Identification of novel risk factors for postoperative severe hypocalcemia in patients with primary hyperparathyroidism undergoing parathyroidectomy: a case control study.

BACKGROUND: Patients with primary hyperparathyroidism (PHPT) are at risk for severe hypocalcemia (SH) following parathyroidectomy (PTX), but limited data exist on the predictors of SH. We aimed to identify risk factors for early postoperative SH after PTX in patients with PHPT and to evaluate the predictive value of clinical parameters. METHODS: A retrospective review of patients with PHPT who underwent PTX between January 2010 and December 2022 was performed. A total of 46 patients were included in the study, with 15 (32.6%) experiencing postoperative SH, 19 (41.3%) having calculi in the ureter or kidney, and 37 (80.4%) having osteoporosis. Patients were divided into SH and non-SH groups based on postoperative serum calcium levels. Preoperative biochemical indicators, bone turnover markers, and renal function parameters were analyzed and correlated with postoperative SH. RESULTS: Statistically significant (P < 0.05) differences were found in preoperative serum calcium (serum Ca), intact parathyroid hormone, serum phosphorus (serum P), serum Ca/P, percentage decrease of serum Ca, total procollagen type 1 intact N-terminal propeptide, osteocalcin (OC), and alkaline phosphatase levels between the two groups. Multivariate analysis showed that serum P (odds ratio [OR] = 0.989; 95% confidence interval [95% CI] = 0.981-0.996; P = 0.003), serum Ca (OR = 0.007; 95% CI = 0.001-0.415; P = 0.017), serum Ca/P (OR = 0.135; 95% CI = 0.019-0.947; P = 0.044) and OC levels (OR = 1.012; 95% CI = 1.001-1.024; P = 0.036) were predictors of early postoperative SH. The receiver operating characteristic curve analysis revealed that serum P (area under the curve [AUC] = 0.859, P < 0.001), serum Ca/P (AUC = 0.735, P = 0.010) and OC (AUC = 0.729, P = 0.013) had high sensitivity and specificity. CONCLUSION: Preoperative serum P, serum Ca/P and osteocalcin levels may identify patients with PHPT at risk for early postoperative SH after PTX.

Severe Hypocalcemia With Denosumab Among Older Female Dialysis-Dependent Patients.

Importance: Dialysis-dependent patients experience high rates of morbidity from fractures, yet little evidence is available on optimal treatment strategies. Chronic kidney disease-mineral and bone disorder is nearly universal in dialysis-dependent patients, complicating diagnosis and treatment of skeletal fragility. Objective: To examine the incidence and comparative risk of severe hypocalcemia with denosumab compared with oral bisphosphonates among dialysis-dependent patients treated for osteoporosis. Design, Setting, and Participants: Retrospective cohort study of female dialysis-dependent Medicare patients aged 65 years or older who initiated treatment with denosumab or oral bisphosphonates from 2013 to 2020. Clinical performance measures including monthly serum calcium were obtained through linkage to the Consolidated Renal Operations in a Web-Enabled Network database. Exposures: Denosumab, 60 mg, or oral bisphosphonates. Main Outcomes and Measures: Severe hypocalcemia was defined as total albumin-corrected serum calcium below 7.5 mg/dL (1.88 mmol/L) or a primary hospital or emergency department hypocalcemia diagnosis (emergent care). Very severe hypocalcemia (serum calcium below 6.5 mg/dL [1.63 mmol/L] or emergent care) was also assessed. Inverse probability of treatment-weighted cumulative incidence, weighted risk differences, and weighted risk ratios were calculated during the first 12 treatment weeks. Results: In the unweighted cohorts, 607 of 1523 denosumab-treated patients and 23 of 1281 oral bisphosphonate-treated patients developed severe hypocalcemia. The 12-week weighted cumulative incidence of severe hypocalcemia was 41.1% with denosumab vs 2.0% with oral bisphosphonates (weighted risk difference, 39.1% [95% CI, 36.3%-41.9%]; weighted risk ratio, 20.7 [95% CI, 13.2-41.2]). The 12-week weighted cumulative incidence of very severe hypocalcemia was also increased with denosumab (10.9%) vs oral bisphosphonates (0.4%) (weighted risk difference, 10.5% [95% CI, 8.8%-12.0%]; weighted risk ratio, 26.4 [95% CI, 9.7-449.5]). Conclusions and Relevance: Denosumab was associated with a markedly higher incidence of severe and very severe hypocalcemia in female dialysis-dependent patients aged 65 years or older compared with oral bisphosphonates. Given the complexity of diagnosing the underlying bone pathophysiology in dialysis-dependent patients, the high risk posed by denosumab in this population, and the complex strategies required to monitor and treat severe hypocalcemia, denosumab should be administered after careful patient selection and with plans for frequent monitoring.

[Post-Thyroidectomy Hypocalcemia: Incidence, Prediction, and Outpatient Management Strategies Based on PTH and Calcium Levels]. / Incidencia de Hipocalcemia Post Tiroidectomía. Factores predictores (PTH, Fósforo, Magnesio) y protocolo de manejo con alta precoz.

INTRODUCTION: PTH measurement has been proposed to predict transient and permanent postoperative hypocalcemia. There is no standard cut-off point or time for sampling. AIM: To report the incidence of post-thyroidectomy hypocalcemia in a high-volume surgical group and propose an outpatient management protocol according to postoperative (PO) calcium levels, iPTH (normal, low, or undetectable), and symptoms. Furthermore, determine postoperative PTH values as predictors of hypocalcemia. METHODS: In 106 patients with total thyroidectomy between 2019 and 2021, pre-and postoperative levels of calcium, magnesium, phosphorus, and iPTH were measured. RESULTS: Transient (< 12 months) and permanent (> 12 months) hypocalcemia was observed in 29% and 1%. Cut-off points to predict hypocalcemia were PTH < 8.8 pg/mL and < 80% decrease in % PTH (d% PTH) the day after surgery. With the proposed management, early discharge is indicated (an average of 1.05 days), and the prescription cost is limited. There is no significant association between PO hypomagnesemia and hyperphosphatemia with PO hypocalcemia. The most widely used treatment is exclusive calcium carbonate (schemes I and II). Patients remain with mild symptoms at two weeks PO in 5% and discontinue oral treatment in 93% in this period. CONCLUSIONS: Protocols for measuring PTH as a hypocalcemia predictor vary. Each center must know and establish its management protocols. With this experience, we demonstrate the usefulness and safety of a management scheme based on calcium, PTH (normal, low, or undetectable), and symptoms with an indication of prophylactic treatment for all patients and a safe outpatient setting at a lower cost than prolonged hospitalization.

Use of the parathyroid hormone assay at H6 post thyroidectomy: an early predictor of hypocalcemia.

PURPOSE: Hypocalcemia linked to a diminished circulating intact parathormone (iPTH) is the most common complication after total thyroidectomy. The objective of this study was to evaluate iPTH as a predictor of post-thyroidectomy hypocalcemia. METHODS: Hundred-and-eight patients who underwent total thyroidectomy were included. Blood samples (iPTH, calcium and albumin) were performed at different times: preoperatively (H0), after removal of the gland (Hdrop), 6 h (H6) and one day (D1) after the surgery. Hypocalcemia was defined by total calcium corrected by serum albumin ≤ 2.10 mmol/l. The area under the ROC curve (AUC) was used to determine the best cut-off value and predictability of iPTH for hypocalcemia in terms of absolute value (ng/L), decrease in the slope (ng/L) and decline (%) between two times. RESULTS: The study included 101 patients. Among them, 39 had hypocalcemia (38.6%). At H6, an iPTH absolute value less than 14.35 ng/L (Se = 0.706; Sp = 0.917) and a decline from the preoperative time of more than 59.5% (Se = 0.850; Sp = 0.820) were predictive of hypocalcemia. Other absolute values, decrease in the sloop and decline between preoperative and postoperative values were less relevant. CONCLUSION: The iPTH 6 h after total thyroidectomy is predictive of hypocalcemia. It might be used to identify patients not at risk of hypocalcemia and earlier discharge could be considered.

Renal complications and quality of life in postsurgical hypoparathyroidism: a case-control study.

PURPOSE: Conventional therapy (calcium and activated vitamin D) does not restore calcium homeostasis in patients with chronic hypoparathyroidism (HypoPT) and is associated with renal complications and reduced quality of life (QoL). The aim of this study was to evaluate in a case-control, cross-sectional study, the rate of renal complications and QoL in two sex- and age-matched cohort of patients with differentiated thyroid cancer with (n = 89) and without (n = 89) chronic post-operative HypoPT (PoHypoPT) and their relationship with the biochemical control of the disease. METHODS: Serum and urinary parameters, renal ultrasound and QoL were assessed by SF-36 and WHO-5 questionnaires. RESULTS: Forty-three (48.3%) PoHypoPT patients reported symptoms of hypocalcemia. Twenty-six (29.2%) patients were at target for all 6 parameters, 46 (51.6%) for 5. The most frequently unmet targets were gender-specific 24-h urinary calcium (44.9%) and serum calcium (37.1%). Serum phosphate, magnesium and 25(OH)D were in the normal range in > 90% of patients. Renal calcifications were found in 26 (29.2%) patients, with no correlation with 24-h urinary calcium. eGFR did not differ between patients and controls. Conversely, patients had a significant higher rate of renal calcifications and a lower SF-36, but not WHO-5, scores. SF-36 scores did not differ between PoHypoPT patients who were, or not, hypocalcemic. CONCLUSIONS: Our study shows that the rate of renal calcifications was higher in patients with PoHypoPT than in those without. This finding, together with the reduced QoL and the presence of hypocalcemic symptoms in about half patients, underscores that the treatment of chronic HypoPT with conventional therapy is suboptimal.

Efficacy, Safety, and Calcium Balance of an Accelerated Citrate Anticoagulated Membrane-Based Plasma Exchange Algorithm.

INTRODUCTION: To assess the safety, efficacy, and calcium flux of an accelerated algorithm for regional citrate anticoagulation in membrane-based plasma exchange. METHODS: This was an observational study in patients receiving citrate anticoagulated, membrane-based plasma exchange at the Canberra Hospital between July 2017 and May 2020. Data were collected prospectively using an electronic medical record and compared to data from our previous published algorithm. RESULTS: There were 134 plasma exchange sessions performed during the observational period. Circuit clotting occurred in 4 sessions, and 1 session was affected by symptomatic hypocalcaemia. A systemic ionized calcium <0.96 mmol/L was seen in 19.4% of sessions, which was a similar frequency to that seen in our previous algorithm. A systemic ionized Ca <0.81 mmol/L occurred in 4 sessions (all asymptomatic). This hypocalcaemia occurred towards the end of the sessions, after switching from albumin to fresh frozen plasma replacement fluid. Median treatment time was 135 min, compared to 219 min in our previously published algorithm. Mean net Ca gain/session was 7.7 ± 2.3 mmol. CONCLUSION: An accelerated algorithm for regional citrate anticoagulation achieves substantial time saving while maintaining efficacy and safety. The 4 episodes of systemic ionized calcium <0.81 mmol/L may have been due to recirculation of infused citrate but, probably more likely, are due to the additional citrate load imposed by use of fresh frozen plasma in these sessions. Future algorithms need to better account for the citrate load present in fresh frozen plasma.

Massive transfusions and severe hypocalcemia: An opportunity for monitoring and supplementation guidelines.

BACKGROUND: Massive transfusion protocols (MTPs) are associated with severe hypocalcemia, contributing to coagulopathy and mortality in severely injured patients. Severity of hypocalcemia following massive transfusion activation and appropriate treatment strategies remain undefined. STUDY DESIGN AND METHODS: This was a retrospective study of all MTP activations in adult trauma patients at a Level 1 trauma center between August 2016 and September 2017. Units of blood products transfused, ionized calcium levels, and amount of calcium supplementation administered were recorded. Primary outcomes were ionized calcium levels and the incidence of severe ionized hypocalcemia (iCa ≤1.0 mmol/L) in relation to the volume of blood products transfused. RESULTS: Seventy-one patients had an MTP activated during the study period. The median amount of packed red blood cells (PRBCs) transfused was 10 units (range 1-52). A total of 42 (59.1%) patients had periods of severe hypocalcemia. Patients receiving 13 or more units of PRBC had a greater prevalence of hypocalcemia with 83.3% having at least one measured ionized calcium ≤1.0 mmoL/L (p = .001). The number of ionized calcium levels checked and the amount of supplemental calcium given in patients who experienced hypocalcemia varied considerably. DISCUSSION: Severe hypocalcemia commonly occurs during MTP activations and correlates with the number of packed red blood cells transfused. Monitoring of ionized calcium and amount of calcium supplementation administered is widely variable. Standardized protocols for recognition and management of severe hypocalcemia during massive transfusions may improve outcomes.

Vitamin D Deficiency and Low Serum Calcium as Predictors of Poor Prognosis in Patients with Severe COVID-19.

BACKGROUND: The severity of Coronavirus Disease 2019 (COVID-19) is a multifactorial condition. An increasing body of evidence argues for a direct implication of vitamin D deficiency, low serum calcium on poor outcomes in COVID-19 patients. This study was designed to investigate the relationship between these two factors and COVID-19 in-hospital mortality. MATERIALS: This is a prospective study, including 120 severe cases of COVID-19, admitted at the department of Reanimation-Anesthesia. Vitamin D was assessed by an immuno-fluoroassay method. Total serum calcium by a colorimetric method, then, corrected for serum albumin levels. The association with in-hospital mortality was assessed using the Kaplan-Meier survival curve, proportional Cox regression analyses and the receiver operating characteristic curve. RESULTS: Hypovitaminosis D and hypocalcemia were very common, occurring in 75% and 35.8% of patients. When analyzing survival, both were significantly associated with in-hospital mortality in a dose-effect manner (pLog-Rank = 0.009 and 0.001 respectively). A cutoff value of 39 nmol/l for vitamin D and 2.05 mmol/l for corrected calcemia could predict poor prognosis with a sensitivity of 76% and 84%, and a specificity of 69% and 60% respectively. Hazard ratios were (HR = 6.9, 95% CI [2.0-24.1], p = 0.002 and HR = 6.2, 95% CI [2.1-18.3], p = 0.001) respectively. CONCLUSION: This study demonstrates the high frequency of hypocalcemia and hypovitaminosis D in severe COVID-19 patients and provides further evidence of their potential link to poor short-term prognosis. It is, therefore, possible that the correction of hypocalcemia, as well as supplementation with vitamin D, may improve the vital prognosis.

Association Between Ionized Calcium Concentrations During Hemostatic Transfusion and Calcium Treatment With Mortality in Major Trauma.

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.

Symptomatic hypocalcemia after treatment for hyperthyroidism in a woman with chromosome 22q11.2 deletion syndrome complicated by Graves' disease: longitudinal changes in the number of subsets of CD4 and CD8 lymphocytes after thyroidectomy.

Chromosome 22q11.2 deletion syndrome is a multisystem genetic disorder that presents with hypocalcemia due to congenital hypoparathyroidism; cardiovascular, renal, and facial anomalies; and skeletal defects. This syndrome is also associated with an increased risk of autoimmune disease. We report here on a 33-year-old Japanese woman with 22q11.2 deletion syndrome complicated by Graves' disease. The patient had facial abnormalities and a history of a surgical procedure for a submucous cleft palate at age 3 years. At age 33, the patient was diagnosed with Graves' disease because both hyperthyroidism and thyroid stimulating hormone receptor antibody were present. The patient's serum calcium level was within the normal range, but symptomatic hypocalcemia developed 1 month after treatment with methimazole was started for thyrotoxicosis. Methimazole was discontinued because it caused liver dysfunction, so the patient underwent total thyroidectomy to treat her Graves' disease. We examined longitudinal changes in the number of subsets of CD4 and CD8 lymphocytes, including regulatory T (T reg) cells and PD-1+CD4+ and PD-1+CD8+ T cells, after treatment by total thyroidectomy. A flowcytometry analysis demonstrated that circulating PD-1+CD4+ and PD-1+CD8+ T cells gradually decreased over time, as did circulating T reg cells and circulating CD19+ B cells. These findings suggest that PD-1-positive CD4+ and CD8+ T cells and T reg cells may have been associated with the autoimmunity in our patient with chromosome 22q11.2 deletion syndrome complicated by Graves' disease.

Misclassification of calcium status in end-stage kidney disease using albumin-adjusted calcium levels.

BACKGROUND: Albumin-adjusted calcium remains widely used in clinical practice with guidelines for chronic kidney disease (CKD) mineral bone disorder recommending the use of serum calcium for monitoring. This is despite ionized calcium being the biologically active fraction. This study aimed to investigate the ability of total calcium and albumin-adjusted calcium to correctly assign calcium status in stage 5/5D CKD across non-dialysis, haemodialysis and peritoneal dialysis patients. METHODS: Over a 6-months, 352 paired serum and ionized calcium samples were collected from stage 5 (n = 58) and 5D (n = 294, 196 haemodialysis, 98 peritoneal dialysis) CKD patients in a tertiary-hospital setting. Albumin-adjusted calcium was calculated using the modified-Payne formula. Ionized calcium was the reference standard. The agreement between the two methods in assigning calcium status was assessed using Cohen's weighted kappa (κ) statistic. RESULTS: Albumin-adjusted calcium was a poor predictor of calcium status compared to ionized calcium in stage 5/5D CKD (observed agreement 0.42, weighted κ 0.20, 95% CI 0.15-0.26). Dialysis dependence was associated with worse agreement (observed agreement 0.38, weighted κ 0.14, 95% CI 0.09-0.19). Total calcium was more reliable, however, remained inaccurate. Calcium status was not more accurately classified in those with higher albumin levels ≥30 g/L (observed agreement 0.47, weighted κ 0.23, 95% CI 0.10-0.36). CONCLUSION: Total calcium provides better approximation of calcium status than albumin-adjusted calcium in stage 5/5D CKD. Albumin-adjusted calcium tends to 'overcorrect' serum calcium upward. Clinicians should use ionized calcium where accurate measure of calcium is indicated, with total calcium used as the next best option where resources are limited.

Effects of injectable calcitriol on mineral metabolism and postpartum health and performance in dairy cows.

Objectives were to determine the effects of an injectable formulation of calcitriol on Ca concentration, risk of clinical diseases, and performance in dairy cows. Cows were blocked by lactation number (1 vs. >1) and calving sequence and, within block, assigned randomly within 6 h of calving to receive subcutaneously vehicle only (CON, n = 450) or 200 (CAL200, n = 450) or 300 µg of 1α,25-dihydroxyvitamin D3 (CAL300, n = 450). Cows were fed the same acidogenic diet prepartum. Blood was sampled before treatment administration and again during the first 11 d postpartum and analyzed for concentrations of ionized Ca (iCa), total Ca (tCa), Mg (tMg), and P (tP), ß-hydroxybutyrate, carboxylated osteocalcin (cOC), and undercarboxylated osteocalcin (uOC). Cows were evaluated for diseases in the first 60 d postpartum. Reproduction and survival were monitored for the first 300 d postpartum. Calcitriol increased concentration of blood iCa (CON = 1.12 vs. CAL200 = 1.23 vs. CAL300 = 1.27 mM), plasma tCa (CON = 2.29 vs. CAL200 = 2.44 vs. CAL300 = 2.46 mM), and plasma tP (CON = 1.72 vs. CAL200 = 2.21 vs. CAL300 = 2.28 mM), and differences were observed during the first 5 d postpartum for iCa and tCa, and the first 7 d postpartum for tP. Concentrations of tMg were lower in calcitriol-treated cows than in CON cows (CON = 0.81 vs. CAL200 = 0.78 vs. CAL300 = 0.75 mM), and differences were observed during the first 5 d postpartum. Calcitriol increased plasma concentrations of cOC (CON = 14.5 vs. CAL200 = 23.0 vs. CAL300 = 19.8 ng/mL) and uOC (CON = 1.6 vs. CAL200 = 3.4 vs. CAL300 = 2.6 ng/mL). Prevalence of subclinical hypocalcemia was less in calcitriol-treated cows (CON = 19.0 vs. CAL200 = 4.7 vs. CAL300 = 9.3%); however, benefits on health were only observed in overconditioned cows (n = 270/1,350). Calcitriol reduced incidence of retained placenta (CON = 14.3 vs. CAL200 = 5.1 vs. CAL300 = 5.9%), puerperal metritis (CON = 12.7 vs. CAL200 = 6.1 vs. CAL300 = 2.5%), and morbidity (CON = 72.1 vs. CAL200 = 57.4 vs. CAL300 = 56.9%) in cows with BCS greater than 3.50, but no benefit on health was observed in cows with BCS equal to or less than 3.50 at parturition. Milk yield did not differ among treatments. Pregnancy at first AI did not differ, but pregnancy rate after the first AI was slower for calcitriol-treated cows because of reduced insemination rate and pregnancy per AI. We found that CAL200 reduced death but increased culling in cows without calving problems. Collectively, results indicate that treatment with calcitriol at parturition was effective in improving concentrations of iCa, tCa, and tP, which reduced the risk of hypocalcemia. Pregnancy rate was reduced by calcitriol treatment, and benefits on health performance were limited to overconditioned cows. Thus, treatment of all cows is not supported, and proper identification of cohorts of cows that benefit from postpartum interventions that increase blood calcitriol or calcium is needed.

Association between serum calcium and prognosis in patients with acute pulmonary embolism and the optimization of pulmonary embolism severity index.

INTRODUCTION: Calcium is an important coagulation factor and hypocalcemia is related to progression and poor prognosis of many cardiopulmonary diseases. However, influence of hypocalcemia on pulmonary thromboembolism (PTE) prognosis has never been reported. This study aimed to explore its prognostic value and optimize the pulmonary embolism severity index (PESI), the widely used prognosis assessment model, based on the value. METHODS: PTE patients' variables in PESI and other related clinical characteristics including admission serum calcium were collected. Associations between these variables and PTE mortality were assessed by logistic regression and cox analysis. Variables significantly associated with 30-day PTE mortality were included to develop a new prognosis prediction rule and then its validity was compared with PESI and simplified PESI (sPESI). RESULTS: 496 PTE patients were included and 49.48% patients had hypocalcemia (serum calcium ≤ 2.13 mmol/L) in admission, showing higher 7-day (P = 0.021), 14-day (P = 0.002), 30-day (13.03% vs 4.98%, P = 0.002) mortalities than patients without hypocalcemia. Adjusting for variables in PESI, hypocalcemia was further revealed to be an independent predictor of 30-day mortality (P = 0.014). The optimal prediction rule contained hypocalcemia and 5 variables in PESI and sPESI, showing higher predictive validity [sensitivity (Sen): 0.930, specificity (Spec): 0.390, area under curve (AUC): 0.800] than PESI (Sen: 0.814, Spec: 0.367, AUC: 0.716) and sPESI (Sen: 0.907, Spec: 0.216, AUC: 0.703). CONCLUSIONS: Hypocalcemia is an independent predictor of the mortality following acute PTE. Based on hypocalcemia, the optimal prediction rule showed higher validity than PESI and sPESI.

Risk Factors for Development of Hypocalcemia in Patients With Cancer Treated With Bone-Modifying Agents.

BACKGROUND: This retrospective analysis describes the prevalence of and risk factors associated with the development of hypocalcemia in patients with cancer receiving bone-modifying agents (BMAs) as supportive care. PATIENTS AND METHODS: Patients with cancer treated with an intravenous or subcutaneous BMA, including pamidronate, zoledronic acid, or denosumab, at a tertiary care/safety net hospital in 2005 through 2015 were included in this retrospective review. We reviewed the medical records for predictive clinical and laboratory parameters and for patient outcomes. RESULTS: A total of 835 patients with cancer received at least one dose of a BMA during the specified time frame; 205 patients (25%) developed hypocalcemia of CTCAE grade ≥1 within 8 weeks of BMA initiation, 18 of whom (8.8%) had grade ≥3, and 3 patients died as a result. Multivariate analysis showed that patients with hematologic malignancy (odds ratio [OR], 1.956; P=.025), bone metastases (OR, 2.443; P=.017), inpatient status (OR, 2.592; P<.001), and deficient baseline vitamin D levels (OR, 2.546; P<.023) were more likely to develop hypocalcemia. Hypercalcemia before BMA administration (OR, 0.474; P=.032) was protective. CONCLUSIONS: Certain patient populations, including those with hematologic malignancies and/or bone metastases, warrant closer monitoring of calcium levels while receiving BMAs because of the high rate of hypocalcemia. Low pretreatment vitamin D levels are associated with the development of hypocalcemia. These data support close monitoring of calcium levels in patients with cancer receiving BMAs, in addition to adequate repletion of vitamin D before initiation of BMAs when possible.

Hypocalcaemia and traumatic coagulopathy: an observational analysis.

BACKGROUND AND OBJECTIVES: Haemorrhage-associated calcium loss may lead to disruption of platelet function, intrinsic and extrinsic pathway-mediated haemostasis and cardiac contractility. Among shocked major trauma patients, we aimed to investigate the association between admission hypocalcaemia and adverse outcomes. MATERIALS AND METHODS: Data were extracted from the Alfred Trauma Registry and the Alfred Applications and Knowledge Management Department for all adult major trauma patients presenting directly from the scene with a shock index ≥1 from 1 July 2014 to 30 June 2018. Patients with pre-hospital blood transfusion were excluded. Ionized hypocalcaemia was defined as <1·11 mmol/l, and acute traumatic coagulopathy was defined as initial INR >1·5. Multivariable logistic regression analysis was used to assess the association between admission hypocalcaemia and acute traumatic coagulopathy that was adjusted for Injury Severity Score, initial GCS, bicarbonate and lactate. RESULTS: There were 226 patients included in final analysis with 113 (50%) patients recording ionized hypocalcaemia on presentation prior to any blood product transfusion. Ionized hypocalcaemia was associated with coagulopathy in patients with shock index ≥1 (adjusted OR 2·9; 95% CI: 1·01-8·3, P = 0·048). Admission ionized hypocalcaemia was also associated with blood transfusion requirement in the first 24 h post-admission in 62·5% of hypocalcaemic patients as compared to 37·5% of normocalcaemic patients (P < 0·001). Admission ionized hypocalcaemia was associated with death at hospital discharge (25·6% among hypocalcaemic patients compared to 15·0% of normocalcaemic patients (P = 0·047)). CONCLUSION: Hypocalcaemia was a common finding in shocked trauma patients and was independently associated with acute traumatic coagulopathy. The early, protocolized administration of calcium to trauma patients in haemorrhagic shock warrants further assessment in randomized controlled trials.

A Nomogram to Predict Hungry Bone Syndrome After Parathyroidectomy in Patients With Secondary Hyperparathyroidism.

BACKGROUND: Parathyroidectomy (PTX) has been demonstrated as an effective treatment for patients with secondary hyperparathyroidism (SHPT) of renal origin. However, severe hypocalcemia, called hungry bone syndrome (HBS), is a common complication following PTX in these patients and can lead to poor clinical outcomes, even death. Therefore, exploring risk factors for HBS and establishing a prediction nomogram allow intensive monitoring and prompt treating this postoperative complication, which is the main purpose of this study. METHODS: From October 2016 to October 2018, PTX with autotransplantation (PTX + AT) procedures were performed in 131 patients with SHPT of renal origin by a surgeon and his team in the Thyroid and Parathyroid Surgery Center, West China Hospital, Sichuan University, China. After applying the inclusion and exclusion criteria, a total of 114 patients were enrolled for analyses in this study. Comprehensive data including preoperative, intraoperative, and postoperative variables were prospectively collected and retrospectively analyzed. The univariate and multivariate logistic regression analyses with internal validation by bootstrapping were used to confirm independent risk factors for postoperative HBS. The nomogram was developed based on the statistical analysis results. Receiver operator characteristic (ROC) curves were drawn to compare the prediction performance among different predictors. RESULTS: The occurrence of postoperative HBS was 76.3% (87 out of 114 patients) in this study. Univariate analysis showed that preoperative intact parathyroid hormone (iPTH), serum alkaline phosphatase, bone-specific alkaline phosphatase (bone-ALP) were significantly higher in HBS group than those in non-HBS group, while preoperative corrected serum calcium and albumin were significantly lower in HBS group than those in non-HBS group. Total weight of resected parathyroid glands was significantly heavier in HBS group versus non-HBS group. Multivariate logistic regression analysis with internal validation by bootstrapping demonstrated preoperative iPTH, bone-ALP, preoperative corrected serum calcium, and total weight of resected parathyroid glands were independently associated with postoperative HBS. The nomogram including the abovementioned four independent predictors was constructed and showed better prediction performance than the other four predictors in terms of postoperative HBS. CONCLUSIONS: On the basis of this study, we found higher preoperative iPTH level, higher bone-ALP level, heavier total weight of resected parathyroid glands, and lower preoperative corrected serum calcium level were independent predictors of postoperative HBS in patients with SHPT of renal origin. The nomogram can expediently, accurately, and objectively predict the risk of postoperative HBS in individual patient with SHPT of renal origin.

Postoperative Hypoparathyroidism After Total Thyroidectomy in Children.

BACKGROUND: Postoperative hypocalcemia because of hypoparathyroidism is the most common complication of total thyroidectomy in children. We hypothesized that most children with postoperative hypocalcemia would be eucalcemic by 12 mo and sought to define risk factors for permanent hypoparathyroidism. METHODS: We retrospectively reviewed children who underwent total thyroidectomy at a single children's hospital from 2012 to 2019. Patients with prior neck surgery were excluded. Indication for operation, final pathologic diagnosis, and postoperative serum calcium up to 12 mo were recorded. Permanent hypoparathyroidism was defined as supplemental calcium requirement beyond 1 y postoperatively. RESULTS: Sixty-eight patients underwent total thyroidectomy. Graves' disease was the most common benign indication for surgery (38 patients). Twenty-six patients (38%) had cancer on final pathology. Central lymph node dissection (CLND) was performed in 12 cancer patients. Twenty-eight patients (41%) had postoperative hypocalcemia. Eight patients (12%) had hypocalcemia at 6 mo. Risk factors for hypoparathyroidism at 6 mo were a cancer diagnosis (odds ratio [OR] 6.7; P = 0.02), CLND (OR 12.6; P < 0.01), and parathyroid tissue in the surgical specimen on pathologic analysis (OR 19.5; P < 0.01). Only two patients (3%) developed permanent hypoparathyroidism, both of whom had thyroidectomy for cancer and underwent CLND. CONCLUSIONS: Children with thyroid cancer are at high risk for postoperative hypocalcemia after total thyroidectomy. The risk is further increased by CLND, which should be performed selectively. A majority of patients with hypoparathyroidism at 6 mo postoperatively regain normal parathyroid function by 1 y. Permanent hypoparathyroidism in children after total thyroidectomy at a pediatric endocrine surgery center is rare.

The dietary management of calcium and phosphate in children with CKD stages 2-5 and on dialysis-clinical practice recommendation from the Pediatric Renal Nutrition Taskforce.

In children with chronic kidney disease (CKD), optimal control of bone and mineral homeostasis is essential, not only for the prevention of debilitating skeletal complications and achieving adequate growth but also for preventing vascular calcification and cardiovascular disease. Complications of mineral bone disease (MBD) are common and contribute to the high morbidity and mortality seen in children with CKD. Although several studies describe the prevalence of abnormal calcium, phosphate, parathyroid hormone, and vitamin D levels as well as associated clinical and radiological complications and their medical management, little is known about the dietary requirements and management of calcium (Ca) and phosphate (P) in children with CKD. The Pediatric Renal Nutrition Taskforce (PRNT) is an international team of pediatric renal dietitians and pediatric nephrologists, who develop clinical practice recommendations (CPRs) for the nutritional management of various aspects of renal disease management in children. We present CPRs for the dietary intake of Ca and P in children with CKD stages 2-5 and on dialysis (CKD2-5D), describing the common Ca- and P-containing foods, the assessment of dietary Ca and P intake, requirements for Ca and P in healthy children and necessary modifications for children with CKD2-5D, and dietary management of hypo- and hypercalcemia and hyperphosphatemia. The statements have been graded, and statements with a low grade or those that are opinion-based must be carefully considered and adapted to individual patient needs based on the clinical judgment of the treating physician and dietitian. These CPRs will be regularly audited and updated by the PRNT.

Prognostic Value of Ionized Calcium Levels in Neonatal Sepsis.

BACKGROUND: Despite recent advances in the treatment of neonatal infection, mortality rates and comorbidities associated with neonatal sepsis remain high. Hypocalcemia has been reported in critically ill patients, especially in as-sociation with sepsis. However, the importance of hypo-calcemia in neonatal sepsis has not been explored in detail. OBJECTIVES: The purpose of this study was to evaluate the prognostic value of hypocalcemia in neonatal sepsis patients and to identify the risk factors associated with sepsis-related mortality. METHODS: This retrospective study examined perinatal data from patients in a level IV neonatal in-tensive care unit between January 2010 and June 2016. Univariate analysis was performed to understand the differences in clinical and laboratory characteristics between patients with and without neonatal sepsis. Neonates with sepsis were further stratified as having ionized hypocalcemia (if serum ionized calcium [iCa] <1.0 mmol/L) or not. Uni- and multivariate logistic regression analyses were utilized to evaluate the predictive potential of iCa for identifying sepsis-related mortality. RESULTS: A total of 472 neonates were enrolled in this study, including 169 neonates diagnosed with culture-proven sepsis and 303 neonates without infection (control group). The comparison of neonates with and without sepsis highlighted significant differences in levels of iCa (0.97 ± 0.26 vs. 1.12 ± 0.25 mmol/L), magnesium (0.75 ± 0.22 vs. 0.89 ± 0.12 mmol/L), and phosphate (2.26 ± 1.08 vs. 1.65 ± 0.85 mmol/L; all p < 0.001). When neonates with sepsis were stratified into 2 subgroups based on serum iCa, neonates with hypocalcemia showed higher rates of organ dysfunction than those with normal iCa, as well as higher rates of cardiovascular system dysfunction (37.35 vs. 17.44%), renal dysfunction (34.94 vs. 30.95%), disseminated intravascular coagulation (26.51 vs. 11.63%), and seizure (16.04 vs. 5.8%; all p < 0.05). Among all neonates who had sepsis, the mortality rate was 13.61%, and this rate was higher among neonates with hypocalcemia than among those with normal iCa (20.48 vs. 6.98%, p < 0.05). Uni- and multivariate analyses showed that acidosis, hypoalbuminemia, hypocalcemia, and hyperphosphatemia were independent prognostic markers of sepsis-related mortality. In receiver-operating characteristic curve analysis, the areas under the curve were 0.70 (95% CI 0.624-0.768; p = 0.0004), 0.74 (95% CI 0.671-0.808; p < 0.0001), 0.73 (95% CI 0.653-0.792; p = 0.0002), and 0.67 (95% CI 0.59-0.737; p = 0.0154) for serum albumin, iCa, phosphate, and acidosis, respectively. Based on these findings, we developed a nomogram to predict sepsis-related mortality. CONCLUSIONS: Hypocalcemia is common in neonates with sepsis and is significantly associated with organ dysfunction and sepsis-related mortality.

Association of transient, persistent, or delayed subclinical hypocalcemia with early lactation disease, removal, and milk yield in Holstein cows.

Our objectives were to evaluate the association of subclinical hypocalcemia (SCH) dynamics with the risk of early lactation disease, removal, and milk production. We conducted a prospective observational cohort study in 407 Holstein cows in 2 dairy herds in New York. Cows were stratified by parity group (144 primiparous, 263 multiparous) and classified into 1 of 4 groups based on postpartum plasma Ca concentrations previously associated with improved milk production or increased risk of disease: normocalcemic (NC; primiparous [Ca] >2.15 mmol/L at 1 and 2 d in milk, n = 67; multiparous [Ca] >1.77 at 1 d in milk and 2.20 mmol/L at 4 d in milk, n = 109); transient SCH (tSCH; primiparous [Ca] ≤2.15 at 1 d in milk and >2.15 mmol/L at 2 d in milk, n = 25; multiparous [Ca] ≤1.77 at 1 d in milk and >2.20 mmol/L at 4 d in milk, n = 50); persistent SCH (pSCH; primiparous [Ca] ≤2.15 mmol/L at 1 and 2 d in milk, n = 33; multiparous [Ca] ≤1.77 at 1 d in milk and ≤2.20 mmol/L at 4 d in milk, n = 34); or delayed SCH (dSCH; primiparous [Ca] >2.15 at 1 d in milk and ≤2.15 mmol/L at 2 d in milk, n = 19; multiparous [Ca] >1.77 at 1 d in milk and ≤2.20 mmol/L at 4 d in milk, n = 70). Evaluated outcomes were development of an adverse event [hyperketonemia (blood ß-hydroxybutyrate concentration ≥1.2 mmol/L at 3, 5, 7, or 10 d in milk), metritis, displaced abomasum, or herd removal in the first 60 d in milk] and average milk yield per day across the first 10 wk of lactation. Multivariable Poisson regression was used to analyze the adverse event outcome and generalized linear mixed models for milk yield analysis. Primiparous cows with tSCH were no more likely to have an adverse event than NC cows [risk ratio = 1.3; 95% confidence interval (CI) = 0.5 to 3.2], whereas multiparous cows tended to have a higher risk for an adverse event than NC cows (risk ratio = 1.4; 95% CI = 0.9 to 2.1). However, pSCH cows were 4.1 (95% CI = 2.1 to 7.9, primiparous) and 1.8 (95% CI = 1.2 to 2.7, multiparous) times more likely, and dSCH cows 3.2 (95% CI = 1.5 to 7.0, primiparous) and 1.9 (95% CI = 1.3 to 2.6, multiparous) times more likely, to have an adverse event than NC cows. Primiparous and multiparous cows with tSCH made more milk per day than NC, pSCH, or dSCH cows across the first 10 wk of lactation. Primiparous cows averaged 28.5 ± 0.7, 31.9 ± 1.1, 29.7 ± 0.9, and 28.7 ± 1.2 kg/d, and multiparous cows averaged 44.6 ± 0.7, 49.1 ± 1.1, 46.4 ± 1.3, and 41.4 ± 0.9 kg/d for NC, tSCH, pSCH, and dSCH cows, respectively. Our results suggest that cows with tSCH adapt well to early lactation, develop fewer disease or removal events than pSCH or dSCH cows, and make more milk than NC, pSCH, or dSCH cows. Cows with pSCH or dSCH, regardless of parity group, are at an increased risk for early lactation disease or removal events.