement determined with DEXA. These results support some surgeons’ subjective sense that intraoperative bone quality following teriparatide treatment is better than indicated by DEXA results. To the authors’ knowledge, this is the first study demonstrating an increase in HU with teriparatide treatment.

Objective This study aims to (1) determine and validate living cartilage allograft transplantation as a novel source for viable osteochondral allograft (OCA) tissues and (2) perform histologic and viability comparisons of living donor cartilage tissues to currently available clinical-grade standard processed grafts. Design Using healthy cartilage from well-preserved contralateral compartments in 27 patients undergoing total knee arthroplasty (TKA) and 10 clinical-grade OCA specimens obtained immediately following operative implantation, standard and living donor OCA quality was evaluated at the time of harvest and following up to 3 weeks of storage on the basis of macroscopic International Cartilage Repair Society grade, histology, and viability. Results Osteochondral samples demonstrated a consistent decrease in viability and histologic quality over the first 3 weeks of storage at 37°C, supporting the utility of an OCA paradigm shift toward early implantation, as was the clinical standard up until recent adoption of transplantation at 14 to 35 days following donor procurement. Samples from the 10 clinical-grade OCAs, implanted at an average of 23 days following graft harvest demonstrated a mean viable cell density of 45.6% at implantation, significantly lower ( P < 0.01) than the 93.6% viability observed in living donor allograft tissues. Conclusions Osteochondral tissue viability and histologic quality progressively decreases with ex vivo storage, even when kept at physiologic temperatures. Currently available clinical OCAs are stored for 2 to 5 weeks prior to implantation and demonstrate inferior viability to that of fresh osteochondral tissues that can be made available through the use of a living donor cartilage program.