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Homozygous familial hypercholesterolaemia (HoFH) is a rare genetic disease characterised by extremely high plasma LDL cholesterol from birth, causing atherosclerotic cardiovascular disease at a young age. Lipoprotein apheresis in combination with lipid-lowering drugs effectively reduce LDL cholesterol, but long-term health outcomes of such treatment are unknown. We aimed to investigate the long-term cardiovascular outcomes associated with lipoprotein apheresis initiated in childhood or adolescence.

ABSTRACTIntroductionHeterozygous familial hypercholesterolemia (HeFH) is a common genetic disorder caused by pathogenic variants in the LDL-C metabolism. Lifelong exposure to elevated LDL-C levels leads to a high risk of premature cardiovascular disease. To reduce that risk, children with HeFH should be identified and treated with lipid-lowering therapy. The cornerstone consists of statins and ezetimibe, but not in all patients this lowers the LDL-C levels to treatment targets. For these patients, more intensive lipid-lowering therapy is needed.Areas coveredIn this review, we provide an overview of the monoclonal antibodies which are currently available or being tested for treating HeFH in childhood.Expert opinionMonoclonal antibodies that inhibit PCSK9 are first in line lipid-lowering treatment options if oral statin and ezetimibe therapy are insufficient, due to intolerance or very high baseline LDL-C levels. Both evolocumab and alirocumab have been shown to be safe and effective in children with HeFH. For children, evolocumab has been registered from the age of 10 years old and alirocumab from the age of 8 years old. The costs of these new agents are much higher than oral therapy, which makes it important to only use them in a selected patient population.

Familial hypercholesterolemia (FH) is one of the most common genetically inherited disorders in the world. Children with severe heterozygous FH (HeFH), i.e. untreated low-density lipoprotein cholesterol (LDL-C) levels above the 90th percentile for age and sex among FH mutation carriers, can have LDL-C levels that overlap levels of children with homozygous FH (HoFH), but treatment regimen and cardiovascular follow-up to prevent cardiovascular disease are less intensive in children with severe HeFH. In children with HoFH, subclinical atherosclerosis can already be present using computed tomography coronary angiography (CTCA). The question remains whether this is also the case in children with severe HeFH who have a high exposure to elevated LDL-C levels from birth onwards as well. We calculated the cumulative LDL-C exposure (CEtotal[mmol]) in four children with severe HeFH and performed computed tomography coronary angiography (CTCA). These children, aged 13, 14, 15 and 18 years, had CEtotalof 71.3, 97.8, 103.6 and 136.1 mmol, respectively. None of them showed abnormalities on cardiovascular imaging, despite high LDL-C exposure. The results of this study, do not give us an indication to recommend performing CTCA routinely in children with severe HeFH.

Objective: To summarise and review articles addressing the quality (validity, reliability, applicability) of seven commonly used definitions of hip osteoarthritis (OA) for epidemiological studies in order to use it primarily [...]

Homozygous familial hypercholesterolaemia (HoFH) is a rare inherited disorder resulting in extremely elevated low-density lipoprotein cholesterol levels and premature atherosclerotic cardiovascular disease (ASCVD). Current guidance about its management and prognosis stems from small studies, mostly from high-income countries. The objective of this study was to assess the clinical and genetic characteristics, as well as the impact, of current practice on health outcomes of HoFH patients globally.

AimsLittle is known about the risk factors that predispose to a rupture of the posterior cruciate ligament (PCL). Identifying risk factors is the first step in trying to prevent a rupture of the PCL from occurring. The morphology of the knee in patients who rupture their PCL may differ from that of control patients. The purpose of this study was to identify any variations in bone morphology that are related to a PCL.Patients and MethodsWe compared the anteroposterior (AP), lateral, and Rosenberg view radiographs of 94 patients with a ruptured PCL to a control group of 168 patients matched by age, sex, and body mass index (BMI), but with an intact PCL after a knee injury. Statistical shape modelling software was used to assess the shape of the knee and determine any difference in anatomical landmarks.ResultsWe found shape variants on the AP and Rosenberg view radiographs to be significantly different between patients who tore their PCL and those with an intact PCL after a knee injury. Overall, patients who ruptured their PCL have smaller intercondylar notches and smaller tibial eminences than control patients.ConclusionThis study shows that differences in the shape of the knee are associated with the presence of a PCL rupture after injury. A smaller and more sharply angled intercondylar notch and a more flattened tibial eminence are related to PCL rupture. This suggests that the morphology of the knee is a risk factor for sustaining a PCL rupture.Cite this article: Bone Joint J2019;101-B:1058–1062.

With an annual incidence rate of 2-5% in high-risk populations, the use of established knee OA as an outcome challenges the feasibility of preventive OA research. Therefore, valid surrogate outcomes, for which short-term changes capture long-term OA incidence, are urgently needed.

AimsOpen reduction is required following failed conservative treatment of developmental dysplasia of the hip (DDH). The Ludloff medial approach is commonly used, but poor results have been reported, with rates of the development of avascular necrosis (AVN) varying between 8% and 54%. This retrospective cohort study evaluates the long-term radiographic and clinical outcome of dislocated hips treated using this approach.Patients and MethodsChildren with a dislocated hip, younger than one year of age at the time of surgery, who were treated using a medial approach were eligible for the study. Radiographs were evaluated for the degree of dislocation and the presence of an ossific nucleus preoperatively, and for the degree of AVN and residual dysplasia at one and five years and at a mean of 12.7 years (4.6 to 20.8) postoperatively. Radiographic outcome was assessed using the Severin classification, after five years of age. Further surgical procedures were recorded. Functional outcome was assessed using the Pediatric Outcomes Data Collection Instrument (PODCI) or the Hip Disability and Osteoarthritis Outcome Score (HOOS), depending on the patient’s age.ResultsA total of 52 children (58 hips) were included. At the latest follow-up, 11 hips (19%) showed signs of AVN. Further surgery was undertaken in 13 hips (22%). A total of 13 hips had a poor radiological outcome with Severin type III or higher. Of these, the age at the time of surgery was significantly higher (p < 0.05) than in those with a good Severin type (I or II). The patient-reported outcomes were significantly worse (p < 0.05) in children with a poor Severin classification.ConclusionThis retrospective long-term follow-up study shows that one in five children with DDH who undergo open reduction using a medial surgical approach has poor clinical and/or radiological outcome. The poor outcome is not related to the presence of AVN (19%), but due to residual dysplasia.Cite this article: Bone Joint J2018;100-B:822–7.

ASCVD /CVD Risk Reduction

AimsThe aim of this study was to assess the current available evidence about when patients might resume driving after elective, primary total hip (THA) or total knee arthroplasty (TKA) undertaken for osteoarthritis (OA).Materials and MethodsIn February 2016, EMBASE, MEDLINE, Web of Science, Scopus, Cochrane, PubMed Publisher, CINAHL, EBSCO and Google Scholar were searched for clinical studies reporting on ‘THA’, ‘TKA’, ‘car driving’, ‘reaction time’ and ‘brake response time’. Two researchers (CAV and JJT) independently screened the titles and abstracts for eligibility and assessed the risk of bias. Both fixed and random effects were used to pool data and calculate mean differences (MD) and 95% confidence intervals (CI) between pre- and post-operative total brake response time (TBRT).ResultsA total of 19 studies were included. The assessment of the risk of bias showed that one study was at high risk, six studies at moderate risk and 12 studies at low risk. Meta-analysis of TBRT showed a MD decrease of 25.54 ms (95% CI -32.02 to 83.09) two weeks after right-sided THA, and of 18.19 ms (95% CI -6.13 to 42.50) four weeks after a right-sided TKA, when compared with the pre-operative value.ConclusionThe TBRT returned to baseline two weeks after a right-sided THA and four weeks after a right-sided TKA. These results may serve as guidelines for orthopaedic surgeons when advising patients when to resume driving. However, the advice should be individualised.Cite this article: Bone Joint J2017;99-B:566–76.

We have investigated whether shape of the knee can predict the clinical outcome of patients after an anterior cruciate ligament rupture. We used statistical shape modelling to measure the shape of the knee joint of 182 prospectively followed patients on lateral and Rosenberg view radiographs of the knee after a rupture of the anterior cruciate ligament. Subsequently, we associated knee shape with the International Knee Documentation Committee subjective score at two years follow-up. The mean age of patients was 31 years (21 to 51), the majority were male (n = 121) and treated operatively (n = 135). We found two modes (shape variations) that were significantly associated with the subjective score at two years: one for the operatively treated group (p = 0.002) and one for the non-operatively treated group (p = 0.003). Operatively treated patients who had higher subjective scores had a smaller intercondylar notch and a smaller width of the intercondylar eminence. Non-operatively treated patients who scored higher on the subjective score had a more pyramidal intercondylar notch as opposed to one that was more dome-shaped. We conclude that the shape of the femoral notch and the intercondylar eminence is predictive of clinical outcome two years after a rupture of the anterior cruciate ligament.Cite this article: Bone Joint J2014;96-B:737–42.

Forearm fractures in children have a tendency to displace in a cast leading to malunion with reduced functional and cosmetic results. In order to identify risk factors for displacement, a total of 247 conservatively treated fractures of the forearm in 246 children with a mean age of 7.3 years (sd3.2; 0.9 to 14.9) were included in a prospective multicentre study. Multivariate logistic regression analyses were performed to assess risk factors for displacement of reduced or non-reduced fractures in the cast. Displacement occurred in 73 patients (29.6%), of which 65 (89.0%) were in above-elbow casts. The mean time between the injury and displacement was 22.7 days (0 to 59). The independent factors found to significantly increase the risk of displacement were a fracture of the non-dominant arm (p = 0.024), a complete fracture (p = 0.040), a fracture with translation of the ulna on lateral radiographs (p = 0.014) and shortening of the fracture (p = 0.019).Fractures of both forearm bones in children have a strong tendency to displace even in an above-elbow cast. Severe fractures of the non-dominant arm are at highest risk for displacement. Radiographs at set times during treatment might identify early displacement, which should be treated before malunion occurs, especially in older children with less potential for remodelling.Cite this article: Bone Joint J2013;95-B:689–93.

We present the long-term outcome, at a median of 18 years (12.8 to 23.5) of open posterior bone block stabilisation for recurrent posterior instability of the shoulder in a heterogenous group of 11 patients previously reported on in 2001 at a median follow-up of six years.We found that five (45%) would not have chosen the operation again, and that four (36%) had further posterior dislocation. Clinical outcome was significantly worse after 18 years than after six years of follow-up (median Rowe score of 60 versus 90 (p = 0.027)). The median Western Ontario Shoulder Index was 60% (37% to 100%) at 18 years’ follow-up, which is a moderate score. At the time of surgery four (36%) had glenohumeral radiological osteoarthritis, which was present in all after 18 years.This study showed poor long-term results of the posterior bone block procedure for posterior instability and a high rate of glenohumeral osteoarthritis although three patients with post-traumatic instability were pleased with the result of their operations.

To provide an overview of prognostic factors of knee osteoarthritis (OA) progression.We searched Medline and Embase up to December 2003 according to a specified search strategy (keywords for disease, location, and study design). Studies that fulfilled predefined criteria were assessed for methodologic quality. Study characteristics and associations were extracted and the results were summarized according to a best evidence synthesis.Of the 1,004 studies found, 37 met the inclusion criteria. Methodologic quality was assessed and only high‐quality studies were included (n = 36). The best evidence synthesis yielded strong evidence that hyaluronic acid serum levels and generalized OA are predictive for progression of knee OA. Sex, knee pain, radiologic severity, knee injury, quadriceps strength, and regular sport activities were not predictive. Conflicting evidence for associations was found for several factors including body mass index and age. Limited evidence for an association with progression of knee OA was found for several factors, including the alignment (varus/valgus) of the joint. Limited evidence for no association with progression of OA was also found for several factors, including meniscectomy, several markers of bone or cartilage turnover, and the clinical diagnosis of localized OA.Generalized OA and level of hyaluronic acid seem to be associated with the radiologic progression of knee OA. Knee pain, radiologic severity at baseline, sex, quadriceps strength, knee injury, and regular sport activities seem not to be related. For other factors, the evidence was limited or conflicting.

Osteophytes, also small ones, are an important imaging feature of OA. However, due to their high prevalence on MR, the question has arisen whether these are truly pathophysiologic features of early OA, a result of physiologic aging, or rather a merely transient phenomenon. The aim of this study was to explore the prevalence of osteophytes on MR in various locations of the knee, with special emphasis on small osteophytes, across multiple large studies conducted in our institution comprising a wide range of subjects at different ages.

Familial hypercholesterolaemia is a common, dominantly inherited disease that results in high concentrations of low-density lipoprotein cholesterol and in premature cardiovascular disease. To prevent cardiovascular disease and premature mortality, patients with the condition need to be identified and to start treatment early in life. In this Review, we discuss the treatment of heterozygous and homozygous familial hypercholesterolaemia in children, including lifestyle modifications, current pharmacological treatment options, and promising novel lipid-lowering treatments. In particular, these new therapies are expected to improve outcomes for patients with severe heterozygous familial hypercholesterolaemia or statin intolerance. For patients with homozygous familial hypercholesterolaemia, lipoprotein apheresis is currently the most valuable therapy available, but new approaches might reduce the need for this effective yet invasive, time-consuming, and expensive treatment.