Emily K. Schaeffer

Vertebral Fractures in Duchenne Muscular Dystrophy Patients Managed With Deflazacort

Background: Corticosteroids are widely used in the management of patients with Duchenne muscular dystrophy (DMD). They improve quality of life in these patients by prolonging ambulation and preserving cardiorespiratory status. However, corticosteroid treatment is associated with a decrease in bone mineral density (BMD) and an increased risk of vertebral fractures (VF). The purpose of this study was to investigate the prevalence of VF in patients with DMD undergoing long-term treatment with the corticosteroid deflazacort. Methods: We retrospectively reviewed 49 male patients with DMD on long-term deflazacort therapy at a single institution. All patients had received deflazacort for at least 2 years. VF prevalence, age at start of deflazacort treatment, duration of treatment, BMD Z-score and patient ambulatory status at the time of fracture were evaluated. Results: Of the 49 patients on long-term deflazacort treatment, 26 had VF. Out of these patients who had VF, 19% showed evidence of VF in their third year of therapy, 50% within 5 years of starting therapy, 69% within 7 years of starting therapy, and 100% within 9 years. The first evidence of VF was observed at mean BMD Z-score, lumbar (L)=−2.2 and whole body (B)=−3.1. Eighty-five percent of these patients had at least 3 collapsed vertebrae. Mean BMD Z-score at the time of or before when multiple fractures were noted was −2.4 (L) and −3.4 (B). Patients who started deflazacort at age 3 to 5, 5 to 7 or 7 to 9 years developed a VF after a mean of 4.7, 5.4, or 5.7 years, respectively. Sixty-two percent of patients had VF by the age of 12 years and 91% of patients by age of 15 years. Twenty-one of 26 patients were ambulatory at the time of VF. Conclusions: Our findings suggest that there is a high risk of VF associated with length of deflazacort use in DMD patients, regardless of age at start of therapy. Level of Evidence: Level III—retrospective therapeutic study.

What Risk Factors and Characteristics Are Associated With Late-presenting Dislocations of the Hip in Infants?

BackgroundMost infants with developmental dysplasia of the hip (DDH) are diagnosed within the first 3 months of life. However, late-presenting DDH (defined as a diagnosis after 3 months of age) does occur and often results in more complex treatment and increased long-term complications. Specific risk factors involved in late-presenting DDH are poorly understood, and clearly defining an associated set of factors will aid in screening, detection, and prevention of this condition.Questions/purposesUsing a multicenter database of patients with DDH, we sought to determine whether there were differences in (1) risk factors or (2) the nature of the dislocation (laterality and joint laxity) when comparing patients with early versus late presentation.MethodsA retrospective review of prospectively collected data from a multicenter database of patients with dislocated hips was conducted from 2010 to 2014. Baseline demographics for fetal presentation (cephalic/breech), birth presentation (vaginal/cesarean), birth weight, maternal age, maternal parity, gestational age, family history, and swaddling history of patients were compared among nine different sites for patients who were enrolled at age younger than 3 months and those enrolled between 3 and 18 months of age. A total of 392 patients were enrolled at baseline between 0 and 18 months of age with at least one dislocated hip. Of that group, 259 patients were younger than 3 months of age and 133 were 3 to 18 months of age. The proportion of patients with DDH who were enrolled and followed at the nine participating centers was 98%.ResultsA univariate/multivariate analysis was performed comparing key baseline demographics between early- and late-presenting patients. After controlling for relevant confounding variables, two variables were identified as risk factors for late-presenting DDH as compared with early-presenting: cephalic presentation at birth and swaddling history. Late-presenting patients were more likely to have had a cephalic presentation than early-presenting patients (88% [117 of 133] versus 65% [169 or 259]; odds ratio [OR], 5.366; 95% confidence interval [CI], 2.44–11.78; p < 0.001). Additionally, late-presenting patients were more likely to have had a history of swaddling (40% [53 of 133] versus 25% [64 of 259]; OR, 2.053; 95% CI, 1.22–3.45; p = 0.0016). No difference was seen for sex (p = 0.63), birth presentation (p = 0.088), birth weight (p = 0.90), maternal age (p = 0.39), maternal parity (p = 0.54), gestational age (p = 0.42), or family history (p = 0.11) between the two groups. Late presenters were more likely to present with an irreducible dislocation than early presenters (56% [82 of 147 hips] versus 19% [63 of 333 hips]; OR, 5.407; 95% CI, 3.532–8.275; p < 0.001) and were less likely to have a bilateral dislocation (11% [14 of 133] versus 28% [73 of 259]; OR, 0.300; 95% CI, 0.162–0.555; p = 0.002).ConclusionsThose presenting with DDH after 3 months of age have fewer of the traditional risk factors for DDH (such as breech birth), which may explain the reason for a missed diagnosis at a younger age. In addition, swaddling history was more common in late-presenting infants. A high index of suspicion for DDH should be maintained for all infants, not just those with traditional risk factors for DDH. Further investigation is required to determine if swaddling is a risk factor for the development of hip dislocations in older infants. More rigorous examination into traditional screening methods should also be performed to determine whether current screening is sufficient and whether late-presenting dislocations are present early and missed or whether they develop over time.Level of EvidenceLevel III, retrospective study.

A Daphnane Diterpenoid Isolated from Wikstroemia polyantha Induces an Inflammatory Response and Modulates miRNA Activity

MicroRNAs (miRNAs) are endogenously expressed single-stranded ∼21–23 nucleotide RNAs that inhibit gene expression post-transcriptionally by binding imperfectly to elements usually within the 3′untranslated region (3′UTR) of mRNAs. Small interfering RNAs (siRNAs) mediate site-specific cleavage by binding with perfect complementarity to RNA. Here, a cell-based miRNA reporter system was developed to screen for compounds from marine and plant extracts that inhibit miRNA or siRNA activity. The daphnane diterpenoid genkwanine M (GENK) isolated from the plant Wikstroemia polyantha induces an early inflammatory response and can moderately inhibit miR-122 activity in the liver Huh-7 cell line. GENK does not alter miR-122 levels nor does it directly inhibit siRNA activity in an in vitro cleavage assay. Finally, we demonstrate that GENK can inhibit HCV infection in Huh-7 cells. In summary, the development of the cell-based miRNA sensor system should prove useful in identifying compounds that affect miRNA/siRNA activity.

Prevention of hip displacement in children with cerebral palsy: a systematic review

To conduct a systematic review and evaluate the quality of evidence for interventions to prevent hip displacement in children with cerebral palsy (CP).

Closed Reduction for Developmental Dysplasia of the Hip: Early-term Results From a Prospective, Multicenter Cohort

BACKGROUND Closed reduction (CR) is a common treatment for infantile developmental dysplasia of the hip. The purpose of this observational, prospective, multicenter study was to determine the early outcomes following CR. METHODS Prospectively collected data from an international multicenter study group was analyzed for patients treated from 2010 to 2014. Baseline demographics, clinical exam, radiographic/ultrasonographic data, and history of previous orthotic treatment were assessed. At minimum 1-year follow-up, failure was defined as an IHDI grade 3 or 4 hip and/or need for open reduction. The incidence of avascular necrosis (AVN), residual dysplasia, and need for further surgery was assessed. RESULTS A total of 78 patients undergoing CR for 87 hips were evaluated with a median age at initial reduction of 8 months (range, 1 to 20 mo). Of these, 8 hips (9%) were unable to be closed reduced initially. At most recent follow-up (median 22 mo; range, 12 to 36 mo), 72/79 initially successful CRs (91%) remained stable. The likelihood of failure was unaffected by initial clinical reducibility of the hip (P=0.434), age at initial CR (P=0.897), or previous treatment in brace (P=0.222). Excluding those hips that failed initial CR, 18/72 hips (25%) developed AVN, and the risk of osteonecrosis was unaffected by prereduction reducibility of the hip (P=0.586), age at CR (P=0.745), presence of an ossific nucleus (P=0.496), or previous treatment in brace (P=0.662). Mean acetabular index on most recent radiographs was 25 degrees (±6 degrees), and was also unaffected by any of the above variables. During the follow-up period, 8/72 successfully closed reduced hips (11%) underwent acetabular and/or femoral osteotomy for residual dysplasia. CONCLUSIONS Following an initially successful CR, 9% of hips failed reduction and 25% developed radiographic AVN at early-term follow-up. History of femoral head reducibility, previous orthotic bracing, and age at CR did not correlate with success or chances of developing AVN. Further follow-up of this prospective, multicenter cohort will be necessary to establish definitive success and complication rates following CR for infantile developmental dysplasia of the hip. LEVEL OF EVIDENCE Level II-prospective observational cohort.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/.Background: Closed reduction (CR) is a common treatment for infantile developmental dysplasia of the hip. The purpose of this observational, prospective, multicenter study was to determine the early outcomes following CR. Methods: Prospectively collected data from an international multicenter study group was analyzed for patients treated from 2010 to 2014. Baseline demographics, clinical exam, radiographic/ultrasonographic data, and history of previous orthotic treatment were assessed. At minimum 1-year follow-up, failure was defined as an IHDI grade 3 or 4 hip and/or need for open reduction. The incidence of avascular necrosis (AVN), residual dysplasia, and need for further surgery was assessed. Results: A total of 78 patients undergoing CR for 87 hips were evaluated with a median age at initial reduction of 8 months (range, 1 to 20 mo). Of these, 8 hips (9%) were unable to be closed reduced initially. At most recent follow-up (median 22 mo; range, 12 to 36 mo), 72/79 initially successful CRs (91%) remained stable. The likelihood of failure was unaffected by initial clinical reducibility of the hip (P=0.434), age at initial CR (P=0.897), or previous treatment in brace (P=0.222). Excluding those hips that failed initial CR, 18/72 hips (25%) developed AVN, and the risk of osteonecrosis was unaffected by prereduction reducibility of the hip (P=0.586), age at CR (P=0.745), presence of an ossific nucleus (P=0.496), or previous treatment in brace (P=0.662). Mean acetabular index on most recent radiographs was 25 degrees (±6 degrees), and was also unaffected by any of the above variables. During the follow-up period, 8/72 successfully closed reduced hips (11%) underwent acetabular and/or femoral osteotomy for residual dysplasia. Conclusions: Following an initially successful CR, 9% of hips failed reduction and 25% developed radiographic AVN at early-term follow-up. History of femoral head reducibility, previous orthotic bracing, and age at CR did not correlate with success or chances of developing AVN. Further follow-up of this prospective, multicenter cohort will be necessary to establish definitive success and complication rates following CR for infantile developmental dysplasia of the hip. Level of Evidence: Level II—prospective observational cohort.

Developmental dysplasia of the hip: addressing evidence gaps with a multicentre prospective international study

There is a lack of high quality evidence available to guide clinical practice in the treatment and management of developmental dysplasia of the hip (DDH). Evidence has been limited by persistent confusion on diagnostic and classification terminology, variability in surgeon decision making and a reliance on single centre, retrospective studies with small patient numbers. To address gaps in knowledge regarding screening, diagnosis and management of DDH, the International Hip Dysplasia Institute began a multicentre, international prospective study on infants with hips dislocated at rest. This review discusses the current state of screening, diagnostic and management practices in DDH and addresses important unanswered questions that will be critical in identifying best practices and optimising patient outcomes. There is insufficient evidence to support universal ultrasound screening; instead, selective screening should be performed by 6-8 weeks of age on infants with risk factors of breech presentation, family history, or history of clinical hip instability. Follow-up of infants with risk factors and normal initial screening should be considered to at least 6 months of age. Brace treatment is a sensible first-line treatment for management of dislocated hips at rest in infants < 6 months of age. Early operative reduction may be considered as there is insufficient evidence to support a protective role for the ossific nucleus in the development of avascular necrosis.

Acetabuloplasty in Closed Triradiate Cartilage

Hip displacement is a common pathology in neuromuscular conditions, and progressive displacement or dislocation is associated with acetabular dysplasia, pain and decreased function and may lead to the need for hip salvage surgery. The Dega-type pelvic osteotomy is commonly used to correct acetabular dysplasia and maximize coverage of the femoral head in patients with open triradiate cartilages. In older patients, where the triradiate cartilage has closed, more complex peri-acetabular osteotomies are typically indicated. However, the Dega osteotomy can be a simple and effective technique to restore hip stability in patients with neuromuscular conditions, even after closure of the triradiate cartilage. While there are limited reports on the use of this technique in this manner, there are reports that suggest it can be effective in both ambulatory and non-ambulatory patients. In this particular case, the Dega osteotomy in combination with varus derotational osteotomy restored ambulation in a patient with closed triradiate cartilages who had stopped ambulating due to pain from hip displacement.

Evaluating the role of prereduction hip traction in the management of infants and children with developmental dysplasia of the hip (DDH): protocol for a systematic review and planned meta-analysis

Introduction Developmental dysplasia of the hip (DDH) affects 4–6 per 1000 live births in developed countries. Effective treatment to realign the hip is necessary to avoid long-term morbidities and maximise functional outcome. Treatment options depend on patient age but typically involve hip bracing and/or reduction under general anaesthetic. Some centres also employ prereduction hip traction. Historical papers suggest traction reduces risk of avascular necrosis (AVN) femoral head and reduces requirement for open reduction. However, several studies including a large retrospective cohort study, dispute this. We propose to perform the first systematic review and meta-analysis to clarify the value of prereduction hip traction in the management of DDH in children under the age of 3 years by identifying whether it impacts on the rate of successful closed reduction (CR) and risk of AVN. Methods and analysis We will search MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials to identify potentially relevant studies. Studies reporting on incidence of successful CR, AVN femoral head and complications associated with prereduction hip traction in children of less than 3 years with DDH will be eligible for inclusion. Only randomised controlled trials, prospective and retrospective case–control and comparative cohort studies will be included in quantitative review. There will be no study design restrictions for inclusion in qualitative review. Following study selection, full-text paper retrieval, data extraction and synthesis, studies will be assessed for risk of bias and heterogeneity. If the included studies are sufficiently homogeneous, then we will perform meta-analysis. A narrative synthesis of the systematic review’s results will also be presented. Ethics and dissemination Formal ethical approval is not required as primary patient data will not be collected. The systematic review’s results will be disseminated through a peer-reviewed publication. Trial registration number CRD42017064254; Pre-results.

Nonoperative Treatment of Type IIA Supracondylar Humerus Fractures: Comparing 2 Modalities.

Background: Although the recommended treatment for Gartland types I and III supracondylar humeral fractures is well-established, the optimal treatment for type II fractures without rotational malalignment remains controversial, involving circumferential casting or closed reduction and pinning. Our institution uses pronated flexion-taping for Gartland type IIA fractures. This theoretically removes external pressure secondary to circumferential casting, potentially decreasing risks of compartment syndrome and mitigating loss of reduction with extension while maintaining optimal flexion position for reduction. To our knowledge, these modalities have not yet been compared. Methods: A retrospective chart review was performed to compare flexion-taping with cuff-and-collar immobilization versus traditional above-elbow casting at 90 to 100 degrees. It was hypothesized that closed reduction and flexion-taping of type IIA supracondylar fractures under sedation in the emergency department would result in comparable, if not superior, maintenance of reduction measured radiographically using Baumann angle and the lateral humeral capitellar angle (LHCA). Charts from 2010 to 2015 were reviewed for all patients between 2 and 8 years of age with type IIA fractures treated with cast or taping. Results: A total of 39 patients were included with 16 in the cast group and 23 in the tape group. Mean age was 4.08±1.72 years across both groups. No significant change in either measure was seen at termination of immobilization (3 to 4 wk postreduction). Final lateral humeral capitellar angle in the taping group was 32.14±5.90 degrees compared with 28.23±7.27 degrees in the casting group (P=0.81). Final Baumann angle was 73.41±4.03 degrees in the taping group compared with 73.75±6.46 degrees (P=0.96). The only complication was a self-limiting rash experienced by 1 patient in the taping group. Conclusions: Both techniques were able to achieve and maintain adequate reduction in all cases with no significant difference in outcome measures. There were no major complications or conversions to surgical treatment. In this cohort, taping resulted in adequate reduction and safe immobilization for type IIA fractures comparable to cast immobilization. Further research will investigate clinical/radiographic outcomes on these patients to assess remodeling and function. Level of Evidence: Level III—retrospective comparative study.

What Is the Impact of Center Variability in a Multicenter International Prospective Observational Study on Developmental Dysplasia of the Hip

BackgroundLittle information exists concerning the variability of presentation and differences in treatment methods for developmental dysplasia of the hip (DDH) in children < 18 months. The inherent advantages of prospective multicenter studies are well documented, but data from different centers may differ in terms of important variables such as patient demographics, diagnoses, and treatment or management decisions. The purpose of this study was to determine whether there is a difference in baseline data among the nine centers in five countries affiliated with the International Hip Dysplasia Institute to establish the need to consider the center as a key variable in multicenter studies.Questions/purposes(1) How do patient demographics differ across participating centers at presentation? (2) How do patient diagnoses (severity and laterality) differ across centers? (3) How do initial treatment approaches differ across participating centers?MethodsA multicenter prospective hip dysplasia study database was analyzed from 2010 to April 2015. Patients younger than 6 months of age at diagnosis were included if at least one hip was completely dislocated, whereas patients between 6 and 18 months of age at diagnosis were included with any form of DDH. Participating centers (academic, urban, tertiary care hospitals) span five countries across three continents. Baseline data (patient demographics, diagnosis, swaddling history, baseline International Hip Dysplasia Institute classification, and initial treatment) were compared among all nine centers. A total of 496 patients were enrolled with site enrolment ranging from 10 to 117. The proportion of eligible patients who were enrolled and followed at the nine participating centers was 98%. Patient enrollment rates were similar across all sites, and data collection/completeness for relevant variables at initial presentation was comparable.ResultsIn total, 83% of all patients were female (410 of 496), and the median age at presentation was 2.2 months (range, 0–18 months). Breech presentation occurred more often in younger (< 6 months) than in older (6–18 months at diagnosis) patients (30% [96 of 318] versus 9% [15 of 161]; odds ratio [OR], 4.2; 95% confidence interval [CI], 2.3–7.5; p < 0.001). The Australia site was underrepresented in breech presentation in comparison to the other centers (8% [five of 66] versus 23% [111 of 479]; OR, 0.3, 95% CI, 0.1–0.7; p = 0.034). The largest diagnostic category was < 6 months, dislocated reducible (51% [253 of 496 patients]); however, the Australia and Boston sites had more irreducible dislocations compared with the other sites (ORs, 2.1 and 1.9; 95% CIs, 1.2–3.6 and 1.1–3.4; p = 0.02 and 0.015, respectively). Bilaterality was seen less often in older compared with younger patients (8% [seven of 93] versus 26% [85 of 328]; p < 0.001). The most common diagnostic group was Grade 3 (by International Hip Dysplasia Institute classification), which included 58% (51 of 88) of all classified dislocated hips. Splintage was the primary initial treatment of choice at 80% (395 of 496), but was far more likely in younger compared with older patients (94% [309 of 328] versus 18% [17 of 93]; p < 0.001).ConclusionsWith the lack of strong prognostic indicators for DDH identified to date, the center is an important variable to include as a potential predictor of treatment success or failure.