Changes in arterial pH do not explain the reductions in ionised calcium observed during COVID-19 infection.

BACKGROUND: Hypocalcaemia predicts coronavirus disease 2019 (COVID-19) severity and mortality. We hypothesized an association between respiratory alkalosis secondary to hypoxia and low ionised calcium (iCa) concentration in patients with COVID-19. METHODS: Arterial blood gas samples taken from January 2019 to March 2021 were retrospectively matched with infection status. Principal components regression was undertaken to determine the correlation between pH, partial pressure arterial oxygen (PaO2), partial pressure arterial carbon dioxide (PaCO2), and iCa. RESULTS: We included 4056 patients (300 COVID-19 detected, 19 influenza detected), corresponding to 5960 arterial blood samples. The COVID-19 detected group had a statistically significantly lower iCa, PaO2 and PaCO2, and more alkalotic pH than infection-free groups. The influenza group had a lower iCa and PaCO2, higher PaO2, and a more alkalotic pH than infection-free groups, but these differences were non-significant. Principal components regression revealed that pH, PaCO2, and PaO2 explain just 2.72 % of the variance in iCa. An increase in pH by 1 unit was associated with an iCa reduction of 0.141 â€‹mmol/L (p â€‹< â€‹0.0001). CONCLUSION: Reduction in iCa concentration in patients with COVID-19 is not associated with pH derangement. Influenza infection was associated with a minor reduction in iCa in our small sample, a hitherto unreported finding, although statistical significance was not demonstrated.

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.

Hypoparathyroidism: Genetics and Diagnosis.

This narrative report summarizes diagnostic criteria for hypoparathyroidism and describes the clinical presentation and underlying genetic causes of the nonsurgical forms. We conducted a comprehensive literature search from January 2000 to January 2021 and included landmark articles before 2000, presenting a comprehensive update of these topics and suggesting a research agenda to improve diagnosis and, eventually, the prognosis of the disease. Hypoparathyroidism, which is characterized by insufficient secretion of parathyroid hormone (PTH) leading to hypocalcemia, is diagnosed on biochemical grounds. Low albumin-adjusted calcium or ionized calcium with concurrent inappropriately low serum PTH concentration are the hallmarks of the disease. In this review, we discuss the characteristics and pitfalls in measuring calcium and PTH. We also undertook a systematic review addressing the utility of measuring calcium and PTH within 24 hours after total thyroidectomy to predict long-term hypoparathyroidism. A summary of the findings is presented here; results of the detailed systematic review are published separately in this issue of JBMR. Several genetic disorders can present with hypoparathyroidism, either as an isolated disease or as part of a syndrome. A positive family history and, in the case of complex diseases, characteristic comorbidities raise the clinical suspicion of a genetic disorder. In addition to these disorders' phenotypic characteristics, which include autoimmune diseases, we discuss approaches for the genetic diagnosis. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

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.

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.

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.

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.

Identification of p.Arg205Cys in CASR in an autosomal dominant hypocalcaemia type 1 pedigree: A case report.

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.

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.

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.

Serum Calcium and Vitamin D levels: Correlation with severity of COVID-19 in hospitalized patients in Royal Hospital, Oman.

INTRODUCTION: Studies have revealed hypocalcemia and low vitamin D levels in severe covid-19 that warrant further research. OBJECTIVE: Our study investigates the correlation between calcium levels at presentation as a primary endpoint and pre-existing calcium levels as a secondary endpoint to the severity of disease presentation and progression. METHOD: Observational cohort study in adults admitted with COVID-19 from March utill September 2020. Multiple clinical scales and laboratory parameters were used to correlate corrected calcium and vitamin D associations with risk factors and outcomes. RESULTS: Four hundred and forty five patients were included in the study. Hypocalcemic patients had more abnormal laboratory parameters and longer hospitalization duration. Hypocalcemia was in 60-75% of all age groups (p-value 0.053), for which 77.97% were ICU admissions (p-value 0.001) and 67.02% were diabetic (p-value 0.347). There were non-significant correlations between Vitamin D and almost all the parameters except for chronic respiratory diseases, which had a P-value of 0.024. CONCLUSION: It can be concluded that hypocalcemia is a significant and reliable marker of disease severity and progression regardless of underlying comorbidities. Vitamin D levels fail to reflect correlation with severity of COVID-19 infections.

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.

Five patients with disorders of calcium metabolism presented with GCM2 gene variants.

The GCM2 gene encodes a transcription factor predominantly expressed in parathyroid cells that is known to be critical for development, proliferation and maintenance of the parathyroid cells. A cohort of 127 Spanish patients with a disorder of calcium metabolism were screened for mutations by Next-Generation Sequencing (NGS). A targeted panel for disorders of calcium and phosphorus metabolism was designed to include 65 genes associated with these disorders. We observed two variants of uncertain significance (p.(Ser487Phe) and p.Asn315Asp), one likely pathogenic (p.Val382Met) and one benign variant (p.Ala393_Gln395dup) in the GCM2 gene in the heterozygous state in five families (two index cases had hypocalcemia and hypoparathyroidism, respectively, and three index cases had primary hyperparathyroidism). Our study shows the utility of NGS in unravelling the genetic origin of some disorders of the calcium and phosphorus metabolism, and confirms the GCM2 gene as an important element for the maintenance of calcium homeostasis. Importantly, a novel variant in the GCM2 gene (p.(Ser487Phe)) has been found in a patient with hypocalcemia.

PTH como predictor de hipocalcemia postiroidectomía total / PTH as a predictor of hypocalcemia after total thyroidectomy

Resumen Objetivo: Evaluar la asociación entre el valor de PTH medido a las 6 h posoperatorias de los pacientes sometidos a una tiroidectomía total, y la presentación de hipocalcemia en las primeras 24 h posoperatorias. Materiales y Método: Estudio analítico retrospectivo que utiliza una base de datos de 173 pacientes operados de tiroidectomía total entre enero de 2016 a diciembre de 2018 en el Hospital Militar de Santiago (HMS). Se revisaron datos demográficos y perioperatorios. Se utilizó curva ROC para evaluar la asociación entre PTH e hipocalcemia en nuestros pacientes. Resultados: 106 pacientes que cumplen criterios de inclusión. Promedio de PTH 30,5 (1,4-169), 58% presentó hipocalcemia, solo 17 pacientes fueron sintomáticos. PTH promedio en pacientes sintomáticos fue de 7,8 pg/ml. Curva ROC con área bajo la curva de 0,83 (0,75-0,92). Considerando valores útiles para la práctica clínica, una PTH menor a 6,3 (valor más bajo en nuestro laboratorio), tiene sensibilidad de 97%. El valor 18 de PTH (límite inferior del rango de normalidad del laboratorio) se obtiene 88,89% de sensibilidad con 66,07% de especificidad. Y con un valor de 47 pg/ml, se obtiene con un 91% de especificidad para predecir pacientes que no tendrían hipocalcemia. Conclusión: Con un valor de PTH disminuido bajo su valor normal, se puede decir que el riesgo de tener hipocalcemia es sobre el 80%, por lo que se debería iniciar tratamiento profiláctico y desistir del alta. En cambio, para definir un valor superior sobre el cual dar de alta precoz con seguridad, faltan más estudios.

Aim: To evaluate the association between PTH (parathormone) value measured at 6 hours postoperatively of patients submitted to total thyroidectomy, and the presentation of hypocalcemia in the first 24 hours. Materials and Method: Retrospective study of 173 patients with total thyroidectomy between January 2016 to December 2018 in HMS. Demographic and perioperative data were reviewed. The ROC curve was used to evaluate the association between PTH and hypocalcemia in our patients. Results: 106 patients meet inclusion criteria. Average of PTH 30.5 (1.4-169), 58% presented hypocalcemia, 17 patients were symptomatic. ROC curve with area under the curve of 0.83 (0.75-0.92) was obtained considering useful values for clinical practice, a PTH less than 6.3 (lowest value in our laboratory), has 97% sensitivity to predict hypocalcemia. If we use the value 18 we obtain 88.89% sensitivity with 66.07% specificity. And with a value of 47, it is obtained with 91% specificity to predict patients who would not have hypocalcemia Conclusion: With a PTH value decreased below its normal value, it can be said that the risk of having hypocalcemia is over 80%, so that prophylactic treatment should be initiated. To define a value on which to register early with security, more study is needed.

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.

Common and specific mineral and metabolic features in dairy cows with clinical metritis, hypocalcaemia or ketosis.

The objectives were to evaluate differences in serum concentration of metabolites, macro minerals and hepatic enzymes at pre and postpartum time-points in dairy cows diagnosed with clinical metritis, hypocalcaemia or ketosis postpartum. A total of 144 Holstein cows from 11 commercial dairy herds in Alberta, (Western Canada) were enrolled in this study. Cows with clinical metritis had lower serum concentrations of glutamate dehydrogenase (GLDH) at pre and postpartum and lower total Ca, albumin, urea, and cholesterol at postpartum when compared to control cows. Cows with hypocalcaemia had greater serum concentrations of Na, Cl, and calculated osmolarity (CalOsmo) at prepartum and lower concentration of total serum Ca, glucose, cholesterol, gamma-glutamyl transpeptidase (GGT), GLDH, total protein and albumin at postpartum. Prepartum serum concentrations of non-esterified fatty acids (NEFA), beta hydroxybutyrate (BHB), Cl, albumin/globulin ratio (A/G), Na, K and sum of Na and K were greater in ketotic cows when compared with control cows. Cows with ketosis had also greater postpartum serum concentrations of NEFA, BHB, GGT and aspartate transaminase (AST) when compared with control cows. Prepartum serum Na and Cl concentrations and CalOsmo were greater in cows diagnosed with hypocalcaemia or ketosis when compared with control cows. Furthermore, postpartum serum concentrations of total Ca, cholesterol, albumin and GLDH were significantly affected by hypocalcaemia or clinical metritis and concentrations of GGT by hypocalcaemia or ketosis. Finally, postpartum serum concentrations of haptoglobin increased in all disease groups when compared with control cows. These results suggest common metabolic features for clinical metritis, hypocalcaemia and ketosis in dairy cows in addition to the specific ones.

Hypocalcemia in trauma patients: A systematic review.

BACKGROUND: During hemorrhagic shock and subsequent resuscitation, pathways reliant upon calcium such as platelet function, intrinsic and extrinsic hemostasis, and cardiac contractility are disrupted. The objective of this systematic review was to examine current literature for associations between pretransfusion, admission ionized hypocalcemia, and composite outcomes including mortality, blood transfusion requirements, and coagulopathy in adult trauma patients. METHODS: This review was reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. We searched Ovid MEDLINE and grey literature from database inception till May 3, 2020. Case series and reports were excluded. Reference lists of appraised studies were also screened for articles that the aforementioned databases might not have captured. The Newcastle-Ottawa Scale was used to assess study quality. RESULTS: A total of 585 abstracts were screened through database searching and alternative sources. Six unique full-text studies were reviewed, of which three were excluded. Admission ionized hypocalcemia was present in up to 56.2% of the population in studies included in this review. Admission ionized hypocalcemia was also associated with increased mortality in all three studies, with increased blood transfusion requirements in two studies, and with coagulopathy in one study. CONCLUSION: Hypocalcemia is a common finding in shocked trauma patients. While an association between admission ionized hypocalcemia and mortality, blood transfusion requirements, and coagulopathy has been identified, further prospective trials are essential to corroborating this association. LEVEL OF EVIDENCE: Systematic review, level III.