High-dose Calcium Research Articles

The Effect of Boric Acid and Calcium Fructoborate on T Helper Cell Differentiation by Influencing Foxp3 and Ror-γt in Rheumatoid Arthritis and Systemic Lupus Erythematosus.

Many animal and human studies indicate that boric acid and calcium fructoborate have effects on helper T cells in immunity. The aim of our study is to evaluate the effects of boric acid and calcium fructoborate on Treg (CD4+Foxp3+) and Th17 (CD4+Ror-γt+) cell populations and related cytokine levels in mononuclear cells isolated from peripheral blood samples of rheumatoid arthritis and systemic lupus erythematosus patients. Newly diagnosed rheumatoid arthritis (n = 10) patients, systemic lupus erythematosus (n = 5) patients, and healthy individuals (n = 9) were included in this study. Consent forms were obtained from all individuals participating the study, blood samples were taken, and peripheral blood mononuclear cells were isolated. Isolated cells were exposed to low-dose and high-dose boric acid and calcium fructoborate in cell culture. Treg and Th17 cell populations were analyzed by flow cytometry after 48h of exposure. IL-2, IL-6, IL-17, IL-23, TNF-α, and TGF-β levels in the culture medium were tested by ELISA method. At the end of the study, in healthy controls, high-dose BA improved the Treg/Th17 population but could not display similar effects on RA and SLE group. However, both boric acid and calcium fructoborate at different doses showed an increasing effect on Ror-γt in RA and SLE group. Different doses of BA and CaF treatment found to have a variable effect on cytokine. Both BA and CaF in low doses decreased TNF-α levels in RA group which shows that these boron compounds could contribute positively to the treatment of autoimmune diseases.

6871 Hungry Bone Syndrome After Parathyroidectomy in End-Stage Kidney Disease: A Case Report Analysis

Abstract Disclosure: R. Rani: None. C. Mullarkey-desapio: None. Introduction: Hungry Bone Syndrome (HBS) is a rare yet severe complication following parathyroidectomy, characterized by pronounced hypocalcemia subsequent to a rapid decline in parathyroid hormone (PTH) levels. Renal hyperparathyroidism (RHPT) carries a heightened risk of HBS compared to primary hyperparathyroidism (PHPT), with prevalence varying from 15% to 25% in PHPT to as high as 75-92% in RHPT. This elevated risk in RHPT is attributed to chronically elevated PTH levels, both in terms of duration and intensity as compared to PHPT. Preoperative predictors for HBS occurrence and severity include younger age, larger gland size, lower preoperative calcium levels, elevated bone turnover markers, and the magnitude of PTH elevation. Case Report: We present a case of a 36-year-old female with End-Stage Renal Disease (ESRD) requiring dialysis, complicated by renal osteodystrophy and a radial fracture, unresponsive to medical therapy, who was admitted for parathyroidectomy. Preoperative labs revealed calcium at 8.3 mg/dL, phosphate at 4.1 mg/dL, alkaline phosphatase (ALP) at 797 IU/L, and an extremely elevated parathyroid hormone (PTH) level at 4139 pg/ml. Within 24 hours of parathyroidectomy (three and a half glands were removed, the largest weighing 0.7gm), her PTH levels declined to the 130s, accompanied by symptomatic hypocalcemia (calcium 6.5mg/dL). Initial management involved intravenous calcium gluconate and subsequent high-dose oral calcium (up to 10-16gm daily) with Calcitriol 1 mcg twice daily. Despite repletion, her calcium levels remained low on postoperative day 4 (calcium 6.8mg/dL, phosphate 1.9 mg/dL, magnesium 1.7mg/dL) with PTH at 131 pg/ml, confirming Hungry Bone Syndrome. After seven days of aggressive intravenous and oral calcium supplementation with high-dose Calcitriol, she was discharged with a calcium level of 8.9mg/dL. Discussion: Management of HBS following renal hyperparathyroidism surgery presents significant challenges due to associated comorbidities and other electrolyte abnormalities, with limited literature providing guidance on prevention and management. Our case demonstrated that early suspicion and aggressive management improved patient outcomes. Suspecting HBS in high-risk individuals and initiating interventions pre and post-surgery, including pre-treatment with calcitriol, bisphosphonates, and early aggressive intravenous calcium supplementation post-surgery, could potentially reduce morbidity and length of hospital stay. Presentation: 6/1/2024

Experiences, acceptability and barriers to calcium supplementation during pregnancy in Dar es Salaam, Tanzania.

Calcium supplementation in pregnancy is recommended in contexts with low dietary calcium intake to reduce the risk of pre-eclampsia and its complications. The World Health Organisation suggested high-dose calcium supplementation (1500-2000 mg/day), divided into three doses and taken at different times from daily iron-folic supplements. We conducted a mixed methods evaluation study to assess experiences, acceptability and barriers to high-dose calcium supplementation from the perspectives of pregnant women and antenatal health care providers at two public health facilities in Dar es Salaam, Tanzania. Descriptive statistics and thematic analysis were used to characterise acceptability, barriers and overall experiences of using high-dose calcium supplementation. Pregnant women in the cohort were aged 19-41 years, with 32.4% being primiparous. The proportion of pregnant women who liked calcium supplements 'a lot' decreased from 50.2% at the first visit to 31.8% at the last antenatal follow-up visit. Adherence was 71.3% (interquartile range: 50.5%, 89.3%), with only 24.0% of the participants taking 90% or more of the required supplements. Although participants expressed positive attitudes towards using calcium supplements, they also voiced concerns about the large size, side effects, the potential to forget and the burden of taking calcium supplements three times per day. Antenatal health care providers also affirmed the high burden of taking calcium supplements in addition to iron-folic acid supplements. Participants expressed the acceptability of using calcium supplements during pregnancy, but adherence to three doses per day posed challenges to pregnant women. Reducing the number of calcium supplement doses per day may improve adherence.

Effectiveness of High Dosage of Calcium, Folic Acid and Vitamin D on Reducing the Risk of Preeclamsion Among Pregnant Women

Aims: to determine the effectiveness of giving high doses of calcium, folic acid and vitamin D to reducing the risk of preeclampsia in the Karawang Health Center in 2023. Methods: the type of research used in this research is quantitative with a cross sectional research design. The population in this study were 68 pregnant women who were at the Karawang Health Center, Karawang Regency. a sample of 45 pregnant women who were at the Karawang Community Health Center in Karawang Regency and bivariate analysis using the chi-square test. Results: Most of the use of high-dose calcium were adherent by 26 people (67.8%), most of the use of folic acid were adherent by as many as 30 people (66.7%), most of the use of vitamin D were not adherent by 27 people (60.0%). Most of the risk of preeclampsia blood pressure in normal pregnant women as many as 25 people (55.6%). Giving high doses of calcium, folic acid and vitamin D is effective in reducing the risk of preeclampsia in the Karawang Health Center in 2023 with (P-Value ≤ 0.05). Conclusion: It can be concluded that giving high doses of calcium, folic acid and vitamin D is effective in reducing the risk of preeclampsia in the Karawang Health Center in 2023.

Zhuyu Pills regulate p53/SLC7A11 signaling pathway-mediated oxidative damage and ferroptosis to treat atherosclerosis

This article aims to investigate the effect of Zhuyu Pills on atherosclerosis(AS) and decipher the underlying mechanism. The mouse model of AS was established by feeding with a high-fat diet for 12 weeks. The 50 successfully modeled mice with the apolipoprotein E knockout(ApoE~(-/-)) were assigned by the random number table method into 5 groups(n=10): model, low-, medium-, and high-dose(130.54, 261.08, 522.16 mg·kg~(-1), respectively) Zhuyu Pills, and atorvastatin calcium(10.40 mg·kg~(-1)). Ten C57BL/6J mice were selected as the blank group. The blank group and model group were administrated with an equal volume of normal saline, and other groups were administrated with corresponding drugs once a day for 12 weeks. At the end of drug intervention, hematoxylin-eosin(HE) staining was employed to observe the pathological changes of fat in the aorta, liver, and epididymis of mice, and the proportion of aortic plaque area, fat area in epididymis, and nonalcoholic fatty liver disease activity score(NAS) were calculated. Lipid and collagen deposition in the aorta was observed by oil red O staining and Masson staining, respectively, and the proportions of lipid and collagen deposition areas were calculated. The serum levels of superoxide dismutase(SOD), malondialdehyde(MDA), glutathione peroxidase(GSH-Px), and iron ion were measured by colorimetry. The expression of cyclooxygenase 2(COX2), ferritin heavy chain 1(FTH1), cystine/glutamate reverse transporter solute carrier family 7 member 11(SLC7A11), and glutathione peroxidase 4(GPX4) in the aorta was detected by the immunofluorescence assay. The level of tumor protein 53(p53) in the aorta was detected by immunohistochemistry. The protein levels of p53 and SLC7A11 in the aorta were determined by Western blot. The mRNA levels of p53, SLC7A11, GPX4, FTH1, prostaglandin G/H synthase 2(PTGS2), and reduced nicotinamide adenine dinucleotide phosphate oxidase 1(NOX1) in mouse aorta were determined by real-time PCR. The results showed that compared with the blank group, the model group showcased enlarged aortic plaque area, increased collagen fiber deposition, liver lipid deposition, and lipid droplets, and enlarged epididymal adipocytes. In addition, the modeling elevated the levels of iron ion and MDA and lowered the levels of SOD and GSH-Px in the serum, promoted the expression of p53 and COX2, down-regulated the protein and mRNA levels of FTH1, SLC7A11, and GPX4, and up-regulated the mRNA levels of PTGS2 and NOX1 in the aorta. Compared with the model group, low-, medium-, and high-dose Zhuyu Pills and atorvastatin calcium reduced the aortic plaque area, collagen deposition, liver lipid deposition, lipid droplets, and epididymal adipocyte volume, lowered the levels of iron ion and MDA and elevated the levels of SOD and GSH-Px in the serum, inhibited the expression of p53 and COX2, up-regulated the protein and mRNA levels of FTH1, SLC7A11, and GPX4, and down-regulated the mRNA levels of PTGS2 and NOX1 in the aorta. In conclusion, Zhuyu Pills exert definite therapeutic effect on aortic plaque in AS mice by regulating the p53/SLC7A11 signaling pathway to alleviate oxidative damage and inhibit ferroptosis.

Positive Vasoreactivity Testing in Pulmonary Arterial Hypertension: Therapeutic Consequences, Treatment Patterns, and Outcomes in the Modern Management Era.

Among patients with pulmonary arterial hypertension (PAH), acute vasoreactivity testing during right heart catheterization may identify acute vasoresponders, for whom treatment with high-dose calcium channel blockers (CCBs) is recommended. However, long-term outcomes in the current era remain largely unknown. We sought to evaluate the implications of acute vasoreactivity response for long-term response to CCBs and other outcomes. Patients diagnosed with PAH between January 1999 and December 2018 at 15 pulmonary hypertension centers were included and analyzed retrospectively. In accordance with current guidelines, acute vasoreactivity response was defined by a decrease of mean pulmonary artery pressure by ≥10 mm Hg to reach <40 mm Hg, without a decrease in cardiac output. Long-term response to CCBs was defined as alive with unchanged initial CCB therapy with or without other initial PAH therapy and World Health Organization functional class I/II and/or low European Society of Cardiology/European Respiratory Society risk status at 12 months after initiation of CCBs. Patients were followed for up to 5 years; clinical measures, outcome, and subsequent treatment patterns were captured. Of 3702 patients undergoing right heart catheterization for PAH diagnosis, 2051 had idiopathic, heritable, or drug-induced PAH, of whom 1904 (92.8%) underwent acute vasoreactivity testing. A total of 162 patients fulfilled acute vasoreactivity response criteria and received an initial CCB alone (n=123) or in combination with another PAH therapy (n=39). The median follow-up time was 60.0 months (interquartile range, 30.8-60.0), during which overall survival was 86.7%. At 12 months, 53.2% remained on CCB monotherapy, 14.7% on initial CCB plus another initial PAH therapy, and the remaining patients had the CCB withdrawn and/or PAH therapy added. CCB long-term response was found in 54.3% of patients. Five-year survival was 98.5% in long-term responders versus 73.0% in nonresponders. In addition to established vasodilator responder criteria, pulmonary artery compliance at acute vasoreactivity testing, low risk status and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels at early follow-up correlated with long-term response and predicted survival. Our data display heterogeneity within the group of vasoresponders, with a large subset failing to show a sustained satisfactory clinical response to CCBs. This highlights the necessity for comprehensive reassessment during early follow-up. The use of pulmonary artery compliance in addition to current measures may better identify those likely to have a good long-term response.

A perfectly imperfect engine: Utilizing the digital twin paradigm in pulmonary hypertension.

Pulmonary hypertension (PH) is a severe medical condition with a number of treatment options, the majority of which are introduced without consideration of the underlying mechanisms driving it within an individual and thus a lack of tailored approach to treatment. The one exception is a patient presenting with apparent pulmonary arterial hypertension and shown to have vaso-responsive disease, whose clinical course and prognosis is significantly improved by high dose calcium channel blockers. PH is however characterized by a relative abundance of available data from patient cohorts, ranging from molecular data characterizing gene and protein expression in different tissues to physiological data at the organ level and clinical information. Integrating available data with mechanistic information at the different scales into computational models suggests an approach to a more personalized treatment of the disease using model-based optimization of interventions for individual patients. That is, constructing digital twins of the disease, customized to a patient, promises to be a key technology for personalized medicine, with the aim of optimizing use of existing treatments and developing novel interventions, such as new drugs. This article presents a perspective on this approach in the context of a review of existing computational models for different aspects of the disease, and it lays out a roadmap for a path to realizing it.

Too Much of a Good Thing: Severe Hypercalcemia Presenting with Lethargy and Kidney Failure.

We present a case of a 58-year-old man with a history of laryngo-pharyngectomy including bilateral thyroidectomy due to hypopharyngeal cancer presenting with lethargy, acute kidney failure, and hypercalcemia. Milk alkali syndrome was diagnosed given the history of high-dose calcium / vitamin D supplementation after ruling out other causes of hypercalcemia. After initial treatment with normal saline, furosemide and denosumab, the patient developed severe symptomatic hypocalcemia as a rare adverse effect of denosumab.

Vascular and renal calcification as a consequence of high-dose calcium and vitamin D drugs

Calcium-containing drugs occupy an important place in the list of anti-osteoporotic agents. Their consumption, often in combination with high doses of vitamin D, has increased significantly over the last couple of decades. Cases of uncontrolled intake of the macronutrient have become more frequent. Aggressive advertising of high-dose calcium supplements with calciferol of foreign production on television played its role in this. Nowadays doctors of various specialties have to face more and more often the consequences of using such preparations. The article describes the mechanism of calcium deposits formation in vessels and kidneys against the background of calcium supplementation. The results of large-scale studies proving the close relationship between high intake of calcium and vitamin D with calcification of vessels, development of cardiovascular diseases and nephrolithiasis are presented. Doubts are raised about the validity and necessity of high-dose calcium supplements in the treatment of skeletal diseases. The possibilities of successful therapy of postmenopausal osteoporosis without the use of such agents are presented on the example of the preparation Osteo-Vit D3, which does not contain calcium and high doses of calciferol, but increases the mineral density of bone tissue and reduces the volume of calcificates in blood vessels and kidneys.

Calcium supplementation for the prevention of pre-eclampsia: Challenging the evidence from meta-analyses.

To investigate the validity of the conclusion from Cochrane reviews and meta-analyses that treatment with calcium supplementation during pregnancy reduces the risk for pre-eclampsia by 55%, which has been influential in international guidelines and future research. Sensitivity analysis of data from Cochrane reviews of trials evaluating high-dose calcium supplementation (of at least 1 g/day) for reduction of pre-eclampsia risk. Systematic review and meta-analysis. The Cochrane reviews and meta-analyses included 13 trials enrolling a total of 15 730 women. Random-effects meta-analysis of these studies resulted in a mean risk ratio (RR, calcium/placebo) of 0.45 (95% confidence interval [CI] 0.31-0.65; p < 0.0001). We carried out a sensitivity analysis of evidence from the relevant Cochrane review, to examine the impact of study size. pre-eclampsia. In the three largest studies, accounting for 13 815 (88%) of total recruitment, mean RR was 0.92 (95% CI 0.80-1.06) and there was no evidence of heterogeneity between studies (I2 = 0). With inclusion of the smaller studies, mean RR decreased to 0.45 and I2 increased to 70%. In assessment of the effect of calcium supplementation on pre-eclampsia risk, the naive focus on the mean of the random-effects meta-analysis in the presence of substantial heterogeneity is highly misleading.

Zhuyu Pills promote polarization of macrophages toward M2 phenotype to prevent atherosclerosis via PPARγ/NF-κB signaling pathway

This article aims to investigate the effect of Zhuyu Pills on atherosclerosis and decipher the underlying mechanism. The mouse model of atherosclerosis was induced by a high-fat diet, and the total modeling period was 12 weeks. A total of 47 ApoE~(-/-) mice successfully modeled were randomized into 5 groups, including 10 in the model group, 9 in each of low-, medium-, and high-dose(130.54, 261.08 and 522.16 mg·kg~(-1)·d~(-1), respectively) Zhuyu Pills groups, and 10 in the atorvastatin calcium(10.40 mg·kg~(-1)·d~(-1)) group. In addition, 10 C57BL/6J mice were included as the normal group. The mice in the normal group and model group were administrated with an equal volume of sterile distilled water, and those in other groups with corresponding agents by gavage once a day for 12 weeks. At the end of drug intervention, the levels of total cholesterol(TC), triglyceride(TG), high-density lipoprotein cholesterol(HDL-C), and low-density lipoprotein cholesterol(LDL-C) were measured by the biochemical method. Hematoxylin-eosin(HE) staining was employed to observe the plaque distribution in the aortic region. The serum levels of pro-inflammatory cytokines tumor necrosis factor-α(TNF-α) and interleukin(IL)-6 in M1 macrophages and anti-inflammatory cytokines IL-13 and IL-4 in M2 macrophages were determined by enzyme-linked immunosorbent assay(ELISA). The expression levels of inducible nitric oxide synthase(iNOS) and arginase-1(Arg-1) were examined by immunofluorescence. Real-time fluorescence quantitative polymerase chain reaction(real-time PCR) was employed to measure the mRNA levels of peroxisome proliferator-activated receptor γ(PPARγ), nuclear factor-κB(NF-κB), Arg-1, and iNOS in the aorta. Western blot was employed to determine the protein levels of PPARγ and NF-κB in the aorta. The results showed that compared with the normal group, the modeling elevated the TC, TG, and LDL-C levels, lowered the HDL-C level, caused large area thickening of the aortic intima, elevated the TNF-α and IL-6 levels, lowered the IL-4 and IL-13 levels, down-regulated the mRNA and protein levels of PPARγ and Arg-1, and up-regulated the mRNA and protein levels of iNOS and NF-κB in the aorta(P&lt;0.01). Compared with the model group, low-, medium-, and high-dose Zhuyu Pills and atorvastatin calcium lowered the TC, TG, and LDL-C levels, elevated the HDL-C level, reduced the plaque area in a concentration-dependent manner, lowered the TNF-α and IL-6 levels, elevated the IL-4 and IL-13 levels, up-regulated the mRNA and protein levels of PPARγ and Arg-1, and down-regulated the mRNA and protein levels of NF-κB and iNOS in the aorta(P&lt;0.05 or P&lt;0.01). In conclusion, Zhuyu Pills may play an anti-atherosclerosis role by regulating PPARγ/NF-κB signaling pathway, inhibiting the polarization of macrophages toward the M1 phenotype, promoting the polarization of macrophages toward the M2 phenotype, and improving the inflammatory microenvironment of macrophages.

How far do we have to go on the road to calcium supplementation?

Sleep disorder is a growing concern, and calcium supplementation is often recommended as a potential intervention for sleep disorders. However, the causal relationship between calcium levels and the incidence of sleep disorders remains unclear. Mendelian randomization techniques utilizing genetic variants that affect calcium levels, can provide valuable insights into causality. This study aims to examine the association between calcium levels and sleep disorders in a diverse population that includes both adolescents and adults, and investigate the effects of calcium levels on sleep disorders. Mendelian randomization analysis was conducted using data from UK Biobank and FinnGen datasets. The inverse-variance weighting (IVW) was selected as the primary method. In addition, traditional mediation analysis was performed on a subset of the NHANES data spanning from 2007 to 2018. Our findings provide evidence supporting a causal relationship between calcium intake and reduced risk of sleep disorders (beta=-0.079, SE=0.0395, P=0.0457). While not reaching statistical significance, other MR methods such as weighted median and Mr-Egger exhibited similar directional trends. Analysis of the NHANES cohort revealed a negative association between calcium levels and the prevalence of sleep disorders in male, black, and physically active populations. However, this association was not observed in other demographic groups. Our results suggested that there is no significant correlation between calcium levels and sleep disorder in non-exercise populations. This raises concerns about the long-term high-dose calcium supplementation in clinical practice, which requires further investigation.

THU234 An Adolescent Patient With Asymptomatic Hypocalcemia And Extensive Cerebral Calcification Due To Pseudohypoparathyroidism Type 1B: A Care Report

Abstract Disclosure: R. Alemzadeh: None. J.D. Ross: None. D. Guillen-Mendoza: None. Background: Pseudohypoparathyroidism (PHP) is a heterogeneous group of disorders due to renal resistance to parathyroid hormone (PTH) resulting in biochemical hypoparathyroidism but with skeletal sensitivity to PTH. Case Presentation: A 15-year-old African American male was incidentally found to have biochemical evidence of severe hypocalcemia during routine evaluation of his bilateral slipped capital-femoral epiphyses. The patient was at age-appropriate stage of puberty with normal height and without any features of hereditary osteodystrophy. However, he had history of mild developmental delay requiring school accommodations. On physical exam, there was some mild dyscoordination with finger and toe-tapping and a Myerson’s sign, negative tetany signs. The biochemical screening revealed markedly low serum calcium (4.9 mg/dL) with elevated phosphorus (7.8 mg/dL) and PTH (1314 pg/mL) levels. His hypocalcemia was accentuated by the presence of severe 25 hydroxy-vitamin D deficiency (7.5 ng/mL) with mild hypomagnesemia (1.4 mg/dL). He had normal renal and thyroid function tests with normal growth factors. There were minimal plasma cyclic AMP responses to a single dose of intravenous teriparatide (Ellsworth-Howard test) consistent with diagnosis of pseudohypoparathyroidism. The skeletal survey showed bowing and under-tubulation of the radius, ulna, tibia, and fibula as well as slipped capital femoral epiphysis bilaterally. His brain CT scan showed symmetrical severe dense calcifications in the basal ganglia, bilateral frontal, parietal and temporal subcortical white matter, pons and right dentate nucleus. Genetic testing did not reveal any GNAS mutations. The patient was initially treated with parenteral calcium followed by high-dose oral calcium supplements and calcitriol. His coexisting hypovitaminosis D and hypomagnesemia were corrected with oral high-dose cholecalciferol and magnesium sulfate, respectively. Conclusions: An incidental finding of severe asymptomatic hypocalcemia and elevated PTH without hereditary osteodystrophy phenotype raised the clinical suspicion of pseudohypoparathyroidism type 1B. This was associated with cerebral calcifications with increasing risk of worsening learning disabilities and minimal neurological findings. Presentation: Thursday, June 15, 2023

SAT223 Persistent Hypocalcemia After Thyroidectomy

Abstract Disclosure: R. Subramani: None. F. Manas: None. A. Kauser: None. S. Yavuz: None. Introduction: Hypocalcemia is one of the serious complications after total thyroidectomy with a reported incidence of 27.4% (transient)and 12.1% (permanent) probably related to iatrogenic parathyroidectomy. Here we report a case of hypocalcemia after thyroidectomy in the setting of normal parathyroid hormone levels. Summary: A 42-year-old female with medical history of multinodular goiter s/p thyroidectomy 2019 on thyroid hormone replacement presented with hypocalcemia since 2021. During the first-year post thyroidectomy, patient was doing well until she acquired COVID-19 in 2020 and started developing symptoms of paresthesia, and muscle spasms. Other parameters such as phosphorus, and 25 OH vitamin D were normal. Despite being on a high-dose calcium supplement 1200 mg every hour for 10 times daily and calcitriol 0.75 mg twice daily, her calcium levels were persistently low ranging between 7.1 to 8 mg/dl and normal albumin levels of 3.9 and 4.3, but parathyroid level (PTH) remained normal (27.7-37.5). The patient was also symptomatic. She was later switched to liquid calcium 1000 mg 6 times daily for better absorption. It is noted that she had recurrent symptomatic hypocalcemia episodes requiring multiple emergency room (ER) visits during times of stress such as viral illness. The patient was treated with a trial of teriparatide, after which her symptoms improved and there were no further ER visits. Her calcium level increased from 7.4 to 8.4 and calcium supplement requirement reduced to 1200 mg daily. During recent outpatient visit, the patient had hypocalcemia episodes after missing teriparatide doses as expected. Conclusion: Despite our patient had normal PTH levels, the parathyroids glands did not respond appropriately to hypocalcemia. Promberger et al studied a case of eight patients with hypocalcemia with normal PTH following thyroidectomy. All these patients had normal PTH levels during post-op period, but persistently low and ionized calcium levels 12 months after surgery. This suggests during persistent hypocalcemia normal parathyroid levels may indicate an inadequate PTH response. In our case, developing hypocalcemia long after surgery and relation to COVID-19 infection may suggest autoimmune phenomenon as developing PTH-antibodies or receptor malfunction, theory yet to be investigated. In cases of severe symptomatic hypocalcemia requiring significant amount of calcium supplement PTH analogs are very effective treatment. Presentation: Saturday, June 17, 2023

Non-inferiority of low-dose compared to standard high-dose calcium supplementation in pregnancy: study protocol for two randomized, parallel group, non-inferiority trials in India and Tanzania

Non-inferiority of low-dose compared to standard high-dose calcium supplementation in pregnancy: study protocol for two randomized, parallel group, non-inferiority trials in India and Tanzania

What more can be done? Prioritizing the most promising antenatal interventions to improve birth weight

BackgroundLow birth weight (LBW) is associated with neonatal mortality and sequelae of lifelong health problems; prioritizing the most promising antenatal interventions may guide resource allocation and improve health outcomes. ObjectiveWe sought to identify the most promising interventions that are not yet included in the policy recommendations of the World Health Organization (WHO) but could complement antenatal care and reduce the prevalence of LBW and related adverse birth outcomes in low- and middle-income settings. MethodsWe utilized an adapted Child Health and Nutrition Research Initiative (CHNRI) prioritization method. ResultsIn addition to procedures already recommended by WHO for the prevention of LBW, we identified six promising antenatal interventions that are not currently recommended by WHO with an indication for LBW prevention, namely: (1) provision of multiple micronutrients; (2) low-dose aspirin; (3) high-dose calcium; (4) prophylactic cervical cerclage; (5) psychosocial support for smoking cessation; and (6) other psychosocial support for targeted populations and settings. We also identified seven interventions for further implementation research and six interventions for efficacy research. ConclusionThese promising interventions, coupled with increasing coverage of currently recommended antenatal care, could accelerate progress toward the global target of a 30% reduction in the number of LBW infants born in 2025 compared to 2006-10.

A modular systematic review of antenatal interventions to address undernutrition during pregnancy in the prevention of low birth weight

BackgroundPoor nutrition during pregnancy can lead to adverse birth outcomes including low birth weight (LBW). ObjectiveThis modular systematic review aimed to provide evidence for the effects of seven antenatal nutritional interventions on the risks of LBW, preterm birth (PTB), small-for-gestational-age (SGA) and stillbirth (SB). MethodsWe searched MEDLINE, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials and CINAHL Complete between April and June 2020, with a further update in September 2022 (Embase only). We included randomized controlled trials (RCTs) and reviews of RCTs to estimate the effect sizes of the selected interventions on the four birth outcomes. ResultsEvidence suggests that balanced protein and energy (BPE) supplementation for pregnant women with undernutrition can reduce the risk of LBW, SGA and SB. Evidence from low and lower middle-income countries (MIC) suggests that multiple micronutrient (MMN) supplementation can reduce the risk of LBW and SGA in comparison with iron or iron and folic acid supplementation and lipid-based nutrient supplements (LNS) with any quantity of energy can reduce the risk of LBW in comparison with MMN supplementation. Evidence from high and upper MIC suggests that supplementation with omega-3 fatty acids (O3FA) can reduce the risk and supplementation with high-dose calcium might possibly reduce the risk of LBW and PTB. Antenatal dietary education programs might possibly reduce the risk of LBW in comparison with standard-of-care. No RCTs were identified for monitoring weight gain followed by interventions to support weight gain in women who are underweight. ConclusionsProvision of BPE, MMN and LNS to pregnant women in populations with undernutrition can reduce the risk of LBW and related outcomes. The benefits of O3FA and calcium supplementation to this population require further investigation. Targeting interventions to pregnant women who are not gaining weight has not been tested with RCTs.

P320 AN UNUSUAL CASE SYNCOPE DUE TO SILENT CORONARY VASOSPASM

Abstract Background Variant angina is a condition due to a transient vasospasm of the epicardial coronary arteries, which usually causes chest pain episodes and may be associated with dangerous arrhythmias. A non–negligible subset of patients can also experience silent myocardial ischemia, defined as objective documentation of myocardial ischemia in the absence of angina or equivalents. This condition is associated with increased cardiac mortality and incidence of acute cardiac events. Description of the case. A 65–years–old man was admitted to our Emergency Department for syncope. He reported palpitations before the event without chest pain. ECG showed biphasic T waves in V2–V6 (Fig 1A), troponin values were normal. Immediately after admission in our coronary care unit for monitoring, he developed dynamic ST segment elevation with signs of inferior and posterior transmural ischemia (Fig 1B) and non–sustained polymorphic ventricular tachycardias (Fig 2), being symptomatic only for palpitations. ECG abnormalities and symptoms quickly resolved after intra–venous nitrates administration. Coronary angiography was performed showing a critical non–occlusive (85%) fixed stenosis at the proximal right coronary artery (Fig 3 A). The lesion was treated by angioplasty and stenting (Fig 3 B) and the patients was discharged on dual anti–platelet therapy, statins and oral high–dose calcium–channel antagonist. Discussion This case underlines first the importance of searching for high–risk features in patients with syncope of non–obvious origin: our patient reported palpitations and ECG changes consistent with myocardial ischemia (even with normal troponin values and echocardiographic findings). A peculiarity of our case is that the patient did not complaint any chest pain despite the presence of ST elevation, a condition known as silent ischemia. The transient nature of ECG modification and ventricular arrhythmias, their dramatic response to nitrates and coronary angiography findings were suggestive of silent vasospasm. Coronary vasospasm induces transient myocardial ischemia and may cause ventricular arrhythmias which in turn can cause syncope due to transient cerebral hypoperfusion or, when sustained, even cardiac arrest and sudden death. We did not perform provocative test with acetylcholine or ergonovine due to the likely vasospastic origin of myocardial ischemia and to their potential risks, especially in the presence of non–sustained plymorphic ventricular tachycardias.

Calcium and Aspirin Supplementation for Prevention of Pre-eclampsia in Moderate to High-Risk Pregnancy: A Randomized Controlled Trial

Background: Pregnancy-induced hypertension is one of the major causes of both maternal and fetal death. Calcium can be prescribed to prevent the development of pre-eclampsia among the population with low calcium intake. However, there are only a few research studies on the effect of calcium alone, the impact of calcium co-administrated with other medications, and the timing of prescription during pregnancy. Materials and Methods: The authors conducted a randomized, single-blind, controlled trial to evaluate the efficacy of high-dose calcium carbonate (CaCO₃) co-administrate with aspirin in women with moderate to high risk of developing pre-eclampsia in reducing the incidence of pre-eclampsia. All pregnant women at 12 to 28 weeks of gestation having a moderate to high risk of developing pre-eclampsia were randomly assigned to receive aspirin with CaCO₃ (3,750 mg/day), or aspirin with standard dose calcium carbonate (1,250 mg/day) until delivery or developed pre-eclampsia. Results: One hundred thirty women underwent randomization with 64 women in the CaCO₃ group and 66 women in the standard dose group. The incidence of pre-eclampsia was six cases in the high-dose group and eight cases in the controlled group (OR 0.8, 95% CI 0.3 to 2.6). The percentage of participants having adverse events related to high-dose and standard dose calcium carbonate did not differ significantly between the groups. Conclusion: The use of CaCO₃ at 3,750 mg/day, co-administrate with low-dose aspirin of 81 mg/day, starting at 12 to 28 weeks of gestation, resulted in a non-significantly difference in the incidence of pre-eclampsia with severe features. Keywords: Calcium carbonate; Pre-eclampsia; Prevention

Genotypic Spectrum and its Correlation with Alopecia and Clinical Response in Hereditary Vitamin D Resistant Rickets: Our Experience and Systematic Review.

Alopecia in hereditary vitamin D resistant rickets (HVDRR) has some correlation with severe rickets and poor overall response. However, these observations are based on small series. Hence, we aim to assess the genotypic spectrum of HVDRR and its correlation with alopecia and clinical response. Seven genetically-proven HVDDR patients from five unrelated families and 119 probands from systematic review were analysed retrospectively for phenotypic and genotypic data and overall response to therapy. In our cohort mean age at rickets onset was 12 (± 3.4) months. Alopecia was present in all patients but one. All patients had poor overall response to oral high-dose calcium and calcitriol and most required intravenous calcium. Genetic analyses revealed four novel variants. On systematic review, alopecia was present in majority (81.5%) and preceded the onset of rickets. Patients with alopecia had higher serum calcium (7.6 vs.6.9mg/dl, p = 0.008), lower 1, 25(OH)2 D (200 vs.320pg/ml, p = 0.03) and similar overall response to oral therapy (28.7% vs. 35.3%, p = 0.56). Alopecia was present in 51.4% of non-truncating (NT) ligand-binding domain (LBD) variants, whereas it was universal in truncating LBD and all DNA binding-domain (DBD) variants. Overall response to oral therapy was highest in LBD-NT (46.4%) as compared to 7.6% in LBD-truncating and 19% in DBD-NT variants. Among LBD-NT variants, those affecting RXR heterodimerization, but not those affecting ligand affinity, were associated with alopecia. Both alopecia and overall response have genotypic correlation. Age at diagnosis and overall response to oral therapy were similar between patients with and without alopecia in genetically proven HVDRR.