Determination of Optimal Vitamin D Dosage in Children with Cholestasis.

BACKGROUND: Vitamin D deficiency in patients with cholestasis is due to impaired intestinal vitamin D absorption, which results from decreased intestinal bile acid concentration. Patients with cholestasis usually do not achieve optimal vitamin D status when a treatment regimen for children without cholestasis is used. However, data on high-dose vitamin D treatment in patients with cholestasis are limited. METHODS: This study is a prospective study that included pediatric patients with cholestasis (serum direct bilirubin > 1 mg/dL) who had vitamin D deficiency (serum 25-hydroxyvitamin D, 25-OHD, < 20 ng/mL). In Phase 1, single-day oral loading of 300,000 IU (or 600,000 IU if weight ≥ 20 kg) of vitamin D2 was administered, followed by an additional loading if serum 25-OHD < 30 ng/mL, and 4-week continuation of treatment using a vitamin D2 dose calculated based on the increment of 25-OHD after first loading. In Phase 2, oral vitamin D2 (200,000 IU/day) was administered for 12 days, followed by 400,000 IU/day of vitamin D2 orally for another 8 weeks if serum 25-OHD < 30 ng/mL. RESULTS: Phase 1: Seven patients were enrolled. Three out of seven patients had a moderate increase in serum 25-OHD after loading (up to 20.3-27.2 ng/mL). These patients had conditions with partially preserved bile flow. The remaining four patients, who had biliary atresia with failed or no Kasai operation, had low increments of serum 25-OHD. Phase 2: Eleven patients were enrolled. Eight out of 11 patients had a moderate increase in serum 25-OHD after 200,000 IU/day of vitamin D2 for 12 days. Serum 25-OHD continued increasing after administering 400,000 IU/day of vitamin D2 for another 8 weeks, with maximal serum 25-OHD of 15.7-22.8 ng/mL. CONCLUSION: Very high doses of vitamin D2 (200,000 and 400,000 IU/day) partly overcame poor intestinal vitamin D absorption and resulted in moderate increases in serum 25-OHD in pediatric patients with cholestasis, particularly when cholestasis was caused by uncorrectable bile duct obstruction.

Vitamin D Deficiency: An Underestimated Factor in Sepsis?

Vitamin D is an important immune modulator that is linked to infection susceptibility. It has been suggested that vitamin D deficiency plays a role in sepsis and septic shock because vitamin-D-related pathways are associated with various immunological, endocrine, and endothelial functions. Previous research has yielded inconclusive results regarding the link between mortality and vitamin D deficiency in sepsis patients. In patients with sepsis and severe vitamin D deficiency, an adequate vitamin D concentration may reduce mortality. Randomized controlled trials to assess the influence of vitamin D supplementation on clinical outcomes in sepsis patients with vitamin D deficiency are uncommon. We will provide an overview of the current knowledge about the relationship between vitamin D and sepsis in this review, as well as consider the potential value of vitamin D supplementation in this situation.

25(OH)Vitamin D Deficiency and Calcifediol Treatment in Pediatrics.

Vitamin D is essential for the normal mineralization of bones during childhood. Although diet and adequate sun exposure should provide enough of this nutrient, there is a high prevalence of vitamin D deficiency rickets worldwide. Children with certain conditions that lead to decreased vitamin D production and/or absorption are at the greatest risk of nutritional rickets. In addition, several rare genetic alterations are also associated with severe forms of vitamin-D-resistant or -dependent rickets. Although vitamin D3 is the threshold nutrient for the vitamin D endocrine system (VDES), direct measurement of circulating vitamin D3 itself is not a good marker of the nutritional status of the system. Calcifediol (or 25(OH)D) serum levels are used to assess VDES status. While there is no clear consensus among the different scientific associations on calcifediol status, many clinical trials have demonstrated the benefit of ensuring normal 25(OH)D serum levels and calcium intake for the prevention or treatment of nutritional rickets in childhood. Therefore, during the first year of life, infants should receive vitamin D treatment with at least 400 IU/day. In addition, a diet should ensure a normal calcium intake. Healthy lifestyle habits to prevent vitamin D deficiency should be encouraged during childhood. In children who develop clinical signs of rickets, adequate treatment with vitamin D and calcium should be guaranteed. Children with additional risk factors for 25(OH)D deficiency and nutritional rickets should be assessed periodically and treated promptly to prevent further bone damage.

The Influence of Conventional Treatment on Symptoms and Complaints in Patients With Chronic Postsurgical Hypoparathyroidism.

Quality of life (QoL) is impaired in patients with chronic hypoparathyroidism (HypoPT). With a recently developed specific patient questionnaire, the 28-item Hypoparathyroid Patient Questionnaire (HPQ 28), we were able to demonstrate an effect of laboratory parameters on symptoms and complaints identified by scales and items of the HPQ 28. Here, we evaluated the effect of conventional treatment modalities on QoL using this specific questionnaire. In this cross-sectional study, we included 49 HypoPT (41 female and 8 male) patients. Laboratory values of total serum calcium, magnesium, phosphate, calcium-phosphate product (CPP), and 24-hour urine for calcium and phosphate were analyzed. Patients completed the HPQ 28 questionnaire during the corresponding visit. Mean age was 57.3 ± 10.5 years and duration of disease 12.6 ± 9.8 years. Most patients (86%, n = 42) were treated with the active vitamin D analogs calcitriol, alfacalcidol, or dihydrotachysterol (DHT). The use of calcium and magnesium supplements influenced scales on HPQ 28 in a dose-dependent manner. We detected a dose-dependent increase on the HPQ 28 scales "depression and anxiety" and "pain and cramps," and the item "numbness and tingling" related to calcitriol. This effect was independent of gender, age, underlying disease, kind of surgery, serum 25-hydroxyvitamin D3, calcium, or phosphate values. This study presents the first data on specific symptoms of HypoPT patients dependent on different treatment modalities. Our data suggest that in part the reduced QoL in these patients might be caused by conventional treatment. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Seven Weeks of High-Dose Vitamin D Treatment Reduces the Need for Infliximab Dose-Escalation and Decreases Inflammatory Markers in Crohn's Disease during One-Year Follow-Up.

BACKGROUND: Seven weeks of high-dose vitamin D treatment decreases intestinal IL17A and IFN-γ mRNA expression in active Crohn's disease (CD). In this follow-up study, we investigated whether seven-week vitamin D treatment affected the infliximab response in the following 45 weeks compared to placebo. METHODS: CD patients (n = 40) were initially randomised into four groups: infliximab + vitamin-D; infliximab + placebo-vitamin-D; placebo-infliximab + vitamin-D; and placebo-infliximab + placebo-vitamin-D. Infliximab (5 mg/kg) or placebo-infliximab was administered at weeks 0, 2 and 6. Vitamin D (5 mg bolus followed by 0.5 mg/day for 7 weeks) or placebo-vitamin D was handed out. After the 7-week vitamin D period, all patients received infliximab during follow-up. Results are reported for Group D+ (infliximab + vitamin-D and placebo-infliximab + vitamin-D) and Group D- (infliximab + placebo-vitamin-D and placebo-infliximab + placebo-vitamin-D). RESULTS: Group D- patients had greater needs for infliximab dose escalation during follow-up compared to group D+ (p = 0.05). Group D+ had lower median calprotectin levels week 15 (p = 0.02) and week 23 (p = 0.04) compared to group D-. Throughout follow-up, group D+ had 2.2 times (95% CI: 1.1-4.3) (p = 0.02) lower median CRP levels compared with group D-. CONCLUSIONS: Seven weeks high-dose vitamin D treatment reduces the need for later infliximab dose-escalation and reduces inflammatory markers. EudraCT no. 2013-000971-34.

High-Dose Cholecalciferol Booster Therapy is Associated with a Reduced Risk of Mortality in Patients with COVID-19: A Cross-Sectional Multi-Centre Observational Study.

The worldwide pandemic of 2019 novel coronavirus disease (COVID-19) has posed the most substantial and severe public health issue for several generations, and therapeutic options have not yet been optimised. Vitamin D (in its "parent" form, cholecalciferol) has been proposed in the pharmacological management of COVID-19 by various sources. We aimed to determine whether COVID-19 mortality was affected by serum 25-hydroxyvitamin D (25(OH)D) levels, vitamin D status, or cholecalciferol therapy, and to elucidate any other predictors of COVID-19 mortality. Patients hospitalised with COVID-19 were opportunistically recruited from three UK hospitals, and their data were collected retrospectively. Logistic regression was used to determine any relationships between COVID-19 mortality and potential predictors, including 25(OH)D levels and cholecalciferol booster therapy. A total of 986 participants with COVID-19 were studied, of whom 151 (16.0%) received cholecalciferol booster therapy. In the primary cohort of 444 patients, cholecalciferol booster therapy was associated with a reduced risk of COVID-19 mortality, following adjustment for potential confounders (ORadj 0.13, 95% CI 0.05-0.35, p < 0.001). This finding was replicated in a validation cohort of 541 patients (ORadj 0.38, 95% CI 0.17-0.84, p = 0.018). In this observational study, treatment with cholecalciferol booster therapy, regardless of baseline serum 25(OH)D levels, appears to be associated with a reduced risk of mortality in acute in-patients admitted with COVID-19. Further work with large population studies needs to be carried out to determine adequate serum 25(OH)D levels, as well as multi-dose clinical trials of cholecalciferol therapy to assess maximum efficacy.

Decrease in Mucosal IL17A, IFNγ and IL10 Expressions in Active Crohn's Disease Patients Treated with High-Dose Vitamin Alone or Combined with Infliximab.

BACKGROUND: Vitamin D treatment may reduce Crohn's disease (CD) activity by modulating the mucosal immune function. We investigated if high-dose vitamin D +/- infliximab modulated the mucosal cytokine expression in active CD. METHODS: Forty CD patients were randomized into: infliximab + vitamin D; infliximab + placebo-vitamin D; placebo-infliximab + vitamin D or placebo-infliximab + placebo-vitamin D. Infliximab (5 mg/kg) and placebo-infliximab were administered at weeks 0, 2 and 6. Oral vitamin D was administered as bolus 200,000 international units (IU) per week 0 followed by 20,000 IU/day for 7 weeks or placebo. Endoscopy with biopsies was performed at weeks 0 and 7 where endoscopic activity was measured and mucosal mRNA cytokine expression was examined. C-reactive protein (CRP), fecal calprotectin and Harvey-Bradshaw Index (HBI) were measured at weeks 0, 2 and 6. RESULTS: High-dose vitamin D treatment alone and combined with infliximab decreased the IL17A, IFNγ and IL10 expression. High-dose vitamin D alone did not significantly decrease the disease activity, CRP or calprotectin. Combined infliximab and vitamin D treatment was not clinically significantly superior to monotherapy with infliximab. CONCLUSIONS: High-dose vitamin D as monotherapy and combined with infliximab decreases IL17A, IFNγ and IL-10 expression in mucosa within treatment groups. This did not induce a statistically significant decreased disease activity. EudraCT no.2013-000971-34.

Effect of Vitamin D Treatment on Dynamics of Stones Formation in the Urinary Tract and Bone Density in Children with Idiopathic Hypercalciuria.

Vitamin D supplementation in patients with urolithiasis and hypercalciuria is considered to be unsafe. We analyzed the impact of vitamin D supplementation on selected health status parameters in children with idiopathic hypercalciuria. The study included 36 children with urolithiasis resulting from excessive calcium excretion. The level of calcium and 25(OH)D (hydroxylated vitamin D - calcidiol) in serum, urinary calcium excretion and the presence of stones in urinary tract were assessed prospectively. Blood and urine samples were collected at the time when the patient was qualified for the study and every three months up to 24 month of vitamin D intake at a dose of 400 or 800 IU/day. At time zero and at 12, and 24 months of vitamin D supplementation, densitometry was performed. Supplementation with vitamin D caused a statistically significant increase in the concentration of 25(OH)D in serum. There were no significant changes in calcium concentration in serum, excretion of calcium in urine but also in bone density. There was no significant increase in the risk of formation or development of stones in the urinary tract. Supplementation with vitamin D (400-800 IU/day) in children with idiopathic hypercalciuria significantly increases 25(OH)D concentration, does not affect calciuria, but also does not improve bone density.

Electrophysiological evaluation of carpal tunnel syndrome female patients after vitamin D replacement / Avaliação eletrofisiológica de pacientes do sexo feminino com síndrome do túnel do carpo após reposição de vitamina D

Abstract Objective: The effects of vitamin D on the central and peripheral nervous system continue to be investigated today. In the present study, we aimed to evaluate pain and electrophysiologic response in patients with carpal tunnel syndrome (CTS) who have undergone replacement therapy due to vitamin D deficiency. Methods: Fifty female patients diagnosed with mild and moderate CTS and accompanied by vitamin D deficiency were included in this study. Nerve conduction study (NCS) was performed before and after vitamin D replacement, and the patient's pain was evaluated with Visual Analogue Scale (VAS). Results: When NCS were compared before and after treatment, there was a statistically significant improvement in the median distal sensory onset latency (DSOL) and sensory conduction velocity (CV) and motor distal latencies (DML) values (p=0.001; p<0.001; p=0.001, respectively). At the same time, there was a decrease in the VAS values in patients (p<0.001). When the two groups were compared there was an improvement in DSOL and sensory CV in both groups, but in DML only in moderate CTS group. Conclusion: In this study, it was shown that mild and moderate CTS patients had an improvement in pain and electrophysiological parameters after vitamin D replacement. Replacing vitamin D in early stages of CTS may be beneficial.

Resumo Objetivo: Os efeitos da vitamina D no sistema nervoso central e periférico continuam sendo investigados atualmente. Neste estudo, objetivamos avaliar a dor e a resposta eletrofisiológica em pacientes com síndrome do túnel do carpo (STC) submetidos a terapia de reposição devido à deficiência de vitamina D. Métodos: Cinquenta pacientes do sexo feminino diagnosticadas com STC leve e moderada e acompanhadas de deficiência de vitamina D foram incluídas neste estudo. O estudo da condução nervosa (ECN) foi realizado antes e após a reposição da vitamina D, e a dor do paciente foi avaliada com a Escala Visual Analógica (EVA). Resultados: Quando a ECN foi comparada antes e após o tratamento, houve uma melhora estatisticamente significativa na latência mediana do início sensorial distal (DSOL) e nos valores de velocidade de condução sensorial (VC) e latência distal motora (LDM) (p=0,001; p<0,001; p=0,001, respectivamente). Ao mesmo tempo, houve uma diminuição dos valores da EVA nos pacientes (p<0,001). Quando os dois grupos foram comparados, houve uma melhora no DSOL e no VC sensorial em ambos, mas no LDM apenas no grupo STC moderado. Conclusão: Neste estudo, foi demonstrado que pacientes com STC leve e moderada apresentaram melhora da dor e parâmetros eletrofisiológicos após a reposição de vitamina D. A substituição da vitamina D nos estágios iniciais da STC pode ser benéfica.

Vitamin D-Dependent Rickets Type II with Alopecia: A Rare Case Report.

Vitamin D-dependent rickets type II is a rare hereditary disorder. It occurs due to mutations in the gene chr. 12q12-q14, which codes for vitamin D receptor. End-organ resistance to 1,25-(OH)2 vitamin D3 and alopecia in severe cases are the characteristic features. We report a case of a 4-year-old boy with loss of hair over the scalp and body - first observed after 1 month of birth. The boy also developed difficulty in walking at the age of 2 year. On analysis, reduced serum calcium level (7.5 mg/dL) and elevated alkaline phosphatase level (625 IU/L) were reported. Initially, the treatment included intramuscularly administered single dose of 600,000 IU vitamin D, followed by 400 IU of vitamin D along with 1 g of supplemental calcium every day. Periodic follow-up was conducted for 2 months. Improvement was observed in the biochemical parameters and X-rays of the distal radial and ulnar metaphyses, although no improvement was observed in alopecia.

Statin Use and 25-Hydroxyvitamin D Blood Level Response to Vitamin D Treatment of Older Adults.

OBJECTIVES: To determine whether statin use alters response of 25-hydroxyvitamin D (25(OH)D) level to vitamin D treatment. DESIGN: Pooled analysis. SETTING: Three double-blind randomized controlled trials that tested different doses of vitamin D. PARTICIPANTS: Participants of three trials (N = 646; mean age 76.3 ± 8.4, 65% female). MEASUREMENTS: In all three trials, 25(OH)D status and statin use were assessed repeatedly over time (baseline, 6 and 12 months). Repeated-measures analysis was used to compare 25(OH)D response to vitamin D treatment at baseline and 6 and 12 months of statin users and nonusers, controlling for age, sex, body mass index, Charlson Comorbidity Index, vitamin D dose, trial, and season. RESULTS: At baseline, 17.5% were statin users, and 65% were vitamin D deficient (25(OH)D < 20 ng/mL). Baseline 25(OH)D levels did not differ significantly between groups at baseline (18.8 for statin users, 17.2 ng/mL for nonusers, P = .07), but according to the longitudinal analyses, the total increase over 12 months in 25(OH)D concentration was significantly lower in statin users (13.1 ng/L) than nonusers (15.9 ng/mL; 21.4% difference; P = .009). CONCLUSION: Of persons aged 60 and older at high risk of vitamin D deficiency, statin users had a 21.4% smaller increase in 25(OH)D serum concentrations over time than nonusers, independent of vitamin D dose and other covariates.

Chronical cervical infections and dysplasia (CIN I, CIN II): Vaginal vitamin D (high dose) treatment: A new effective method?

In a small praxis/ambulance study we evaluated data of 200 women with chronical recurrent cervical infections and with a cervix dysplasia (CIN 1, CIN 2). who got after the primary therapy a treatment with vitamin D vaginal suppositories (12.500 IU, 3 nights a week, for 6 weeks). We found that - when compared with the lactobacillus vaginal suppositories - the high dose vitamin D vaginal treatment might be more effective. Vitamin D showed very good anti-inflammatory effects. In the survey after six weeks therapy 79% of the women had "less vaginal problems," "less discharge" and "less problems with the sexual intercourse." Objectively after six weeks therapy only 7% of the patients still had bacterial and/or fungal vaginal infections that required a treatment. We found that vitamin D is reabsorbed by the vaginal mucosa, but the reabsorption may be individually very different. In the CIN 1 group we found six weeks after treatment good antidysplastic effects, in the CIN 2 group we often found no or only temporary antidysplastic effects. So this vaginal vitamin D treatment method might be an option for the therapy and prevention of chronical cervical infections and maybe of a cervic dysplasia CIN 1 (good antiinflammatory effects, antidysplastic effects). This small study is not representative. We need much bigger studies with much more dates and with a longer follow up. Caution: At the moment we do not know, if the vaginal vitamin D treatment with 12500 IE is possible in pregnancy. We have no experience. Therefore we recommend an effective contraception during the application.

Cardiovascular and renal complications to postsurgical hypoparathyroidism: a Danish nationwide controlled historic follow-up study.

We aimed to identify all patients with postsurgical hypoparathyroidism (HypoPT) and to evaluate their risks of renal complications and cardiovascular disease in relation to their disease and its treatment. We identified possible patients through the Danish National Patient Registry and a prescription database. Case status was adjudicated by review of individual patients' hospital records. For each patient with postsurgical HypoPT due to surgery for nonmalignant diseases between 1988 and 2012, three age-matched (± 2 years) and gender-matched controls were selected from the general background population. The prevalence of postsurgical HypoPT was 22 per 100,000 inhabitants. We identified 688 patients who had undergone neck surgery since 1988 with subsequent hypocalcaemia and inappropriate low parathyroid hormone (PTH) levels that necessitated treatment with calcium and/or vitamin D supplementation for more than 6 months. The average age at diagnosis was 49 years (range, 17-87 years), and 88% were women. Sixteen percent of all patients had had neck surgery prior to the operation causing HypoPT. Compared with controls, patients with HypoPT had an increased risk of renal complications (hazard ratio [HR], 3.67; 95% confidence interval [CI], 2.41-5.59) and hospitalization due to seizures (HR, 3.82; 95% CI, 2.15-6.79), whereas there was no increased risk of cardiac arrhythmias (HR, 1.11; 95% CI, 0.79-1.57) or cardiovascular disease or death (HR, 0.89; 95% CI, 0.73-1.09). In conclusion, although risk of seizures and renal complications is increased, mortality and risk of cardiovascular diseases or arrhythmias is not increased in patients with HypoPT. Further study should try to determine how to reduce the risk of seizures and renal complications in HypoPT.