Mode of Anesthesia and Bladder Management Following Orthopaedic Surgery in Children With Cerebral Palsy: A System Level Analysis.

Background: Postoperative urinary retention (POUR) is a surgical complication more prevalent in children with neurodisability and associated with an increase length of hospitalization. Risk factors include pre-existing bladder dysfunction, type and duration of surgery, anesthesia medications, postoperative opioid pain management, and patient demographics. The purpose of this investigation was (1) to determine the frequency of POUR following hip/lower limb orthopaedic procedures in which epidural analgesia was used for pain management; (2) to explore factors influencing postoperative bladder management.

Development of Contractures in DMD in Relation to MRI-Determined Muscle Quality and Ambulatory Function.

Background: Joint contractures are common in boys and men with Duchenne muscular dystrophy (DMD), and management of contractures is an important part of care. The optimal methods to prevent and treat contractures are controversial, and the natural history of contracture development is understudied in glucocorticoid treated individuals at joints beyond the ankle.

Objective: To describe the development of contractures over time in a large cohort of individuals with DMD in relation to ambulatory ability, functional performance, and muscle quality measured using magnetic resonance imaging (MRI) and spectroscopy (MRS).

A new murine model of Barth syndrome neutropenia links TAFAZZIN deficiency to increased ER stress-induced apoptosis.

Barth syndrome is an inherited X-linked disorder that leads to cardiomyopathy, skeletal myopathy, and neutropenia. These symptoms result from the loss of function of the enzyme TAFAZZIN, a transacylase located in the inner mitochondrial membrane that is responsible for the final steps of cardiolipin production. The link between defective cardiolipin maturation and neutropenia remains unclear.

A Longitudinal Study of Quantitative Muscle Strength and Functional Motor Ability in Ambulatory Boys with Duchenne Muscular Dystrophy.

Background: Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic disorder, that is characterized by progressive muscle degeneration and loss of ambulation between 7-13 years of age. Novel pharmacological agents targeting the genetic defects and disease mechanisms are becoming available; however, corticosteroid (CS) therapy remains the standard of care.

Objective: The purpose of this longitudinal study was to elucidate the effect of CS therapy on the rate of muscle strength and gross motor skill decline in boys with DMD and assess the sensitivity of selected outcome measures.

Fascia Iliaca Pain Block Results in Lower Overall Opioid Usage and Shorter Hospital Stays than Epidural Anesthesia After Hip Reconstruction in Children With Cerebral Palsy.

Introduction And Objective: Epidural anesthesia (EA) is often used for pain control in children with cerebral palsy (CP) who undergo hip reconstructions. The purpose of this study is to determine if preoperative fascia iliaca (FI) pain blocks would improve pain scores, decrease opioid use, and result in shorter hospital stays in comparison to the use of EA.

Methods: This is a nonrandomized retrospective cohort study examining 60 consecutive patients with CP who underwent hip reconstruction utilizing either a fascia iliac compartment nerve block (FICNB) (N=37) or continuous lumbar epidural (N=22) from January 2017 to March 2019.

Molecular alterations due to Col5a1 haploinsufficiency in a mouse model of classic Ehlers-Danlos syndrome.

Type V collagen is a regulatory fibrillar collagen essential for type I collagen fibril nucleation and organization and its deficiency leads to structurally abnormal extracellular matrix (ECM). Haploinsufficiency of the Col5a1 gene encoding α(1) chain of type V collagen is the primary cause of classic Ehlers-Danlos syndrome (EDS). The mechanisms by which this initial insult leads to the spectrum of clinical presentation are not fully understood.

Outcomes of MCGR at > 3 year average follow-up in severe scoliosis: who undergoes elective revision vs UPROR?

Purpose: The purpose of this study was to evaluate mid-term outcomes of magnetically controlled growing rods (MCGR), evaluate factors associated with unplanned return to the operating room (UPROR) vs achieving full length. Full length was defined as achieving > 85% of the elongating portion of the rod.

Methods: IRB approved retrospective single site study.

Genetic basis for an evolutionary shift from ancestral preaxial to postaxial limb polarity in non-urodele vertebrates.

In most tetrapod vertebrates, limb skeletal progenitors condense with postaxial dominance. Posterior elements (such as ulna and fibula) appear prior to their anterior counterparts (radius and tibia), followed by digit-appearance order with continuing postaxial polarity. The only exceptions are urodele amphibians (salamanders), whose limb elements develop with preaxial polarity and who are also notable for their unique ability to regenerate complete limbs as adults.

Longitudinal changes in energy cost during walking in boys with Duchenne Muscular Dystrophy (DMD).

Background: In boys with DMD, muscle weakness progresses in a proximal to distal pattern, leading to compensatory gait strategies, including hyperlordosis and equinus, that increase energy cost and accelerate the loss of walking capacity.

Research Question: The purpose of this study was to determine the changes in the energy cost of walking that occur with disease progression and to determine the optimal normalization scheme for the longitudinal assessment of the energy cost of walking in boys with DMD.

Methods: Energy cost was assessed with the COSMED K4b.

Pharmacokinetics and Exposure-Response of Vosoritide in Children with Achondroplasia.

Background And Objective: Vosoritide, an analog of C-type natriuretic peptide, has been developed for the treatment of children with achondroplasia. The pharmacokinetics of vosoritide and relationships between plasma exposure and efficacy, biomarkers, and safety endpoints were evaluated in a phase II, open-label, dose-escalation study (N = 35 patients aged 5-14 years who received daily subcutaneous injections for 24 months) and a phase III, double-blind, placebo-controlled study (N = 60 patients aged 5-18 years randomized to receive daily subcutaneous injections for 52 weeks).

Methods: Pharmacokinetic parameters for both studies were obtained from non-compartmental analysis.

Corrigendum to "Exploring translational gaps between basic scientists, clinical researchers, clinicians, and consumers: Proceedings and recommendations arising from the 2020 mine the gap online workshop" [Osteoarthritis Cartilage Open 29 (2021) 100163].

[This corrects the article DOI: 10.1016/j.ocarto.

Baseline patient reported outcome measurement information system (PROMIS) scores in children with idiopathic scoliosis and their relation to the SRS-22.

Purpose: PROMIS is becoming the most commonly utilized patient-reported outcome measure (PROM) in adult orthopaedics, but its adoption has lagged in pediatrics. Limited baseline data exists in pediatric-specific orthopaedic diagnoses. The objective of this study was to determine baseline PROMIS scores in patients with idiopathic scoliosis and to evaluate for correlations with the SRS-22.

Localized chondro-ossification underlies joint dysfunction and motor deficits in the mouse model of osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a genetic disorder that features wide-ranging defects in both skeletal and nonskeletal tissues. Previously, we and others reported that loss-of-function mutations in FK506 Binding Protein 10 () lead to skeletal deformities in conjunction with joint contractures. However, the pathogenic mechanisms underlying joint dysfunction in OI are poorly understood.

Unexpected contribution of fibroblasts to muscle lineage as a mechanism for limb muscle patterning.

Positional information driving limb muscle patterning is contained in connective tissue fibroblasts but not in myogenic cells. Limb muscles originate from somites, while connective tissues originate from lateral plate mesoderm. With cell and genetic lineage tracing we challenge this model and identify an unexpected contribution of lateral plate-derived fibroblasts to the myogenic lineage, preferentially at the myotendinous junction.

Identification of Missense Extracellular Matrix Gene Variants in a Large Glaucoma Pedigree and Investigation of the N700S Thrombospondin-1 Variant in Normal and Glaucomatous Trabecular Meshwork Cells.

Purpose: Primary open-angle glaucoma (POAG) is a complex heterogeneous disease. While several POAG genes have been identified, a high proportion of estimated heritability remains unexplained. Elevated intraocular pressure (IOP) is a leading POAG risk factor and dysfunctional extracellular matrix (ECM) in the trabecular meshwork (TM) contributes to elevated IOP.

A Randomized, Double-Blind, Placebo-Controlled, Global Phase 3 Study of Edasalonexent in Pediatric Patients with Duchenne Muscular Dystrophy: Results of the PolarisDMD Trial.

Background: Edasalonexent (CAT-1004) is an orally-administered novel small molecule drug designed to inhibit NF-κB and potentially reduce inflammation and fibrosis to improve muscle function and thereby slow disease progression and muscle decline in Duchenne muscular dystrophy (DMD).

Objective: This international, randomized 2 : 1, placebo-controlled, phase 3 study in patients ≥4 - < 8 years old with DMD due to any dystrophin mutation examined the effect of edasalonexent (100 mg/kg/day) compared to placebo over 52 weeks.

Methods: Endpoints were changes in the North Star Ambulatory Assessment (NSAA; primary) and timed function tests (TFTs; secondary).

HOXA13 in etiology and oncogenic potential of Barrett's esophagus.

Barrett's esophagus in gastrointestinal reflux patients constitutes a columnar epithelium with distal characteristics, prone to progress to esophageal adenocarcinoma. HOX genes are known mediators of position-dependent morphology. Here we show HOX collinearity in the adult gut while Barrett's esophagus shows high HOXA13 expression in stem cells and their progeny.

Tendon and motor phenotypes in the mouse model of recessive osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is characterized by short stature, skeletal deformities, low bone mass, and motor deficits. A subset of OI patients also present with joint hypermobility; however, the role of tendon dysfunction in OI pathogenesis is largely unknown. Using the mouse model of severe, recessive OI, we found that mutant Achilles and patellar tendons were thinner and weaker with increased collagen cross-links and reduced collagen fibril size at 1- and 4-months compared to wildtype.

Reticulocalbin 3 is involved in postnatal tendon development by regulating collagen fibrillogenesis and cellular maturation.

Tendon plays a critical role in the joint movement by transmitting force from muscle to bone. This transmission of force is facilitated by its specialized structure, which consists of highly aligned extracellular matrix consisting predominantly of type I collagen. Tenocytes, fibroblast-like tendon cells residing between the parallel collagen fibers, regulate this specialized tendon matrix.

Alterations of a serum marker of collagen X in growing children with osteogenesis imperfecta.

Abnormalities in the structure and/or processing of type I collagen cause osteogenesis imperfecta and result in bone fragility, abnormal bone growth and short stature. Type I collagen is expressed in the growth plate but the mechanisms by which abnormalities in collagen I contribute to growth plate dysfunction and growth retardation are unknown. The non-collagenous domain (NC1) of type X collagen (CXM) is released from the hypertrophic zone of active growth plates and is a marker for new endochondral bone formation.

Exploring translational gaps between basic scientists, clinical researchers, clinicians, and consumers: Proceedings and recommendations arising from the 2020 mine the gap online workshop.

Objective: To provide a summary of the translational gaps in musculoskeletal research as identified in the Mine the Gap workshop and propose possible solutions.

Methods: The Mine the Gap online workshop was hosted on October 14th and 15th, 2020. Five international panels, each comprised of a clinician, clinical researcher and basic scientist, presented gaps and proposed solutions for the themes of biomechanics, pain, biological measurements, phenotypes and imaging.