Regulatory and Ethical Aspects of Orthobiologic Therapies.

Orthobiologic therapies show significant promise to improve outcomes for patients with musculoskeletal pathology. There are considerable research efforts to develop strategies that seek to modulate the biological environment to promote tissue regeneration and healing and/or provide symptomatic relief. However, the regulatory pathways overseeing the clinical translation of these therapies are complex, with considerable worldwide variation. The introduction of novel biologic treatments into clinical practice raises several ethical dilemmas. In this review, we describe the process for seeking approval for biologic therapies in the United States, Europe, and Japan. We highlight a number of ethical issues raised by the clinical translation of these treatments, including the design of clinical trials, monitoring outcomes, biobanking, "off-label" use, engagement with the public, marketing of unproven therapies, and scientific integrity.

The CPUP Hip Score predicts displacement of the hip in children with cerebral palsy.

AIMS: The Uppföljningsprogram för cerebral pares (CPUP) Hip Score distinguishes between children with cerebral palsy (CP) at different levels of risk for displacement of the hip. The score was constructed using data from Swedish children with CP, but has not been confirmed in any other population. The aim of this study was to determine the calibration and discriminatory accuracy of this score in children with CP in Scotland. METHODS: This was a total population-based study of children registered with the Cerebral Palsy Integrated Pathway Scotland. Displacement of the hip was defined as a migration percentage (MP) of > 40%. Inclusion criteria were children in Gross Motor Function Classification System (GMFCS) levels III to V. The calibration slope was estimated and Kaplan-Meier curves produced for five strata of CPUP scores to compare the observed with the predicted risk of displacement of the hip at five years. For discriminatory accuracy, the time-dependent area under the receiver operating characteristic curve (AUC) was estimated. In order to analyze differences in the performance of the score between cohorts, score weights, and subsequently the AUC, were re-estimated using the variables of the original score: the child's age at the first examination, GMFCS level, head shaft angle, and MP of the worst hip in a logistic regression with imputation of outcomes for those with incomplete follow-up. RESULTS: The discriminatory accuracy of the score in the new population of 367 children was high (AUC 0.78 (95% confidence interval (CI) 0.71 to 0.86)). The calibration of the score was insufficient (slope 0.48 (95% CI 0.31 to 0.65)), and the absolute risks of displacement of the hip in this population were overestimated. The AUC increased with re-estimated weights (0.85 (95% CI 0.79 to 0.91)). CONCLUSION: The CPUP Hip Score had a high ability to discriminate between children at different levels of risk for displacement of the hip. The score overestimated the absolute risks of displacement in this population, which may have resulted from differences in the way children were initially registered in the two programmes. The results are promising, but the score weights may need re-estimation before its clinical application in Scotland. Cite this article: Bone Joint J 2022;104-B(5):640-644.

Leisure Time Physical Activity in Children and Young People With Cerebral Palsy: A Population-Based Study.

PURPOSE: To describe leisure time physical activity in children and young people with cerebral palsy and identify barriers and facilitators to participation. METHODS: Leisure time physical activity participation was derived from a national cerebral palsy register and associated factors were analyzed. Barriers and facilitators to participation were investigated through a survey. RESULTS: Leisure time physical activity participation was recorded. Outcomes of participation decreased with increasing Gross Motor Function Classification System level. Leisure time physical activity "not in club" for 11- to 18-year-olds was significantly lower than for those aged 5 to 10 years for Gross Motor Function Classification System level II. The survey supported that disability and disliking help were common barriers and parental encouragement and enjoyment were common facilitators. CONCLUSIONS: Data from the register and survey provide insight into factors influencing leisure time physical activity participation in young people with cerebral palsy and how to increase.

Population-based normative data for the Scoliosis Research Society 22r, EQ-5D, and VAS questionnaires among individuals aged 20 to 69 years.

AIMS: To provide normative data that can assess spinal-related disability and the prevalence of back or leg pain among adults with no spinal conditions in the UK using validated questionnaires. METHODS: A total of 1,000 participants with equal sex distribution were included and categorized in five age groups: 20 to 29, 30 to 39, 40 to 49, 50 to 59, and 60 to 69 years. Individuals with spinal pathologies were excluded. Participants completed the Scoliosis Research Society-22 (SRS-22r), visual analogue scale (VAS) for back/leg pain, and the EuroQol five-dimension index (EQ-5D/VAS) questionnaires, and disclosed their age, sex, and occupation. They were also categorized in five professional groups: doctors, nurses, allied health professionals, office workers, and manual workers. RESULTS: The mean age of all participants was 43.8 years (20 to 69). There was no difference in the SRS-22r, EQ-5D, or VAS scores among male and female participants (p > 0.05). There was incremental decrease in SRS-22r total scores as the age increased. The mean EQ-5D index score (0.84) ranged little across the age groups (0.72 to 0.91) but reduced gradually with increasing age. There was difference between the SRS-22r total score (4.51), the individual domain scores, and the EQ-5D score (index: 0.94 and VAS: 89) for the doctors' group compared to all other occupational categories (p < 0.001). Doctors had a younger mean age of participants, which may explain their improved spinal health. There was no difference in the total or sub-domain SRS-22r and EQ-5D scores between the other four occupational groups. CONCLUSION: This study provides the first normative data for the SRS-22r, EQ-5D, and VAS for back/leg pain questionnaires among adults in the UK. We recorded an excellent correlation between the three assessment tools with individuals who reported less back and leg pain having better quality of life and greater function. The participants' age, rather than their sex or profession, appears to be the major determinant for spinal health and quality of life. Cite this article: Bone Jt Open 2022;3(2):130-134.

Percutaneous Fixation of Posterior Malleolar Fractures in Patients With Unstable Ankle Fractures Treated With a Fibular Intramedullary Nail: A Description of a Technique and Review of Outcomes.

OBJECTIVES: To (1) describe the percutaneous technique used to reduce and fix a posterior malleolar fracture with anteroposterior screws in patients managed with a fibular intramedullary nail, (2) describe the selection of patients to whom this technique can be applied, and (3) report the clinical and patient reported outcome of this intervention. DESIGN: Retrospective review. SETTING: Academic orthopaedic trauma center. PATIENTS: Thirty-two consecutive patients with a mean age of 65 years (range, 39-90) over a thirteen-year period identified from a prospective database. INTERVENTION: Unstable ankle fractures managed surgically with a fibular nail and percutaneous fixation of the posterior malleolar component. MAIN OUTCOME MEASUREMENTS: The primary short-term outcome was complications related to posterior malleolar fracture fixation. The primary mid-term outcome was the Olerud-Molander Ankle Score. Secondary outcomes included the Manchester-Oxford Foot Questionnaire, EuroQol-5D, health, pain, and satisfaction. RESULTS: Thirty of the 32 (94%) posterior malleolar fractures united uneventfully. Postoperative loss of talar reduction occurred in 2 patients (6.3%), which in 1 patient (3.1%) eventually required a hindfoot nail arthrodesis. There were no soft-tissue complications related to the anteroposterior screws or the fibular nail fixation. At a mean follow-up of 3.7 years (range, 1-8), the median Olerud-Molander Ankle Score, Manchester-Oxford Foot Questionnaire, EuroQol-5D, health, pain, and satisfaction scores were 80.0, 23.4, 0.85, 80.0, 85.0, and 87.5, respectively. CONCLUSIONS: Percutaneous ankle fracture fixation with a fibular nail and posterior malleolar screws results in reliable fracture stabilization, good patient outcomes, and high treatment satisfaction. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

The impact of the COVID-19 pandemic on spinal surgery.

The impact of the coronavirus disease (COVID-19) pandemic on healthcare services around the world has been unprecedented. Surgical specialities, in particular, had to respond rapidly and adapt to continue to meet the needs of their patients in this ever-evolving and uncertain situation. With the cancellation of elective surgery and outpatient clinics, the majority of work carried out by spinal surgeons was obliterated. It was imperative emergency spinal care continued throughout the pandemic, with the creation of guidelines to assist spinal surgeons manage patients appropriately. Alongside assisting on the frontline, spinal surgeons had to triage referrals to ensure urgent care was still provided, undertake outpatient clinics virtually and ensure educational opportunities were available for colleagues. Paediatric spinal surgery was affected by the pandemic; although the virus did not significantly impact children to the same extent, a notable consequence of the lockdown restrictions was a reduction in GP referrals into the specialist service. In the event of any future pandemics, national spinal organizations have created guidelines to assist in the prioritization and care of spinal pathologies. While a 'return to normality' is a long way off, the impact of the past year will undoubtedly change spinal surgeons and their practice forever.

The surgical treatment of spinal deformity in children with non-ambulatory myelomeningocele.

AIMS: To report the outcome of spinal deformity correction through anterior spinal fusion in wheelchair-bound patients with myelomeningocele. METHODS: We reviewed 12 consecutive patients (7M:5F; mean age 12.4 years (9.2 to 16.8)) including demographic details, spinopelvic parameters, surgical correction, and perioperative data. We assessed the impact of surgery on patient outcomes using the Spina Bifida Spine Questionnaire and a qualitative questionnaire. RESULTS: The mean follow-up was 5.4 years (2 to 14.9). Nine patients had kyphoscoliosis, two lordoscoliosis, and one kyphosis. All patients had a thoracolumbar deformity. Mean scoliosis corrected from 89.6° (47° to 151°) to 46.5° (17° to 85°; p < 0.001). Mean kyphosis corrected from 79.5° (40° to 135°) to 49° (36° to 65°; p < 0.001). Mean pelvic obliquity corrected from 19.5° (8° to 46°) to 9.8° (0° to 20°; p < 0.001). Coronal and sagittal balance restored to normal. Complication rate was 58.3% (seven patients) with no neurological deficits, implant failure, or revision surgery. The degree of preoperative spinal deformity, especially kyphosis and lordosis, correlated with increased blood loss and prolonged hospital/intensive care unit stay. The patients reported improvement in function, physical appearance, and pain after surgery. The parents reported decrease in need for everyday care. CONCLUSION: Anterior spinal fusion achieved satisfactory deformity correction with high perioperative complication rates, but no long-term sequelae among children with high level myelomeningocele. This resulted in physical and functional improvement and high reported satisfaction. Cite this article: Bone Joint J 2021;103-B(6):1133-1141.

Hip displacement in children with cerebral palsy.

AIMS: The migration percentage (MP) is one criterion used for surgery in dislocated or displaced hips in children with cerebral palsy (CP). The MP at which a displaced hip can no longer return to normal is unclear. The aim of this paper was to identify the point of no return of the MP through a large population-based study. METHODS: All children registered on the Cerebral Palsy Integrated Pathway Scotland surveillance programme undergo regular pelvic radiographs. Any child who had a MP measuring over 35% since the programme's inception in 2013, in at least one hip and at one timepoint, was identified. The national radiography database was then interrogated to identify all pelvic radiographs for each of these children from birth through to the date of analysis. A minimum of a further two available radiographs following the initial measurement of MP ≥ 35% was required for inclusion. RESULTS: A total of 239 children (346 hips) were identified as suitable for analysis at a mean of 6.5 years (2.0 to 14.8) follow-up. In all, 1,485 radiographs taken both prior to and after a hip had a MP ≥ 35% were examined and the MP measured to identify any progression of displacement. Interrogation of the data identified that hips with a MP up to 46% returned to a MP below 40% without intervention, and all hips with a MP equal to or greater than 46% displaced further and the MP did not return to the normal range. Statistical analysis showed the result to be 98% specific with this degree of certainty that hips reaching a MP ≥ 46% would not spontaneously regress. CONCLUSION: These findings are clinically relevant in showing that it may be reasonable to continue to monitor hips with a MP not exceeding 46%. This threshold will also guide referral for further management of a displacing hip. Cite this article: Bone Joint J 2021;103-B(2):411-414.

Dandy-Walker Syndrome Associated with Scoliosis: Clinical Presentation, Preoperative Assessment, and Treatment.

Dandy-Walker syndrome (DWS) affects the posterior cranial fossa resulting in characteristic dysmorphic facial and body features. Scoliosis is not typically reported as an extracranial manifestation of this condition. We present a 12-year-old female patient who developed a right thoracic scoliosis measuring 60° with increased lumbar lordosis. Scoliosis correction was indicated to alleviate back pain, improve cosmesis, and prevent respiratory complications. A multidisciplinary preoperative assessment included cardiac, respiratory, anaesthetic, and neurology reviews. She underwent a posterior spinal fusion from T2 to L3 with pedicle hook/screw and rod instrumentation and a combination of locally harvested autologous and allograft bone. This resulted in excellent deformity correction and a balanced spine in the coronal and sagittal planes. The patient made an uneventful recovery and returned gradually to her normal level of activities. She was monitored in clinic until she completed her growth (4 years after surgery); the satisfactory surgical outcome was maintained at follow-up and was associated with high patient satisfaction. Scoliosis can occur in children with DWS with resemblance to adolescent idiopathic scoliosis in regard to type of coronal deformity, age at presentation, surgical techniques, and postoperative recovery. Early identification of scoliosis in patients with DWS can allow preoperative planning and prompt surgical management in order to reduce the risk of significant morbidity which can occur if the scoliosis is allowed to deteriorate. Excellent deformity correction can be achieved and maintained beyond skeletal maturity in order to improve physical appearance, as well as preserve level of function and quality of life.

Hip displacement and dislocation in a total population of children with cerebral palsy in Scotland.

AIMS: The purpose of this study was to compare the prevalence of hip displacement and dislocation in a total population of children with cerebral palsy (CP) in Scotland before and after the initiation of a hip surveillance programme. PATIENTS: A total of 2,155 children with CP are registered in the Cerebral Palsy Integrated Pathway Scotland (CPIPS) surveillance programme, which began in 2013. Physical examination and hip radiological data are collected according to nationally agreed protocols. METHODS: Age, Gross Motor Function Classification System (GMFCS) level, subtype of CP, migration percentage (MP), and details of hip surgery were analyzed for all children aged between two and 16 years taken from a time of census in March 2019 and compared to the same data from the initial registration of children in the CPIPS. Displacement of the hip was defined as a MP of between 40% and 99%, and dislocation as a MP of 100%. RESULTS: A total of 1,646 children were available for analysis at the time of the census and 1,171 at their first registration in CPIPS. The distribution of age, sex, and GMFCS levels were similar in the two groups. The prevalence of displacement and dislocation of the hip before surveillance began were 10% (117/1,171) and 2.5% (29/1,171) respectively, and at the time of the census were 4.5% (74/1,646) and 1.3% (21/1,646), respectively. Dislocation was only seen in GMFCS levels IV and V and displacement seen in 90.5% (67/74) of these levels and 9.5% (7/74) in levels I to III. In total, 138 children had undergone hip surgery during the study period. The hip redisplaced after the initial surgery in 15 children; seven of these had undergone a second procedure and at the time of the census the hips in all seven had a MP < 40. CONCLUSION: Hip surveillance appears to be effective and has reduced the prevalence of hip displacement by over half and dislocation almost by half in these children. Cite this article: Bone Joint J 2020;102-B(3):383-387.

The effect of femoral orientation on the measurement of the head shaft angle: an ex-vivo study.

This laboratory study evaluates head shaft angle (HSA) reliability using ranges of simulated femoral orientation often seen in children with cerebral palsy. A dry femur was mounted in a jig that enabled the bone to be positioned in a range of internal and external rotation (-40° to + 40°) and flexion (0°-60°), alone or in combination. A metal wire was placed as a surrogate physis to give two HSA angles of 140° and 160°. Radiographs were taken of the femur in differing combinations of rotation, flexion and the two HSA angles. The HSA was measured by four independent observers on two separate occasions. Intraclass correlation coefficients (ICCs) were used to assess interobserver and intraobserver reliability. The HSA was accurately measured within ± 5° when the femur was positioned between 20° internal rotation and 40° external rotation. Flexion up to 60° did not affect the accuracy of the measurement. The interobserver reliability for the HSA was excellent with an ICC of 0.9970 [95% confidence interval (CI): 0.9995-0.9983] for the first measurement and 0.9988 for the second (95% CI: 0.9979-0.9993, all P < 0.01). The intraobserver reliability was also excellent with an ICC of not less than 0.990 for all four observers (95% CI: 0.9806-0.9986, all P < 0.01). There was excellent interobserver and intraobserver reliability when measuring the HSA in an experimental model provided femoral rotation lay within 20° internal and 40° external rotation and less than 60° of flexion.