25-OH Vitamin Research Articles

Vitamin D status, vitamin D receptor gene polymorphism, and haplotype in patients with cutaneous leishmaniasis: Correlation with susceptibility and parasite load index.

CL endemicity was reported worldwide including in Saudi Arabia, imposing a major challenge on the health authorities. Vitamin D and its receptor (VDR) are key modulators of the immune response where the VDR is expressed. A remarkable lack of data exists in humans about the contribution of vitamin D and polymorphisms of the VDR gene in protozoan infections, especially cutaneous leishmaniasis (CL). This is the first work conducted to assess the relationship between vitamin D status, polymorphisms of the VDR gene (BsmI, ApaI, TaqI, and FokI), and VDR haplotype with parasite tissue load and susceptibility to CL. Fifty-two patients with confirmed CL (21 patients receiving vitamin D medication and 31 patients not receiving it) and 46 control subjects participated in this cross-sectional investigation. VDR genotyping was determined by restriction fragment length polymorphism analysis. Serum levels of 25-OH vitamin D were assessed using the ELISA method in all participants. The skin biopsy quantified the parasite load based on the Ridley parasitic index. The mean serum level of 25-OH vitamin D in CL patients who were not receiving vitamin D therapy was significantly lower compared to CL patients on vitamin D therapy and controls (p <0.001 for both) and CL patients with no history of vitamin D therapy had a significantly higher frequency of vitamin D deficiency compared to CL patients on vitamin D therapy and controls (p < 0.05). Compared to CL patients with no history of vitamin D therapy, CL patients receiving vitamin D therapy had a significantly lower mean size of the lesion and RPI (p = 0.02, .03 respectively). The frequency of genotype "aa" and its "a" allele in ApaI SNP of VDR was significantly lower in CL patients compared to controls (p = 0.006 and 0.03 respectively). However, patients with CL had a considerably greater frequency of the "A" allele than the controls (p = 0.03), suggesting its role in CL susceptibility. There was no statistically significant difference between the two groups in the genotype and allele frequency distributions of BsmI, TaqI, and FokI (p > 0.05). When compared to controls, CL cases had a considerably greater frequency of the "B-A-T-F" haplotype (p = 0.04), and a significantly lower frequency of the "B-a-T-F" haplotype (p = 0.01) suggesting that these haplotypes may have the potential susceptibility or protection against CL respectively. The "Aa" genotype in ApaI SNP of VDR had considerably lower levels of vitamin D with higher parasite load compared to the "AA" and: aa" genotypes (p = 0.02,0.02 respectively). A significant negative correlation was found between the parasite load and 25-OH vitamin D levels (r2 = -0.53, p< 0.001). According to these findings, vitamin D levels and "ApaI" VDR gene polymorphisms could affect the parasite load and susceptibility to infection, whereas BsmI, FokI, and TaqI polymorphisms did not. Correction of vitamin D levels may aid in CL management.

Sex differences in vitamin D and behavioral profiles among children with allergic diseases.

Previous studies have suggested that vitamin D has a protective effect on allergic diseases, while an individual's sex may have a moderating effect on the relationship between vitamin D and allergic-related immunity. This study aimed to determine the role of vitamin D in children with coexisting allergic diseases in the context of sex differences and to explore the behavioral profiles of these patients. We recruited a total of 103 children with atopic diseases and divided them into four groups: males with one allergic disease (MA1, n = 20), males with two or more allergic diseases (MA2, n = 26), females with one allergic disease (FA1, n = 30), and females with two or more allergic diseases (FA2, n = 27). We measured serum calcium levels using the colorimetric method and serum 25-OH vitamin D total levels using electrochemiluminescence immunoassay. We found that MA2 had significantly lower vitamin D levels than MA1 and FA2. The levels of IgE were negatively correlated with vitamin D in females, whereas the levels of IgE were not significantly correlated with vitamin D in males. Furthermore, serum IgE was significantly correlated with children's adaptive skills, and different sexes were associated with different aspects of adaptive skills. Our findings suggest a protective role of vitamin D in the development of one allergic disease against the coexistence of allergic diseases in males, as well as extend the evidence for sex differences in immunity by demonstrating a sex-different correlation between IgE and vitamin D and the relationship between IgE and children's adaptive skills.

#2868 PREDICTION OF MAJOR GASTROINTESTINAL BLEEDING EVENTS IN HEMODIALYSIS

Abstract Background and Aims INitiativeS on advancing Patients’ outcomes In REnal disease (INSPIRE) is an academia and industry collaboration set forth to identify critical investigations needed to advance the practice of medicine in nephrology. At the inaugural INSPIRE meeting, the group came to a consensus that major bleeding events represent potentially preventable complications that occur more frequently in people with kidney disease versus the general population [1]. Given the most common class of bleeding event is gastrointestinal bleeding (GIB) [2], the INSPIRE group assessed if a machine learning model could be developed to assist with determining a hemodialysis (HD) patient's 180-day GIB hospitalization risk. Method Model was developed using adult HD patient data from United States (2017-2020). Patient data was randomly split (50% training, 30% validation, and 20% testing). HD treatments ≤180 days before GIB hospitalization were classified as positive observations, and others were negative observations. Datasets were randomly sampled to build an XGBoost model that considered 386 exposures initially and was refined to the top 50 exposures. Unseen testing dataset was used to determine final model performance. Results The incidence of 180-day GIB hospitalization was 1.18% in the HD population (n = 451,579), and 1.16% among patients in the testing dataset (n = 27,991). The model showed an area under the curve = 0.69, sensitivity = 57.9%, specificity = 68.9%, accuracy = 68.8% and balanced accuracy = 63.4%. Exposures with largest effect size observed via Shapley values were older age (group mean GIB event = 68.2 years vs no GIB event = 63.4 years), shorter days since last all-cause hospital admission (group mean GIB event = 203.2 days vs no GIB event = 253.2 days), and higher serum 25-hydroxy (OH) vitamin D levels from most recent lab (group mean GIB event = 33.4 ng/mL vs no GIB event = 30.5 ng/mL). Other important predictors included lower hemoglobin and iron indices, longer dialysis vintage, and proton pump inhibitor use (Fig. 1). Conclusion The machine learning model appears suitable for early detection of GIB event risk in HD, yet prospective testing is needed. The association between higher 25OH vitamin D and GIB events was unexpected and warrants investigation. A consistent signal has been observed in warfarin users without kidney disease among which 25OH vitamin D levels of 30–100 ng/mL were shown to associate with the highest GIB risk [3].

#5525 NEPHROTOXICITY OF CHIMERIC ANTIGEN RECEPTOR T CELL (CAR-T) THERAPY: ACUTE KIDNEY INJURY AND ELECTROLYTE DISORDERS

Abstract Background and Aims Chimeric antigen receptor T cell therapy (CAR-T) has improved the prognosis of patients with refractory hematologic malignancies. The most important toxicities are the cytokine release syndrome (CRS), where interleukin 6 (IL-6) plays a major role, and the immune effector cell-associated neurotoxicity syndrome (ICANS). A low incidence of acute kidney injury (AKI) with a high frequency of electrolyte imbalance has been described with CAR-T therapy. The aim of our study is to describe the nephrotoxicity of CAR-T therapy and to focus on AKI and the physiopathology of hypophosphatemia. Method A prospective single-center case series was performed which included all patients undergoing CAR-T therapy between 2020 and 2022. Clinical data included medical history, previous chemotherapy treatments, concomitant treatments, and clinical evolution. Daily monitoring of renal function, electrolytes and IL-6 was obtained after infusion of CAR-T. A urine sample was obtained on days 0, +7 and +14 with parathyroid hormone (PTH) and 25-OH vitamin D. AKI was classified according to the KDIGO criteria. Results 40 patients received CAR-T therapy during the follow-up period. The median age was 62 years. The same number of men as women were included. The most frequent comorbidities were hypertension (27.5%), followed by diabetes (12.5%) and chronic kidney disease (12.5%). 12 patients presented AKI. Baseline serum creatinine (SCr) in patients with AKI was 0.9 mg/dL (0.68-1.04) with a SCr peak of 1.27 mg/dL (1.1-1.7). The time from CAR-T therapy infusion to SCr peak was 6.5 days (4-10). Of these 12 patients, 8 presented stage 1, 3 stage 2, and 1 stage 3 AKI. There were no differences between the AKI and non-AKI group in baseline characteristics, inflammatory markers, CRS, ICANS or hospital length stay. Hypophosphatemia was the most frequent electrolyte imbalance, occurring in 36 patients (90 %), 22 (61 %) patients experienced moderate hypophosphatemia (phosphorus &amp;lt; 2 mg/dL) while 14 (39 %) patients experienced mild hypophosphatemia. 29 patients (72 %) presented hypokalemia and 25 patients (62.5 %) hyponatremia. Patients with moderate hypophosphatemia had a significantly higher elevation of IL-6 but there were no differences in PTH or vitamin D (Table 1). Although there were no significant differences in fractional excretion of filtered phosphate (FEPO4), patients with moderate hypophosphatemia trend to have higher FEPO4 values. Conclusion Electrolyte disturbances are common in CAR-T therapy, with hypophosphatemia being the most frequent. There is probably a mechanism for renal phosphorus loss related to systemic inflammation. AKI is less frequent and has mild characteristics in these patients.

#6569 PREDICTION OF ALL-CAUSE MORTALITY FOR CHRONIC KIDNEY DISEASE PATIENTS USING FOUR MODELS OF MACHINE LEARNING

Abstract Background and Aims Prediction tools developed from general population data to predict all-cause mortality are not adapted to patients with chronic kidney disease (CKD), as this population has a higher risk of mortality. This study aimed to create a clinical prediction tool with good predictive performance to predict 2-year all-cause mortality in patients with stage 4 or 5 CKD using an innovative approach with machine learning models and a synthetic population. Method The national, observational, descriptive and prospective Photo-Graphe 3 study was used to create the learning database. Four models (i) logistic regression; (ii) deep learning; (iii) random forest and (iv) Bayesian network were used to create four prediction tools. The performance of each model, including the area under the receiver operating characteristic curve (AUC-ROC) value, accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), was evaluated and compared using 10-fold cross-validation. The prediction tool with the best performance was selected and optimized using a synthetic population and the explanatory variables most related to mortality. The synthetic population was created by the Bayesian imputation method. The variables most associated with 2-year all-cause mortality were determined by compromising the number of variables selected and the AUC-ROC value when successively adding the variable according to its percentage variance value. The performance of the optimized prediction tool in predicting 2-year mortality was then evaluated by 10-fold cross validation. Results All prediction tools except the one developed with the random forest model showed satisfactory discrimination (AUC-ROC ≥ 0.70). Overall, the prediction tools developed using the Bayesian network and logistic regression tended to have better performance. Although not significantly different from logistic regression, the prediction tool developed using the Bayesian network was chosen for further development because of its advantages. From the 534 patients in the study population, a synthetic population of 2000 patients (survivor:death ratio = 1:1) was created. The seven most informative variables ranked in descending order were: age, ESA, CV history, smoking status, 25-OH vitamin D level, PTH level, and ferritin level (Figure 1). The optimized clinical prediction tool had satisfactory internal performance. The mean accuracy was 73.8% (SD = 3.6), the mean AUC-ROC was 0.81 (SD = 0.03), the mean sensitivity was 71.0% (SD = 5.4), the mean specificity was 76.5% (SD = 3.0), the mean PPV was 75.1% (SD = 3.2), and the mean NPV was 72.6% (SD = 4.1). Conclusion Bayesian network model was used to create a seven-variable prediction tool to predict the 2-year all-cause mortality in patients with stage 4–5 CKD. This prediction tool has a satisfactory performance. Prior to external validation, the proposed prediction tool can be used at: https://bit.ly/3JPhrkh for research purpose. This is the first time that a synthetic population has been applied to create predictive models. In this study, the synthetic population showed its advantage in dealing with sample size issues in developing predictive models and in improving the performance of the prediction tool in terms of sensitivity and PPV.

#4768 25 HYDROXYVITAMIN D ASSOCIATES WITH GASTROINTESTINAL BLEEDING IN DIALYSIS

Abstract Background and Aims The INSPIRE collaborative group built a prediction model that showed serum 25 hydroxyvitamin D concentration (25OH Vit D) may be a predictor of gastrointestinal bleeding (GIB) hospitalizations in dialysis patients [1]. Unexpectedly, 25OH Vit D levels in the target range (i.e., &amp;gt;30 ng/mL) were most associated with GIB hospitalization risk. We aimed to further investigate the association between GIB episodes and 25OH Vit D levels, considering the onset of a GIB comorbidity or a GIB hospitalization event in the next 180 days. Method Analysis used data from adult (age ≥18 years) dialysis patients in the United States who had one or more 25OH Vit D lab measurement between 01-Jan-2018 to 31-Mar-2021. We identified GIB episodes (comorbidity or hospitalization observations) that were within ≤180 days after a 25OH Vit D measurement. GIB episodes and types were based on ICD-10 diagnosis code clusters defined by the United States Healthcare Cost and Utilization Project [2]. We calculated the percent of GIB comorbidities that onset, or GIB hospitalizations that occurred, by categories of 25OH Vit D levels (&amp;lt;15, ≥15 to &amp;lt;30, ≥30 to &amp;lt;50, ≥50 to &amp;lt;100, or ≥100 ng/mL). Results Among 347,165 adult dialysis patients who had a 25OH Vit D lab measurement(s), 3.2% (n = 11,038) experienced ≥1 GIB comorbidity and 6.7% (n = 23,389) experienced ≥1 GIB hospitalization. In total, 16.5% (n = 4,873) of these patients had ≥1 GIB comorbidity and hospitalization. GIB episodes were within ≤180 days after a 25OH Vit D measurement for 5,558 GIB comorbidity and 21,862 GIB hospitalization observations. We found patients with 25OH Vit D levels that were &amp;lt;15 ng/mL or ≥50 ng/mL exhibited the lowest GIB comorbidity and GIB hospitalization rates (Figure 1A &amp; B). Patients with 25OH Vit D levels that were between ≥15 ng/mL and &amp;lt;50 ng/mL had the highest GIB comorbidity and GIB hospitalization rates. This observation was consistently observed for all GIB types, including upper, lower, and unspecified GIB episodes. Conclusion Findings showed serum 25OH Vit D levels are associated with 180-day GIB episodes in dialysis patients. The highest GIB rates were found in patients with a 25OH Vit D level between 15–50 ng/mL versus all other levels. This finding was consistent for the onset of a of GIB comorbidity and the occurrence of a GIB hospitalization, and in both cases was associated with 2-fold higher GIB rates. Outside the kidney failure population, 25OH vitamin D levels in the range of 30–100 ng/mL have been shown to be associated to higher GIB risk in warfarin users [3]. These findings may question recommendations in kidney disease that suggest repletion of 25OH Vit D levels to ≥30 ng/mL, which has been a controversy for more than a decade. Nonetheless, further analyses are needed and should consider adjustments for patient factors (e.g. age, sex, medications) and competing risks (non-GIB hospitalization events).

#4787 VITAMIN D AND PARATHYROID HORMONE PREDICT INCIDENT MAJOR ADVERSE CARDIAC EVENTS IN PATIENTS STARTING HAEMODIALYSIS: A REAL-WORLD ANALYSIS

Abstract Background and Aims Despite its advantages, haemodialysis (HD) is associated with increased cardiovascular mortality and morbidity, with some studies reporting 48% higher mortality, within 2 years of starting treatment. HD patients are known to suffer from vitamin D deficiency which has been linked to excess CV mortality and morbidity. We aimed to investigate the prognostic significance of vitamin D in predicting incident Major Adverse Cardiovascular Events (MACE) within 5 years of commencing HD. Method A retrospective cohort study was performed using electronic medical records from a global federated research network from the US (TriNetX). The TriNetX network was searched on 31st January 2023. The cohorts commenced HD post-diagnosis of End-Stage Kidney Disease. Data censoring for MACE was invoked prior to the index event of HD. Vitamin D (25-hydroxyvitamin D and 1,25 dihydroxy Vitamin D) concentrations were the first reported result within 3 months of starting HD. Cohorts were grouped according to biomarker-specific thresholds and 1:1 propensity-score matched for age, gender, and co-morbidities (hypertension, diabetes mellitus and smoking status). Logistical regression produced odds ratios with 95% CI for 5-year MACE. MACE was defined, a priori, as a composite of ischaemic heart disease, angina pectoris, acute myocardial infarction, heart failure, AF, stroke, and all-cause mortality. All statistical analysis was performed on the TriNetX online platform. Results The results are shown below. There was no association between outcome and PTH at 55 pg/ml threshold. Only results that reached statistical significance (p&amp;lt;0.05) are shown. Patients with a 25-OH Vitamin D concentration &amp;lt;24 ng/ml or 1,25-diOH Vitamin D at &amp;lt;35 pg/ml had significantly more events, as shown below. Conclusion Circulating plasma levels of cholecalciferol and calcitriol are predictive of CV outcomes in patients commencing HD; however, the risk profile is different between low levels of active and inactive vitamin D. As the incident HD population are at increased risk of CV mortality and morbidity, cholecalciferol and calcitriol should be included in assessing overall risk.

Determination of 25 OH Vitamin D in Pediatric Population

Vitamin D plays a fundamental role in overall health, especially in the pediatric population where bone growth is at its maximum. In this work, we will report the experience of our biochemistry laboratory in the evaluation of vitamin D deficiency in the pediatric population by assessing 25 OH vitamin D levels. A vitamin D deficiency was found in 51% of our patients, mainly in the age group between 6 and 11 years old, hence the interest of integrating vitamin D supplementation in the national program of nutrition in children.

Anti- SARS-CoV-2 IgG and IgM Levels in Iraqi General Population.

Acquired immunity plays an important role in the prevention of viral infections. SARS-CoV-2 is an infection that leads to a pandemic. The development of specific anti-SARSCoV- 2 antibodies may play a vital role in disease prevention and control. Thus IgG antibody screening in the general population provides information on the immunological status of the community. To clarify the SARS-CoV-2 immune status in the general population. A cross-sectional study was conducted in Kirkuk province during the period from 15 May 2022 to 11 September 2022. The samples were collected from voluntary subjects and informed consent was taken from each participant before their enrolment in the study. SARS-CoV-2 IgG, SARSCoV- 2 IgM, 25-OH Vitamin D, Vitamin B12, and Folate were determined using the Electrochemiluminescence Immunoassay (eCLIA) technique with the instrument NIPIGON-Robot R1Automated ECL Analyzer (Canada). The overall IgG mean concentration was 37.75 ± 23.18 COI, with a median of 39.99 COI and a range of 0.25 - 87.23 COI. Additionally, 93% of tested samples were with concentrations of more than 1 COI. The highest frequency (18.2%) was for the IgG concentration of 51 to 60 COI, while the lowest frequency (1.3%) was for the concentration of 81 - 90 COI. The IgG was significantly higher (P = 0.046) in males (39.87 ± 24.04 COI) than that in females (35.12 ± 21.89 COI). The IgM overall concentration was 0.569 ± 0.456 COI, with a median of 0.489 COI and a range of 0.17 - 6.40 COI. The mean serum level of folic acid concentration was 9.03 ± 5.72 ng/ml, with a median of 7.476 ng/ml and a range of 0.60 - 20.00 ng/ml. The mean serum concentration of vitamin B12 was 462.65 ± 349.18 pg/ml, with a median of 353 pg/ml and a range of 13.05 - 2000 pg/ml. The mean serum concentration of vitamin D was 18.29 ± 18.42 ng/ml with a median of 12.44 ng/ml and a range of 3 - 100 ng/ml. IgG and IgM serum levels did not show a significant correlation with serum levels of folic acid, vitamin D, and vitamin B12. However, there was a significant correlation between folic acid and vitamin D (r = 0.197; P = 0.012); vitamin B12 and vitamin D (r = 0.253, P = 0.001). While there was a non-significant correlation between folic acid and vitamin D serum levels (r = 0.129, P = 0.10). General population IgG antibody concentration reflects a high rate of herd immunity. Folic acid was with a mean value of about half of the upper normal limit and only 17.7% were with low values. Vitamin B12, only 6.3% of the population had values lower than normal. However, the range of vitamin B12 was wide. While vitamin D values were lower than the normal limit at 82.6%. However, a large scale well designed was warranted to evaluate COVID-19 national immune response.

TUMOR INDUCED OSTEOMALACIA: A CASE REPORT

Background:Tumor-induced osteomalacia (TIO), which is also known as oncogenic osteomalacia, is an uncommon paraneoplastic syndrome characterized by a renal phosphate loss causing hypophosphatemia, leading to rickets in children and osteomalacia in adults. It is caused by mesenchymal tumors, which secrete FGF-23 (fibroblast growth factor-23) and rarely other phosphotonins. It can present with a wide range of symptoms and there is often a delay in its diagnosis. Early diagnosis is important and surgical excision can cure the disease in most patients, thus preventing the complications.We report a case of TIO, who was diagnosed at an early stage and underwent curative surgery. Case presentation: A 30 years old female presented with pain in both legs, more severe in the left leg since about 1 year. She also had difficulty in walking, low back ache, muscle pain, mild pain in both the knee joints as well. On examination, she had limping gait, muscle power in the left leg was grade 3-4 otherwise, there was no significant findings on examination. Blood investigations showed elevated alkaline phosphatase (ALP)- 387IU/ml, low serum phosphorus- 1.2mg/dl, normal calcium - 9.8mg/dl, 25-OH Vitamin D- 24.69ng/ml, Parathyroid hormone (PTH)- 61pg/ml.Other blood tests were unremarkable. X- rays of both the legs and pelvis showed a classicalpseudo-fracture in proximal part of both the fibulae and proximal part of the right femur. This suggested hypophosphatemicosteomalacia. TmP/GFR was found to be very low (1.4mg/dl), which confirmed renal phosphate wasting. Later we got Fibroblast growth factor – 23 (FGF-23)- 617RU/ml, which was elevated. This confirmed FGF-23 related hypophosphatemicosteomalacia. In view of the patients age, onset of symptoms, lack of family history, absence of dental and hearing abnormalities, we suspected an acquired rather than a genetic cause. The patient underwent whole body Gallium-68 DOTANOC PET scan, which revealed somatostatin receptor expressing soft tissue density lesion in subcutaneous plane in the mid- anterior right leg, suggestive of FGF-23 secreting mesenchymal tumor.The patient was initially treated with replacement dose of oral phosphorus and calcitriol, along with calcium and vitamin D supplements. Later the patient underwent surgery for excision of the tumor in the right leg. The tumor was around 2cm size and the histopathology was suggestive of gaint cell rich tumor- possibly a phosphaturic mesenchymal tumor. Post surgery, the patient had significant improvement in her symptoms, gait improved and pain reduced. The serum phosphorus level was 3.8mg/dl post-operatively. The serum phosphorus level was maintained without phosphorus replacement. The patient was advised to repeat FGF-23 levels, but the patient failed to get it done. Conclusion: The diagnosis of TIO requires high index of suspicion and should always be looked as a differential diagnosis when we are evaluating a patient with osteomalacia. A detailed history and examination followed by a step wise biochemical evaluation and imaging is important to diagnose TIO in early stages. Surgical resection of the causative tumor will lead to definitve cure of the disease in most patients and avoids the complications like osteoporosis and fractures, thus improving the quality of life of the patients.

The influence of vitamin D on handgrip strength in elderly trauma patients

Background and objectivesThe treatment of elderly patients is an increasing challenge and the long-term sequelae often affect activities of daily living and quality of life in those patients. Handgrip strength (HGS) appears as a promising value to predict the outcome after trauma in elderly patients and to assess the overall muscle strength. Besides the possible role of psychological and hormonal factors, vitamin D may have a positive influence. Furthermore, some data suggest that Vitamin D is beneficial regarding muscle strength and possibly prevents further falls and injuries in orthogeriatric patients. The purpose of this study was to identify if Vitamin D is an influencing factor for HGSin elderly trauma patients.Materials and methods94 elderly patients in a Level I Trauma Center aged 60 years or older were prospectively enrolled and HGS as well as serum 25-OH Vitamin D concentration (VDC) were measured. In addition, the standardized questionnaires Barthel Index (BI), Parker Mobility Score (PMS), Short Physical Performance Battery (SPPB), Strength, Assistance with walking, Rise from a chair, Climb stairs and Falls (SARC-F) and European Quality of Life 5 Dimensions 5 Levels Questionnaire (EQ-5D-5L), were used to record mental health status and demographic data.ResultsHGS is mainly related to age and sex in elderly trauma patients. HGS was higher in men (meanmale = 27.31 kg (± 8.11), meanfemale = 15.62 kg (± 5.63), p < 0.001 and decreased with age (βage = − 0.58, p < 0.001). A significant negative correlation between HGS and VDC exists in the overall sample (βVDC = − 0.27, pVDC < 0.008), which still remains after adjusting for age (pVDC < 0.004), but is not significant after adjustment for both main confounders, age and sex (pVDC < 0.08). Furthermore, the HGS was lower in pateints who reported frequent falls, stumbling, dizziness or a late onset of menopause, and decreased if patients felt anxious or depressed during measurements (βanxiety+depression = − 0.26, panxiety+depression < 0.01).ConclusionsThese results do not support the hypothesis that Vitamin D has a positive influence on muscle strength measured by HGS. Nevertheless, this study could confirm the usefulness of HGS as a tool to detect the risk for frequent falls or stumbling. Furthermore, HGS seems to be associated with dizziness and age at onset of menopause. A significant decrease of HGS could also be shown in patients with anxiety and depression. This underlines the importance of interdisciplinary treatment of elderly trauma patients and needs to be taken into account for further studies, as especially the psychological motivation seems to have a significant influence and is sometimes not considered enough in elderly musculo-skeletal patients.

Sufficient vitamin D is favorable for children with persistent and chronic immune thrombocytopenia.

Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by isolated thrombocytopenia in the absence of other disorders. Vitamin D (VD) has been shown to modulate the immune system and its deficiency is linked to many immunological disorders. Supplementation with VD in ITP has promising results. This work aims at evaluating VD values in children with persistent and chronic ITP and the effect of its deficiency on disease severity and treatment response. A case-control study including 50 persistent and chronic ITP patients and 50 healthy controls was conducted. 25 OH vitamin D level was determined using ELISA technique. VD median value was significantly higher among the control group than that of the patients' group (28 vs 21.5 and p = 0.002). Severe deficiency was detected significantly more among the patients' group than the control group (12 (24%) vs 3 (6%), p = 0.048) respectively. Forty-four percent of complete responders belong to sufficient VD category ((15/34) ~ 44% (p = 0.005)) representing all patients with sufficient VD status (n = 15). Also, a positive correlation between serum level of vitamin D and mean PLT count was observed (r = 0.316, p value = 0.025). Sufficient vitamin D was associated with better treatment response and less disease severity. Vitamin D supplementation may be a new therapeutic option for chronic ITP.

COVID-19 Biomarkers Comparison: Children, Adults and Elders.

Background and Objectives: this study aimed to research links between C-reactive protein (CRP), lactate dehydrogenase (LDH), creatinekinase (CK), 25-OH vitamin D (25-OHD), ferritin (FER), high-density lipoprotein cholesterol (HDL)cholesterol and clinical severity in patients from the western part of Romania, and compare their potential use as biomarkers for intensive care units (ICU) admission and death in children, adults and elders. Materials and Methods: this study is a retrospective cohort study, performed on patients positively diagnosed with COVID-19. Available CRP, LDH, CK 25-OH vitamin D, ferritin, HDL cholesterol and clinical severity were recorded. The following were assessed: median group differences, association, correlation and receiver operating characteristic. Results: 381 children, 614 adults and 381 elders were studied between 1 March 2021 and 1 March 2022. Most children and adults presented mild symptomatology (53.28%, 35.02%, respectively), while most elders presented severe symptomatology (30.04%). ICU admission was 3.67% for children, 13.19% for adults and 46.09% for elders, while mortality was 0.79% for children, 8.63% for adults and 25.1% for elders. With the exception of CK, all other biomarkers showed some significant associations with clinical severity, ICU admission and death. Conclusions: CRP, LDH, 25-OH vitamin D, ferritin and HDL are important biomarkers for COVID-19 positive patients, especially in the pediatric population, while CK was mostly within normal ranges.

Vitamin D and Osteogenesis Imperfecta in Pediatrics.

Osteogenesis Imperfecta (OI) is a heterogeneous group of inherited skeletal dysplasias characterized by bone fragility. The study of bone metabolism, in these disease, is problematic in terms of clinical and genetic variability. The aims of our study were to evaluate the importance of Vitamin D levels in OI bone metabolism, reviewing studies performed on this topic and providing advice reflecting our experience using vitamin D supplementation. A comprehensive review on all English-language articles was conducted in order to analyze the influence of vitamin D in OI bone metabolism in pediatric patients. Reviewing the studies, contradictory data were found on the relationship between 25OH vitamin D levels and bone parameters in OI, and in several studies the baseline levels of 25OH D were below the threshold value of 75 nmol/L. In conclusion, according to the literature and to our experience, we highlight the importance of adequate vitamin D supplementation in children with OI.

Abstract #1407259: Milk-Alkali Syndrome, an Unlikely Consequence of 1,25 (OH) Vitamin D (Calcitriol) Titration in Hypoparathyroidism

Milk-Alkali Syndrome (MAS) is among the leading causes of hypercalcemia often following over-supplementation of exogenous calcium and may present with renal failure and metabolic alkalosis after onset of symptoms. We describe a patient with unusual precipitation of hypercalcemia, likely due to increased calcitriol (1,25 OH vitamin D) titration while on calcium supplements in the context of postoperative hypoparathyroidism. 64-year-old female with a history of parathyroidectomy treated with calcium citrate (675mg daily), 25-OH vitamin D (4000IU daily) and calcitriol 0.25mcg BID for 20 years was found by PCP to have calcium of 7.2 (8.8-10.2mg/dl) for which calcitriol was increased to 0.5mcg BID. After one month of calcitriol titration, patient reported to the ED with fatigue, loss of balance and confusion for 15 days. Labs showed calcium 18.9 (8.8-10.2mg/dl), 25-OH vitamin D 84 (>30ng/ml), 1,25-OH vitamin D 31.2 (19.9-79.3pg/ml), phosphorus 3 (1.6-2.4mg/dl), PTH 6.5 (15-65pg/ml), creatinine of 3 (0.5-1.0mg/dl) and bicarbonate of 30 (22-29mmol/L). There was no evidence of nephrocalcinosis on renal ultrasound. She was treated with calcitonin 400 units BID for four days, zoledronic acid 3mg IV once and fluids. Serum calcium decreased to 9.2mg/dl with improvement in symptoms and she was discharged on calcitriol 0.5mcg am/0.25mcg pm and calcium citrate/25-OH vitamin D (675mg/4000IU daily). She continued to experience intermittent paresthesias with serum calcium levels ranging from 6.5-9.5mg/dl. Further workup revealed 24-hour urinary calcium 7390mg (<300 mg/24hrs), serum creatinine 1.4mg (0.5-1.0 mg/dl) and 25-OH vitamin D 77 (>30 ng/ml). Treatment was adjusted with initiation of hydrochlorothiazide 12.5mg BID, calcitriol lowered to 0.25mcg BID, calcium citrate 516mg/daily and 25-OH vitamin D was held. One month later, repeat 24-hour urinary calcium decreased to 280mg (<300 mg/24hrs) along with stabilization of serum calcium and resolution of paresthesias. The pathogenesis of MAS from exogenous calcium in the setting of increased doses of calcitriol is not well known. The only factor that changed was the doubling of the calcitriol dose one month before hospitalization suggesting a robust response to calcitriol. 24hr urine calcium helped direct therapy, as the patient had hypercalciuria, denoting inadequate retention in the absence of PTH. Serum calcium stabilized at lower doses of calcium supplementation after adding HCTZ. A better understanding of calcitriol's pharmacokinetics could explain the appropriate, individualized supplementation and the need for close monitoring of calcium if adjusting the calcitriol dose.

Abstract #1406447: A Case of Severe Hypercalcemia After Recovery from Rhabdomyolysis that was Refractory to Hemodialysis

Rhabdomyolysis (RBD) is severe skeletal muscle injury which often results in acute kidney injury (AKI) and significant electrolytes abnormalities. We herein describe a case of severe hypercalcemia that occurred during the recovery phase of RBD that was successfully treated with intravenous (IV) pamidronate. A 58-year-old male with history of cirrhosis, IgA nephropathy and chronic kidney disease presented with lower extremity weakness and was found to have AKI due to statin-induced RBD. Creatinine Kinase (CK) was > 30000 U/L [30-200], BUN 78 mg/dl [ 6-22], Creatinine 5.78 mg/dl [ 0.77-1.25], corrected Calcium (Ca) 7.0 mg/dl [8.6- 10.2], Ionized Ca 2.5 mg/dl [4.5- 5.3], Phosphorus 6.7 mg/dl [2.3-4.7], 25-OH Vitamin D 4.8 ng/ml [30 -80] and Parathyroid hormone (PTH) 333 ng/ml [8.7-77.1]. The patient received IV calcium gluconate, vitamin D supplementation and hemodialysis (HD) and was started on calcitriol 0.25 mg three times a week. He was discharged on calcitriol, calcium acetate and vitamin D with a corrected Ca of 9.1 mg/dl. One week later, the patient was readmitted with confusion and a corrected Ca of 15.3 mg/dl, phosphorus of 7 mg/dl, CK of 131 U/L, 25- OH vitamin D 10 ng/ml, PTH 11.4 ng/ml. Additional workup for hypercalcemia was unremarkable. His hypercalcemia persisted despite HD with low calcium baths, gentle IV hydration, and IV furosemide. Calcitonin 4 units/kg was initiated but his Ca remained 12.4mg/dl after 48 hours. IV pamidronate 30 mg was given and within 5 days, his Ca level was 9.4 mg/dl, reaching a nadir of 8.9 mg/dl. RBD is commonly associated with hypocalcemia in the acute phase. Hypercalcemia can also occur in the recovery phase, but few reports exist and the appropriate management has not been established. As in our case, overtreatment of hypocalcemia may exacerbate hypercalcemia. The pathophysiology of the hypercalcemia may be due to mobilization of Ca from injured muscles and soft tissue deposits. Secondary hyperparathyroidism can also contribute to a hypercalcemic response. Hypercalcemia due to RBD is usually self-limited but more severe cases can occur. Few have reported on the use of bisphosphonates for this condition. In our case, multiple treatments were not successful in lowering calcium. Despite concerns that bisphosphonates may not successfully lower calcium, since hypercalcemia was not mediated by bone turnover, calcium decreased after bisphosphonate therapy and no adverse effects were experienced. Therefore, bisphosphonate therapy can be considered in refractory post-rhabdomyolysis hypercalcemia.

Abstract #1399984: Hypercalcemia Secondary to Vitamin D Toxicity Treated with Glucocorticoids

Vitamin D toxicity is a rare cause of hypercalcemia and there is no consensus on active treatment. Though glucocorticoids can decrease intestinal calcium absorption, increase urinary calcium excretion, and reduce levels of biologically active vitamin D metabolites, its use in vitamin D toxicity is controversial. Here we present a case of hypercalcemia secondary to hypervitaminosis D treated with glucocorticoids. A 77-year-old female with a history of vitamin D deficiency and prior admission for hypercalcemia attributed to lithium use (discontinued in December 2021) presented to the emergency room for hypercalcemia on outpatient labs. Labs were notable for calcium 14.6 mg/dL, albumin 3.8 g/dL, ionized calcium above detectable limits (>7.3 mg/dL), PTH 22.9 pg/mL, 25-OH vitamin D 135 ng/mL, 1,25-OH vitamin D 67.2 pg/mL (reference range: 19.9-79.3 pg/mL), estimated GFR 23 mL/min/1.73 m2, and undetectable lithium level. Additional workup included normal SPEP/UPEP, parathyroid hormone-related peptide, retinol and retinyl palmitate vitamin A, and computed-tomography of the chest, abdomen, and pelvis without signs of malignancy. History obtained from family revealed the patient had been supplementing with at least 10,400 IU of cholecalciferol daily, along with at least 180 mg of calcium daily (unknown if elemental or calcium carbonate). She was hydrated with isotonic intravenous fluids, given calcitonin 4 units/kg for 3 days, and prednisone 20 mg daily for 2 days. Following day 3 of calcitonin, prednisone was replaced with hydrocortisone 40 mg twice daily. Calcium improved to 10.8 mg/dL and she was discharged on hydrocortisone at same dose and frequency. Upon two-week follow up, calcium had improved to 10.0 mg/dL thus hydrocortisone was tapered to 20 mg twice daily. Due to a misunderstanding, she discontinued hydrocortisone resulting in an increased calcium of 12.2 mg/dL several weeks later. Four weeks upon resumption of hydrocortisone, the calcium improved to 10.2 mg/dL and the hydrocortisone was tapered to 10 mg twice daily. Five weeks later (approximately 4 months since starting hydrocortisone), the calcium was 10.4 mg/dL, the PTH was 19 pg/mL, and 25-OH vitamin D was 37.1 ng/mL. There are no guidelines or consensus on the treatment for vitamin D-induced hypercalcemia. In this case, glucocorticoids were shown to be an effective treatment for hypercalcemia secondary to vitamin D toxicity; the worsening of hypercalcemia upon accidental discontinuation and resolution following resumption of hydrocortisone further supports this conclusion. Though the expected duration of treatment is unclear, our case suggests long-term glucocorticoids are likely necessary.

Serum Vitamin D Status in Older Adults: A Cohort Study.

Vitamin D is best known as a key regulator of bone metabolism and calcium and phosphate homeostasis. This study aimed to assess the effect of different factors on the five-year changes in serum vitamin D concentration among older adults. This cohort study was conducted on adults aged ≥60 years living in Amirkola, in the North of Iran, from 2012 to 2017. Serum 25-hydroxyvitamin D (25-OH vitamin D) concentrations of <20, 20-29.99, and ≥30 ng/mL, respectively, were used to designate vitamin D deficiency, insufficiency, and sufficiency. Any variation between the second and baseline values of the 25-OH vitamin D concentration was reported as a five-year difference. Data were analyzed using SPSS version 17.0, and Chi square, t test, one-way ANOVA, and Tukey HSD post hoc tests were employed. P values less than 0.05 were considered statistically significant. The mean serum concentration of 25-OH vitamin D at baseline and follow-up examination in 1011 individuals was 34.68±33.18 and 23.88±14.91, respectively (P<0.001). Following a five-year follow-up, vitamin D deficiency, insufficiency, and sufficiency were found in 452 (44.7%), 334 (33.0%), and 225 (22.3%) cases, respectively. The reduction in serum 25-OH vitamin D concentration after five years was significantly influenced by the administration of vitamin D (P=0.013) and calcium (P=0.007) supplements, serum profile of parathyroid hormone (PTH) (P=0.010), calcium (P=0.021), and phosphorous (P=0.021). However, age, sex, body mass index, metabolic syndrome, and physical activity had no significant impact (P>0.05). Regardless of age, sex, body mass index, metabolic syndrome, or physical activity, the mean serum concentration of vitamin D decreased over a five-year follow-up.

Abstract #1402502: Hypercalcemia of Malignancy in Pregnancy, a Management Dilemma

Hypercalcemia of Malignancy (HCM) is a complication that is typically managed with bisphosphonates (BP). However, BP are not studied in pregnant patients with HCM and avoided due to potential adverse outcomes on mother and fetus thus limiting available options to manage hypercalcemia in pregnancy. We describe a case of HCM in a pregnant patient managed with Zoledronic acid. 36-year-old female, 32 weeks pregnant diagnosed during pregnancy with stage IV Breast cancer with liver and bone metastases, was admitted with hypercalcemia with no previous history. She did not have renal stones, polyuria, constipation, bone pain, fractures or taking calcium supplements. Lab data showed high calcium 12.9mg/dl, low PTH 5pg/ml, 25-OH vitamin D 15.5ng/ml, 1,25 OH vitamin D 70.28pg/ml, high PTHrP 6.1pmol/L. She received IV fluids and calcitonin with minimal benefit. After weighing risks and benefit and discussion with other teams, she was given IV Zoledronic acid. With chemotherapy and hypercalcemia, she developed severe emesis and decreased oral intake resulting in dehydration, low magnesium and phosphorus. She developed arrhythmia, frequent uterine contractions and fetal tachycardia and was treated for preterm labor with steroids, penicillin prophylaxis, aggressive hydration, and electrolyte replacement. Preterm delivery was safely avoided. After 4 days of BP dose, calcium normalized to 8.2 mg/dL and she was stable to be discharged home. She later received second cycle of chemotherapy and had uncomplicated vaginal delivery at 38 weeks with no neonatal complications. There are few studies on use of BP in pregnancy showing no increased risk of serious adverse effects. A systematic review of 51 cases with exposure to BP before or during pregnancy did not result in skeletal abnormalities or congenital malformations in the infants. In another case control study of 36 women with BP exposure, no major teratogenic effects were found but rates of neonatal complications were increased in women with systemic diseases, as were spontaneous abortions for women with bone disease. One case of 24 weeks pregnant female with metastatic breast cancer, pamidronate improved HCM and uterine contractions with no adverse effects on neonate. In our patient, treating hypercalcemia was necessary to avoid severe complications. We treated her with zoledronic acid as it is more effective then pamidronate at normalizing calcium and has similar safety profile. We optimized hydration status and monitored electrolytes to mitigate risk of side effects expected from BP use with good maternal and fetal results. More studies are required to determine safe use of BP in pregnant patients to guide management and avoid complications of HCM in mother and fetus.

Abstract #1406692: A Case of Anaplastic Thyroid Carcinoma and Hypocalcemia: Should We Be Monitoring for Hypocalcemia?

Anaplastic thyroid carcinoma is one of the most aggressive and fatal forms of cancer. We present a patient with anaplastic thyroid carcinoma who developed hypocalcemia after diagnosis. A 77-year-old female with a history of hypertension and DM2 presented to the hospital for difficulty breathing and neck fullness for 2 weeks. Upon arrival, she developed stridor and was emergently intubated. Blood pressure was 155/75 mmHg, pulse was 80 beats per minute and respiratory rate 18 per minute on mechanical ventilation. A firm and diffusely enlarged thyroid was palpated on examination with difficulty discerning thyroid borders. CT scan revealed diffuse heterogenous enlargement of the thyroid measuring 43x40mm, a large mass of the right lobe with extracapsular extension, and invasion of surrounding structures. Initial admission labs showed TSH 0.010UIU/mL (0.35-5.5 UIU/mL), free T4 2.56 ng/dL (0.9-1.8 ng/dL), calcium 8.7mg/dL (8.6-10.4 mg/dL), magnesium 3.1mg/dL (1.8-2.5 mg/dL), phosphorus 4.9mg/dL (2.5-4.5 mg/dL), and creatinine 1.1mg/dL (0.50 - 1.20 mg/dL). She was started on high dose steroids for airway edema, which was continued for biochemical hyperthyroidism. A biopsy was positive for anaplastic thyroid carcinoma, and she was started on paclitaxel and carboplatin. On day 7, her corrected calcium dropped to 7.9mg/dL and ionized calcium was 3.72mg/dL (<4.60 or >5.10 mg/dL). PTH level was 61.68pg/mL (9-75 pg/mL) and 25OH vitamin D was 10.3ng/mL (25-80 ng/mL). She was given 1g of intravenous calcium gluconate and began daily calcium 500mg twice daily and cholecalciferol 5000IU daily. Genomic testing was positive for BRAF and targeted therapy with dabrafenib and trametinib was initiated. After 23 days of BRAF targeted therapy, a repeat CT showed radiographic improvement of the thyroid mass, measuring 33x20mm. Calcium levels improved to 9.8mg/dL. Repeat TSH was 0.086UIU/mL and free T4 was 0.730ng/dL and she was started on levothyroxine supplementation. She was transferred to a long-term care facility a few months later with plans for repeat blood work but ultimately passed away 3 months after initial diagnosis. The cause of hypocalcemia in this case is likely multifactorial. She was a critically ill patient with significant vitamin D deficiency, which can be contributing factors. However, the normal PTH level suggests that there may have been some degree of parathyroid dysfunction. Mechanisms that have been proposed for this are mass effect or tumor infiltration from thyroid cancer. Calcium levels should be checked upon diagnosis of anaplastic thyroid cancer and monitored closely throughout the clinical course.