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

C -Reactive Protein, Leukocyte Count and Neutrophils: A Diagnostic Aid in Acute Appendicitis

Background: Malnutrition is known to be a poor prognostic factor affecting the outcome of pediatric cancers. The objective of this study was to assess the pre-existing malnutrition in newly diagnosed pediatric cancer patients presenting at the Pediatric Oncology Department, Children Hospital, PIMS and their number of hospital admissions due to causes other than chemotherapy. Methodology: Data of 44 newly diagnosed children with cancer was analyzed to find out the association of nutritional status according to z-score for weight and height for age, body mass index (BMI) and mid-upper arm circumference (MUAC) with their number of hospital admissions for 6 months since their date of diagnosis. Results: The mean age of the study subjects was 4.25 ± 2.85 years, out of which 33(75%) were males and 11(25%) females. Most of the patients were diagnosed with leukemia or lymphoma.  Nutritional status evaluation of thirty patients who got admitted was mild to moderate wasting in 24(80%) assessed by weight for age, mild to moderate stunting in 21 (70%) according to height for age and mild to severe malnutrition in 10 (33%) based on body mass index and mid upper arm circumference (MUAC). There was significant association between nutritional status of patients at the time of diagnosis with additional hospitalization with p value less than 0.05 Conclusion: Malnutrition at the time of diagnosis is significantly associated with an increase in the number of hospital admissions in pediatric cancer patients. Key words: Hospitalization, Malnutrition, Oncology, Pediatric &nbsp

Characterization of Mannose Binding Lectin (MBL) Levels in Type-2 Diabetes Mellitus Patients Amongst Pakistani Population

Introduction: Mannose Binding Lectin (MBL) is a pattern recognizing molecule in the Lectin complement pathway and acts by activating the complement cascade via binding with ligands. There is evidence of increased autoreactivity of Mannose Binding Lectin in various diseases especially diabetes. MBL deficiency can reduce pathogen clearance and impair atherogenic lipoprotein removal whereas higher levels are associated with exaggerated immune response due to complement activation in the presence of hyperglycemia. Aims & Objectives: This study aims to find out the association of MBL (Mannose Binding Lectin) with different clinical parameters in healthy controls and type 2 DM patients to predict disease outcome in type 2 diabetics. Mean level of MBL in type 2 diabetics and healthy population will be compared to characterize MBL levels amongst diabetics helping the clinicians to stratify patients according to disease severity. Place and duration of study: It was a cross sectional analytical study conducted at Chughtai Institute of Pathology from July 2019 to January 2020 on samples collected nationwide at Chughtai Lab collection centres. Material & Methods: We selected 300 adult male and females in this study after taking informed consent based on strict inclusion and exclusion criteria. Of these 200 were known cases of type 2 diabetes mellitus and 100 healthy controls. .Fasting blood samples were drawn from both groups were analyzed for hs-CRP, HbA1c, creatinine, Total Cholesterol, Alanine amino transfer as (ALT), HDL-Cholesterol, LDL-Cholesterol, Glucose, Triglyceride, and Mannose Binding lectin. eGFR (Estimated Glomerular Filtration rate) was calculated for each patient and control. Data was analyzed via Graph Pad Prism 5 and SPSS version 23.0, p value ? 0.05 was taken as significant. Results: Mean age of the participants was 47.9 years in diabetic group and 39.3 years in healthy controls. The healthy population had a mean MBL level of 110.1 (SD±3.94) pg/ml and mean MBL level of diabetic group was 197.9 (SD±12.84) pg/ml (p<0.05). No differences in MBL levels were detected based on gender distribution. There was a significant difference among HbA1c, LDL-C, HDL-C, Fasting Glucose, TG, creatinine and eGFR amongst the diabetic and the healthy group (p<0.05). There was a negative correlation between MBL levels and plasma glucose and a positive correlation between the former and HDL-C in the healthy controls. In diabetic patients having MBL above 178pg/ml, a positive correlation of HbA1C with MBL was found. CRP in the healthy population resembled levels in patients with elevated MBL and the ratio Trig/HDL was higher in this subgroup having a positive correlation with MBL. Conclusion: MBL plays a role in pathophysiology of diabetes mellitus and elevated MBL having positive correlation with HbA1c might show association of glycemic control with the biomarker levels. A direct relationship of MBL with development of cardiovascular complications in type 2 diabetics was suggested by a positive association of MBL with TG to HDL-C ratio