Association of Serum Calcium With Infarct Size and Severity in Acute Ischemic Stroke: A Rural Hospital-Based Cross-Sectional Study.

Background One of the major mediators of ischemic neuronal cell death is calcium. It has been found that elevated serum calcium is associated with a better prognosis in patients with ischemic stroke. This study highlights the association of serum calcium, albumin-corrected calcium, and ionic calcium with the size of acute ischemic stroke as well as severity outcome in terms of the National Institutes of Health Stroke Scale (NIHSS) score and Barthel Index. Methods This cross-sectional study was conducted on 85 cases of acute ischemic stroke (based on a computerized tomography scan of the brain) from September 2019 to October 2021. All included patients had undergone complete clinical history, systemic examination, as well as estimation of serum total calcium, albumin corrected calcium, and ionic calcium. NIHSS score and Barthel Index were used to access the severity of each subject.  Results A significant positive correlation was seen between infarct size with NIHSS with a correlation coefficient of 0.35. A significant negative correlation was seen between infarct size with serum calcium, albumin-corrected calcium, and Barthel Index with a correlation coefficient of -0.483, -0.354, and -0.365 respectively. No correlation was seen between infarct size and ionic calcium with a correlation coefficient of 0.082. Conclusion It can be concluded that higher normal levels of serum calcium and albumin-corrected calcium are associated with a smaller-sized infarct and had less severity index among patients with acute ischemic stroke.

Prevalence of hypercalcemia in primary hypoadrenocorticism in dogs: Multicenter, retrospective study.

BACKGROUND: Hypoadrenocorticism is an important differential for hypercalcemia. The etiology of hypercalcemia in hypoadrenocorticism in dogs is unclear. OBJECTIVE: To review the prevalence of hypercalcemia and use statistical models to identify clinical, demographic, and biochemical variables associated with hypercalcemia in dogs with primary hypoadrenocorticism. ANIMALS: One hundred ten dogs with primary hypoadrenocorticism; 107 with recorded total calcium (TCa), 43 recorded ionized calcium (iCa). METHODS: Multicenter retrospective observational study at 4 UK referral hospitals. Univariable logistic regression analyses were performed to assess the association between independent variables of signalment, hypoadrenocorticism type (glucocorticoid only deficient hypoadrenocorticism [GHoC] vs glucocorticoid and mineralocorticoid deficient hypoadrenocorticism [GMHoC]), clinicopathological variables and hypercalcemia. Hypercalcemia was defined as elevated TCa, an elevated iCa, or both elevated TCa and iCa (Model 1) or as elevated iCa (Model 2). RESULTS: Overall prevalence of hypercalcemia was 34.5% (38/110). The odds of hypercalcemia (Model 1) were increased (P < .05) in dogs with GMHoC ([vs GHoC], OR [odds ratio] = 3.86, 95% confidence interval [CI] 1.105-13.463), higher serum creatinine (OR = 1.512, 95% CI 1.041-2.197), and higher serum albumin (OR = 4.187, 95% CI 1.744-10.048). The odds of ionized hypercalcemia (Model 2) were increased (P < .05) with reduced serum potassium concentration (OR = 0.401, 95% CI 0.184-0.876) and younger age (OR = 0.737, 95% CI 0.558-0.974). CONCLUSIONS AND CLINICAL IMPORTANCE: This study identified several key clinical and biochemical variables associated with hypercalcemia in dogs with primary hypoadrenocorticism. These findings aid understanding of the pathophysiology and etiology of hypercalcemia in dogs with primary hypoadrenocorticism.

Sample stability and heparin interference in ionized calcium and ionized magnesium measurements in horses using the Stat Profile Prime Plus co-oximetry electrolyte analyzer.

BACKGROUND: The determination of iCa and iMg is important in veterinary medicine, but their immediate determination in whole blood is not always possible. Their stability in other sample types and the existence of interferences must be evaluated before its use. OBJECTIVES: We aimed to analyze the effects of storage time on the stability of iCa, iMg, and other analytes in whole blood, plasma, and serum samples in horses and assess the interference of heparin in these measurements. METHODS: Whole blood, heparin-plasma, and serum samples from 10 horses were stored at 4°C and analyzed 1, 2, 3, 4, 5, 6, 7, 8, 24, 48, and 168 hours after sample collection using the Stat Profile Prime Plus Vet equipment (Nova Biomedical, Waltham, MA, USA). Results were analyzed by ANOVA or mixed-effect models. RESULTS: The concentration of iCa, iMg, total calcium (tCa), total magnesium (tMg), and the ratios iCa/tCa and iMg/tMg did not differ up to 168 hours when compared to the initial time. Total Ca, iMg, and tMg were not significantly different among sample types, but iCa concentrations were slightly but significantly lower in plasma. Freezing at -20°C did not affect iCa, iMg, tCa, and tMg. The pH increased in serum and plasma after 8 hours, and a mild negative correlation existed between plasma iCa concentration and pH. A negative correlation was observed also between the ratios iCa/tCa or iMg/tMg and pH in plasma and serum. A significant decrease in iCa and iMg was detected when comparing homemade syringes at high heparin concentration (~200-300 U heparin/mL) and commercial lithium-heparin tubes (20-30 U/mL). CONCLUSIONS: Samples stored at 4°C can be used to determine iCa and iMg concentrations up to 7 days after collection. Other metabolites are stable for up to 8 hours; heparin interference should be taken into account if using homemade heparin syringes.

Associations between serum electrolyte and short-term outcomes in patients with acute decompensated heart failure.

INTRODUCTION: There is a dearth of comprehensive studies on the association between serum electrolyte and adverse short-term prognosis of Chinese patients with acute decompensated heart failure (ADHF). PATIENTS AND METHODS: A total of 5166 patients with ADHF were divided into four serum electrolyte-related study populations (potassium (n = 5145), sodium (n = 5135), chloride (n = 4966), serum total calcium (STC) (n = 4143)) under corresponding exclusions. Different logistic regression models were utilized to gauge the association between these electrolytes or the number of electrolyte abnormalities and the risk of a composite of all-cause mortality or 30-day heart failure (HF) readmission. RESULTS: In multivariable adjusted analysis, patients with potassium below 3.5 mmol/L (odds ratios (ORs) 1.45; 95% confidence interval (CI):1.07-1.95), 4.01-4.50 mmol/L (OR: 1.29, CI: 1.02-1.62), 4.51-5.00 mmol/L (OR: 1.43, CI: 1.08-1.90) and above 5.00 mmol/L (OR: 1.74, CI: 1.21-2.51) had an increased risk of outcome when compared with potassium at 3.50-4.00 mmol/L. Sodium levels were inversely related to the risk of a composite outcome (<130 mmol/L: OR: 2.73 (95% CI, 1.81-4.12); 130-134 mmol/L: OR, 1.97 (CI, 1.45-2.68); 135-140 mmol/L: OR, 1.45 (CI, 1.17-1.81); p for trend < 0.001) in comparison with sodium at 141-145 mmol/L. Chloride < 95 mmol/L corresponded to a higher risk of a composite outcome with an OR of 1.65 (95% CI, 1.16-2.37) in contrast to chloride levels at 101-105 mmol/L. In addition, the adjusted ORs (95% CI) for a composite outcome comparing the STC < 2.00 and 2.00-2.24 vs. 2.25-2.58 mmol/L were 0.98 (0.69-1.43) and 1.13 (0.89-1.44), respectively. Besides that, the number of electrolyte abnormalities was positively related to the risk of a composite outcome (N = 1, OR 1.40, 95% CI: 1.13-1.73; N = 2, OR 2.51, 95% CI: 1.85-3.42; N = 3, OR 2.47, 95% CI: 1.45-4.19; p for trend < 0.001) in comparison with N = 0. CONCLUSIONS: A deviation of potassium levels from 3.50 to 4.00 mmol/L, lower sodium levels and hypochloremia were associated with poorer short-term prognosis of ADHF. Furthermore, the number of electrolyte abnormalities positively correlated with adverse short-term prognosis of patients with ADHF. Key MessagesADHF patients with baseline serum potassium at first half part of normal range (3.50-4.00 mmol/L) may herald the lowest risk of recent cardiovascular events.Serum sodium and chloride levels exhibit discrepancies in terms of risk of short-term adverse events of ADHF patients.The number of electrolyte abnormalities is a significant predictor of poor short-term prognosis in patients with ADHF. CLINICAL TRIAL REGISTRATION URL: http://www.chictr.org.cn/showproj.aspx?proj=23139. Unique identifier: ChiCTR-POC-17014020.

Prognostic Role of Red Cell Distribution Width and Other Routine Clinico-Pathological Parameters in Dogs with Acute Pancreatitis.

This study aimed to assess the prognostic value of red cell distribution width (RDW) RDW-to-calcium ratio (RDW/Ca), neutrophils-to-lymphocytes ratio (N/L), platelets-to-lymphocytes ratio (P/L) and other easy to obtain and inexpensive hematological and biochemical parameters in dogs with acute pancreatitis. This is a multicenter, retrospective cohort study including 70 client-owned dogs. The accuracy of clinical and laboratory variables to predict short-term death (i.e., dead by 14 days) was tested by calculating the area under the receiver-operating characteristic curve (AUC). Independent predictors of death were identified using the multivariable Cox proportional hazards regression model. The survival rate was 72.9% (51 dogs) and 19 dogs died within 14 days of admission from AP. RDW and blood urea nitrogen (BUN) had good accuracy to predict short-term dead with AUC of 0.74 and 0.70 at the cut-off of >12.7% and >42 mg/dL, respectively. According to the multivariable model, RDW (hazard ratio and 95% confidence interval [HR, 95% CI] = 5.08, 95% CI = 1.14−22.67; p = 0.03), BUN (HR = 1.00, 95% CI = 1.00−1.01; p < 0.01) and bilirubin (HR = 2.46, 95% CI = 1.38−4.39; p < 0.01) were independent predictors of death. The results indicate that RDW, BUN and bilirubin are useful predictors of short-term death in dogs with acute pancreatitis.

The Frequency of Vitamin D and Calcium Deficiencies Among Women of Reproductive Age in Wadi Etba, Southern Region of Libya.

Background Vitamin D (VD) is the sunshine vitamin. Its deficiency is widely spread worldwide and is implicated in various health problems that have serious financial, mental, and physical health burdens. In Libya, it also has a high incidence as many studies have been conducted on this issue, but the exact situation of VD deficiency in the southern region of Libya remains unclear. Aim  The aim of this study is to investigate the frequency of VD deficiency and calcium status among females of reproductive age in Wadi Etba (located in the southern region of Libya). Material and methods This study included 622 females aged 20-40 years attending the Rural Hospital and Private Clinics in Wadi Etba for various health issues during the last five years. The study population was further subdivided into two age groups; 20-30 years and 31-40 years. VD and calcium were measured to determine the VD status among the study population. Results In general, 489 females had sub-optimal VD (<30 ng/mL), representing 78.6% of the total subjects. Normal VD levels were represented only by 133 subjects (21.4%). VD deficiency was represented by 354 subjects (57%) of the total subjects. A total of 232 (37%) subjects were VD-deficient females (18.3 ± 5.5 ng/ml), 122 subjects (20%) were considered poor (severe deficient, VD <10 ng/ml) represented with a mean serum VD of 8.2 ± 0.6. Furthermore, deficiency cases dominated the older age group. Regarding calcium (Ca+2) levels, 31% had lower than the normal range, 68% had normal range, and only 1% showed high Ca+2 levels. On the other hand, there was no correlation between serum levels of VD and Ca+2 levels. Conclusion VD deficiency has become a widespread condition in the southern region of Libya. Therefore, we recommended making lifestyle changes, including extending the exposure time to the sunlight radiation, fortifying foods and drinks with VD, and taking supplementary doses of VD to reduce the high incidence of VD deficiency.

Serum Levels of Interleukin-1ß and Disease Progression in Multiple Myeloma Patients: A Case and Control Study.

OBJECTIVE: Multiple myeloma  (MM) is known as an incurable heterogeneous plasma cell malignancy that presents with a variety of clinical manifestations. Inflammation plays an important role in this disease. Cytokines and Chemokines cause the progression of the disease. One of them is interleukin-1ß (IL-1ß), which may be involved in the pathogenesis of MM. Other markers such as calcium, albumin, creatinine, globulins, and total protein are also used to diagnose and prognosis patients. The main purpose of this study was to evaluate the serum level of IL-1ß and various forms of calcium (total calcium, ionized calcium, and corrected calcium), albumin, creatinine, globulin, and total protein on stage-I of MM patients and healthy controls. METHODS: Serum samples from 30 stage-I MM patients and 30 healthy subjects as controls were examined in this study. The protein concentrations of serum IL-1ß was assessed by enzyme-linked immunosorbent assay (ELISA), total calcium, albumin, creatinine, total protein, and globulin Measured by auto analyzer BT3000, an electrolyte analyzer was used to measure ionized calcium (Ca++) and a special equation was used to calculate the corrected calcium. RESULT: The mean level of IL-1ß was significantly elevated in stage-I MM. The mean levels of IL-1ß were 7.04±1.15 ng/ml in stage-I MM and 3.12± 0.90 ng/ml in controls (p<0.001). The mean levels of total calcium (total Ca) were 9.45±0.56 mg/dl in stage-I MM and 9.09±0.43mg/dl in controls (p=0.008). The mean levels of ionized calcium (Ca++) was 4.65±0.28mg/dl in stage-I MM and 4.75±0.33mg/dl in controls (p=0.2). The mean ratio of serum ionized calcium to total calcium (Ca++/ total Ca) was 0.49±0.054 in stage-I MM and 0.52±0.047 in controls (p=0.02). The mean ratio of serum ionized calcium to corrected calcium (Ca++/corrected Ca) was 0.42±0.033 in stage-I MM and the Mean ratio of serum ionized calcium to calcium total (Ca++/ total Ca) was 0.52±0.047 in controls, Comparison of the mean of the two groups shows a significant difference (p<0.001). The mean level of albumin was 1.72±0.35 g/dl in stage-I MM and4.32±0.41g/dl in controls (p<0.001). The mean level of total protein was 12.65±0.81g/dl in stage-I MM and 7.07±0.4 g/dl in controls (p<0.001). The mean level of globulin was 11.00±0.96 mg/dl in stage-I MM and 2.85±0.77 mg/dl in controls (p<0.001). The mean level of creatinine was 1.15±0.25 mg/dl in stage-I MM and 0.96±0.15 mg/dl in controls (p=0.001). CONCLUSION: The results of the study indicate the possible involvement of IL-1ß at stage-I MM and it can indicate the role of chemokines in the disease process, especially in the early stages. Changes in the chemical profiles mentioned can help in the diagnosis and prognosis of the disease.

Association of Total Calcium With Serum Uric Acid Levels Among United States Adolescents Aged 12-19 Years: A Cross-Sectional Study.

Aims: Evidence of a link between total calcium (CA) and serum uric acid (SUA) is absent in adolescents. Thus, this study aimed to determine the relationship between total CA levels and SUA levels in United States adolescents. Methods: A cross-sectional study analyzed a sample composed of 8,309 United States adolescents aged 12-19 years from the National Health and Nutrition Examination Survey database (1999-2006 survey cycle). Multivariable linear regression analyses and multivariable logistic regression analyses were used to assess the correlation of total CA with SUA levels and hyperuricemia. Furthermore, the dose-response relationship of total CA and SUA levels was analyzed using smooth curve fitting (penalized spline method). Results: According to multivariable linear regression analysis, every 1 mg/dL increase in total CA level is associated with a 0.33 mg/dL (ß = 0.33, 95% CI: 0.27-0.40, p < 0.001) increase in SUA. Multivariable logistic regression analyses showed that every 0.1 mg/dL increase in total CA level is linked with an 8% increased risk of hyperuricemia (OR = 1.08, 95% CI: 1.06-1.10, p < 0.001). The analyses of smooth curve fitting revealed that total CA levels were linearly correlated with SUA levels (P non-linearity = 0.152). The results were highly stable in all subgroups. The interaction analysis results presented that race/ethnicity had an interactive role in associating total CA with SUA levels. Conclusions: In United States adolescents, total CA levels were linearly and positively correlated with SUA levels.

Effects of altering prepartum and postpartum dietary cation-anion difference on calcium concentrations and blood metabolites of Holstein dairy cows.

We determined effects of pre- and postpartum dietary cation-anion difference (DCAD) on urine pH, serum calcium and hormone concentrations, and milk production with 48 multiparous Holstein cows (average body weight = 706 ± 7.3 kg). Treatments were 3 prepartum DCAD concentrations (0, -100, or -180 mEq/kg dry matter [DM]) and 2 postpartum DCAD concentrations (+250 or +350 mEq/kg DM) starting 29 days before parturition through 90 days in milk. Prepartum urine pH was lower (p < 0.05) for -180 than for -100 or 0 DCAD, and postpartum urine pH was higher (p < 0.05) for +350 than for +250 DCAD. Prepartum serum total and ionized calcium and hydroxyproline were greater (p < 0.05) for -180 than for -100 and 0 DCAD, whereas parathyroid hormone was greater (p < 0.05) for 0 than for -100 and -180 DCAD. After calving, negative prepartum DCAD increased (p < 0.05) serum total and ionized calcium, but effects varied by sampling day. Pre- and postpartum DCAD did not affect milk yield or milk fat, but milk protein percent and total solids were increased (p < 0.05) by negative prepartum DCAD. Feeding an acidogenic diet prepartum improved postpartum calcium status without major effects on milk yield and composition.

Low Plasma Ionized Calcium Is Associated With Increased Mortality: A Population-based Study of 106 768 Individuals.

CONTEXT: Low circulating total calcium or albumin-adjusted calcium has been associated with higher mortality, especially in hospital settings; however, these measures tend to misclassify patients with derangements in calcium homeostasis. OBJECTIVE: As the association of the biologically active ionized calcium with mortality is poorly elucidated, we tested the hypothesis that low plasma ionized calcium is associated with higher risk of all-cause and cause-specific mortality in the general population. METHODS: We included 106 768 individuals from the Copenhagen General Population Study. Information on all-cause and cause-specific mortality was from registries and risks were calculated using Cox regression and competing-risks regression by the STATA command stcompet. RESULTS: During a median follow-up period of 9.2 years, 11 269 individuals died. Each 0.1 mmol/L lower plasma ionized calcium below the median of 1.21 mmol/L was associated with a multivariable adjusted hazard ratio of 1.23 (95% CI, 1.10-1.38) for all-cause mortality. Corresponding hazard ratios for cancer and other mortality were 1.29 (1.06-1.57) and 1.24 (1.01-1.53), respectively. In contrast, for cardiovascular mortality, only high plasma ionized calcium was associated with mortality with a hazard ratio of 1.17 (1.02-1.35) per 0.1 mmol/L higher plasma ionized calcium above the median. We found no interactions between plasma ionized calcium and preexisting cardiovascular or renal disease on all-cause mortality. CONCLUSION: In the general population, low plasma ionized calcium was associated with increased all-cause, cancer, and other mortality, while high levels were associated with increased cardiovascular mortality.

Cutaneous xanthoma causing hypercalcaemia in a cat.

CASE SUMMARY: A 5-year-old male neutered cat weighing 3.56 kg presented owing to the development of two masses over the dorsal cervical and cranial thoracic areas, as well as weight loss, inappetence and vomiting. Diagnostic tests revealed a grossly lipaemic sample with hypercholesterolaemia (440 mg/dl; reference interval [RI] 90.0-205.0), hypercalcaemia (>16.0 mg/dl [RI 8.0-11.8]) and urine specific gravity 1.022 (RI ⩾1.035). When re-presented 9 months later, fasted blood analyses revealed elevated ionised calcium (1.87 mmol/l [RI 1.11-1.38]), persistently elevated total calcium, normal phosphate and persistent minimally concentrated urine with calcium oxalate dihydrate crystals. Ultrasound-guided fine-needle aspiration of the masses produced blood-tinged purulent fluid with negative culture results. Excisional biopsies of both masses were undertaken, and histopathology was consistent with cutaneous xanthoma. No organisms were identified with special staining, and deep-tissue culture did not grow bacteria or fungi. Postoperatively, repeat fasted biochemical analysis revealed persistent hypercholesterolaemia with normal triglycerides, and normalisation of ionised and total calcium levels. Based on these findings, a diagnosis of cutaneous xanthoma causing hypercalcaemia due to primary dyslipidaemia was made. The cat was reported to be significantly improved in comfort and energy levels postoperatively and a transition to a fat-restricted diet was instituted. Eight months after xanthoma removal no recurrence was reported. RELEVANCE AND NOVEL INFORMATION: To our knowledge, this is the first report of cutaneous xanthoma and associated granulomatous inflammation causing hypercalcaemia due to dyslipidaemia in a cat. Familial hypercholesterolaemia is an example of a primary condition that could cause dyslipidaemia in cats, and further studies are warranted to better describe the genetic characteristics. Xanthoma formation and the resultant granulomatous inflammation should be considered in cases of hypercalcaemia.

Effects of restricted dietary phosphorus supply to dry cows on periparturient calcium status.

Restricted dietary P supply to transition dairy cows has recently been reported to beneficially affect the Ca balance of periparturient cows. The objective of the present study was to determine whether this effect on the Ca balance can be reproduced when limiting the P-restricted feeding to the last 4 wk of gestation. A total of 30 dairy cows in late pregnancy were randomly assigned to a dry cow diet with either low or adequate P content (0.16 and 0.30% P in DM, respectively) to be fed in the 4 wk before expected calving. After calving, all cows received the same lactating cow ration with adequate P content (0.46% P in DM). Blood was collected daily from 4 d antepartum until calving, at calving (d 0), 6 and 12 h after calving (d +0.25 and d +0.5, respectively) and on days +1, +2, +3, +4 and +7 relative to calving. Blood gas analyses were conducted to determine the concentration of ionized Ca in whole blood ([Ca2+]), and plasma was assayed for concentrations of inorganic phosphorus ([Pi]), total calcium, parathyroid hormone ([PTH]), 1,25-dihydroxyvitamin D ([1,25-(OH)2D3]), and CrossLaps ([CTX]), a biomarker for bone resorption (Immunodiagnostic Systems GmbH). Repeated-measures ANOVA was conducted to study treatment, time, and lactation number effects. The mean [Ca2+] in P-deprived cows remained above the threshold of 1.10 mmol/L throughout the study, and values were higher compared with cows on adequate P supply between d 0 and d +2 and on d +4. The [Ca2+] differed between treatments at the sampling times d 0, d +0.25, d +0.5, d +2, and d +4. Plasma [PTH] and [1,25-(OH)2D3] did not differ between treatments, but P-deprived cows had greater [CTX] than cows with adequate P supply at d +1, d +2, and d +7. These results indicate that restricted dietary P supply to during the last 4 wk of the dry period improves the Ca homeostasis of these cows in the first days of lactation, an effect that seems to be primarily driven by increased bone tissue mobilization.

Diagnostic performance of predicted ionized calcium in dogs with total hypercalcemia and total hypocalcemia.

BACKGROUND: Abnormal total calcium (tCa) values do not necessarily imply dysregulated ionized calcium. OBJECTIVES: We aimed to evaluate the diagnostic performance of predicted ionized calcium (piCa) regarding true calcium status in dogs with abnormal tCa. METHODS: This was a cross-sectional multicenter study. piCa and its prediction interval (PI) were calculated in 114 dogs, from three different hospitals, with either increased (62) or decreased tCa (52), All dogs also had ionized calcium and a biochemical profile available. The sensitivity, specificity, predictive values, and diagnostic discordance of piCa to confirm ionized hypercalcemia (iHyperCa) and ionized hypocalcemia (iHypoCa) were calculated using logistic regression analysis. RESULTS: iHyperCa was found in 28% and 66% of hyperphosphatemic and non-hyperphosphatemic dogs with tCa above the reference interval upper limit, respectively. The piCa correctly classified dogs with iHyperCa in 72.2% of those with hyperphosphatemia and 93.2% of those without hyperphosphatemia. Comparatively, elevating the tCa threshold to 12 mg/dL properly classified dogs 50% and 75% of the time in hyperphosphatemic and non-hyperphosphatemic dogs, respectively. iHypoCa was found in only 31/52 (60%) dogs with decreased tCa. The piCa correctly classified 55.2 to 100% of dogs with iHypoCa depending on the hospital. The PI demonstrated high sensitivity for iHyperCa (100%) and high specificity for both iHyperCa (100%) and iHypoCa (100%). CONCLUSIONS: Evaluating tCa alone does not reliably determine ionized calcium status. Even with hyperphosphatemia, piCa and its PI represent a reliable alternative to interpret abnormal tCa values when ionized calcium measurements are not available. However, if the tCa reference interval is notably different from 7.6 to 11.4 mg/dL, piCa values might be under/overestimated.

Adjusted calcium concentration as a predictor of ionized hypocalcemia in hypoalbuminemic dogs.

BACKGROUND: Ionized calcium (iCa) is the biologically active fraction of total calcium (tCa) with clinical relevance to evaluate calcium homeostasis, but not all primary veterinarians have access to serum iCa. Formulas that adjust tCa to correct for variability in serum protein concentrations were not designed to predict iCa and are considered unreliable surrogates for iCa. OBJECTIVES: To determine whether adjusted calcium concentration (aCa) can predict ionized hypocalcemia in hypoalbuminemic dogs without hyperphosphatemia. ANIMALS: A total of 262 hypoalbuminemic dogs without hyperphosphatemia. METHODS: Retrospective review of paired tCa and iCa. Patients were included if serum albumin concentration was ≤2.5 g/L and serum phosphorus concentration was ≤5 mg/dL. The aCa was calculated using tCa (mg/dL) - serum albumin concentration (g/dL) + 3.5 (g/dL). Sensitivity, specificity, positive (PPVs) and negative (NPVs) predictive values, and accuracy were determined for tCa and aCa at predicting any (<1.13 mmol/L) and moderate (<1.02 mmol/L) ionized hypocalcemia. Patients also were stratified into mild-to-moderate (2.0-2.5 g/dL) and severe hypoalbuminemia (<2.0 g/dL). RESULTS: A total of 4296 dogs had paired results of which 262 met the inclusion criteria. Of these, 35 (13.4%) dogs had iCa < 1.13 mmol/L and 13 dogs (5.0%) had concentrations <1.02 mmol/L. The sensitivity, specificity, NPVs and PPVs of a decreased tCa and aCa for detecting moderate ionized hypocalcemia were 100% and 92.3%, 57.8% and 94.8%, 100% and 99.6%, and 11.0% and 48.2%, respectively, and accuracy was 60.0% and 94.7%, respectively. CONCLUSIONS: A low aCa was useful to detect ionized hypocalcemia in hypoalbuminemic nonhyperphosphatemic dogs. A normal aCa indicated that moderate ionized hypocalcemia was unlikely.

Changes in the Relationship between Ionized and Total Calcium in Clinically Healthy Dairy Cows in the Period around Calving.

We aimed to establish a model for prediction of iCa from tCa, using multivariable regressions with diverse blood constituents. Blood was taken from 14 cows at days -2, 0, 2, 4, 7, and 14 relative to parturition. Cows were clinically healthy, and no hypocalcaemia prophylaxis and treatment were applied. Total calcium and further parameters were determined from frozen serum. Ionized calcium, blood gases, and electrolytes were determined from heparin-stabilized blood samples. Linear regression between iCa and tCa was estimated. Precision improved only slightly using a multivariable model. Best precision was achieved when estimating the iCa:tCa ratio from other blood constituents. To identify the reason behind the poorly predictive value of tCa for iCa, the relative changes of iCa and tCa around calving were calibrated to the respective values of day -2 (=100%) for each cow. An increase in the iCa:tCa ratio was observed from 0.43 at day -2 to 0.48 at day 0, followed by a gradual decrease towards 0.43 at day 7. We conclude that routine measurement of iCa should be implemented in the diagnosis of hypocalcaemia. An optimized estimate of iCa from tCa with non-esterified fatty acids (NEFA), beta-hydroxybutyric acid, cholesterol, and phosphorous as co-predictors is still poorly satisfying.

Evaluation of a New Automated Routine Measurement for Serum Adjusted Ionized Calcium (at pH 7.4) in Patients Suspected of Calcium Metabolic Disease.

BACKGROUND: Total calcium is a less accurate test in predicting ionized calcium (Ca2+) in patients suspected of calcium metabolic disease. Nevertheless, total calcium continues to be used as routine measurement instead of adjusted Ca2+ (at pH 7.4). In the current study we evaluate a new multichannel instrument, the ISE Module E1200 for adjusted Ca2+ (at pH 7.4), containing three different ion-selective electrode (ISE) units. METHODS: Serum from 1350 patients was compared to the ABL835 flex and KoneLab. Total calcium was also evaluated on the Dimension Vista 1500 system. Correlations between instruments were assessed by Deming regression and degree of agreement by Cohen's kappa (κ). RESULTS: Analytical imprecisions for the three ISE units for adjusted Ca2+ (at pH 7.4) was between 0.36% and 2.52%, and for pH between 0.32% and 3.24%. Results were comparable for each ISE unit (r = 0.797-0.917; all P < 0.0001) and in high-throughput settings (r = 0.871; P < 0.0001). The degree of agreement between instruments was moderate to good (κ = 0.52-0.77). In contrast, there was a very poor agreement (κ = -0.14) for total calcium with discrepancy in 53.4% of the samples. CONCLUSIONS: The new ISE Module E1200 is comparable with the ABL835 flex and KoneLab 30i and therefore may be used for routine analysis of serum adjusted Ca2+ (at pH 7.4). The measured adjusted Ca2+ (at pH 7.4) was less comparable with very poor agreement to total calcium measured on the Dimension Vista 1500 system.

[The role of adipose tissue and laboratory predictors of primary osteoporosis.]

The purpose of this work was to determine the information content of alkaline phosphatase (ALP), total calcium (Ca) as predictors for the diagnosis of osteoporosis. By laboratory methods, 2451 people were divided into two groups according to the presence/absence of metabolic syndrome (MetS+ / MetS-): 1946 women (MetS- 1119, MetS+ 827) and 505 men (MetS- 264, MetS+ 241). Patients with laboratory signs of liver pathology are excluded. In women: MetS+ levels of ALP and Ca significantly differ from MetS- (p<0.0001), no differences were found for men. ALP synchronously change the indicators of TG, HDL, LDL, ALT, AST, Ca, demonstrating a positive relationship (p<0.001), the indicators do not exceed the threshold values. MetS- women in pre- and postmenopausal women significantly differ in ALP: 63.90 E / l vs 79.10 E / l (p<0.0001).

Resolution of hypercalcemia in primary hyperparathyroidism with vitamin D replacement.

Vitamin D deficiency is common in patients with primary hyperparathyroidism. We present a case of primary hyperparathyroidism with a positive parathyroid scan and history of nephrolithiasis. The patient had normal albumin and renal function but was vitamin D deficient. After treatment with vitamin D for 13 months, her parathyroid hormone values declined in parallel with the elevation in vitamin D. Although her total calcium normalized, her ionized calcium remained elevated throughout treatment. We believe vitamin D deficiency should be carefully monitored in primary hyperparathyroidism.

Calcium state estimation by total calcium: the evidence to end the never-ending story.

Background Total blood calcium (TCa) is routinely used to diagnose and manage mineral and bone metabolism disorders. Numerous laboratories adjust TCa by albumin, though literature suggests there are some limits to this approach. Here we report a large retrospective study on agreement rate between ionized calcium (iCa) measurement and TCa or albumin-adjusted calcium measurements. Methods We retrospectively selected 5055 samples with simultaneous measurements of iCa, TCa, albumin and pH. We subgrouped our patients according to their estimated glomerular filtration rate (eGFR), albumin levels and pH. We analyzed each patient's calcium state with iCa as reference to determine agreement rate with TCa and albumin-adjusted calcium using Payne, Clase, Jain and Ridefelt formulas. Results The Payne formula performed poorly in patients with abnormal albumin, eGFR or pH levels. In patients with low albumin levels or blood pH disorders, Payne-adjusted calcium may overestimate the calcium state in up to 80% of cases. Similarly, TCa has better agreement with iCa in the case of hypoalbuminemia, but performed similarly to the Payne formula in patients with physiological albumin levels. The global agreement rate for Clase, Jain and Ridefelt formulas suggests significant improvement compared to Payne calcium adjustment but no significant improvement compared to TCa. Conclusions Total and albumin-adjusted calcium measurement leads to a misclassification of calcium status. Moreover, accurate calcium state determination depends on blood pH levels, whose measurement requires the same pre-analytical restrictions as iCa measurement. We propose that iCa should instead become the reference method to determine the real calcium state.

Derivation and Internal Validation of an Equation for Albumin-adjusted Calcium at a Tertiary Hospital in Selangor, Malaysia

@#Introduction: Total calcium concentration is widely used to assess body calcium status although limited by many confounding factors. Thus, this study aimed to derive and internally validate an albumin-adjusted calcium equation for a selected Malaysian population. Method: This cross-sectional study involved 1011 adults at an emergency department of a tertiary hospital. Patients who had total calcium, ionised calcium and albumin measurements taken simultaneously were included. Derivation of the albumin-adjusted calcium equation was based on the adjustment equation obtained from the Association for Clinical Biochemistry and Laboratory Medicine 2015 position paper. Additionally, the equation was internally validated and compared with ionised calcium (gold standard) and the conventional Payne’s equation. Results: The newly derived equation = total calcium + 0.017 (41.35 – albumin). Internal validation exhibited the amount of shrinkage of 0.049. It tends to overestimate the adjusted calcium by a mean difference of 0.029 mmol/L compared to Payne’s equation. The comparison between Payne’s equation and the new equation with ionised calcium reclassified 402 and 486 patients, respectively into different calcium status. When both equations were compared, calcium status classification significantly differed in all and hypoalbuminaemic subjects by 90 and 16 patients, respectively. Conclusion: Locally derived albumin-adjusted calcium equation differed statistically in calcium status classification when compared to the Payne’s equation. However, to confirm this significance, the result must be compared to ionised calcium under strict, controlled preanalytical conditions. In terms of clinical significance, there was no difference in classification of calcium status between Payne’s and the new equation at medical decision limits.