河南省1～7岁健康儿童血清25(OH)D水平分析

目的 了解河南省1～7岁健康儿童维生素D营养状况,为儿童合理补充维生素D、防治维生素D缺乏提供科学依据.方法 采用分层整群随机抽样法,选取河南省六个地区的妇幼保健院和社区卫生服务站进行体检的1～7岁健康儿童392名,采用化学发光法检测血清25 (OH)D水平,比较不同年龄段、不同性别儿童维生素D不足与缺乏情况.结果 392名1～7岁健康儿童血清25(OH)D平均水平为42.7±15.8nmol/L,不足与缺乏率达59.4％ (233/392),男女童之间差异无统计学意义(=0.500,P=0.618;x2 =0.051,P=0.822);不同年龄组维生素D平均水平及其不足与缺乏比例差异具有统计学意义(F=12.748,P＜0.001;x2=37.077,P＜0.001);维生素D水平随年龄增长而降低,不足与缺乏比例随年龄增长而升高.结论 河南省1～7岁健康儿童维生素D营养状况较差,且与年龄密切相关,应适当增加儿童日照时间,加强合理补充维生素D的科普宣传.     

外周维生素D结合蛋白、25-羟维生素D和原发性肝细胞癌风险的关系

目的 25-羟维生素D[25(OH) D)]已被证明与原发性肝细胞癌(HCC)的发生有关,但对于维生素D结合蛋白(VDBP)在原发性肝细胞癌发生中的作用却知之甚少.作者检测了25(OH)D的主要载体维生素D结合蛋白(VDBP),研究其在25(OH)D与原发性肝细胞癌风险中的作用.方法 收集146例HCC患者和249名对照组的血样,检测血浆VDBP和25(OH)D的浓度.采用logistic回归计算比值比(OR)和95％可信区间(CI),评估外周血VDBP、25(OH)D与原发性肝细胞癌的发生风险之间的关系.结果 血浆VDBP浓度与HCC风险之间呈负相关;血浆25(OH)D与HCC风险呈正相关.只有在25(OH)D浓度高于中位数的人群中,VDBP升高显著,降低了HCC风险.在VDBP浓度低于中位数的人群中,高浓度的25(OH)D显著提高了HCC风险.结论 高浓度的VDBP可结合更多的25(OH)D,减少游离25(OH)D的生物利用度,同时检测VDBP和25(OH)D水平对于确定维生素D与HCC风险的相关性非常重要.     

Vitamin D and aging: beyond calcium and bone metabolism

Background

Low serum 25-hydroxyvitamin D (25[OH]D) levels are common and may be associated with morbidity and mortality (and indeed with frailty more generally). This association is not restricted to the links between vitamin D and calcium and bone metabolism.

Objective

To review the influences of vitamin D on the aging process other than those related to bone and calcium. Its effect on mortality is also assessed.

Methods

The PubMed database was searched for English-language articles relating to vitamin D, using the following MeSH terms: vitamin D, mortality, cardiovascular diseases, and frailty. In addition, searches were carried out with Google.

Results

Although some of the reported results have proved controversial, overall the evidence seems to support an association between low serum 25[OH]D levels and mortality rates (all-cause and cardiovascular). Frailty is a condition frequently associated with low serum 25[OH]D levels.

Conclusion

The aging process and mortality are associated with low vitamin D levels. Prospective controlled trials are warranted to determine whether vitamin D supplements can increase longevity and reduce the incidence of certain conditions.     

1,25‐Dihydroxy‐vitamin D3 regulates NK‐cell cytotoxicity,cytokine secretion,and degranulation in women with recurrent pregnancy losses

Vitamin D has a pivotal role in regulating immune responses by promoting Th2 immune responses and suppressing Th1 responses. Propensities to a Th1 immune response and increased NK‐cell levels and cytotoxicity have been reported in women with recurrent pregnancy losses (RPL). In women with RPL, vitamin D deficiency is prevalent; however, the effect of vitamin D on NK cells is largely unknown. In this study, we demonstrated that CD69⁺ activating receptor expression on NK cells was significantly decreased by incubation with 1,25(OH)₂D₃ in a dose‐dependent manner, while CD158a and CD158b inhibitory receptor expression was upregulated. The degranulation marker CD107a was significantly downregulated on NK cells following incubation with 1,25(OH)₂D₃. NK‐cell conjugation with K562 target cells was not affected by 1,25(OH)₂D₃; however, depolarization of perforin granules in conjugated NK cells was significantly increased. TLR4 expression on NK cells was significantly decreased and TNF‐α and IFN‐γ production was significantly reduced by 1,25(OH)₂D₃ through interference with NF‐κB. Our results suggest 1,25(OH)₂D₃ has immune regulatory effects on NK cell cytotoxicity, cytokine secretion and degranulation process as well as TLR4 expression. Potential therapeutic application of 1,25(OH)₂D₃ for dysregulated NK‐cell immunity should be explored in the future.     

Single Ultra-High-Dose Cholecalciferol to Prevent Vitamin D Deficiency in Pediatric Hematopoietic Stem Cell Transplantation

Vitamin D deficiency is prevalent among childhood hematopoietic stem cell transplantation (HSCT) recipients and associated with inferior survival at 100 days after transplantation. Achieving and maintaining therapeutic vitamin D levels in HSCT recipients is extremely challenging in the first 3 to 6 months after transplantation due to poor compliance in the setting of mucositis and the concomitant use of critical transplantation drugs that interfere with vitamin D absorption. We sought to evaluate the safety and efficacy of a single, ultra-high-dose of vitamin D given before childhood HSCT to maintain levels in a therapeutic range during the peritransplantation period. Ten HSCT recipients with pretransplantation 25-OH vitamin D (25OHD) level <50?ng/mL and with no history of hypercalcemia, nephrolithiasis, or pathological fractures were enrolled on this pilot study. A single enteral vitamin D dose (maximum 600,000?IU) was administered to each patient based on weight and pretransplantation vitamin D level before the day of HSCT. Vitamin D levels between 30 and 150?ng/mL were considered therapeutic. All patients received close clinical observation and monitoring of 25OHD levels, calcium, phosphate, parathyroid hormone, urine calcium/creatinine ratio, and n-telopeptide for safety and efficacy assessment. The mean age of the study subjects was 5.8?±?4.9 years, and the mean pretransplantation 25OHD level was 28.9?±?13.1?ng/mL. All patients tolerated single, ultra-high-oral dose of vitamin D under direct medical supervision. No other oral vitamin D supplements were administered during the observation window of 8 weeks. Three of 10 patients received 400?IU/day of vitamin D in parenteral nutrition only for 5 days during the study window. A mean peak serum vitamin D level of 80.4?±?28.6?ng/mL was reached at a median of 9 days after the vitamin D dose. All patients achieved a therapeutic vitamin D level of >30?ng/mL. Mean vitamin D levels were sustained at or above 30?ng/mL during the 8-week observation window. There were no electrolyte abnormalities attributed to the ultra-high-dose of vitamin D. Most patients had mildly elevated urine calcium/creatinine ratios during treatment, but none showed clinical or radiologic signs of nephrocalcinosis or nephrolithiasis. Our findings indicate that single ultra-high-oral dose vitamin D treatment given just before HSCT is safe and well tolerated in the immediate peritransplant period in children. Patients in our study were able to achieve and sustain therapeutic vitamin D levels throughout the critical period during which vitamin D insufficiency is associated with decreased overall survival. Larger prospective studies are needed to address the impact of single ultra-high-dose vitamin D treatment on HSCT outcomes.     

HLA Haploidentical Stem Cell Transplant with Pretransplant Immunosuppression for Patients with Sickle Cell Disease

Allogeneic stem cell transplantation (HCT) is curative in patients with severe sickle cell disease (SCD), but a significant number of patients lack an HLA-identical sibling or matched unrelated donor. Mismatched related (haploidentical) HCT with post-transplant cyclophosphamide (PTCY) allows expansion of the donor pool but is complicated by high rates of graft failure. In this report we describe a favorable haploidentical HCT approach in a limited cohort of SCD patients with significant comorbidities. To reduce the risk of graft failure we administered the conditioning regimen of rabbit antithymocyte globulin, busulfan, and fludarabine preceded with 2 courses of pretransplant immunosuppressive therapy (PTIS) with fludarabine and dexamethasone. Graft-versus-host disease (GVHD) prophylaxis consisted of PTCY on days +3 and +4 followed by tacrolimus and mycophenolate mofetil starting on day +5. Four patients (ages 13, 19, 19, and 23 years) received T cell–replete haploidentical stem cell infusion. All patients engrafted with 99.9% to 100% donor chimerism, and all patients continued with stable engraftment at the last follow-up (5 to 11 months post-transplant). Time to neutrophil engraftment was 14 to 26 days. Two patients had high levels of donor-specific anti-HLA antibodies, which required the implementation of an antibody management protocol. This facilitated neutrophil engraftment on day +16 and day +26, respectively. One patient developed grade I acute GVHD, which resolved. Three patients developed mild, limited skin GVHD that responded to conventional immunosuppressive therapy. Human herpesvirus-6 viremia was detected in 3 patients but resolved without treatment. One patient developed asymptomatic cytomegalovirus viremia that responded appropriately to standard therapy with ganciclovir. The prompt, stable engraftment and low toxicity in the post-transplant period makes PTIS with haploidentical transplant a promising option for patients with SCD.     

Poor Health Related Quality of Life Among Patients of Sickle Cell Disease

Background:

Sickle cell disease (SCD) is characterized by chronic hemolytic anemia and vascular occlusion, causing recurrent painful episodes, neuro-cognitive deficits, organ failures and death in early adulthood. Besides the medical consequences, most of the families with a child of SCD have to cope with financial and social crisis. Quality of life (QOL) is a broad multidimensional concept that usually includes subjective evaluations of both positive and negative aspects of life. Other than health; emotional well being, social dysfunction, chronic pain and fatigability are also important aspects of overall quality of life that add to the complexity of its measurement.

Aim:

The present case control study was designed to determine the health related quality of life (HRQoL) in patients of sickle cell disease and to compare it with patients of other chronic non-communicable diseases.

Setting and Design:

Case control study conducted at tertiary health care facility of Central India.

Material and Methods:

The present study conducted to measure HRQoL among patients of SCD and patients of other chronic non-communicable diseases. A translated and pretested version of WHO SF-36 questionnaire was used to measure HRQoL.

Results:

We observed that there was significantly lower HRQoL among SCD patients.

Conclusion:

Besides merely pharmacotherapy, restoration of overall quality of life should be the mainstay of management of patients with SCD.     

Hypovitaminosis D in a Young Lebanese Population: Effect of GC Gene Polymorphisms on Vitamin D and Vitamin D Binding Protein Levels

Bioactive vitamin D is a steroid hormone transported in blood via the vitamin D binding protein (DBP). Our study aimed to investigate the vitamin D status in a young Lebanese population and study the association of hypovitaminosis with levels of DBP. Polymorphisms in the GC gene that encodes DBP were also screened. Blood samples were collected from 179 university students. Vitamin D status and DBP levels were assayed by enzyme‐linked immunosorbent assay (ELISA). DNA was extracted from 128 participants, and genotyping of the two GC gene SNPs, rs7041, and rs4588, was carried out by restriction fragment length polymorphism. Forty‐seven percent of participants had hypovitaminosis D (<20 ng/ml). A significant positive correlation was observed between vitamin D status and DBP. Genotyping data showed that participants carrying the rs7041 GG and rs4588 AA genotypes had higher concentrations of DBP than those carrying other genotypes. Four allelic versions of the GC gene were observed, one of which, GC*3, was encountered for the first time in this study, and was found to be associated with both normal vitamin D and high DBP levels. Modifying genes such as GC could therefore affect DBP levels, and contribute, along with environmental factors, to the hypovitaminosis D observed in sunny countries.     

Outcomes of Unrelated Donor Stem Cell Transplantion with Post-Transplant Cyclophosphamide for Graft-versus-Host Disease Prophylaxis in Patients with Severe Sickle Cell Disease

Unrelated donor (URD) hematopoietic cell transplantation (HCT) in children with sickle cell disease (SCD) is associated with a high incidence of rejection and graft-versus-host disease (GVHD). We report on the first 4 patients with severe SCD who underwent URD HCT using a novel myeloablative and immunosuppressive regimen composed of busulfan, fludarabine, and antithymocyte globulin with a single dose of post-transplant cyclophosphamide along with tacrolimus and mycophenolate mofetil for GVHD prophylaxis. Three patients engrafted and remain disease-free after a median follow-up period of 2.5 years. One patient had primary graft failure attributed to low stem cell content of the graft. Of interest, none of the engrafted patients developed acute or chronic GVHD. This preparative regimen along with the use of post-transplant cyclophosphamide offers a promising approach for unrelated donor transplants in patients with SCD and needs further corroboration in larger number of patients.     

Relationship of Vitamin D Binding Protein Polymorphisms and Lung Function in Korean Chronic Obstructive Pulmonary Disease

Purpose

Multiple genetic factors are associated with chronic obstructive pulmonary disease (COPD). The association of gene encoding vitamin D binding protein (VDBP, GC) with COPD has been controversial. We sought to investigate the types of GC variants in the Korean population and determine the association of GC variants with COPD and lung function in the Korean population.

Materials and Methods

The study cohort consisted of 203 COPD patients and 157 control subjects. GC variants were genotyped by the restriction fragment-length polymorphism method. Repeated measures of lung function data were analyzed using a linear mixed model including sex, age, height, and pack-years of smoking to investigate the association of GC genetic factors and lung function.

Results

GC1F variant was most frequently observed in COPD (46.1%) and controls (42.0%). GC1S variant (29.0% vs. 21.4%; p=0.020) and genotype 1S-1S (8.3% vs. 3.4%; p=0.047) were more commonly detected in control than COPD. According to linear mixed model analysis including controls and COPD, subjects with genotype 1S-1S had 0.427 L higher forced expiratory volume in 1 second (FEV₁) than those with other genotypes (p=0.029). However, interaction between the genotype and smoking pack-year was found to be particularly significant among subjects with genotype 1S-1S; FEV₁ decreased by 0.014 L per smoking pack-year (p=0.001).

Conclusion

This study suggested that GC polymorphism might be associated with lung function and risk of COPD in Korean population. GC1S variant and genotype 1S-1S were more frequently observed in control than in COPD. Moreover, GC1S variant was more common in non-decliners than in rapid decliners among COPD.     

Laryngeal Spasm Mimicking Asthma and Vitamin D Deficiency

We present a woman with heterozygous carnitine palmitoyl transferase 2 (CPT-2) deficiency who in the last 6 months suffered from episodic dyspnea and choking. Symptoms could not be attributed to her muscular energy defect, since heterozygous CPT-2 deficiency is usually asymptomatic or causes only mild muscle fatigability. Myopathy is usually triggered by concurrent factors, either genetic (additional muscle enzymes defects) or acquired (metabolic stress). The patient was referred to our respiratory clinic for suspect bronchial asthma. Spirometry showed mild decrease in inspiratory flows. Methacholine challenge was negative. Dyspnea was triggered by hyperventilation-induced hypocapnia, which produced marked decrease in airflow rates, particularly in inspiratory flows, consistent with laryngospasm. Nutritional assessment of the patient showed low serum level of calcium and vitamin D, attributable to avoidance of milk and dairy products for lactose intolerance and to insufficient sunlight exposure. After calcium and vitamin D supplementation episodic laryngospasm disappeared and hypocapnic hyperventilation test induced very mild change in airflow rates. Calcium and vitamin D deficiency may favour laryngeal spasm mimicking asthma, particularly in subjects with underlying myopathy.     

湛江市区学龄前儿童25-羟维生素D水平研究

目的 调查湛江地区学龄前（0~6岁）健康儿童25-羟维生素D[25（OH）D]水平,了解该人群中维生素D的健康状态。方法选取2017年6月1日~2018年5月31日在我检验中心进行体检的0~6岁儿童共3164例,测定25（OH）D水平,比较不同性别、不同季节的25（OH）D水平。结果 湛江市儿童血清25（OH）D总体水平为（42.75±12.20）ng/ml,男童为（42.27±11.88）ng/ml、女童为（42.93±12.58）ng/ml,不同性别儿童的25（OH）D水平差异无统计学意义（P＞0.05）。25（OH）D缺乏和不足的比例随着儿童年龄的增加而增多;秋季25（OH）D水平较其他季节略低。结论 湛江市区0~6岁儿童中缺乏和不足率均随年龄的成长而增高,应积极采取有效措施监督和提高儿童维生素D水平,以减少维生素D相关疾病的发生,提高健康水平。     

Parathyroid hormone, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D concentration in elderly patients

Summary In 50 patients of a geriatric hospital (33 women, aged 65–96 years, mean age 80 years, and 17 men, aged 68–91, mean age 78.3 years) calcium, albumin, phosphate, urea, creatinine, parathyroid hormone, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D were determined. Forty patients with serum creatinine levels up to 1.4 mg/dl (124 mol/l) and 10 patients with creatinine concentrations 1.5 mg/dl (132mol/l) were evaluated. In patients with normal creatinine, a positive correlation was found between parathyroid hormone and age (r=0.41;P<0.01). In patients with elevated creatinine, negative correlations were found in 1,25-dihydroxyvitamin D and calcium (r=–0.724;P<0.05), 1,25dihydroxyvitamin D and creatinine (r=–0.79;P<0.01) and 1,25-dihydroxyvitamin D and phosphate (r=–0.87;P< 0.002). The best correlation was observed in patients with elevated serum creatinine for 1,25-dihydroxyvitamin D and phosphate (r=–0.91;P< 0.001). The results suggest that low levels of calcium and phosphate stimulate the 1-hydroxylation of 25-hydroxyvitamin D even in advanced age and that the calcium metabolism of these patients is frequently disturbed. Nineteen patients had low levels of 25-hydroxyvitamin D, indicating an insufficient supply of vitamin D or rare exposure to sunlight. In 49 of 50 patients, one ore more of the parameters of calcium metabolism were outside the normal range.Abbreviations 25-OH-D 25-hydroxyvitamin D - 1,25(OH)₂D 1,25-dihydroxyvitamin D - PTH parathyroid hormone Supported by the Deutsche Forschungsgemeinschaft (Schm 405–407)     

Ethical Challenges in Hematopoietic Cell Transplantation for Sickle Cell Disease

Hematopoietic cell transplantation (HCT) using an HLA-identical sibling donor offers a very high likelihood of cure with good outcomes for patients with sickle cell disease (SCD), and alternative donor HCT for SCD is an area of active clinical research. Thus, HCT is a potential option for a growing number of patients with SCD. This expanded use of HCT has raised several ethical questions. Who is eligible for HCT, in terms of both disease severity and psychosocial factors? Should affected children with matched sibling donors undergo HCT only when they have declared themselves as having significant symptomatology? Regarding donors, special ethical challenges include the use of preimplantation genetic diagnosis to conceive an HLA-identical sibling. In this review, we critically analyze various ethical challenges related to HCT for SCD, and offer recommendations to guide clinical care.