Efficacy and Safety of Statin Treatment in Children with Familial Hypercholesterolemia: Outcomes of 20 Years of Experience.

BACKGROUND: The objective of this retrospective cohort study was to present the experience of 20-year-long comprehensive care of pediatric patients with familial hypercholesterolemia (FH) in a single academic center. METHODS AND RESULTS: The study included 84 children aged 1-18 years with FH. For the whole study group, 535 medical visits were recorded. The mean follow-up period was 33.6 months. Molecular testing performed in 55 children (65%) provided genetic confirmation of the diagnosis in 36 children (43%). Twenty-seven children (32%) were treated pharmacologically with statins. Follow-up during the treatment averaged 29 months. Treatment with statins was associated with a mean reduction in total cholesterol and LDL-cholesterol levels of 24 and 33% from the baseline. Symptoms of statin intolerance occurred incidentally and did not require amendment in the treatment protocol. Significantly higher values of body weight, height, and BMI were found only among girls older than 10 years who were treated with statins. CONCLUSIONS: These data confirm a high efficacy and a good safety profile of statin treatment in children with FH, demonstrating no harm to physical development. However, there is a need for further cause-and-effect research regarding associations between long-term treatment with low-cholesterol, low-fat diets, statin therapy, and excessive weight gain.

Can vitamin D be an adjuvant therapy for juvenile rheumatic diseases?

Vitamin D, known for its essential role in calcium and bone homeostasis, has multiple effects beyond the skeleton, including regulation of immunity and modulation of autoimmune processes. Several reports have shown suboptimal serum 25 hydroxyvitamin D [25(OH)D] levels in people with different inflammatory and autoimmune rheumatic conditions, and an association between 25(OH)D levels, disease activity and outcomes. Although most available data pertain to adults, insights often are extended to children. Juvenile rheumatic diseases (JRDs) are a significant health problem during growth because of their complex pathogenesis, chronic nature, multisystemic involvement, and long-term consequences. So far, there is no definitive or clear evidence to confirm the preventive or therapeutic effect of vitamin D supplementation in JRDs, because results from randomized controlled trials (RCTs) have produced inconsistent outcomes. This review aims to explore and discuss the potential role of vitamin D in treating selected JRDs. Medline/PubMed, EMBASE, and Scopus were comprehensively searched in June 2023 for any study on vitamin D supplementary role in treating the most common JRDs. We used the following keywords: "vitamin D" combined with the terms "juvenile idiopathic arthritis", "juvenile systemic scleroderma", "juvenile systemic lupus erythematosus", "juvenile inflammatory myopathies", "Behcet disease", "periodic fever syndromes" and "juvenile rheumatic diseases". Observational studies have found that serum 25(OH)D concentrations are lower in juvenile idiopathic arthritis, juvenile systemic lupus erythematosus, juvenile systemic scleroderma, Behcet disease and proinflammatory cytokine concentrations are higher. This suggests that vitamin D supplementation might be beneficial, however, current data are insufficient to confirm definitively the complementary role of vitamin D in the treatment of JRDs. Considering the high prevalence of vitamin D deficiency worldwide, children and adolescents should be encouraged to supplement vitamin D according to current recommendations. More interventional studies, especially well-designed RCTs, assessing the dose-response effect and adjuvant effect in specific diseases, are needed to determine the potential significance of vitamin D in JRDs treatment.

Guidelines for Preventing and Treating Vitamin D Deficiency: A 2023 Update in Poland.

Introduction: All epidemiological studies suggest that vitamin D deficiency is prevalent among the Polish general population. Since vitamin D deficiency was shown to be among the risk factors for many diseases and for all-cause mortality, concern about this problem led us to update the previous Polish recommendations. Methods: After reviewing the epidemiological evidence, case-control studies and randomized control trials (RCTs), a Polish multidisciplinary group formulated questions on the recommendations for prophylaxis and treatment of vitamin D deficiency both for the general population and for the risk groups of patients. The scientific evidence of pleiotropic effects of vitamin D as well as the results of panelists' voting were reviewed and discussed. Thirty-four authors representing different areas of expertise prepared position statements. The consensus group, representing eight Polish/international medical societies and eight national specialist consultants, prepared the final Polish recommendations. Results: Based on networking discussions, the ranges of total serum 25-hydroxyvitamin D concentration indicating vitamin D deficiency [<20 ng/mL (<50 nmol/L)], suboptimal status [20-30 ng/mL (50-75 nmol/L)], and optimal concentration [30-50 ng/mL (75-125 nmol/L)] were confirmed. Practical guidelines for cholecalciferol (vitamin D3) as the first choice for prophylaxis and treatment of vitamin D deficiency were developed. Calcifediol dosing as the second choice for preventing and treating vitamin D deficiency was introduced. Conclusions: Improving the vitamin D status of the general population and treatment of risk groups of patients must be again announced as healthcare policy to reduce a risk of spectrum of diseases. This paper offers consensus statements on prophylaxis and treatment strategies for vitamin D deficiency in Poland.

Prevalence of Vitamin D Deficiency in Patients Treated for Juvenile Idiopathic Arthritis and Potential Role of Methotrexate: A Preliminary Study.

Background: Vitamin D deficiency is reported in rheumatological diseases in adults. The aim was to evaluate the prevalence of vitamin D deficiency in children with juvenile idiopathic arthritis (JIA) and to investigate potential correlations between vitamin D status and clinical factors, laboratory traits, and medical treatment, including methotrexate (MTX) and glucocorticoids (GCs). Methods: In 189 patients aged 3−17.7 years, with JIA in the stable stage of the disease, anthropometry, clinical status, serum 25-hydroxyvitamin D [25(OH)D], calcium (Ca), phosphate (PO4), total alkaline phosphatase (ALP), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were assessed. Results: Median 25(OH)D level was 15.00 ng/mL, interquartile range (IQR) 12.00 ng/mL. Vitamin D deficiency was found in 67.2% and was independent of sex, disease manifestation, and CRP, ESR, ALP, or PO4 levels. Higher doses of MTX corresponded with lower 25(OH)D levels using both univariate and multivariate models (p < 0.05). No such trend was found for GCs treatment. Serum Ca was lower in patients treated with GCs (p = 0.004), MTX (p = 0.03), and combined GCs/MTX (p = 0.034). Conclusions: JIA patients are vitamin D depleted independently of disease activity or inflammatory markers. MTX therapy may be an iatrogenic factor leading to inadequate 25(OH)D levels. Vitamin D supplementation should be considered in all children with JIA, particularly those receiving long-term MTX therapy.

Non-disease specific patient-reported outcome measures of health-related quality of life in juvenile idiopathic arthritis: a systematic review of current research and practice.

Juvenile idiopathic arthritis (JIA), as a chronic condition, is associated with symptoms negatively impacting health-related quality of life (HRQL). Regarding growing interest in the implementation of the patient-reported outcome measures (PROMs), we aimed to review the non-disease specific PROMs addressing HRQL assessment, potentially useful in the clinical care of JIA and daily practice. A systematic literature search was conducted using MEDLINE/PubMed, Google Scholar, Scopus and Embase databases (1990 to 2021), with a focus on the recent 5-years period. Entry keywords included the terms: "children", "adolescents", "JIA", "chronic diseases", "HRQL", "PROMs" and wordings for the specific tools. Several available PROMs intended to measure HRQL, non-specific to JIA, were identified. The presented outcomes differed in psychometric properties, yet all were feasible in assessing HRQL in healthy children and those with chronic diseases. Both EQ-5D-Y and PedsQL have already been tested in JIA, showing relevant reliability, validity, and similar efficiency as disease-specific measurements. For PROMIS® PGH-7 and PGH-7 + 2, such validation and cross-cultural adaptation need to be performed. Considering the future directions in pediatric rheumatology, the large-scale implementation of PROMIS® PGH-7 and PGH-7 + 2 in JIA offers a particularly valuable opportunity. The PROMs reflect the patient perception of the chronic disease and allow to understand child's opinions. The PROMs may provide an important element of the holistic medical care of patients with JIA and a standardized tool for clinical outcomes, monitoring disease severity and response to treatment.

Daily oligofructose-enriched inulin intake impacts bone turnover markers but not the cytokine profile in pediatric patients with celiac disease on a gluten-free diet: Results of a randomised, placebo-controlled pilot study.

BACKGROUND: Bone metabolism disturbances are commonly observed in patients with newly diagnosed celiac disease (CD). The only available treatment for CD-the intake of a gluten-free diet (GFD)-has been found to be insufficient in effectively improving bone health in some patients. Therefore, there is an urgent need to modify the GFD so as to allow for the provision of all the necessary nutrients and improved absorption. Prebiotics intake reportedly improves the absorption of bone-related vitamin D and calcium as well as bone metabolism. The effect of prebiotic intake on bone health in CD patients has not been studied yet. This study aimed to evaluate the effect of oligofructose-enriched inulin intake on bone metabolism and immune response in children with CD on a GFD. METHODS: A total of 34 children with CD were randomised into two groups receiving 10 g of oligofructose-enriched inulin (Synergy 1) or a placebo (maltodextrin) for three months, together with a strict GFD. The children's bone metabolism marker levels and cytokine profiles were analysed before and after the intervention. RESULTS: After supplementation, the concentration of osteocalcin increased significantly in children receiving Synergy 1, while the concentration of bone alkaline phosphatase increased in both groups, independent of supplementation. After the intervention, the level of pyridinoline increased significantly in the placebo group, resulting in a concentration that was two times higher than that in the Synergy 1 group, in which it remained stable. Moreover, the plasma concentrations of N-terminal telopeptides of type I collagen decreased in both the groups, whereas the tartrate-resistant acid phosphatase 5b level increased particularly in the Synergy 1 group. The intervention did not lead to immunological response changes. CONCLUSIONS: The proposed supplementation beneficially altered bone metabolism, through increased bone formation rates and decreased bone resorption process rates. Supplementation of GFD with prebiotic oligofructose-enriched inulin may be a promising auxiliary therapy for bone metabolism improvements in children with CD.

Evidence of a significant vitamin D deficiency among 9-13-year-old Polish children: results of a multicentre study.

PURPOSE: To evaluate the extent to which the population of Polish preadolescents is vitamin D deficient and to assess seasonal variations in vitamin D status. PARTICIPANTS AND METHODS: A total of 720 healthy children aged 9-13 years (409 girls, 311 boys) residing in 6 representative geographical locations in Poland were studied. A parental-assisted questionnaire provided data on nutritional habits, vitamin D supplements and sun exposure. Serum concentration of 25-hydroxyvitamin was determined twice, after the winter in March and after the summer in October. RESULTS: In March, vitamin D deficiency (25-50 nmol/L) was found in 64%, and severe deficiency (< 25 nmol/L) in 20.2% of children. In October, the deficiency and severe deficiency were still noticed in 25.9 and 0.1% of children, respectively. The mean serum concentration of 25-OHD was 52% higher in October (55.4 ± 14.0 nmol/L) than in March (36.4 ± 13.5 nmol/L), (p < 0.01). In children with 25-OHD < 50 nmol/L in March, their 25-OHD concentration increased by 64% through March to October (32.5 ± 8.2 vs. 53.2 ± 7.9 nmol/L, p < 0.01). An association was found between 25-OHD concentration and regular consumption of vitamin D supplements, cod-liver oil and fish. CONCLUSIONS: The majority of preadolescent Polish boys and girls show vitamin D deficiency after the winter period, although a distinct amelioration over summertime is found in this age group. There is a need to implement effective prevention and intervention strategies in the management of vitamin D deficiency among schoolchildren in Poland, with the supplementation throughout the entire year.

Beneficial Effect of Oligofructose-Enriched Inulin on Vitamin D and E Status in Children with Celiac Disease on a Long-Term Gluten-Free Diet: A Preliminary Randomized, Placebo-Controlled Nutritional Intervention Study.

Prebiotics have been shown to improve absorption of some nutrients, including vitamins. This pilot study evaluated the effect of the prebiotic oligofructose-enriched inulin (Synergy 1) on fat-soluble vitamins status, parathormone, and calcium-related elements in pediatric celiac disease (CD) patients (n = 34) on a strict gluten-free diet (GFD). Participants were randomized into a group receiving 10 g of Synergy 1 or placebo (maltodextrin) together with a GFD. At baseline and after 3 months of intervention, 25-hydroxyvitamin D [25(OH)D], parathormone, vitamin E and A, calcium, phosphate, magnesium, total protein, and albumin were determined. Concentration of 25(OH)D increased significantly (p < 0.05) by 42% in CD patients receiving Synergy 1 in GFD, whereas no change was observed in placebo. Vitamin D status reached an optimal level in 46% of patients receiving Synergy 1. No significant difference in parathormone, calcium, and phosphate levels was observed. Concentration of vitamin E increased significantly (p < 0.05) by 19% in patients receiving Synergy 1, but not in the placebo. Vitamin A levels were not changed. Supplementation of GFD with Synergy 1 improved vitamin D and vitamin E status in children and adolescents with CD and could be considered a novel complementary method of management of fat-soluble vitamins deficiency in pediatric CD patients.

The Association Between Long-Term Acenocoumarol Treatment and Vitamin D Deficiency.

OBJECTIVE: Both vitamin D and K2 are involved in a number of metabolic processes, including bone metabolism; however, associations between the vitamins are not fully understood. The aim of the study was to evaluate serum concentrations of 25-hydroxyvitamin D [25(OH)D] in adult patients receiving long-term acenocoumarol (AC) treatment. PARTICIPANTS AND METHODS: In this cross-sectional study, 58 Caucasian patients (31 women, 27 men) with a median age of 65 years receiving long-term AC therapy were evaluated and compared with 35 age- and gender-matched healthy controls. The AC treatment was used due to recurrent venous thromboembolism (34.5%), atrial fibrillation (31%), or mechanical heart valve prostheses (34.5%). Medical records and a questionnaire were used to obtain information about chronic diseases, smoking habits, and the duration of therapy and weekly dose of AC. Anthropometric measurements were performed, and serum concentration of 25(OH)D and total alkaline phosphatase (ALP) activity were measured. RESULTS: Among the 58 patients receiving long-term AC treatment, a high proportion (46.6%) demonstrated significant vitamin D deficiency with concentrations of 25(OH)D lower than 20 ng/mL. The median concentration of 25(OH)D in subjects receiving AC was significantly lower compared to the control group [20.4 (17.4; 26.1) vs. 28.2 (24; 32.7); p < 0.001]. No differences were found between women and men receiving AC therapy. In patients receiving AC, a negative correlation was found between the concentration of 25(OH)D and the weekly dose of AC (r = -0.337, p = 0.01). Patients with concentrations of 25(OH)D < 20 ng/mL were found to have a significantly higher median dose of AC, compared to those with concentrations of 25(OH)D ≥ 20 ng/mL [21 (17; 31) vs. 17 (12; 28); p = 0.045]. CONCLUSION: In conclusion, treatment with AC is associated with low 25-hydroxyvitamin D levels, although the path leading to this phenomenon is not entirely clear. Long-term administration of AC in adults may increase the risk of chronic vitamin D deficiency, thus, effective supplementation of vitamin D in these individuals needs careful consideration.

Vitamin D supplementation guidelines.

Research carried out during the past two-decades extended the understanding of actions of vitamin D, from regulating calcium and phosphate absorption and bone metabolism to many pleiotropic actions in organs and tissues in the body. Most observational and ecological studies report association of higher serum 25-hydroxyvitamin D [25(OH)D] concentrations with improved outcomes for several chronic, communicable and non-communicable diseases. Consequently, numerous agencies and scientific organizations have developed recommendations for vitamin D supplementation and guidance on optimal serum 25(OH)D concentrations. The bone-centric guidelines recommend a target 25(OH)D concentration of 20ng/mL (50nmol/L), and age-dependent daily vitamin D doses of 400-800IU. The guidelines focused on pleiotropic effects of vitamin D recommend a target 25(OH)D concentration of 30ng/mL (75nmol/L), and age-, body weight-, disease-status, and ethnicity dependent vitamin D doses ranging between 400 and 2000IU/day. The wise and balanced choice of the recommendations to follow depends on one's individual health outcome concerns, age, body weight, latitude of residence, dietary and cultural habits, making the regional or nationwide guidelines more applicable in clinical practice. While natural sources of vitamin D can raise 25(OH)D concentrations, relative to dietary preferences and latitude of residence, in the context of general population, these sources are regarded ineffective to maintain the year-round 25(OH)D concentrations in the range of 30-50ng/mL (75-125nmol/L). Vitamin D self-administration related adverse effects, such as hypercalcemia and hypercalciuria are rare, and usually result from taking extremely high doses of vitamin D for a prolonged time.

Endothelial injury markers with high-dose intravenous iron therapy in renal failure.

Endothelial injury is prevalent in patients with chronic renal failure (CRF) and may be exacerbated by commonly used intravenous (IV) iron therapy. The effects of high-dose IV iron sucrose treatment (200 mg daily in 250 mL of 0.9% saline, administered over 1 hour, median treatment duration 5 days) on circulating endothelium and/or tissue injury markers such as hepatocyte growth factor, thrombomodulin, von Willebrand factor, and C-reactive protein levels were studied. The markers were determined in 24 anemic (mean hemoglobin 9.48 g/dL) pre-dialysis (median creatinine clearance 21.5 mL/min) patients with CRF and defined absolute and/or functional iron deficiency. The measurements were performed before iron administration and 24 hours after the last infusion. All the markers remained unchanged following the IV iron therapy (all p < 0.172); no thrombotic or other adverse effects were observed. In conclusion, the above high-dose IV iron sucrose supplementation does not cause evident endothelial or other tissue injury in patients with CRF, and is clinically safe.