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Purpose: Hypocalcemia is associated with increased mortality in trauma patients with hemorrhagic shock who require massive transfusion protocols (MTPs). Despite known risks of potentiating hypocalcemia with blood product administration, there is little research discussing appropriate calcium replacement. The purpose of this study was to evaluate the ability of a standardized calcium replacement protocol to reduce the incidence of hypocalcemia in trauma patients undergoing MTP., Methods: This retrospective, single-center, pre-post study evaluated the use of a calcium replacement protocol during MTP. Adult trauma patients with MTP orders who received at least one "round" of product transfusion were included. Patients were excluded if their ionized calcium (iCa) levels were unavailable or they were transferred to a higher level of care within 4 hours of presentation. The primary outcome was incidence of hypocalcemia (iCa of <1.1 mg/dL) within 24 hours of MTP initiation. Secondary endpoints included the incidence of severe hypocalcemia (iCa of <0.9 mg/dL), time to first calcium dose, total calcium dose administered (mEq), resolution of hypocalcemia within 24 hours, hypercalcemia, adherence to the calcium replacement protocol, and mortality., Results: The incidence of hypocalcemia within 24 hours was significantly lower in the postprotocol group (63% vs 95.2%; P = 0.006). There was not a significant difference in the incidence of severe hypocalcemia between the groups (39.1% vs 69.1%; P = 0.083). Time to first calcium dose was significantly shorter in postprotocol patients compared to preprotocol patients (median [interquartile range], 5.5 [0-21] minutes vs 43 [22.8-73] minutes; P < 0.0001), and postprotocol patients were administered more calcium during MTP (40.8 [27.2-54.4] mEq vs 27.2 [14-32.2] mEq; P = 0.005). Adherence to the protocol was seen in only 37% of patients in the postprotocol group. There was no difference in the rate of adverse events or overall mortality., Conclusion: Trauma patients who received massive transfusion of blood products had a significantly lower incidence of hypocalcemia after a calcium replacement protocol was implemented., (© American Society of Health-System Pharmacists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: Vitamin D deficiency co-exists with and can confuse the diagnosis of primary hyperparathyroidism (PHPT). Vitamin D replete (VDR) status may prevent significant postparathyroidectomy hypocalcaemia; however, reports from previous studies are conflicting. This study aimed to assess differences in early and/or late postoperative hypocalcaemia and length of stay (LOS) postparathyroidectomy between VDR and vitamin D non-replete (VDNR) PHPT patients., Methods: This was a retrospective cohort study of a prospectively maintained single surgeon operative database. All records of patients who underwent parathyroidectomy over a four-year period (July 2014 to December 2018) were extracted. Data were collected on vitamin D and corrected calcium levels pre- and postoperatively as well as postoperative complications and LOS., Results: On presentation, there were 91 (47.9%) VDR and 99 (52.1%) VDNR patients. Following vitamin D therapy there were 148 (77.9%) VDR and 42 (22.1%) VDNR. The multivariate analysis showed that vitamin D status was the only significant factor impacting on the hypocalcaemia symptoms (OR 4.9, 95% CI 1.8-13.7, p  = 0.002) and the most significant factor for the calcium supplementation (OR 6.5, 95% CI 2.1-19.4, p  = 0.001). Bilateral neck exploration was associated with increased likelihood of transient hypocalcaemia ( p  = 0.007) but no other post-op complication. Median LOS was significantly shorter for VDR (1 day) versus VDNR (1.5 days) patients ( p  = 0.001)., Conclusion: There is a statistically significant increased likelihood of postoperative hypocalcaemia symptoms, requirement for calcium supplements and increased LOS in VDNR patients. This study suggests optimising preoperative vitamin D status improves patient experience and could reduce healthcare costs.

Background: The transient acute hypocalcemia (HypoCa) is the most prevalent complication after total thyroidectomy, detected primarily by subnormal intact parathyroid hormone (iPTH) and calcium levels. However, the need for calcium supplementation is ambiguous in patients who exhibit low iPTH with normal calcium levels. The aim of this study was to evaluate complementary predictors of HypoCa in this scenario., Methods: A retrospective cohort study with of 1597 consecutive patients undergoing total thyroidectomy, with or without neck dissection, from January 2014 to December 2018 at a single institution. Patients with an iPTH <12 pg/mL and a total calcium level ≥8 mg/dL in the first 8 h after surgery were included., Results: 1597 patients identified with low postoperative iPTH without overt calcium deficiency was diagnosed. The transient HypoCa in that specific subgroup was 509 (31.9%). Multivariate analysis indicated that HYPOCA was associated with bilateral level VI neck dissection and pre- to postoperative calcium reduction >38 pg/mL. To better illustrate the model, we plotted a nomogram with the variables selected for the final model., Conclusion: Total thyroidectomy patients who exhibit low postoperative iPTH levels without overt calcium deficiency should be considered for calcium replacement therapy when they a marked drop in iPTH postoperatively and underwent bilateral level VI neck dissection., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Denosumab is a human monoclonal antibody antiresorptive agent used for the treatment of bone metastasis in different cancer types, including breast cancer. Hypocalcemia is a known adverse effect of denosumab, and early supplementation plays an important role in the prevention and management of hypocalcemia., Case Report: A 63-year-old female with stage IV estrogen receptor-positive breast cancer with diffuse bone metastasis experienced severe, prolonged hypocalcemia following a single dose of denosumab. The patient also had several risk factors for denosumab-associated hypocalcemia. Despite not receiving additional doses of denosumab, the patient required multiple hospitalizations and outpatient infusions of calcium to resolve her symptomatic hypocalcemia.Management and outcome: Severe hypocalcemia associated with denosumab can be prevented or mitigated by recognizing the risk factors for hypocalcemia and supplementing with vitamin D/calcium. Proposed risk factors include poor renal function, hypoparathyroidism, insufficient calcium intake, and diffuse metastatic bone disease. Studies suggest that early supplementation before starting denosumab can lower this risk., Discussion: Several cases of severe hypocalcemia associated with denosumab have been reported. However, to the authors' knowledge, this is the first report that highlights the importance of early vitamin D/calcium supplementations for a patient with diffuse metastatic bone disease with pre-existing low levels of calcium.

Rationale: Autosomal dominant hypocalcaemia type 1 (ADH1) is a genetic disease characterized by benign hypocalcemia, inappropriately low parathyroid hormone levels and mostly hypercalciuria. It is caused by the activating mutations of the calcium-sensing receptor gene (CASR), which produces a left-shift in the set point for extracellular calcium., Patient Concerns: A 50-year-old man presenting with muscle spasms was admitted into the hospital. He has a positive familial history for hypocalcemia. Auxiliary examinations demonstrated hypocalcemia, hyperphosphatemia, normal parathyroid hormone level and nephrolithiasis. A missense heterozygous variant in CASR, c 613C > T (p. Arg205Cys) which has been reported in a familial hypocalciuric hypercalcemia type 1 patient was found in the patient's genotype. It is the first time that this variant is found associating with ADH1. The variant is predicted vicious by softwares and cosegregates with ADH1 in this pedigree. CASR Arg205Cys was deduced to be the genetic cause of ADH1 in the family., Diagnosis: The patient was diagnosed with ADH1 clinically and genetically., Interventions: Oral calcitriol, calcium and hydrochlorothiazide were prescribed to the patient., Outcomes: After the treatments for 1 week, the patient's symptom was improved and the re-examination revealed serum calcium in the normal range. A 3-month follow-up showed his symptom was mostly relieved., Lessons: The variant of CASR Arg205Cys, responsible for ADH1 in this family, broadened the genetic spectrum of ADH1. Further and more studies are required to evaluate the correlation between genotype and phenotype in ADH1 patients., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Transfusion of citrated blood products may worsen resuscitation-induced hypocalcemia and trauma outcomes, suggesting the need for protocolized early calcium replacement in major trauma. However, the dynamics of ionized calcium during hemostatic resuscitation of severe injury are not well studied. We determined the frequency of hypocalcemia and quantified the association between the first measured ionized calcium concentration [iCa] and calcium administration early during hemostatic resuscitation and in-hospital mortality., Methods: We performed a retrospective cohort study of all admissions to our regional level 1 trauma center who (1) were ≥15 years old; (2) presented from scene of injury; (3) were admitted between October 2016 and September 2018; and (4) had a Massive Transfusion Protocol activation. They also (1) received blood products during transport or during the first 3 hours of in-hospital care (1st3h) of trauma center care and (2) had at least one [iCa] recorded in that time. Demographic, injury severity, admission shock and laboratory data, blood product use and timing, and in-hospital mortality were extracted from Trauma Registry and Transfusion Service databases and electronic medical records. Citrate load was calculated on a unit-by-unit basis and used to calculate an administered calcium/citrate molar ratio. Univariate and multivariable logistic regression analyses for the binary outcome of in-hospital death were performed., Results: A total of 11,474 trauma patients were admitted to the emergency department over the study period, of whom 346 (3%; average age: 44 ± 18 years; 75% men) met all study criteria. In total, 288 (83.2%) had hypocalcemia at first [iCa] determination; 296 (85.6%) had hypocalcemia in the last determination in the 1st3h; and 177 (51.2%) received at least 1 calcium replacement dose during that time. Crude risk factors for in-hospital death included age, injury severity score (ISS), new ISS (NISS), Abbreviated Injury Scale (AIS) head, admission systolic blood pressure (SBP), pH, and lactate; all P < .001. Higher in-hospital mortality was significantly associated with older age, higher NISS, AIS head, and admission lactate, and lower admission SBP and pH. There was no relationship between mortality and first [iCa] or calcium dose corrected for citrate load., Conclusions: In our study, though most patients had hypocalcemia during the 1st3h of trauma center care, neither first [iCa] nor administered calcium dose corrected for citrate load were significantly associated with in-patient mortality. Clinically, hypocalcemia during early hemostatic resuscitation after severe injury is important, but specific treatment protocols must await better understanding of calcium physiology in acute injury., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 International Anesthesia Research Society.)

Objectives. Hungry bone syndrome (HBS) is a severe and underdiagnosed complication of parathyroidectomy in the treatment of primary hyperparathyroidism (PHP) and secondary hyper-parathyroidism to chronic kidney disease (SHP-CKD). Methods. A longitudinal study was conducted to compare the postoperative outcomes of patients who developed HBS in two different time frames: before and after implementing a protocol with an intensive electrolytic monitoring and an algorithm regarding electrolytic supplementation. Results. Overall, 77 parathyroidectomies were included. In PHP, a protocol implementation led to an increased admission of patients in the Intermediate Care Unit for intensive electrolytic monitoring (p<0.001) and an increased rate of oral calcium replacement during hospital stay (p=0.013) compared to pre-protocol era. In SHP-CKD, duration of intravenous calcium replacement was reduced (p=0.010). The prevalence of HBS (9.8% in PHP and 58.3% in SHP-CKD) was similar between the two periods, although its diagnosis had an increased trend in PHP since the protocol implementation. None of the diagnosis of HBS was established due to hypocalcemic symptoms in the post-protocol era (contrary to pre-protocol period, p=0.021). Both hypocalcemia length and duration of surgical ward hospitalization were reduced (p=0.047 and p=0.042, respectively). Conclusions. An improved assessment of hyperparathyroidism and a decrease in HBS severity were noted in the post-protocol era. We strongly recommend the implementation of a standardized protocol with an intensive phosphocalcium monitoring in the high-risk patients who undergo parathyroidectomy due to hyperparathyroidism as it improves the health care and management of HBS., (© 2021 Joana Lima Ferreira et al., published by Sciendo.)

This study aimed to evaluate the effects of oral administration of calcium (Ca) formate in the postpartum of high-producing dairy cows on calcemia, on other blood biochemical markers, and on the occurrence of diseases at the beginning of lactation. One hundred and twenty healthy Holstein cows, distributed according to the lactation order (first, second, third and fourth to sixth), were treated or not with oral Ca formate (two doses: one after calving and one 24 h later; equivalent to 50 g of Ca per dose), comprising 8 groups (n = 15). The following variables were measured in the blood serum of samples collected after calving (0 h) and after 24, 48, 72, and 96 h: total Ca, phosphate (P), magnesium (Mg), non-esterified fatty acids (NEFA), beta-hydroxybutyrate (BHB), glucose, total protein (TP), albumin (Alb), urea nitrogen (BUN), aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT). Blood BHB was also measured at 7, 14, and 21 DIM. For the assessment of disease occurrence, cows were distributed in treated (n = 60) and untreated (n = 60) groups and in hypocalcemic (n = 71) and normocalcemic (n = 49) groups. Two-way repeated measures ANOVA and a chi-square test were used for comparisons. The lactation order did not influence the studied blood constituents, except for primiparous cows which had the highest calcemia. Serum Ca was lower up to 24 h and increased after 48 h and subclinical hypocalcemia (SCH) ([Ca] < 2.125 mmol/L) was more frequent in cows with a higher number of lactations. Treatment with Ca formate had no effect on the variation of serum Ca and the other studied variables in the first days of lactation. Treated and untreated cows did not differ in terms of milk yield at 21 DIM, the presentation of diseases at the beginning of lactation, the rate of discard or death up to 60 DIM and the frequency of SCH (60 % and 58 %, respectively). Hypocalcemic cows became more ill (64.8 % vs. 42.9 %; P = 0.028) and had a higher frequency of retained placenta (43 % vs. 20.7 %; P < 0.001). Oral administration of Ca formate after calving and 24 h later is not justified as a preventive measure to be adopted indiscriminately in dairy herds. Studies involving larger number of animals may clarify whether the selective treatment of cows with a higher risk of hypocalcemia is advantageous., (Copyright © 2020. Published by Elsevier B.V.)

Introduction: Hypocalcaemia in pregnancy remains a major health issue, particularly in the developing world where daily calcium intakes are suboptimal. This electrolyte imbalance can lead to severe maternofoetal and childhood consequences. Calcium supplementation, amongst others, contributes significantly to meeting calcium demands in pregnancy. With ionised calcaemia as the gold standard for diagnosis, total calcaemia and albumin-corrected calcaemia in other pathological states have been found to overestimate the burden of hypocalcaemia. The main objectives of this study are to describe the blood calcium level (total, albumin corrected, and ionised calcaemia) and associated maternofoetal outcomes while identifying determinants of calcium supplementation and ionised hypocalcaemia. This study will also evaluate the sensitivity and specificity of albumin corrected calcaemia as a diagnostic tool for hypocalcaemia (ionised calcaemia as the gold standard) among pregnant women in the Nkongsamba Regional Hospital, Cameroon., Methods: Our study will target a total of 1067 term pregnant women who shall be included consecutively into the study as they arrive the maternity of the Nkongsamba Regional Hospital for their last antenatal care visit. Data shall be collected using a semi-structured interview-administered questionnaire and blood samples collected for total plasma calcium, albumin and serum ionized calcium assays. Additional data will be collected at birth (maternal and foetal variables; foetal outcomes evaluated as secondary outcomes). Total calcaemia and albuminemia shall be measured by atomic absorption spectrophotometry, while ionised calcaemia will be measured by ion-selective electrode potentiometry(using MSLEA15-H electrolyte analyzer) per standard BIOLABO and MSLEA15 protocols, respectively. Data will be analysed using the statistical softwares epi-Info version 7.2.2.16 and STATA version 16., Expected Research Outcome: This study will present a more precise estimate of the burden of hypocalcaemia in late pregnancy as well as identify and analyse the different factors associated with calcium supplementation and ionised hypocalcaemia among term pregnant women in a developing world setting. Maternofoetal outcomes associated with hypocalcaemia will be determined as well as the sensitivity and specificity of total and albumin-corrected calcaemia in diagnosing hypocalcaemia. Our findings will contribute significantly to designing or strengthening interventions to control this electrolyte imbalance., Competing Interests: The authors have declared that no competing interests exist.

The aim of this study was to evaluate different treatments of postpartum subclinical hypocalcemia in dairy cows with emphasis on PTH response. Twenty four cows with subclinical hypocalcemia (Ca 1.4-2.0 mmol/L), out of 180 Holstein cows tested, were assigned in one of three equal groups: (1) CON received no Ca supplementation, (2) PO-Ca received 1000 mL of oral Ca suspension, immediately after establishing hypocalcemia, and 500 mL of the suspension 12 h after, (3) IV-Ca intravenously received 500 mL of Ca immediately after establishing hypocalcemia. The blood samples were taken up to 48 h after initial treatment for determination of Ca, iP, Mg and PTH concentrations. Urine pH was also evaluated up to 48 h after initial treatment. Compered to CON cows that were hypocalcemic up to the 48 h, Ca concentrations were significantly higher in PO-Ca up to hour 8 and IV-Ca up to hour 24. At first 2 h, PTH concentrations were significantly lower, compared to CON, only in IV-Ca, while at hour 4 PTH concentrations were significantly lower in both treated groups. At hours 24 and 48, PTH concentrations were significantly lower only in PO-Ca compared to CON group. Urine pH values in CON indicate alkalosis and were significantly lower both in PO-Ca and IV-Ca group, up to 12 h and 24 h respectively. In conclusion, both treatments mitigated hypocalcemia in cows, but with significantly different PTH response. Due to adequate PTH response, normocalcemia is established in CON and expected transient hypocalcemia is avoided in IV-Ca cows., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Traumatic injury is a major cause of morbidity and mortality, and hemorrhage is a primary factor. Evidence exists that major trauma patients are at high risk of hypocalcemia. The purpose of this study was to determine the incidence and rate of calcium replacement in major trauma patients requiring operative intervention, and to investigate the impact of hypocalcemia on rate of transfusion and mortality. A retrospective analysis was conducted of all top-tier trauma activations presenting to our institution during a 12-month period. A total of 638 activations were identified; 441 were excluded, primarily because of lack of operative intervention. Patients were predominantly male following blunt trauma. The mean initial calcium level was 8.11 mg/dL and 8.64 mg/dL, correcting for albumin levels. An acute decline was noted when initial serum calcium levels and intraoperative calcium levels were compared (7.51 mg/dL). Intraoperative ionized calcium levels were on the low end of the normal range, and 28.42% received supplemental calcium. Patients in our cohort arrived hypocalcemic, which has been previously associated with increased mortality. Patients requiring operative intervention are at increased risk of hypocalcemia. Recognition of this potential is key for improved outcomes., Competing Interests: Research reported in this publication was supported by grants from the National Institute of General Medical Sciences of the National Institutes of Health under Award No. P30GM110703 and P20GM103424. Additional support was provided by the Noel Foundation and by the Abe Sadoff Distinguished Chair in Bioinformatics and Lisa Burke Bioinformatics Endowed Professorship, Louisiana State University Shreveport., (Copyright © by the American Association of Nurse Anesthetists.)

Postoperative hypocalcemia is a well-described outcome following thyroid and parathyroid surgery with symptoms ranging from clinically insignificant laboratory findings to tetany and seizures. The aims of this study were 1. To identify the characteristics and management patterns of postoperative hypocalcemia in head and neck endocrine surgery patients and 2. To compare outcomes between patients treated with empiric calcium and patients treated using a biochemically driven calcium replacement algorithm. Clinical electronic medical record (EMR) data was collected from patients who had undergone total thyroidectomy, completion thyroidectomy, and/or parathyroidectomy at Wake Forest Baptist Medical Center (WFBMC), a tertiary referral and academic institution. Between July 1, 2016, and June 30, 2017, 298 adult patients underwent surgery by a WFBMC Head & Neck (H&N) endocrine surgeon. Objective calcium and parathyroid hormone levels, postoperative supplementation with calcium and Vitamin D, 30-day physician access line (PAL) phone call utilization, emergency department (ED) encounters, and readmission rates were queried. The overall rate of hypocalcemia was 17.4%. No statistically significant difference in PAL utilization, ED visits, or readmissions was found between the empiric supplementation group and those whose supplementation was biochemically directed (PAL 5.0% vs. 5.0% [p = 0.983], ED visit 3.3% vs. 2.5% [p = 0.744], Readmission 1.7% vs. 0% [p = 0.276]). The overall postoperative rates of hypocalcemia and hypoparathyroidism following H&N endocrine surgery were consistent with the reported literature. Neither method of calcium supplementation was superior in reducing PAL utilization, ED encounters, or readmission., (Copyright © 2020 Elsevier Inc. All rights reserved.)

A four-year-old girl presented with accidental ingestion of 200 tablets of Calcarea phosphorica . Although she was asymptomatic, she was found to have marked hypocalcaemia with a prolonged QTc interval on electrocardiogram. She was successfully treated with intravenous calcium, followed by oral maintenance.

Hypoparathyroidism during pregnancy is a very rare endocrine disorder. The majority of cases are postsurgical (75%). Managing pregnant or nursing women with hypoparathyroidism is challenging due to complications arising from either under- or overtreatment, including premature delivery or fetal death, abortion, stillbirth, perinatal death, and neonatal tetany. Specific adaptations are needed within each time period to meet the fetal, neonatal, and maternal calcium requirements. A systematic search was performed on PubMed using the search terms "pregnancy" and "hypoparathyroidism." Included were articles published in English between January 1, 1966, and January 1, 2018. We provide an overview of all published cases (n = 43) of hypoparathyroidism in pregnancy, including a case report of a 29-year-old pregnant woman who underwent a total thyroidectomy before her current pregnancy because of a therapy-resistantant Graves' disease. The procedure was complicated by postsurgical hypoparathyroidism. She carried out the pregnancy to term with minor complaints of paresthesia and muscle cramps. Furthermore, we discuss treatment, complications, and follow-up of hypoparathyroidism in pregnancy. Treatment of hypoparathyroidism in pregnancy should still be individualized, depending on the patient's complaints and serum levels of calcium, which should be maintained in the lower normal range of 2.15 to 2.55 mmol/l, according to the literature. We recommend monitoring calcium levels every 3 to 4 weeks throughout the pregnancy, within 1 week postpartum, and monthly during lactation to ensure normocalcemia., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Due to the sudden increase of calcium demand at the onset of lactation many high yielding dairy cows experience a certain level of hypocalcaemia following parturition. The incidence of hypocalcaemia (parturient paresis) increases with age but also depends on many other factors such as the acid-base status and the availability of calcium as well as other minerals and trace elements. Hypocalcaemia can easily be treated by supplementation of calcium parenterally or orally, nonetheless, prophylaxis of the condition should be the main focus in modern dairy farming, in order to avoid its negative effects. Oral administration of calcium around parturition is the simplest way of prophylaxis, but results in a high work load and requires exact knowledge of the date of parturition. The latter also applies for the parenteral administration of vitamin D 3 , which should be injected 1 week before parturition. Additionally, repeated treatment with vitamin D increases the risk for calcinosis. Reducing the calcium concentration of the ration fed during the late dry period also decreases the risk for hypocalcaemia by activating the mechanisms for calcium homeostasis within the body. The induction of a mild (compensated) metabolic acidosis to increase the sensitivity of parathormone receptors and enhance intestinal calcium uptake may also be employed to prevent milk fever. For this purpose, a DCAD (dietary cation anion difference) diet is fed during the late dry period, in which the concentrations of strong cations (potassium and sodium) as well as strong anions (sulfate and chloride) are altered. This may either be achieved by reducing the potassium concentration (partial-DCAD) or by adding anionic salts (full-DCAD). This method, especially the full-DCAD variant, requires a substantial level of surveillance and monitoring. Suitable prophylactic measures for the prevention of hypocalcaemia must be chosen individually for each farm, depending on the incidence of hypocalcaemia as well as personnel and structural resources., Competing Interests: Die Autoren bestätigen, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Randomized clinical trials (RCTs) support the use of prehospital plasma in traumatic hemorrhagic shock, especially in long transports. The citrate added to plasma binds with calcium, yet most prehospital trauma protocols have no guidelines for calcium replacement. We reviewed the experience of two recent prehospital plasma RCTs regarding admission ionized-calcium (i-Ca) blood levels and its impact on survival. We hypothesized that prehospital plasma is associated with hypocalcemia, which in turn is associated with lower survival., Methods: We studied patients enrolled in two institutions participating in prehospital plasma RCTs (control, standard of care; experimental, plasma), with i-Ca collected before calcium supplementation. Adults with traumatic hemorrhagic shock (systolic blood pressure ≤70 mm Hg or 71-90 mm Hg + heart rate ≥108 bpm) were eligible. We use generalized linear mixed models with random intercepts and Cox proportional hazards models with robust standard errors to account for clustered data by institution. Hypocalcemia was defined as i-Ca of 1.0 mmol/L or less., Results: Of 160 subjects (76% men), 48% received prehospital plasma (median age, 40 years [interquartile range, 28-53 years]) and 71% suffered blunt trauma (median Injury Severity Score [ISS], 22 [interquartile range, 17-34]). Prehospital plasma and control patients were similar regarding age, sex, ISS, blunt mechanism, and brain injury. Prehospital plasma recipients had significantly higher rates of hypocalcemia compared with controls (53% vs. 36%; adjusted relative risk, 1.48; 95% confidence interval [CI], 1.03-2.12; p = 0.03). Severe hypocalcemia was significantly associated with decreased survival (adjusted hazard ratio, 1.07; 95% CI, 1.02-1.13; p = 0.01) and massive transfusion (adjusted relative risk, 2.70; 95% CI, 1.13-6.46; p = 0.03), after adjustment for confounders (randomization group, age, ISS, and shock index)., Conclusion: Prehospital plasma in civilian trauma is associated with hypocalcemia, which in turn predicts lower survival and massive transfusion. These data underscore the need for explicit calcium supplementation guidelines in prehospital hemotherapy., Level of Evidence: Therapeutic, level II.

Aim: Hyperparathyroidism in chronic kidney disease-mineral and bone disorder is associated with significant morbidity and mortality. Parathyroidectomy is widely carried out as treatment despite complications such as hypocalcaemia post-surgery. Our centre has been using an ALP-based protocol to replace calcium postoperatively to prevent hypocalcaemia. We aim to describe and audit our calcium replacement protocol post-parathyroidectomy METHODS: We, retrospectively, analyse 167 end-stage kidney disease patients who had parathyroidectomy with auto-implantation in Singapore General Hospital between January 2008 and December 2013. Their calcium replacement postoperatively was initiated upon patient arrival back in ward on the same day of surgery based on their pre-op ALP prior to occurrence of hypocalcaemia. Patient demographics, surgical and laboratory parameters were reviewed from medical records. Changes in calcium postoperatively were reported to look for incidence of calcium derangement., Results: Mean calcium levels between pre-operation day and post-operation day 7 ranged from 2.31 to 2.70 mmol/L. Decline in serum calcium was common in all patients prior to starting calcium replacement. Eighteen patients (10.9%) experienced hypocalcaemia immediately post-operation prior to commencement of IV calcium replacement. Patients with immediate post-operation hypocalcaemia had lower pre-operation calcium but higher pre-operation alkaline phosphatase (ALP) and pre-operation intact parathyroid hormone. Hypercalcaemia is common likely from aggressive IV calcium replacement using the protocol. The average length of stay for patients prior to calcium stabilization and discharge was 9 days., Conclusion: Implementation of an ALP-based prophylactic calcium replacement protocol with daily serum calcium monitoring can ameliorate severe hypocalcaemia post-parathyroidectomy.

Background: Symptomatic hypocalcemia is a common complication of total thyroidectomy. Management strategies include responsive treatment initiation for symptoms or prevention by routine or parathyroid hormone-directed calcium supplementation. The comparative cost-effectiveness of even the most often utilized strategies is unclear., Methods: A Markov cohort model was created to compare routine supplementation with calcium alone (RS), postoperative parathyroid hormone-based selective supplementation with calcium and calcitriol (SS), and no supplementation (NS) in asymptomatic patients. Patients could remain asymptomatic or develop symptomatic hypocalcemia, managed with outpatient oral supplementation or intravenous calcium infusion and administered either inpatient or outpatient. Effectiveness was measured in quality-adjusted life years. Sensitivity analyses were performed to test model parameter assumptions., Results: RS was the preferred strategy, costing $329/patient and resulting in 0.497 quality-adjusted life years, which was only marginally better compared to SS ($373 for 0.495 quality-adjusted life years). NS was most costly at $4,955 for 0.491 quality-adjusted life years. Preference for RS over SS was sensitive to the probability of developing symptoms and the probability of symptom treatment with intravenous supplementation. On probabilistic sensitivity analysis, RS was preferred in 75.4% of scenarios., Conclusion: After total thyroidectomy, a preventative calcium supplementation strategy should be strongly considered. In this data-driven theoretical model, RS was the least costly option and resulted in an incremental gain in quality-adjusted life years., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Hypomagnesemia with secondary hypocalcemia is a rare autosomal recessive disorder which manifests in early infancy with generalized seizures, other symptoms of neuromuscular irritability, and growth disturbances. Homozygous mutations in the magnesium transporter gene, transient receptor potential melastatin 6 (TRPM6), cause the disease. Here, we present an 8-month-old Turkish boy with a novel mutation of TRPM6. The patient, son of first-degree cousins, was hospitalized because of recurrent seizures and mild hypotonia. He had seizures since the newborn period and he had been treated with phenobarbital but there was no favorable response to therapy. His past history also revealed hypocalcemia detected on the newborn period but serum magnesium levels were not studied at that time. During hospitalization, we detected hypocalcemia, hypomagnesemia, and normal parathormone levels. Abdominal ultrasound was normal. Magnesium excretion was slightly increased. Considering the consanguinity of the parents and clinical features of the patients, genetic testing of the TRPM6 gene was performed and a novel homozygous mutation was detected as c.3178A>T. He was started on magnesium and calcium supplementation and he is symptom-free for 1 year. We would like to call attention to the measurement of serum magnesium levels in children with hypocalcemic convulsions. Early and appropriate treatment with magnesium supplementation is crucial.

Hypocalcemia is a common postpartum condition in dairy cows, which negatively affects health and production. Intravenous Ca infusions are commonly included in calving protocols to prevent or mitigate the effect of hypocalcemia in multiparous cows. Thus, we sought to contrast the effect of intravenous Ca infusion against voluntary oral Ca intake on Ca metabolism. Serum total Ca (tCa) and whole-blood ionized Ca (iCa) were monitored in 24 multiparous Holstein cows after parturition. Precalving diets were formulated with a positive dietary cation-anion difference of 172 mEq/kg of DM and contained 4.1 g of Ca/kg of DM. At parturition, cows were blocked by calving sequence and calcemic status as either normocalcemic (cutoff threshold of iCa ≥1.10 mmol/L) or hypocalcemic (cutoff threshold of iCa <1.10 mmol/L). Cows in each block were randomly assigned to 1 of 2 treatments: either an oral source of Ca (Ca-Oral; n = 12) or an intravenous source of Ca (Ca-IV; n = 12). Cows in the Ca-Oral group were offered a 20-L commercial Ca suspension (48 g of Ca) for voluntary consumption. The supplement contained Ca carbonate, Ca formate, Ca propionate, and other minerals and vitamins (Farm-O-San Reviva, Trouw Nutrition, Amersfoort, the Netherlands). Cows in the Ca-IV group received a 450-mL intravenous Ca solution (13 g of Ca) that contained 298 mg/mL of Ca gluconate, 33 mg/mL of magnesium chloride, and 82 mg/mL of boric acid (AmosCAL, Kommer-Biopharm BV, Heiloo, the Netherlands). Both treatments were initiated within 25 ± 10 min after calving. The oral Ca suspension was offered to cows in a 25-L bucket and was available for 10 min. All cows in the Ca-Oral group voluntarily consumed the entire 20 L of the Ca suspension within 5 min. Blood samples for Ca analyses were collected at 0 (before treatment initiation), 1, 3, 10, and 18 h relative to treatment, and at 0700 and 1900 h for the next 2 consecutive days, to represent the 24-, 36-, 48-, and 60-h sampling time points. In Ca-IV cows, both iCa and tCa concentrations peaked at 1 h (1.54 mmol/L for iCa and 2.85 mmol/L for tCa) and declined to a nadir at 24 h following treatment initiation (0.94 mmol/L for iCa and 1.74 mmol/L for tCa). Although whole-blood iCa and serum tCa were higher at 1 and 3 h in Ca-IV cows, concentrations of iCa were greater for Ca-Oral cows at 18, 24, and 36 h and for tCa at 24 and 36 h. Our data indicate that intravenous Ca infusion immediately induced a state of hypercalcemia followed by lower whole-blood iCa and serum tCa concentrations 24 h later compared with oral Ca., (The Authors. Published by FASS Inc. and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

Trauma is a leading cause of death in the United States, and uncontrolled hemorrhage is often the primary cause of mortality. Massive transfusions provide lifesaving treatment for the bleeding trauma patient; yet, this is not a benign intervention. Calcium levels can be significantly decreased with rapidly transfused blood products due to the citrate preservative that is added. Citrate binds to the patient's endogenous calcium when blood products are administered, rendering calcium inactive. As a result, undesirable physiological effects can occur. Although there is a plethora of evidence reporting the negative effects of hypocalcemia during resuscitation, the research for standardization of calcium monitoring and replacement during a massive transfusion event is less robust. Consequently, monitoring and replacement of this vital electrolyte are often overlooked. Trauma department employees at an urban academic hospital were given a pretest to assess their knowledge of calcium monitoring and replacement during a massive transfusion. On the basis of test results and a need for staff education, a short, animated video was designed and distributed for viewing. Following the educational video, a posttest was administered and yielded higher scores when compared with the pretest (p = .001). Lack of knowledge and national standards may be root causes for hypocalcemia. Educational interventions such as innovative, brief videos can be effective for enhancing staff members' knowledge and improving patient care.

Objective: To assess the utility of rapid parathyroid hormone (PTH) values in predicting transient post-operative hypocalcemia in patients with unplanned parathyroidectomy during total or completion thyroidectomy., Methods: All patients who underwent total or completion thyroidectomy between January 2010 and January 2015 were reviewed. Incidences of post-operative hypocalcemia were compared in patients with and without unplanned parathyroidectomy. Unplanned parathyroidectomy was defined as intra-operative incidental or intentional parathyroidectomy. Logistic regression assessed for predictors of hypocalcemia and optimum amount of calcium supplementation., Results: Thirty-eight (13.6%) patients had evidence of incidental parathyroidectomy and 39/280 (13.9%) patients had parathyroid autotransplantation intra-operatively. Central neck dissection and malignancy were identified as risk factors for unplanned parathyroidectomy (p = 0.001, p = 0.060). Patients with unplanned parathyroidectomy were more likely to have hypocalcemia (p = 0.002) and hypoparathyroidism (p < 0.0005). PTH value was the only significant predictor of hypocalcemia in these patients. In patients with a post-operative PTH of ≤15, initial calcium supplementation ≥ 1000 mg decreased the risk of hypocalcemia (p < 0.05)., Conclusion: Post-operative PTH value predicts hypocalcemia in patients undergoing total and completion thyroidectomy with unplanned parathyroidectomy. In patients with a post-operative PTH < 15, initial calcium supplementation with ≥1000 mg of elemental calcium is recommended., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: It is unclear whether clinical courses of hungry bone syndrome (HBS) after parathyroidectomy (PTX) in peritoneal dialysis (PD) and hemodialysis (HD) patients are different. The present study aimed to investigate the possible differences of postoperative hypocalcemia and hyperkalemia between PD and HD patients., Methods: We performed retrospectively 29 PD patients as the PD group and 169 HD patients as the HD group undergoing successful total PTX with autotransplantation. Calcium supplement after surgery was recorded. Higher levels of serum potassium during and immediately after surgery were recorded as K + d0 . K + d3 was recorded as peak pre-dialysis serum potassium level 3 days post-surgery., Results: There were 157 (92.90%) patients in HD group and 22 (75.86%) patients in PD group suffered from HBS after surgery, with significant difference between the groups (P = 0.004). Patients in PD group had significantly shorter intravenous calcium supplement duration (P = 0.037) and significantly smaller intravenous calcium supplement dosage (P = 0.042) and total calcium supplement dosage during hospitalization (P = 0.012) than patients in HD group. The levels of serum K + d0 (P < 0.001) and K + d3 (P < 0.001) were both significantly lower in PD group than those in HD group. Peritoneal dialysis was one of the independent influencing factors with negative correlation for calcium supplement, serum K + d0 and serum K + d3 ., Conclusions: Compared with HD patients, the clinical course of HBS after PTX in PD patients was alleviated. Efforts should be devoted to individual perioperative management for PD patients undergoing PTX.

Background: Thyroidectomy is the main intervention for thyroid malignancies and some benign thyroid diseases. Its most common complication is hypocalcaemia, which requires oral or intravenous calcium therapy. The aim of this meta-analysis was to assess the efficacy of routine calcium supplementation with or without vitamin D in preventing hypocalcaemia post-thyroidectomy., Methods: Systematic searches of the PubMed, EMBASE, and Cochrane Library databases were performed. The qualities of the included articles were assessed using the Cochrane risk of bias tool. The studies' qualities of outcomes and strengths of evidence were evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool. Data analysis was performed using Review Manager 5.3, and odds ratio (ORs) with their 95% confidence intervals (CIs) were computed for dichotomous data., Results: Ten randomized controlled trials (RCTs) were included. The combined study recruited 1620 patients (343 men and 1277 women) who underwent total thyroidectomy alone or with neck dissection. Calcium supplementation decreased the risk of transient postoperative hypocalcaemia (OR 0.48 [95% CI, 0.31-0.74]; P < .001) but did not decrease the demand for intravenous supplementation or the rate of permanent hypocalcaemia compared to no treatment. Calcium and vitamin D supplementation significantly reduced the rate of transient hypocalcaemia and the demand for intravenous supplementation compared to either no treatment (OR 0.21 [95% CI, 0.11-0.40]; P < .001 and OR 0.26 [95% CI, 0.10-0.69]; P = .007, respectively) or calcium alone (OR 0.39 [95% CI, 0.18-0.84]; P = .02 and OR 0.18 [95% CI, 0.07-0.47]; P < .001, respectively), but did not decrease the rate of permanent hypocalcaemia. GRADE-based confidence was moderate., Conclusion: Postoperative calcium supplementation is effective for preventing post-thyroidectomy hypocalcaemia. Calcium plus vitamin D was more effective than calcium alone in preventing postoperative hypocalcaemia and decreasing the demand for intravenous calcium supplementation. Further, well-designed RCTs with larger sample sizes are required to validate our findings.

AIMS To assess the effect of the administration of two oral Ca boluses on concentrations of total Ca, β-hydoxybutyrate (BHB) and non-esterified fatty acids (NEFA) in serum, and urine pH, in recently calved pasture-fed dairy cows. METHODS Friesian or Friesian cross Jersey cows from one dairy farm were blocked by age and randomly assigned to no treatment (control; n=14), or treatment (n=13) with two oral Ca boluses administered approximately 12 hours apart, with the first bolus being given within 14 hours of calving. Each bolus weighed 198 g and contained 43 g of Ca; 31 g of Ca from calcium chloride and 12 g of Ca from calcium sulfate. Cows were enrolled over three calendar days, and all cows were managed in one group during the 24-hour study period. Blood samples were collected at 0, 1, 2, 4, 8, 12, 13, 14, 16, 20 and 24 hours after the initial treatment. Serum from each time point was analysed for concentrations of total Ca, and from 0, 12, and 24 hours for NEFA and BHB. Urine was collected at 0, 12 and 24 hours for pH measurement and pH was categorised as <7 or ≥7. The effect of treatment on percentage change in concentrations of Ca in serum relative to 0 hours, and concentrations of NEFA, BHB and urine pH, was examined using multivariable repeated measures mixed models with cow as a random effect. RESULTS In the final multivariable model for percentage change in concentrations of Ca, there was an interaction between time and treatment (p=0.004), with the percentage increase being higher in treatment than control cows at 1, 2, 4, 8 and 13 hours. At 12 hours, 5/13 (41%) treated cows had a urine pH <7compared to 0/12 (0%) control cows (p<0.001), and at 24 hours 13/13 (100%) treated cows had urine pH <7 compared to 0/12 (0%) control cows (p<0.001). Over the 24-hour period, mean concentrations of NEFA or BHB in serum were similar in treated and control cows (p>0.3). CONCLUSIONS AND CLINICAL RELEVANCE Oral treatment with two Ca boluses increased concentrations of total Ca in serum and decreased urine pH in pasture-fed cows. This bolus has the potential to reduce the prevalence and duration of subclinical hypocalcaemia in recently calved cows.

The main objective of this study was to determine how feeding different dietary calcium (Ca) concentrations in combination with a negative dietary cation-anion difference (DCAD) would affect the cow's response to induced hypocalcemia. We conducted an experiment with multiparous, nonlactating, nonpregnant Holstein cows fed a negative DCAD (average -18.2 across all diets) for 21 d with low (LC; 0.45% Ca; n = 5), medium (MC; 1.13% Ca; n = 6), or high (HC; 2.02% Ca; n = 6) concentrations of dietary Ca. Urine and blood samples were collected and urine pH measured daily during the 21-d feeding period prior to hypocalcemia challenge. Cows were then subjected to a controlled induction of hypocalcemia to determine how dietary Ca intake affected the response to a hypocalcemia challenge. On days 22, 23, and 24, hypocalcemia was induced with an intravenous infusion of 5% EGTA in 2 different cows from each treatment daily. During infusion, blood samples were collected every 15 min until 60% of prechallenge ionized calcium (iCa) concentrations were achieved. Samples were collected postinfusion at 0, 2.5, 5, 10, 15, 30, and every 30 min thereafter until 90% of prechallenge iCa was reached. Blood pH, hematocrit, and serum total Ca (tCa), sodium (Na), potassium (K), phosphorous (P), magnesium (Mg), and serotonin did not differ (P > 0.05) among treatments during the feeding period. Blood iCa (P = 0.04) and glucose (P = 0.03) were significantly elevated in HC compared with LC and MC cows during the feeding period. Urine pH was less than 6.0 in all cows, but was lowest in LC (P = 0.02) compared with MC and HC cows during the feeding period. Urine Ca, P, Mg, and deoxypyridinoline did not differ among treatments (P > 0.05). Cows fed HC maintained higher concentrations of iCa (P = 0.03) during the challenge period than MC (P = 0.04), and LC (P = 0.004), and required a longer time to reach 60% of whole blood iCa, and required more EGTA to reach 60% iCa than MC or LC cows (P = 0.01). Serum tCa decreased in all cows during infusion (P < 0.0001) but did not differ among treatments. Serotonin concentrations were elevated in MC cows compared with HC and LC cows during EGTA infusion (P = 0.05), suggesting an interdependent relationship between iCa and serotonin. Cows fed HC had a slower rate of decrease in iCa, but not tCa, when induced with hypocalcemia, indicating potential metabolic benefits of feeding higher dietary Ca in combination with a negative DCAD.

Purpose: The objective of this retrospective analysis was to present our single-center experience with intravenous (IV) calcium replacement and regional citrate anticoagulation in pediatric apheresis therapy with the aim of developing a standard operating procedure to minimize symptomatic hypocalcemia., Methods: We analyzed apheresis procedures in patients <18 years of age over a 2-year time period (Jan 2012 to Dec 2014). Procedures in tandem with other extracorporeal therapies, including continuous renal replacement therapy, extracorporeal liver support, and extracorporeal membrane oxygenation, were excluded., Results: Two-hundred and six patients underwent 1176 procedures. All procedures were performed with acid citrate dextrose formula A (ACD-A) for anticoagulation and IV calcium replacement. The majority of procedures (56.7%) were therapeutic plasma exchange (TPE). The average rate of IV calcium chloride (2.16 mg/mL of elemental calcium) was 60.4 ± 21.4 mL/h while inlet flow rate was 43.7 ± 16.3 mL/min. Patients experienced hypocalcemia in 63 of 1176 procedures (5.3%), including 48 episodes (4.1%) of hypocalcemia during apheresis treatment. Two procedures with hypocalcemia had symptoms: one slight lip twitch and one patient with abdominal pain. No hemodynamic alterations were noted in any procedure associated with hypocalcemia. Hypocalcemia was seen the least with RCE. For patients with hypocalcemia prior to the apheresis session, we used a calcium infusion running at 1.6 times the inlet flow rate., Conclusion: Running IV calcium at 1.4 times the inlet flow rate resulted in a lower incidence of hypocalcemia than reported in literature describing other approaches to apheresis. It nearly eliminated episodes of symptomatic hypocalcemia., (© 2017 Wiley Periodicals, Inc.)

Most studies demonstrating that diets with low dietary cation-anion difference (DCAD) reduce hypocalcemia in cows add enough anions to the diet to reduce urine pH below 7.0. One objective of these experiments was to determine whether there is any benefit to periparturient plasma Ca concentration if diet anion addition results in a lesser degree of acidification of the cow and urine pH does not go below 7.0. Another method for reducing hypocalcemia involves feeding a prepartal diet that is Ca deficient. This places the cow in negative Ca balance before calving, stimulating parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D secretion before calving and thus promoting Ca homeostasis at calving. As practiced in the field, low-Ca diets are often about 0.5% Ca. Our second objective was to determine whether a 0.46% Ca diet would be sufficiently low in Ca to stimulate PTH secretion before calving. A meta-analysis of the literature suggests that a 0.5% Ca, low-DCAD diet will reduce hypocalcemia better than a 0.7% Ca diet. A third objective was to compare periparturient plasma Ca in cows fed 0.46 or 0.72% Ca diets with similar DCAD. In experiment 1, anions (primarily chloride) or anions plus Ca were added to a 1.4% K basal diet to create the following diets: 0.46% Ca and +167 mEq/kg of DCAD, 0.46% Ca and -13 mEq/kg of DCAD, and 0.72% Ca and -17 mEq/kg of DCAD. In experiment 2, the same amounts of anion were added to a 2.05% K basal diet to create the following diets: 0.46% Ca and +327 mEq/kg of DCAD, 0.46% Ca and +146 mEq/kg of DCAD, and 0.72% Ca and +140 mEq/kg of DCAD. In experiment 1, cows fed the diet with 0.46% Ca and +167 mEq/kg of DCAD had significantly lower plasma Ca concentration after calving than cows fed the 0.46 or 0.72% Ca diets with anions. Periparturient plasma Ca concentrations did not differ in cows fed the low-DCAD diets with 0.46 or 0.72% Ca. Urine pH was reduced from 8.27 in the diet with 0.46% Ca and +167 mEq/kg of DCAD to 7.07 and 7.41 in the 0.46 and 0.72% Ca anion diets, respectively. Precalving plasma PTH and 1,25-dihydroxyvitamin D concentrations were similar in cows fed the 0.46% Ca diets and the 0.72% Ca diets, suggesting that the 0.46% Ca diets were not low enough in Ca to place the cow in negative Ca balance before calving. In experiment 2, adding the anion supplements to a 2.05% K diet did not reduce urine pH below 8.0. Periparturient plasma Ca concentrations did not differ in cows in any group in experiment 2. Precalving diets that are 0.46% Ca fed ad libitum are too high in Ca to stimulate Ca homeostasis before calving. Adding anions to a diet can benefit periparturient cow plasma Ca concentration, but only if it alters acid-base status enough to reduce urine pH below 7.5., (The Authors. Published by FASS Inc. and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).)

Objectives: To assess the relationship between admission serum calcium levels and in-hospital mortality in all hospitalized patients., Methods: All adult hospitalized patients who had admission serum calcium levels available between years 2009 and 2013 were enrolled. Admission serum calcium was categorized based on its distribution into six groups (<7.9, 7.9 to <8.4, 8.4 to <9.0, 9.0 to <9.6, 9.6 to <10.1, and ≥10.1 mg/dL). The odds ratio (OR) of in-hospital mortality by admission serum calcium, using the calcium category of 9.6-10.1 mg/dL as the reference group, was obtained by logistic regression analysis., Results: 18,437 patients were studied. The lowest incidence of in-hospital mortality was associated with admission serum calcium within 9.6 to <10.1 mg/dL. A higher in-hospital mortality rate was observed in patients with serum calcium <9.6 and ≥10.1 mg/dL. Also, 38% and 33% of patients with admission serum calcium <7.9 and ≥10.1 mg/dL were on calcium supplements before admission, respectively. After adjusting for potential confounders, both serum calcium <8.4 and ≥10.1 mg/dL were associated with an increased risk of in-hospital mortality with ORs of 2.86 [95% confidence interval (CI) 1.98-4.17], 1.74 (95% CI 1.21-2.53), and 1.69 (95% CI 1.10-2.59) when serum calcium were within <7.9, 7.9 to <8.4, and ≥10.1 mg/dL, respectively., Conclusion: Hypocalcemia and hypercalcemia on admission were associated with in-hospital mortality. Highest mortality risk is observed in patients with admission hypocalcemia (<7.9 mg/dL). One-third of patients with hypercalcemia on admission were on calcium supplements.

The effects of prophylactic oral Ca supplementation on blood mineral status and markers of energy balance were evaluated on 205 multiparous Jersey cows at a commercial dairy. Postpartum, cows were systematically assigned to control (n = 105) or oral Ca supplementation (CaOS; 50 to 60 g of Ca as boluses; n = 100) at 0 and 1 d in milk (DIM). Blood samples for analysis of serum minerals (Ca, P, Mg, K, Na, Fe, Zn, and Cu) were collected before and 1 h after treatment at 0 and 1 DIM, and at 2 DIM. Urine pH was measured immediately before and 1 h after treatment administration (n = 96). A subset of 74 cows was evaluated for plasma glucose and fatty acid concentrations at 0, 1, and 2 DIM. Cows were classified according to their initial calcemic status (Ca status) as normocalcemic (NC; serum Ca >2.12 mmol/L) or subclinically hypocalcemic (SCH; serum Ca ≤2.12 mmol/L). Average serum Ca concentration was higher in CaOS than control cows (2.12 vs. 2.06 mmol/L); this treatment effect was higher for SCH [CaOS (2.03 mmol/L); control (1.89 mmol/L)] than NC cows [CaOS (2.22 mmol/L); control (2.22 mmol/L)]. The incidence of subclinical hypocalcemia was lower for CaOS than control cows (53 vs. 65%); however, at 2 DIM the prevalence of subclinical hypocalcemia tended to be higher for CaOS cows, mostly because it was higher for CaOS-NC than control-NC cows (70 vs. 25%). Urine pH was lower for CaOS than control cows (6.10 vs. 7.04). Lower serum Mg concentration was detected for CaOS-SCH (1.06 mmol/L) than for control-SCH (1.10 mmol/L) cows. Cows in the CaOS group had higher serum K (4.68 vs. 4.53 mmol/L), lower plasma glucose (2.97 vs. 3.10 mmol/L), and at 2 DIM higher plasma fatty acid concentrations (0.43 vs. 0.35 mmol/L) than control cows. Our results showed that postpartum serum Ca concentration increases with oral Ca supplementation, but calcemic status influenced treatment response. Future studies should evaluate the long-term implications on production and reproduction of oral Ca supplementation in Jersey cows., (The Authors. Published by FASS Inc. and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).)

Hypocalcemic toxicity, because of return of citrate anion to the donor, is the major toxicity of apheresis platelet donation. Oral calcium carbonate, given prophylactically at the start of donation, has shown limited ability to alleviate this toxicity. We examined whether repeated prophylactic doses of calcium carbonate, or of a liquid preparation containing calcium citrate, calcium phosphate, and vitamin D 3 , would be more effective at preventing symptoms of hypocalcemic toxicity. Symptoms were reported by 48% of donors who received no prophylaxis and 60% of donors who received 1000 mg of oral calcium carbonate at the start of, and every 20 minutes during, donation (P = 0.711). Only 19.2% of donors who received the liquid preparation (1000 mg calcium, 1000 IU vitamin D 3 ) reported symptoms (P = 0.040 versus no prophylaxis, P = 0.039 versus calcium carbonate). This difference was not because of gender, weight, age, or blood volume of the donor. Neither calcium preparation prevented a measurable fall in plasma ionized calcium during donation. We conclude that liquid calcium citrate/calcium phosphate/vitamin D 3 provides effective prophylaxis against hypocalcemic toxicity during platelet donation, however it does not prevent a fall in plasma ionized calcium., (© 2017 Wiley Periodicals, Inc.)

Objective To identify the risk of clinical hypocalcemia in the first hours after thyroidectomy. Study Design Prospective observational study. Setting Single-institution tertiary hospital in Madrid, Spain. Subjects and Methods A total of 123 patients who underwent total or completion thyroidectomy between June 2010 and March 2012 were included. Pre- and postoperative intact parathyroid hormone (iPTH) levels were obtained. Patients remain hospitalized a minimum of 48 hours until blood calcium stabilized. Calcium and/or vitamin D supplements were prescribed only when signs or symptoms of hypocalcemia developed. Receiver operating characteristic curve analysis was employed to evaluate the postoperative iPTH level and the pre- to postoperative decrease in iPTH levels. Two cutoff values were determined to stratify the risk of developing clinical hypocalcemia into 3 groups. Results The areas under the receiver operating characteristic curve were 0.991 for the postoperative iPTH and 0.998 for the decrease in iPTH. An iPTH decrease of 80% had 100% sensitivity to detect patients who developed clinical hypocalcemia, while a postoperative iPTH <3 pg/mL had 100% specificity. Thus, patients with an iPTH decrease ≤80% are at a very low risk of clinical hypocalcemia, and patients with a postoperative iPTH <3 pg/mL are at a very high risk. Patients with an iPTH decrease >80% and a postoperative iPTH ≥3 pg/mL are at intermediate risk. No significant correlation was found between the time when the sample was obtained and iPTH values. Conclusion This study stablishes a very accurate test to stratify the risk of clinical postthyroidectomy hypocalcemia based on pre- and postoperative iPTH levels.

Background: Exchange blood transfusion (EBT) is a form of whole blood transfusion in which the total blood volume is replaced within a few hours. In perinatal and neonatal medicine, EBT is most often used in the management of severe anaemia or severe hyperbilirubinaemia in the first week of life. Hypocalcaemia, one of the common morbidities associated with EBT, is thought to arise from the chelating effects of the citrate commonly used as an anticoagulant in the donor's blood. This disorder manifests with muscular and nervous irritability and cardiac arrhythmias., Objectives: To determine whether the use of prophylactic calcium reduces the risk of hypocalcaemia-related morbidities and death among newborn infants receiving EBT., Search Methods: We used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 5), MEDLINE via PubMed (1966 to 29 June 2016), Embase (1980 to 29 June 2016), and CINAHL (1982 to 29 June 2016). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials., Selection Criteria: All randomised and quasi-randomised trials of prophylactic intravenous calcium in EBT for newborns., Data Collection and Analysis: Two review authors independently assessed and extracted data on methods, participants, interventions, and outcomes (mean total and ionised serum calcium before and after EBT and the presence of adverse events such as hypoglycaemia, apnoea, cardiac arrest, and death immediately after EBT). We reported results as means difference (MD) with 95% confidence intervals (CI) for continuous outcomes and risk ratio (RR) and risk differences (RD) and 95% CIs for dichotomous outcomes. We assessed quality using the Cochrane 'Risk of bias' assessment tool and the GRADE system., Main Results: We found only one quasi-randomised trial with 30 participants that met our inclusion criteria. In the small trial, total and ionised serum calcium levels were measured immediately before and immediately after EBT. All the participants were included in the final analysis and all the important outcomes were reported. Primary outcomesThere was one death in each group (RR 1.00, 95% CI 0.07 to 14.55; RD 0.00, 95% CI -0.18 to 0.18; participants = 30; studies = 1). The study did not report the presence of cardiac arrhythmias within one week of EBT and the number of infants with serum calcium levels (total less than 8 mg/dL (2 mmol/L) or ionised less than 4.4 mg/dL (1.1 mmol/L)).Pair-wise comparison of EBT with intravenous 10% calcium gluconate versus EBT without intravenous calcium (change from baseline) showed mean total serum calcium was raised in the intervention group compared to the control group (MD -0.46, 95% CI -0.81 to -0.11; participants = 30; studies = 1). Very low-quality evidence also indicated an increase in the levels of mean ionised serum calcium in the intervention group compared to the control group (MD -0.22, 95% CI -0.33 to -0.11; participants = 30; studies = 1). Secondary outcomesAdverse reactions to intravenous calcium therapy included cardiac arrest in one neonate in the intervention arm (RR 3.00, 95% CI 0.13 to 68.26; RD 0.07, 95% CI -0.10 to 0.23; participants = 30; studies = 1). There was apnoea and hypoglycaemia (RR 1.00, 95% CI 0.07 to 14.55; RD 0.00, 95% CI -0.18 to 0.18; participants = 30; studies = 1) in the two neonates who died. Data were not available for other major secondary outcomes such as the number of infants with reduced serum magnesium, reduced parathormone, increased calcitonin, presence of seizures, carpopedal spasm, jitteriness and prolonged QTc interval on electrocardiography within one week of EBT., Authors' Conclusions: Very low-quality data from one quasi-randomised controlled trial suggested that the mean serum total and ionised calcium increased in the study group but decreased in the control group immediately after EBT. However, the mean values of total and ionised calcium in both arms of studies remained within international reference ranges. Unfortunately, data were not available to assess the trend of total and ionised serum calcium to the end of the first week after EBT. Therefore, due to the very low quality of evidence available, it is difficult to support or reject the continual use of prophylactic intravenous calcium in newborn infants receiving EBT. Researchers are encouraged to conduct more robustly designed trials with larger numbers of participants, and particularly, addressing the pattern of differences based on gestational age of participants, type of anticoagulant used, and the volume of blood used.

Objective: The aim of this study was to evaluate the use of prophylactic oral calcium after total thyroidectomy in the prevention of symptomatic hypocalcemia, and to develop a rational strategy of oral calcium supplementation following this type of surgery., Subjects and Methods: Prospective study including 47 patients undergoing total thyroidectomy from January 2007 to February 2012. The patients were allocated to one of the following groups: I (no postoperative calcium) or II (oral calcium 3 g per day). Oral calcium was started at the first postoperative day and administered until the sixth postoperative day. The patients were followed up for a minimum of 6 months and evaluated with a minimum of five measurements of ionized calcium: preoperative, 16 hours after surgery, seventh postoperative day, and at postoperative days 90 (PO90) and 180 (PO180). The cohort included three men and 44 women, of whom 24 (51.9%) had benign thyroid disease, and 23 had suspected or confirmed malignant disease., Results: When compared with Group II, Group I had significantly higher rates of postoperative biochemical hypocalcemia at PO1 and PO180, and of symptomatic hypocalcemia at PO1, PO7, and PO90. Other data were not significantly different between the groups., Conclusion: We conclude that postoperative calcium supplementation effectively prevents symptomatic and biochemical hypocalcemia after total thyroidectomy, and can be safely used after this procedure. The presented strategy of oral calcium supplementation may be implemented in a viable manner.

A 23-year-old male patient presented with cognitive decline and seizures. Examination revealed Chvostek's and Trousseau's signs. Investigations revealed hypocalcaemia, hyperphosphatemia and normal intact parathyroid hormone levels. Imaging showed calcifications in bilateral basal ganglia, thalamus and dentate nuclei. Interictal electroencephalogram showed theta range slowing of background activity and bilateral temporo-occipital, irregular, sharp and slow wave discharges, which accentuated during hyperventilation, photic stimulation and eye closure. Appearance of epileptiform discharges after eye closure, hyperventilation and photic stimulation may suggest presence of central neural hyperexcitability due to hypocalcaemia. These features may be an equivalent of peripheral neuromuscular hyperexcitability (Chvostek's and Trousseau's signs) that occurs in hypocalcaemia. The clinical and electroencephalographic features completely reversed with correction of serum calcium without antiepileptic medications. It is important for clinicians to recognise these reversible changes, as it can help to avoid misdiagnosis and long-term administration of antiepileptic becomes unnecessary., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Symptomatic hypocalcaemia is an uncommon finding in patients with malignant tumours. We describe a patient with advanced metastatic breast cancer who developed severe hypocalcaemia caused by the combination of osteoblastic metastases and a permanent postoperative hypoparathyroidism. The patient failed to be treated with the conventional replacement therapy and was submitted effectively to radionucleotide therapy with 153 Sm., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Introduction: Hypoparathyroidism is a rare disorder characterized by low serum calcium levels and high serum phosphate levels, and low or inappropriately normal levels of parathyroid hormone (PTH). This disease is commonly treated with calcium supplements and active vitamin D metabolites or analogues, but large doses of these supplements are often utilized to relieve the symptoms caused by hypocalcemia, without guarantee of a physiological normalization of calcium-phosphate homeostasis. Areas covered: Several studies have investigated replacement therapy with recombinant human PTH [rhPTH (1-84) and rhPTH (1-34)] for subjects with hypoparathyroidism. In 2015, The Food and Drug Administration (FDA) approved, in the United States, rhPTH (1-84), named Natpara®, a bioenginerred rhPTH, for the management of chronic hypoparathyroidism not well controlled with conventional therapy. This article evaluates the safety and tolerability of rhPTH (1-84) in patients with chronic hypoparathyroidism, and also describes the studies conducted so far on rhPTH (1-34) used for chronic hypoparathyroidism. Expert opinion: The research done in this field has shown that replacement treatment with rhPTH is an attractive option for subjects with hypoparathyroidism who are unable to maintain stable and safe serum and urinary calcium levels. However, since therapy with rhPTH is a long-term management option in hypoparathyroidism, more long-term safety data are needed.

We identified three infants with dilated cardiomyopathy (DCM) secondary to severe vitamin D deficieny and hypocalcaemia. All infants were exclusively breast fed, from dark skinned ethnic backgrounds, born and living in Ireland. None of these pregnant mothers or infants received the recommended vitamin D supplementation. Each infant presented in heart failure and required inotropic support as well as calcium and vitamin D replacement. Cardiac function subsequently improved. This highlights the public health issue that many high risk pregnant mothers and infants are not receiving the recommended vitamin D supplementation.

Background: Postoperative hypocalcemia is the most common complication after total thyroidectomy. Postoperative parathyroid hormone (PTH) measurement is one of the methods to detect or prevent postoperative hypocalcemia. Prophylactic oral calcium supplementation is another method to prevent early postoperative hypocalcemia. The aim of this study is to detect the accurate timing of PTH and evaluate efficacy of routine oral calcium supplementation for postoperative hypocalcemia., Methods: A total of 106 patients were performed total thyroidectomy. Rotuine oral calcium supplementation was given to group 1 and no treatment to group 2 according to randomization. Serum calcium and PTH level of patients in group 2 at postoperative 6, 12 and 24 h and patients in both groups at postoperative day 7 were evaluated. Patients were compared according to age, sex, operation findings, serum calcium and PTH levels and symptomatic hypocalcemia., Results: Half of the patients (50%) were in group 1. Most of the patients were female (83%). The most common etiology of thyroid disease was multinodular goiter (64.1%). Oral calcium supplementation was given to 18 (33.9%) patients in group 2. Symptomatic hypocalcemia for group 1 and 2 was found to be 1.9 and 33.9% respectively (p < 0.05). No statistical difference can be observed regarding the timing of serum biomarkers., Conclusion: Serum PTH levels at postoperative 12 and 24 h can predict early post-thyroidectomy hypocalcemia. Prophylactic oral calcium supplementation therapy can prevent early post-thyroidectomy hypocalcemia with advantages of being cost effective and safe., (Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Although some experimental targets involved in calcium deposition are emerging, no intervention has been described to reliably reverse vascular calcification (VC). We report a case of severe VC regression in a parathyroidectomized patient on hemodialysis over 12-year follow-up, highlighting the use of calcium-free phosphate binders and a 2.5 mEq/L calcium dialysate for reducing calcium loading, despite persistent asymptomatic hypocalcemia occurrences. This case suggests that phosphate-binder choice and calcium dialysate concentration could be influenced by other components of CKD-MBD besides biochemical parameters, such as the presence of VC, so concluding that asymptomatic hypocalcemia may not be as harmful as once supposed, and conferring greater prognostic weight to the presence of VC than to calcium levels.
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Purpose: Denosumab-associated hypocalcaemia (DAH) has been reported in patients with osteoporosis or metastatic bone disease and is associated with stages 4 and 5 chronic kidney disease (CKD, estimated glomerular filtration rate <30 mL/min/1.73m 2 ). Other risk factors for hypocalcaemia have not been fully elucidated. We aimed to investigate the incidence of hypocalcaemia amongst patients receiving denosumab and to identify clinical features associated with this adverse event., Methods: Retrospective cohort study between June 2013 and June 2014 of patients administered denosumab (60/120 mg) at a tertiary hospital in Melbourne, Australia, to identify the incidence of an albumin-adjusted serum calcium concentration <2.10 mmol/L or ionized calcium <1.13 mmol/L within 6 months of treatment. Univariable and multivariable logistic regression analyses were performed to identify clinical features associated with DAH., Results: One hundred and fifty-five patients were administered denosumab (100 osteoporosis, 55 bone metastases). Twenty-two patients (14% [95%CI 9.1-20.7]) developed hypocalcaemia: 55% were men, and 55% had osteoporosis. Eighty-six per cent had a 25-hydroxyvitamin D concentration >50 nmol/L, and 91% were on calcium/colecalciferol supplementation. Stages 4 and 5 CKD (adjusted odd ratio [aOR] 4.71, 95%CI 1.61-13.79, p = 0.005) and male sex (aOR 4.30, 95%CI 1.69-10.96, p = 0.002) were associated with DAH. No patients were documented as having hypocalcaemic symptoms. One patient received intravenous calcium gluconate treatment., Conclusions: The incidence of denosumab-associated hypocalcaemia was 14% (95%CI 9.1-20.7) within 6 months of treatment despite widespread use of appropriate calcium/colecalciferol supplementation. Stages 4 and 5 CKD and male sex were associated with subsequent hypocalcaemia. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Objective: To study the clinical characteristics of childhood- and adolescent- onset hypoparathyroidism. Methods: The clinical data of 128 hypoparathyroidism patients with onset before the age of 18 years were collected and analyzed retrospectively. Results: The predominant features of the hypoparathyroidism were carpopedal spasm (89.3%, 108/121) and seizures (66.1%, 84/127). Intracranial calcification was identified in 89.4%(101/113) of the patients. Duration is an independent predictive factor ( OR =1.483, P =0.011) for intracranial calcification. All the patients were treated with calcium and vitamin D or its metabolites. Hypercalciuria was associated with serum calcium ( P =0.016). Conclusions: Carpopedal spasm and seizures were the main manifestations of childhood- and adolescent- onset hypoparathyroidism. Calcium and vitamin D or its metabolites are effective. Monitoring the concentration of serum and urinary calcium is of highly importance for the prevention of hypercalciuria.

Background: Citrate toxicity is one of the most frequent complications of apheresis procedures. It is caused by the infusion of the acid citrate dextrose (ACD), which chelates the calcium ions., Aims: The aim of this study is to assess the effectiveness of prophylactic continuous infusion of calcium gluconate over intermittent bolus infusion to reduce citrate toxicity during large volume peripheral blood stem cell collection., Materials and Methods: We retrospectively analysed the records of PBSC collection procedures performed from March 2010 to December 2013. Donors were selected as per the set guidelines. Machine used to perform the procedures was Cobe spectra. The study population was divided into 2 groups. One composed of intermittent intravenous bolus infusion at the onset of hypocalcaemic symptoms, the other composed of calcium gluconate administration as continuous infusion throughout the procedure., Result: The most common reported hypocalcaemic symptoms were mild perioral paresthesia followed by digital numbness. Of the 50 individuals who were injected with bolus calcium 40 (80%) individuals suffered from symptoms of hypocalcaemia, whereas 23 of 66 individuals (34.8%) suffered from hypocalcaemia in the continuous infusion group. This difference was significant (P < 0.001). Both groups were compared with respect to age, gender ratio, weight of the individuals, total blood volume processed, ACD used, calcium gluconate dose used, time taken for the procedure, the product volume. Significant difference was noticed only with respect to the product volume. This implies that the groups were comparable with respect to parameters such as age, gender ratio, weight of the individuals, total blood volume processed, ACD used, calcium gluconate dose used, and the time taken for the procedure. Also that significantly more products (244 v/s 204 ml) was collected in the continuous infusion group., Conclusions: Our results show that prophylactic continuous IV administration of low dose calcium-gluconate throughout the PBSC harvesting procedure reduced the incidence as well as the severity of citrate related toxicity. This increases his/her tolerance to withstand longer durations of the procedure and collect more volume of the product, hence may reduce the number of sittings of the procedure., (Copyright © 2016 Elsevier Ltd. All rights reserved.)