Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8–13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05–6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50–75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life. Funding Pfizer, Amgen, Merck Sharp & Dohme, Sanofi–Aventis, Daiichi Sankyo, and Regeneron

Meta-analysis on Materials and Techniques for Laparotomy Closure: The MATCH Review

BACKGROUND: The aim of this systematic review and meta-analysis was to evaluate closure materials and suture techniques for emergency and elective laparotomies. The primary outcome was incisional hernia after 12 months, and the secondary outcomes were burst abdomen and surgical site infection. METHODS: A systematic literature search was conducted until September 2017. The quality of the RCTs was evaluated by at least 3 assessors using critical appraisal checklists. Meta-analyses were performed. RESULTS: A total of 23 RCTs were included in the meta-analysis. There was no evidence from RCTs using the same suture technique in both study arms that any suture material (fast-absorbable/slowly absorbable/non-absorbable) is superior in reducing incisional hernias. There is no evidence that continuous suturing is superior in reducing incisional hernias compared to interrupted suturing. When using a slowly absorbable suture for continuous suturing in elective midline closure, the small bites technique results in significantly less incisional hernias than a large bites technique (OR 0.41; 95% CI 0.19, 0.86). CONCLUSIONS: There is no high-quality evidence available concerning the best suture material or technique to reduce incisional hernia rate when closing a laparotomy. When using a slowly absorbable suture and a continuous suturing technique with small tissue bites, the incisional hernia rate is significantly reduced compared with a large bites technique.status: publishe

Diaphragmatic crural augmentation utilising cross-linked porcine dermal collagen biologic mesh (Permacol) in the repair of large and complex para-oesophageal herniation: a retrospective cohort study

OBJECTIVE: To evaluate the safety, efficacy and durability of selective integration of porcine dermal collagen (Permacol) biologic mesh for crural re-construction in large or complex para-oesophageal hernia surgery. BACKGROUND: Surgical repair of para-oesophageal herniation has been associated with high rates of failure. The utilisation of prosthetic mesh is controversial with complications including erosion and fistulation. Long-term outcomes for biologic mesh crural augmentation are unclear. METHODS: A retrospective analysis of patients who underwent a biologic mesh (PermacolTM) augmented cruroplasty in the repair of large and/or complex para-oesophageal hernia was performed utilising the prospectively maintained oesophago-gastric database at the Royal Devon and Exeter Hospital between October 2004 and January 2013. This technique was selectively used for patients where the lateral extent of the diaphragmatic-crural defect prevented the fashioning of a sound, tension-free repair with sutures alone, or previous surgery had failed. Successful outcome was defined by resolution of symptoms and structural integrity of the repair. RESULTS: Fifty one procedures were performed on 49 patients (15 male), median age 75 (range 25-91). Post-operative morbidity included 2 (3.9 %) oesophageal injuries managed conservatively, and 2 (3.9 %) patients who suffered early repair breakdown requiring immediate surgical re-intervention. Four patients (8 %) required endoscopic dilatation due to dysphagia, one (2 %) in the early post-operative phase. The median follow-up was 36 months (range 6-105). All patients reported initial symptomatic resolution. Two patients (4 %) were demonstrated to have breakdown of their repair during the follow-up period, both of whom underwent revision mesh-augmented surgery and are re-incorporated in this series. Late-onset dysphagia in two (4 %) patients may be mesh-related, but no other complications were observed and a Kaplan-Meier analysis of this series predicts a symptom-free rate of approximately 94 % at 5 years. CONCLUSIONS: The selective integration of biologic mesh to augment the crural repair in para-oesophageal hernia with extensive diaphragmatic defects appears to be safe, effective and infers the potential of long-term satisfactory outcomes