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Biomechanical and clinical studies have shown that the hip joint capsule plays an important role in maintaining stability and hip mechanics, including rotation and translation. The recent literature has shown that capsule closure after hip arthroscopy helps to restore stability. Without restoration of the native anatomy, the hip joint may translate when patients engage in activities that place force across the hip, leading to either microinstability or frank dislocation. The purpose of this note is to describe our preferred technique of capsular closure or plication during hip arthroscopy.

Genu varus malalignment can lead to medial compartment overload and progression of ipsilateral compartment osteoarthritis. To slow this process, a medial opening wedge proximal tibial osteotomy (PTO) can be performed. This type of PTO is indicated in patients with genu varus malalignment and isolated medial compartment osteoarthritis of the knee, prior to or concurrent with medial compartment cartilage procedures or meniscal transplants, chronic posterolateral corner deficiency, or chronic anterior cruciate ligament deficiency. When treating ligamentous instability, a PTO can be performed in isolation, with simultaneous ligament reconstruction, or as a staged procedure with the osteotomy first, followed by ligament reconstruction if instability persists. Failure to address malalignment in cases of concurrent ligament reconstruction leads to increased stress on the graft and potential graft failure. One distinct advantage of this procedure is the ability to correct deformities in the sagittal and coronal planes. The purpose of this article was to describe our technique used to perform a medial opening wedge PTO.

Background: Avulsion fractures of the anterior tibial spine in young athletes are injuries similar to anterior cruciate ligament (ACL) injuries in adults. Sparse data exist on the association between anterior tibial spine fractures (ATSFs) and later ligamentous laxity or injuries leading to ACL reconstruction., Purpose: To better delineate the incidence of delayed instability or ACL ruptures requiring delayed ACL reconstruction in young patients with prior fractures of the tibial eminence., Study Design: Case series; Level of evidence, 4., Methods: We identified 101 patients between January 1993 and January 2012 who sustained an ATSF and who met inclusion criteria for this study. All patients had been followed for at least 2 years after the initial injury and were included for analysis after completion of a questionnaire via direct contact, mail, and/or telephone. If patients underwent further surgical intervention and/or underwent later ACL reconstruction, clinical records and operative reports pertaining to these secondary interventions were obtained and reviewed. Differences between categorical variables were assessed using the Fisher exact test. The association between time to revision ACL surgery and fracture type was assessed by Kaplan-Meier plots. The association between need for revision ACL surgery and age, sex, and mechanism of surgery was assessed using logistic regression., Results: Nineteen percent of all patients evaluated underwent delayed ACL reconstruction after a previous tibial spine fracture on the ipsilateral side. While there were a higher proportion of ACL reconstructions in type II fractures, there was not a statistically significant difference in the number of patients within each fracture group who went on to undergo later surgery (P = .29). Further, there was not a significant association between fracture type, sex, or mechanism of injury as it related to the progression to later ACL reconstruction. However, there was a significant association between age at the time of injury and progression to later ACL reconstruction (P = .02). For every year increase in age at the time of injury, the odds of going on to undergo delayed ACL reconstruction were greater by a factor of 1.3 (95% CI, 1.1-1.6)., Conclusion: Although an ATSF is a relatively rare injury, our cohort of patients suggests that a subset of young patients with all types of tibial spine fractures will require later ACL reconstruction. There is a need to counsel patients that a delayed ACL rupture is a potential risk after an ATSF, especially as children approach skeletal maturity. Further patient follow-up and prospective studies are required., (© 2016 The Author(s).)

Valgus knee alignment in excess of physiological valgus leads to excessive loading of the lateral compartment, which can potentially increase the risk of osteoarthritis and can place the medial knee structures at risk of chronic attenuation. Varus-producing distal femoral osteotomies have been proposed for correction of valgus malalignment, to relieve tension on medial-sided structures, as well as to off-load the lateral compartment. Understanding that symptomatic valgus deformity of the knee represents a complex problem that is magnified in the setting of lateral compartment arthritis or medial ligamentous incompetence, we present our preferred technique for a varus-producing distal femoral osteotomy using plate osteosynthesis and cancellous bone allograft.

Meniscal ramp lesions are more frequently associated with anterior cruciate ligament (ACL) injuries than previously recognized. Some authors suggest that this entity results from disruption of the meniscotibial ligaments of the posterior horn of the medial meniscus, whereas others support the idea that it is created by a tear of the peripheral attachment of the posterior horn of the medial meniscus. Magnetic resonance imaging (MRI) scans have been reported to have a low sensitivity, and consequently, ramp lesions often go undiagnosed. Therefore, to rule out a ramp lesion, an arthroscopic evaluation with probing of the posterior horn of the medial meniscus should be performed. Several treatment options have been reported, including nonsurgical management, inside-out meniscal repair, or all-inside meniscal repair. In cases of isolated ramp lesions, a standard meniscal repair rehabilitation protocol should be followed. However, when a concomitant ACL reconstruction (ACLR) is performed, the rehabilitation should follow the designated ACLR postoperative protocol. The purpose of this article was to review the current literature regarding meniscal ramp lesions and summarize the pertinent anatomy, biomechanics, diagnostic strategies, recommended treatment options, and postoperative protocol.

There has been growing interest in recent years on the functional importance of the ligamentum teres and its role in hip stability. Partial or complete tearing has previously been treated with debridement or radiofrequency ablation with good results; however, a subset of patients will continue to experience persistent pain or instability with injury to this structure. Advances in arthroscopic instruments and techniques have led to our ability to provide improved care for these patients by performing a ligamentum teres reconstruction. The purpose of this technical note is to describe our method of ligamentum teres reconstruction with a tibialis anterior allograft.

The menisci are important structures within the knee and play a critical role in maintaining proper stability, load distribution, and joint lubrication. Injury to these structures can significantly alter the complex biomechanics of the knee and thus affect the health and longevity of the joint. Meniscal root tears are increasingly recognized as an important pathologic condition that results in a nonfunctional meniscus if not properly repaired. Whereas early treatment of meniscal tears traditionally focused on removal of the injured tissue, recent attention on the long-term consequences of partial or total meniscectomy has led to increased attempts at meniscal repair whenever possible. This article details our anatomic anterior root repair procedure using a transtibial double-tunnel pullout technique.

The dynamic function of the acetabular labrum makes it an important structure for both hip stability and motion. Because of this, injuries to the labrum can cause significant dysfunction, leading to altered hip kinematics. Labral repair is the gold standard for symptomatic labral tears to keep as much labral tissue as possible; however, in cases where the labrum has been injured to such a degree that it is either deficient or repair is not possible, arthroscopic labral reconstruction is preferred. This article describes our preferred approach for reconstruction of the acetabular labrum using iliotibial band autograft.

Violation of the posterior femoral cortex, commonly referred to as posterior wall blowout, can be a devastating intraoperative complication in anterior cruciate ligament (ACL) reconstruction and lead to loss of graft fixation or early graft failure. If cortical blowout occurs despite careful planning and adherence to proper surgical technique, a thorough knowledge of the anatomy and alternative fixation techniques is imperative to ensure optimal patient outcomes. This article highlights anatomic considerations for femoral tunnel placement in ACL reconstruction and techniques for avoidance and salvage of a posterior wall blowout.

Posterolateral corner injuries represent a complex injury pattern, with damage to important coronal and rotatory stabilizers of the knee. These lesions commonly occur in association with other ligament injuries, making decisions regarding treatment challenging. Grade III posterolateral corner injuries result in significant instability and have poor outcomes when treated nonoperatively. As a result, reconstruction is advocated. A thorough knowledge of the anatomy is essential for surgical treatment of this pathology. The following technical note provides a diagnostic approach, postoperative management, and details of a technique for anatomic reconstruction of the 3 main static stabilizers of the posterolateral corner of the knee.

Background: Lateral compartment osteoarthritis of the knee can be a challenging pathology in the younger, active population due to limited treatment options and high patient expectations. Distal femoral osteotomy (DFO) has been reported to be a potential treatment option., Purpose: To perform a systematic review on the survival, outcomes, and complications of DFO for treatment of genu valgum with concomitant lateral compartment osteoarthritis of the knee., Study Design: Systematic review; Level of evidence, 4., Methods: A systematic review of the literature was performed using the Cochrane Database of Systematic Reviews, the Cochrane Central Registry of Controlled Trials, PubMed, and MEDLINE from 1980 to present. Inclusion criteria were as follows: outcomes of opening- and closing-wedge DFOs performed for treatment of genu valgum with concomitant lateral compartment osteoarthritis of the knee, English language, minimum 2-year follow-up, and human studies. Data abstracted from the selected studies included type of osteotomy (opening vs closing), survival rate, patient-reported and radiographic outcomes, and complications., Results: Fourteen studies met the inclusion criteria and were considered for the review. A total of 9 closing-wedge and 5 opening-wedge DFO studies were included. All were retrospective studies and reported good to excellent patient-reported outcomes after DFO. Survival decreased with increasing time from surgery, with 1 study reporting a 100% survival rate at 6.5 years, compared with 21.5% at 20 years in another study. A low rate of complications was reported throughout the review., Conclusion: Highly heterogeneous literature exists for both opening- and closing-wedge DFOs for the treatment of isolated lateral compartment osteoarthritis with valgus malalignment. A mean survival rate of 80% at 10-year follow-up was reported, supporting that this procedure can be a viable treatment option to delay or reduce the need for joint arthroplasty. A low complication rate was observed, with symptomatic hardware being the most prevalent postoperative complication.

Posterior wall blowout can be a devastating intraoperative complication in anterior cruciate ligament reconstruction. This loss of osseous containment can cause difficulty with graft fixation and can potentially lead to early graft failure if unrecognized and left untreated. If cortical blowout occurs despite careful planning and proper surgical technique, a thorough knowledge of the local anatomy and surgical salvage options is paramount to ensure positive patient outcomes. This article highlights our preferred salvage technique using suspensory cortical fixation with a screw and washer construct.

Post-traumatic or postsurgical flexion contractures of the knee can significantly limit function and lead to gait abnormalities. In this setting, interventions to regain full extension may include bracing, physical therapy, and open or arthroscopic surgery. Open surgical approaches to restore full motion often demand extensive recovery and promote further adhesions and loss of motion, which has led to the advent of arthroscopic techniques to address these pathologies. We present a safe, effective, and reproducible arthroscopic technique for posteromedial capsular release to address knee flexion contractures.

Restoration of anteroposterior laxity after an anterior cruciate ligament reconstruction has been predictable with traditional open and endoscopic techniques. However, anterolateral rotational stability has been difficult to achieve in a subset of patients, even with appropriate anatomic techniques. Therefore, differing techniques have attempted to address this rotational laxity by augmenting or reconstructing lateral-sided structures about the knee. In recent years, there has been a renewed interest in the anterolateral ligament as a potential contributor to residual anterolateral rotatory instability in anterior cruciate ligament-deficient patients. Numerous anatomic and biomechanical studies have been performed to further define the functional importance of the anterolateral ligament, highlighting the need for surgical techniques to address these injuries in the unstable knee. This article details our technique for an anatomic anterolateral ligament reconstruction using a semitendinosus tendon allograft.

The identification of mosaicism is important in establishing a disease diagnosis, assessing recurrence risk, and genetic counseling. Next-generation sequencing (NGS) with deep sequence coverage enhances sensitivity and allows for accurate quantification of the level of mosaicism. NGS identifies low-level mosaicism that would be undetectable by conventional Sanger sequencing. A customized DNA probe library was used for capturing targeted genes, followed by deep NGS analysis. The mean coverage depth per base was approximately 800×. The NGS sequence data were analyzed for single-nucleotide variants and copy number variations. Mosaic mutations in 10 cases/families were detected and confirmed by NGS analysis. Mosaicism was identified for autosomal dominant (JAG1, COL3A1), autosomal recessive (PYGM), and X-linked (PHKA2, PDHA1, OTC, and SLC6A8) disorders. The mosaicism was identified either in one or more tissues from the probands or in a parent of an affected child. When analyzing data from patients with unusual testing results or inheritance patterns, it is important to further evaluate the possibility of mosaicism. Deep NGS analysis not only provides insights into the spectrum of mosaic mutations but also underlines the importance of the detection of mosaicism as an integral part of clinical molecular diagnosis and genetic counseling., (Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)

RNA interference (RNAi) methods for insects are often limited by problems with double-stranded (ds) RNA delivery, which restricts reverse genetics studies and the development of RNAi-based biocides. We therefore delegated to insect symbiotic bacteria the task of: (i) constitutive dsRNA synthesis and (ii) trauma-free delivery. RNaseIII-deficient, dsRNA-expressing bacterial strains were created from the symbionts of two very diverse pest species: a long-lived blood-sucking bug, Rhodnius prolixus, and a short-lived globally invasive polyphagous agricultural pest, western flower thrips (Frankliniella occidentalis). When ingested, the manipulated bacteria colonized the insects, successfully competed with the wild-type microflora, and sustainably mediated systemic knockdown phenotypes that were horizontally transmissible. This represents a significant advance in the ability to deliver RNAi, potentially to a large range of non-model insects., (© 2016 The Authors.)

Background: There is no consensus in the literature regarding the impact of false positive newborn screening results on early health care utilization patterns. We evaluated the impact of false positive newborn screening results for medium-chain acyl-CoA dehydrogenase deficiency (MCADD) in a cohort of Ontario infants., Methods: The cohort included all children who received newborn screening in Ontario between April 1, 2006 and March 31, 2010. Newborn screening and diagnostic confirmation results were linked to province-wide health care administrative datasets covering physician visits, emergency department visits, and inpatient hospitalizations, to determine health service utilization from April 1, 2006 through March 31, 2012. Incidence rate ratios (IRRs) were used to compare those with false positive results for MCADD to those with negative newborn screening results, stratified by age at service use., Results: We identified 43 infants with a false positive newborn screening result for MCADD during the study period. These infants experienced significantly higher rates of physician visits (IRR: 1.42) and hospitalizations (IRR: 2.32) in the first year of life relative to a screen negative cohort in adjusted analyses. Differences in health services use were not observed after the first year of life., Conclusions: The higher use of some health services among false positive infants during the first year of life may be explained by a psychosocial impact of false positive results on parental perceptions of infant health, and/or by differences in underlying health status. Understanding the impact of false positive newborn screening results can help to inform newborn screening programs in designing support and education for families. This is particularly important as additional disorders are added to expanded screening panels, yielding important clinical benefits for affected children but also a higher frequency of false positive findings.

Background: Patient-centered health care for children with inborn errors of metabolism (IEM) and their families is important and requires an understanding of patient experiences, needs, and priorities. IEM-specific patient groups have emerged as important voices within these rare disease communities and are uniquely positioned to contribute to this understanding. We conducted qualitative interviews with IEM patient group representatives to increase understanding of patient and family experiences, needs, and priorities and inform patient-centered research and care., Methods: We developed a sampling frame of patient groups representing IEM disease communities from Canada, the United States, and United Kingdom. With consent, we interviewed participants to explore their views on experiences, needs, and outcomes that are most important to children with IEM and their families. We analyzed the data using a qualitative descriptive approach to identify key themes and sub-themes., Results: We interviewed 18 organizational representatives between February 28 and September 17, 2014, representing 16 IEMs and/or disease categories. Twelve participants voluntarily self-identified as parents and/or were themselves patients. Three key themes emerged from the coded data: managing the uncertainty associated with raising and caring for a child with a rare disease; challenges associated with the affected child's life transitions, and; the collective struggle for improved outcomes and interventions that rare disease communities navigate., Conclusion: Health care providers can support children with IEM and their families by acknowledging and reducing uncertainty, supporting families through children's life transitions, and contributing to rare disease communities' progress toward improved interventions, experiences, and outcomes.

Symptomatic neuromas of the sural nerve are a rare but significant cause of pain and debilitation in athletes. Presentation is usually in the form of chronic pain and dysesthesias or paresthesias of the lateral foot and ankle. Treatment traditionally ranges from conservative measures, such as removing all external compressive forces, to administration of nonsteroidal anti-inflammatory drugs, vitamin B6, tricyclic antidepressants, antiepileptics, or topical anesthetics. This article reports a case of sural nerve entrapment in a 34-year-old male triathlete with a history of recurrent training-induced right-sided gastrocnemius strains. The patient presented with numbness in the right lateral foot and ankle that had persisted for 3 months, after he was treated unsuccessfully with extensive nonoperative measures, including anti-inflammatory drugs, activity modification, and a dedicated physical therapy program of stretching and strengthening. Orthopedic assessment showed worsening pain with forced passive dorsiflexion and manual pressure applied over the distal aspect of the gastrocnemius. Plain radiographs showed normal findings, but in-office ultrasound imaging showed evidence of sural nerve entrapment with edema and neuromatous scar formation in the absence of gastrocnemius or soleus pathology. Percutaneous ultrasound-guided hydrodissection of the sural nerve at the area of symptomatic neuroma and neural edema was performed the same day. The patient had complete relief of symptoms and full return to the preinjury level of participation in competitive sports. This case report shows that hydrodissection, when performed by an experienced physician, can be an effective, minimally invasive technique for neurolysis in the setting of sural nerve entrapment, resulting in improvement in clinical symptoms., (Copyright 2015, SLACK Incorporated.)

Neuralgia and neuroma secondary to iatrogenic saphenous nerve injury have been described in the setting of orthopedic surgical interventions. However, postoperative neuropathic pain caused by saphenous neuroma in the setting of orthopedic trauma has not been reported. We present a case of a 43-year-old woman with a symptomatic saphenous neuroma after an open, laterally angulated tibial fracture. The diagnosis was confirmed in the clinical setting, and treatment consisted of neurolysis and partial neurectomy, resulting in complete pain relief and functional recovery. This case demonstrates the diagnosis and treatment strategy for a symptomatic posttraumatic saphenous neuroma in the setting of a healed, open distal one-third tibial fracture.

The primary treatment outcomes of a phase 2, randomized, double-blind, pilot study evaluating safety, physiological, and pharmacological effects of elosulfase alfa in patients with Morquio A syndrome are herewith presented. Patients aged ≥7 years and able to walk ≥200 m in the 6-min walk test (6MWT) were randomized to elosulfase alfa 2.0 or 4.0 mg/kg/week for 27 weeks. The primary objective was to evaluate the safety of both doses. Secondary objectives were to evaluate effects on endurance (6MWT and 3-min stair climb test [3MSCT]), exercise capacity (cardio-pulmonary exercise test [CPET]), respiratory function, muscle strength, cardiac function, pain, and urine keratan sulfate (uKS) levels, and to determine pharmacokinetic parameters. Twenty-five patients were enrolled (15 randomized to 2.0 mg/kg/week and 10 to 4.0 mg/kg/week). No new or unexpected safety signals were observed. After 24 weeks, there were no improvements versus baseline in the 6MWT, yet numerical improvements were seen in the 3MSCT with 4.0 mg/kg/week. uKS and pharmacokinetic data suggested no linear relationship over the 2.0-4.0 mg/kg dose range. Overall, an abnormal exercise capacity (evaluated in 10 and 5 patients in the 2.0 and 4.0 mg/kg/week groups, respectively), impaired muscle strength, and considerable pain were observed at baseline, and there were trends towards improvements in all domains after treatment. In conclusion, preliminary data of this small study in a Morquio A population with relatively good endurance confirmed the acceptable safety profile of elosulfase alfa and showed a trend of increased exercise capacity and muscle strength and decreased pain., (© 2015 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc.)

Leigh syndrome (LS) is a rare heterogeneous progressive neurodegenerative disorder usually presenting in infancy or early childhood. Clinical presentation is variable and includes psychomotor delay or regression, acute neurological or acidotic episodes, hypotonia, ataxia, spasticity, movement disorders, and corresponding anomalies of the basal ganglia and brain stem on magnetic resonance imaging. To date, 35 genes have been associated with LS, mostly involved in mitochondrial respiratory chain function and encoded in either nuclear or mitochondrial DNA. We used whole-exome sequencing to identify disease-causing variants in four patients with basal ganglia abnormalities and clinical presentations consistent with LS. Compound heterozygote variants in ECHS1, encoding the enzyme enoyl-CoA hydratase were identified. One missense variant (p.Thr180Ala) was common to all four patients and the haplotype surrounding this variant was also shared, suggesting a common ancestor of French-Canadian origin. Rare mutations in ECHS1 as well as in HIBCH, the enzyme downstream in the valine degradation pathway, have been associated with LS or LS-like disorders. A clear clinical overlap is observed between our patients and the reported cases with ECHS1 or HIBCH deficiency. The main clinical features observed in our cohort are T2-hyperintense signal in the globus pallidus and putamen, failure to thrive, developmental delay or regression, and nystagmus. Respiratory chain studies are not strikingly abnormal in our patients: one patient had a mild reduction of complex I and III and another of complex IV. The identification of four additional patients with mutations in ECHS1 highlights the emerging importance of this pathway in LS.

Venous thromboembolism (VTE) prophylaxis after total joint arthroplasty is considered best practice. However, over the past 5 years, there has been considerable debate about the ideal prophylactic regimen or modality. The American Academy of Orthopaedic Surgeons and the American College of Chest Physicians published their most recent clinical practice guidelines about VTE prophylaxis in 2011 and 2012, respectively. In addition, the Surgical Care Improvement Project published their latest recommendations in 2014. In this review, commonly used VTE prophylaxis options and the latest clinical guidelines will be discussed., (Copyright 2015, SLACK Incorporated.)

Introduction: We describe a safe surgical technique for arthroscopic decompression of a suprascapular notch cyst in the setting of compressive suprascapular neuropathy., Step 1 Position the Patient: Position the patient in the standard beach-chair position., Step 2 Mark Anatomic Landmarks: Palpate and mark the subcutaneous landmarks of the shoulder in preparation for later arthroscopy., Step 3 Diagnostic Arthroscopy: Create standard anterior and posterior portals for glenohumeral visualization., Step 4 Perform Suprascapular Cyst Decompression Through a Lateral Subacromial Approach: Establish accessory superior and lateral portals and transition to a lateral viewing portal to perform suprascapular notch decompression., Step 5 Release the Transverse Scapular Ligament: Establish a G Portal and release the transverse scapular ligament using arthroscopic scissors., Step 6 Closure: Perform arthroscopic lavage of the subacromial space and glenohumeral joint and close arthroscopic portals., Results: As suprascapular nerve entrapment is a relatively rare entity, with only a limited number of studies from which to draw conclusions regarding the outcomes of arthroscopic suprascapular nerve release, Shah et al. recently reported on their results in twenty-four patients using this surgical technique.IndicationsContraindicationsPitfalls & Challenges.

Background: Pediatric avulsion fractures of the anterior tibial spine are injuries similar to anterior cruciate ligament injuries in adults. Sparse data exists on the association between anterior tibial spine fractures (ATSFs) and injury to the meniscus or cartilage of the knee joint in children. This research presents a retrospective review of clinical records, imaging, and operative reports to characterize the incidence of concomitant injury in cases of ATSFs in children. The purpose of this study was to better delineate the incidence of associated injuries in fractures of the anterior tibial spine in the pediatric population., Methods: We identified 58 patients who sustained an ATSF and met inclusion criteria for this study between 1996 and 2011. The subjects were separated by the Myers and McKeever classification into type I, II, and III fractures, and each of these were subclassified by associated injury pattern., Results: 59% of children with an ATSF had an associated soft tissue or other bony injury diagnosed by magnetic resonance imaging or arthroscopy. The most prevalent associated injuries were meniscal entrapment, meniscal tears, and chondral injury. We found no meniscal or chondral injury associated with type I fractures. Twenty-nine percent of type II injuries demonstrated meniscal entrapment, 33% showing meniscal tears. Seven percent demonstrated chondral injury. Forty-eight percent of type III fractures had entrapment, whereas 12% showed meniscal tears. Eight percent had a chondral injury., Conclusions: A majority (59%) of displaced ATSF had either concomitant meniscal, ligamentous, or chondral injury. This finding suggests that magnetic resonance imaging evaluation is an important aspect of the evaluation of these injuries, particularly in type II and type III patterns. To date, this study reports the largest number of patients to evaluate the specific question of concomitant injuries in ATSFs in the pediatric population., Level of Evidence: Level IV.

Background: Improvements in health care for children with chronic diseases must be informed by research that emphasizes outcomes of importance to patients and families. To support a program of research in the field of rare inborn errors of metabolism (IEM), we conducted a broad scoping review of primary studies that: (i) focused on chronic pediatric diseases similar to IEM in etiology or manifestations and in complexity of management; (ii) reported patient- and/or family-oriented outcomes; and (iii) measured these outcomes using self-administered tools., Methods: We developed a comprehensive review protocol and implemented an electronic search strategy to identify relevant citations in Medline, EMBASE, DARE and Cochrane. Two reviewers applied pre-specified criteria to titles/abstracts using a liberal accelerated approach. Articles eligible for full-text review were screened by two independent reviewers with discrepancies resolved by consensus. One researcher abstracted data on study characteristics, patient- and family-oriented outcomes, and self-administered measures. Data were validated by a second researcher., Results: 4,118 citations were screened with 304 articles included. Across all included reports, the most-represented diseases were diabetes (35%), cerebral palsy (23%) and epilepsy (18%). We identified 43 unique patient- and family-oriented outcomes from among five emergent domains, with mental health outcomes appearing most frequently. The studies reported the use of 405 independent self-administered measures of these outcomes., Conclusions: Patient- and family-oriented research investigating chronic pediatric diseases emphasizes mental health and appears to be relatively well-developed in the diabetes literature. Future research can build on this foundation while identifying additional outcomes that are priorities for patients and families.

Background: chronic proximal hamstring tendinopathies is a disabling activity related condition. Currently, there is no well-accepted or extensively documented non-operative treatment option that provides consistently successful results., Purpose: to evaluate the efficacy of ultrasound guided platelet-rich plasma injections in treating chronic proximal hamstring tendinopathies., Methods: a total of 18 consecutive patients were retrospectively analyzed. All patients received a single injection of platelet rich plasma via ultra-sound guidance by a single radiologist. Outcome measures included a questionnaire evaluating previous treatments, visual analog scale (VAS) for pain, subjective improvement, history of injury, and return to activity., Results: the patient population included 12 females and 6 males. The average age at the time of the injection was 42.6 years (19-60). Provocative activities included running, biking, swimming. The average body mass index of patients was 22.9 (17.2-30.2). The average time of chronic pain prior to receiving the first injection was 32.6 months (6-120). All patients had attempted other forms of non-surgical treatment prior to entering the study. The average VAS pre-injection was 4.6 (0-8). Six months after the injection, 10/18 patients had 80% or greater improvement in their VAS. Overall, the average improvement was 63% (5-100). The only documented side effect was post-injection discomfort that resolved within seventy-two hours., Conclusion: chronic hamstring tendinopathy is a debilitating condition secondary to the pain, which limits an athlete's ability to perform. For refractory cases of chronic insertional proximal hamstring injuries, platelet-rich plasma injections are safe and show benefit in the majority of patients in our study, allowing return to pre-injury activities., Study Design: Case series; Level of evidence, 4.

Objectives: Baseline data from the Morquio A Clinical Assessment Program (MorCAP) revealed that individuals with Morquio A syndrome show substantial impairment in multiple domains including endurance and respiratory function (Harmatz et al., Mol Genet Metab, 2013). Here, 1- and 2-year longitudinal endurance and respiratory function data are presented., Methods: Endurance was assessed using the 6-minute walk test (6MWT) and the 3-minute stair climb test (3MSCT). Respiratory function was evaluated by measuring forced vital capacity (FVC) and maximum voluntary ventilation (MVV). Data were analyzed using repeated measures ANCOVA models. Annualized estimates of change were determined using model estimates and interpolation., Results: 353, 184, and 78 subjects were assessed at Year 0 (baseline), Year 1, and Year 2, respectively. The overall annualized estimate of change (SE) in 6MWT distance was -4.86±3.25m; a larger decline of -6.84±5.38m was observed in the subset of subjects meeting the inclusion/exclusion criteria of the Phase 3 clinical trial of elosulfase alfa (≥5years of age with baseline 6MWT distance ≥30 and ≤325m). In contrast, little change (-0.14±0.60stairs/min) was observed in 3MSCT. Annualized changes (SE) in FVC and MVV were 2.44±0.68% and 1.01±2.38%, respectively. FVC and MVV increased in patients aged ≤14years, but decreased in older patients., Conclusions: The natural history of Morquio A syndrome is characterized by progressive impairment of endurance as measured by the 6MWT. Longitudinal trends in FVC and MVV showing increase in younger patients, but decrease in older patients, are likely to be influenced by growth. Changes in 6MWT may represent a sensitive measure of disease progression in ambulatory Morquio A patients., (Copyright © 2014. Published by Elsevier Inc.)

Introduction: Nearly all children in Canada with an inherited metabolic disease (IMD) are treated at one of the country's Hereditary Metabolic Disease Treatment Centres. We sought to understand the system of care for paediatric IMD patients in Canada in order to identify sources of variation and inform future research priorities., Methods: Treatment centres were contacted by email and invited to complete a web-based survey. The questionnaire addressed, for each centre, the population size served and scope of practice, available human resources and clinic services and research capacity. Survey responses were analyzed descriptively., Results: We received responses from 13 of the 14 treatment centres invited to participate. These centres represent at least 85% of the Canadian population, with over half of the centres located in southern Ontario and Quebec. All centres reported paediatric patients with IMDs as their main patient population. A variety of dedicated staff was identified; every centre reported having at least one physician and one dietician. The most common ancillary services available included telehealth (11/12 respondents) and biochemical genetic laboratory testing (10/12), with a high variability of access to on-site laboratory tests. A majority of centres indicated access to additional off-site services, but barriers to these were reported. All but one centre indicated previous experience with research., Conclusions: The variation we identified in the organization of care highlights the need to investigate the association between practice differences and health outcomes for paediatric IMD patients to inform policies that establish equitable access to services that are beneficial.

Although open reduction and internal fixation (ORIF) has been the standard of care for acetabular fractures, recent advancements in minimally invasive techniques have allowed percutaneous fixation to gain popularity. Percutaneous technique has been described in the literature as an adjuvant to ORIF. However, isolated percutaneous fixation has the advantage of limiting soft tissue disruption, length of surgery, and blood loss when compared with ORIF. The technique also allows for earlier return to activity and better pain control when compared with nonsurgical management. This article reviews both indications and limitations, while highlighting the technique for percutaneous fixation of both anterior and posterior column acetabular fractures., (Copyright 2014, SLACK Incorporated.)

The current study compared tunnel diameter as an independent risk factor for fixation failure from the coracoid after transcoracoid coracoclavicular reconstruction. The effect of variation in coracoid size and scapular bone density on fixation failure was also studied. Sixty-two cadaveric scapulae were randomized into 1 of 4 groups: a control group with no coracoid hole, a group with a 4-mm transcoracoid tunnel, a group with a 6-mm transcoracoid tunnel, and a group with a socket technique using a 6-mm hole superiorly with a 4-mm hole inferiorly. Bone density measures for all specimens were performed. Coracoid dimensions were quantified. Using a cortical button device, all specimens were loaded to failure with an Instron servohydraulic testing machine (Instron Corp, Canton, Massachusetts). All drilled specimens failed by button pullout, and all control specimens failed by coracoid fracture. Average pullout strength for each tunnel subgroup was as follows: 4 mm, 296.9 N; 6 mm, 146.2 N; 6-4 socket, 261.8 N; control, 762.9 N. No difference was found with respect to tunnel subgroups in base height (P=.25) or bone density (P=.44). Load to failure for the control group was significantly higher than for the other 3 techniques. The 4-mm tunnel load to failure was significantly higher than that for the 6-mm tunnel (P=.006). No difference was found between the 4-mm tunnel and the 6-4 socket technique (P=.853). Although it was not statistically significant, a very strong trend was seen toward increased strength of the 6-4 socket over the 6-mm tunnel (P=.051). The study results show that when employing a transcoracoid reconstruction technique, a 4-mm tunnel technique is significantly stronger than a 6-mm tunnel technique. None of the coracoids drilled with the various tunnels approached the strength of the native coracoid controls using a looped wire technique., (Copyright 2014, SLACK Incorporated.)

Background: Tubular gauze dressings are commonly used, but have potential to cause iatrogenic finger ischemia., Objectives: To inform health care providers of an avoidable complication and to discuss appropriate methods of prevention and treatment., Case Report: We discuss a teenage female's finger that narrowly avoided amputation after a tubular gauze dressing caused iatrogenic ischemia. Surgical decompression using a novel technique successfully salvaged the finger. Operative intervention for this complication has previously been unreported., Conclusion: It is important that circumferential digital dressings are applied correctly. Vascular insufficiency from an occlusive dressing is an iatrogenic and avoidable complication. Successful operative decompression may be indicated to minimize tissue loss and improve circulation., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Across all areas of health care, decision makers are in pursuit of what Berwick and colleagues have called the "triple aim": improving patient experiences with care, improving health outcomes, and managing health system impacts. This is challenging in a rare disease context, as exemplified by inborn errors of metabolism. There is a need for evaluative outcomes research to support effective and appropriate care for inborn errors of metabolism. We suggest that such research should consider interventions at both the level of the health system (e.g., early detection through newborn screening, programs to provide access to treatments) and the level of individual patient care (e.g., orphan drugs, medical foods). We have developed a practice-based evidence framework to guide outcomes research for inborn errors of metabolism. Focusing on outcomes across the triple aim, this framework integrates three priority themes: tailoring care in the context of clinical heterogeneity; a shift from "urgent care" to "opportunity for improvement"; and the need to evaluate the comparative effectiveness of emerging and established therapies. Guided by the framework, a new Canadian research network has been established to generate knowledge that will inform the design and delivery of health services for patients with inborn errors of metabolism and other rare diseases.

We investigate the dependence of solar wind fluctuations measured by the Wind spacecraft on scale and on the degree of alignment between oppositely directed Elsasser fields. This alignment controls the strength of the nonlinear interactions and, therefore, the turbulence. We find that at scales larger than the outer scale of the turbulence the Elsasser fluctuations become on average more antialigned as the outer scale is approached from above. Conditioning structure functions using the alignment angle reveals turbulent scaling of unaligned fluctuations at scales previously believed to lie outside the turbulent cascade in the "1/f range." We argue that the 1/f range contains a mixture of a noninteracting antialigned population of Alfvén waves and magnetic force-free structures plus a subdominant population of unaligned cascading turbulent fluctuations.

The Dartmouth Institute for Health Policy and Clinical Practice Atlas Project found "staggering variations" in the quality and quantity of end-of-life care provided to Medicare patients with severe chronic illness across the United States. Particularly concerning is the finding that more care is provided to patients who live in "high-supply" areas, irrespective of the effectiveness of care, and that more care often equaled inappropriate care that increased patients' suffering at the end of life. Patients in "lower supply" areas typically received better, more appropriate levels of care and reported higher levels of satisfaction with the care they received.

Phenylalanine hydroxylase deficiency is an autosomal recessive disorder that results in intolerance to the dietary intake of the essential amino acid phenylalanine. It occurs in approximately 1:15,000 individuals. Deficiency of this enzyme produces a spectrum of disorders including classic phenylketonuria, mild phenylketonuria, and mild hyperphenylalaninemia. Classic phenylketonuria is caused by a complete or near-complete deficiency of phenylalanine hydroxylase activity and without dietary restriction of phenylalanine most children will develop profound and irreversible intellectual disability. Mild phenylketonuria and mild hyperphenylalaninemia are associated with lower risk of impaired cognitive development in the absence of treatment. Phenylalanine hydroxylase deficiency can be diagnosed by newborn screening based on detection of the presence of hyperphenylalaninemia using the Guthrie microbial inhibition assay or other assays on a blood spot obtained from a heel prick. Since the introduction of newborn screening, the major neurologic consequences of hyperphenylalaninemia have been largely eradicated. Affected individuals can lead normal lives. However, recent data suggest that homeostasis is not fully restored with current therapy. Treated individuals have a higher incidence of neuropsychological problems. The mainstay of treatment for hyperphenylalaninemia involves a low-protein diet and use of a phenylalanine-free medical formula. This treatment must commence as soon as possible after birth and should continue for life. Regular monitoring of plasma phenylalanine and tyrosine concentrations is necessary. Targets of plasma phenylalanine of 120-360 μmol/L (2-6 mg/dL) in the first decade of life are essential for optimal outcome. Phenylalanine targets in adolescence and adulthood are less clear. A significant proportion of patients with phenylketonuria may benefit from adjuvant therapy with 6R-tetrahydrobiopterin stereoisomer. Special consideration must be given to adult women with hyperphenylalaninemia because of the teratogenic effects of phenylalanine. Women with phenylalanine hydroxylase deficiency considering pregnancy should follow special guidelines and assure adequate energy intake with the proper proportion of protein, fat, and carbohydrates to minimize risks to the developing fetus. Molecular genetic testing of the phenylalanine hydroxylase gene is available for genetic counseling purposes to determine carrier status of at-risk relatives and for prenatal testing.

Riboflavin, or vitamin B2, is a precursor to flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) molecules, required in biological oxidation-reduction reactions. We previously reported a case of a newborn female who had clinical and biochemical features of multiple acyl-CoA dehydrogenation deficiency (MADD), which was corrected by riboflavin supplementation. The mother was then found to be persistently riboflavin deficient, suggesting that a possible genetic defect in riboflavin transport in the mother was the cause of the transient MADD seen in the infant. Two recently-identified riboflavin transporters G protein-coupled receptor 172B (GPR172B or RFT1) and riboflavin transporter 2 (C20orf54 or RFT2) were screened for mutations. Two missense sequence variations, c.209A>G [p.Q70R] and c.886G>A [p.V296M] were found in GPR172B. In vitro functional studies of both missense variations showed that riboflavin transport was unaffected by these variations. Quantitative real-time PCR revealed a de novo deletion in GPR172B spanning exons 2 and 3 in one allele from the mother. We postulate that haploinsufficiency of this riboflavin transporter causes mild riboflavin deficiency, and when coupled with nutritional riboflavin deficiency in pregnancy, resulted in the transient riboflavin-responsive disease seen in her newborn infant. This is the first report of a genetic defect in riboflavin transport in humans., (© 2010 Wiley-Liss, Inc.)

The oral and maxillofacial surgeon (OMS) plays a critical role when it comes to listening and answering patients' questions regarding prognosis, course of treatment, and overall expectations of what lies ahead. The OMS should remain an advocate for the patient, always keeping in mind that it is the patient's wishes that must be respected. The surgeon should champion patients' autonomy and cooperate with their families and other clinicians to ensure that patients have a "good death," defined as one that is pain free, peaceful, and dignified, at a place of their choosing with the relatives present and without futile heroic interventions. Indeed, the relationship and open communication between patient and surgeon may be one of the best treatments that the patient can have., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the effect of endovascular nonthermal irreversible electroporation (NTIRE) on blood vessels., Materials and Methods: Specially made endovascular devices with four electrodes on top of inflatable balloons were used to apply electroporation pulses. Finite element simulations were used to characterize NTIRE protocols that would not induce thermal damage to treated tissues. Right iliac arteries of eight rabbits were treated with 90 NTIRE pulses. Angiograms were performed before and after the procedures. Arterial specimens were harvested at 7 and 35 days. Evaluation included hematoxylin and eosin, elastic von Giessen, and Masson trichrome stains. Immunohistochemistry of selected slides included smooth muscle actin (SMA), proliferating cell nuclear antigen, von Willebrand factor (VWF), and S-100 antigen., Results: At 7 days, all NTIRE-treated arterial segments displayed complete, transmural ablation of vascular smooth muscle cells (VSMC). At 35 days, similar damage to VSMC was noted. In most cases, the elastic lamina remained intact, and endothelial layer regenerated. Occasional mural inflammation and cartilaginous metaplasia were noted. After 5 weeks, there was no evidence of significant VSMC proliferation, with the dominant process being wall fibrosis with regenerated endothelium., Conclusions: NTIRE can be applied in an endovascular approach. It efficiently ablates vessel wall within seconds and with no damage to extracellular structures. NTIRE has possible applications in many fields of clinical cardiology, including arterial restenosis and cardiac arrhythmias., (Copyright © 2010 SIR. Published by Elsevier Inc. All rights reserved.)

Autosomal dominant osteogenesis imperfecta (OI) is caused by mutations in the genes (COL1A1 or COL1A2) encoding the chains of type I collagen. Recently, dysregulation of hydroxylation of a single proline residue at position 986 of both the triple-helical domains of type I collagen alpha1(I) and type II collagen alpha1(II) chains has been implicated in the pathogenesis of recessive forms of OI. Two proteins, cartilage-associated protein (CRTAP) and prolyl-3-hydroxylase-1 (P3H1, encoded by the LEPRE1 gene) form a complex that performs the hydroxylation and brings the prolyl cis-trans isomerase cyclophilin-B (CYPB) to the unfolded collagen. In our screen of 78 subjects diagnosed with OI type II or III, we identified three probands with mutations in CRTAP and 16 with mutations in LEPRE1. The latter group includes a mutation in patients from the Irish Traveller population, a genetically isolated community with increased incidence of OI. The clinical features resulting from CRTAP or LEPRE1 loss of function mutations were difficult to distinguish at birth. Infants in both groups had multiple fractures, decreased bone modeling (affecting especially the femurs), and extremely low bone mineral density. Interestingly, "popcorn" epiphyses may reflect underlying cartilaginous and bone dysplasia in this form of OI. These results expand the range of CRTAP/LEPRE1 mutations that result in recessive OI and emphasize the importance of distinguishing recurrence of severe OI of recessive inheritance from those that result from parental germline mosaicism for COL1A1 or COL1A2 mutations.

We report here the results of treatment in a panel of 65 inborn errors of metabolism, obtained in the 25th year of a longitudinal project, first reported in 1983. The phenotypic impact of these 65 diseases was scored before and after treatment using a consistent set of parameters, which we have retained to measure change in clinical phenotype throughout the project. We observed significant improvements in the response to treatment for the disease set as a whole. The number of conditions for which there is no response to treatment has progressively decreased; from 31 in 1983, to 20 in 1993, to 17 in 2008. Concomitantly, there has been an increase in the number of conditions that fully respond to treatment (from 8 in 1983 and 1993, to 20 in 2008), and in those for which there is a partial response. Reasons for improved treatment responses include new small molecules, new enzyme replacement therapies, more conditions that can be treated by organ and cell transplantation, and new experimental approaches to substrate reduction and chaperone assisted therapy. However, the most important and new development was not found in one or other particular therapeutic modality but in the access to new knowledge surrounding the individual diseases via the Internet and related resources. Our longitudinal analysis of treatment efficacy for this subset of inborn errors of metabolism continues to constitute a robust and representative assessment of our ability to restore more normal homeostasis in the inborn errors of metabolism.

Objective: Despite limited scientific evidence about its risks and benefits, full-body CT screening is available to self-referred individuals. The purpose of this study was to develop a scientific knowledge base about patient expectations of the procedure and to determine whether characteristics of patients influence their expectations of its health benefits., Materials and Methods: Facilities from six diverse, geographically representative U.S. regions performing full-body CT screening were used as the study sites. A pretest only descriptive survey design was used to study 94 patient volunteers scheduled to undergo full-body CT screening. Descriptive statistics were used in examining information about the demographics, health, and knowledge characteristics of the patients. The chi-square test for independence and Spearman's correlation coefficient for ranked data were used to analyze associations among patient characteristics and responses to expectation statements. An alpha value of 0.05 was the level of significance., Results: Survey participants were 35-65 years old, predominantly white, married, and health conscious with income and educational levels several times above the national averages. The patients' highest expectations related to consumer empowerment and their lowest expectations related to the limitations of the procedure. The five patient characteristics found to have significant associations with patient expectations were patient sex; referral method; level of personal health concern; number of other health screening procedures patient had undergone; and patients' self-estimations of their current health status., Conclusion: This study provided quantitative and descriptive data that are consistent with and add to the existing, primarily anecdotal, knowledge base about patients' expectations of full-body CT screening. These findings can be used to educate patients before they provide informed consent for the procedure.

Recent studies have shown that a subgroup of phenylketonuric patients respond to high doses of BH4 (20 mg/kg) by a decrease of plasma phenylalanine. A clinically significant response has been defined as a decrease in phenylalanine by more than 30% within 24 h, after a BH4 challenge. We report our experience with 37 patients diagnosed with hyperphenylalaninemia, mild, moderate, or classical Phenylketonuria (PKU) using a seven day combined BH4 and phenylalanine load. Nine of the 37 patients responded with a 30% decrease in their phenylalanine levels in the first 8 h of treatment. A total of 17 patients (46%) had a decrease of at least 30% during the study period. This study confirms that a significant number of patients with mild to moderate PKU will respond to a BH4 load. Furthermore, it confirms that the seven-day phenylalanine test is more sensitive in detecting BH4 responsive patients.