Serum Calcium Concentrations Research Articles

Predictors of Developmental Defects of Enamel in Primary Maxillary Central Incisors Using Bayesian Model Selection

Introduction: Localized non-inheritable developmental defects of tooth enamel (DDE) are classified as enamel hypoplasia (EH), opacity (OP), and post-eruptive breakdown (PEB) using the enamel defects index. To better understand the etiology of DDE, we assessed the linkages amongst exposome variables for these defects during the specific time duration for enamel mineralization of the human primary maxillary central incisor enamel crowns. In general, these two teeth develop between 13 and 14 weeks in utero and 3–4 weeks’ postpartum of a full-term delivery, followed by tooth eruption at about 1 year of age. Methods: We utilized existing datasets for mother-child dyads that encompassed 12 weeks’ gestation through birth and early infancy, and child DDE outcomes from digital images of the erupted primary maxillary central incisor teeth. We applied a Bayesian modeling paradigm to assess the important predictors of EH, OP, and PEB. Results: The results of Gibbs variable selection showed a key set of predictors: mother’s prepregnancy body mass index (BMI); maternal serum concentrations of calcium and phosphorus at gestational week 28; child’s gestational age; and both mother’s and child’s functional vitamin D deficiency (FVDD). In this sample of healthy mothers and children, significant predictors for OP included the child having a gestational period >36 weeks and FVDD at birth, and for PEB included a mother’s prepregnancy BMI <21.5 and higher serum phosphorus concentration at week 28. Conclusion: In conclusion, our methodology and results provide a roadmap for assessing timely biomarker measures of exposures during specific tooth development to better understand the etiology of DDE for future prevention.

Some indicators of nutritional security of children with restrictive types of nutrition

Following vegetarian diets means, to varying degrees, the exclusion of animal products from diets, which, if poorly planned, can lead to deficiency of some nutrients. Aim of the study was to evaluate some indicators of nutritional security of children with a restrictive type of nutrition and living in the territory of a long-term military conflict in the Donbass. Material and methods. 80 school-age children following restrictive diets were examined. All patients were divided into two groups: 40 children following a dairy-free diet (group 1), 40 children on a vegetarian type of diet (group 2). The control group consisted of 30 children who adhere to the traditional type of diet. Calcium, ferritin, vitamin B12 and zinc content in blood serum were studied in all children, living in Donbass. Results. In group 1 deficiency of calcium was found in 60.0 %, of zinc – in 32.5 %, of vitamin B12 – in 15.0 %, a decrease in ferritin content – in 22.5 %. In group 2 level of ferritin was declined in 55.0%, zinc deficiency was detected in 37.5 %, vitamin B12 deficiency – in 30.0 %, calcium deficiency – in 10.0 %. Conclusions. For children on a long-term dairy-free diet, calcium and zinc deficiency is characteristic, as well as a decrease in tissue iron reserves. Children who observe lactovegetarianism are characterized by a deficiency of zinc and vitamin B12, as well as a decrease in the concentration of ferritin in the blood serum. Children living in the Donbass in the conditions of a long military conflict and adhering to restrictive types of nutrition can be considered as a risk group for the development of deficient conditions. To correct the identified imbalance, it is necessary to develop programs for the supplementation of macro- and micronutrients.

Mendelian randomisation and colocalization analyses reveal novel drug targets for the prevention of kidney stone disease by modulating serum calcium and phosphate concentrations

Mendelian randomisation and colocalization analyses reveal novel drug targets for the prevention of kidney stone disease by modulating serum calcium and phosphate concentrations

Effects of Different Galacto-Oligosaccharide Supplementation on Growth Performance, Immune Function, Serum Nutrients, and Appetite-Related Hormones in Holstein Calves.

Our previous study showed that early supplementation with 10 g/(d·head) of galacto-oligosaccharides (GOS) in newborn Holstein dairy calves reduced the incidence of diarrhea and improved growth performance and mineral absorption. Since the dose of 10 g/(d·head) was the lowest by dose screening in our previous study, the present study was designed to investigate whether a lower amount of GOS has similar effects on growth performance, immune function, serum nutrients in newborn Holstein heifer calves, and to further investigate its effect on appetite-related hormones. Twenty-eight healthy newborn (1 day of age) Holstein heifers with similar average body weight (41.18 ± 1.90 kg) were randomly divided into four groups (n = 7): the control group (CON group), which received heated raw milk, and three experimental groups, which received heated raw milk supplemented with 2.5 (GOS2.5 group), 5 (GOS5 group), and 10 g/(d·head) (GOS10 group) GOS. All heifer calves were fed the same starter for 28 d. Supplementation with GOS linearly increased the final body weight, average daily gain, and feed efficiency in heifer calves (p < 0.01). Compared with the control group, the average daily gain and feed efficiency of heifer calves were significantly higher in the GOS5 and GOS10 groups than in the control group (p < 0.05). Furthermore, supplementation with GOS quadratically enhanced the starter and total average daily feed intake of the heifers (p < 0.01), especially in the GOS2.5 and GOS5 groups, (p < 0.05 vs. CON). The serum concentration of immunoglobulin A was linearly increased by GOS supplementation (p < 0.05), and the levels in the GOS5 and GOS10 groups were significantly higher than those in the CON group. Meanwhile, GOS linearly decreased serum interleukin-1β and interleukin-6 concentrations (p < 0.05). The serum concentration of triglycerides was also linearly decreased (p < 0.05), whereas total protein and blood urea nitrogen were linearly increased (p < 0.05). Supplementation with GOS linearly decreased the serum concentration of leptin (p < 0.05) but increased cholecystokinin and glucagon-like peptide-1 (p < 0.05). Increasing doses of GOS linearly improved serum calcium and copper concentrations (p < 0.01) and quadratically enhanced the concentration of magnesium, which peaked in the GOS5 group (p < 0.05). In conclusion, GOS supplementation reduced the incidence of diarrhea and improved the growth performance and immune function of Holstein heifer calves.

Differences in ventricular wall composition may explain inter-patient variability in the ECG response to variations in serum potassium and calcium.

Objective: Chronic kidney disease patients have a decreased ability to maintain normal electrolyte concentrations in their blood, which increases the risk for ventricular arrhythmias and sudden cardiac death. Non-invasive monitoring of serum potassium and calcium concentration, [K+] and [Ca2+], can help to prevent arrhythmias in these patients. Electrocardiogram (ECG) markers that significantly correlate with [K+] and [Ca2+] have been proposed, but these relations are highly variable between patients. We hypothesized that inter-individual differences in cell type distribution across the ventricular wall can help to explain this variability. Methods: A population of human heart-torso models were built with different proportions of endocardial, midmyocardial and epicardial cells. Propagation of ventricular electrical activity was described by a reaction-diffusion model, with modified Ten Tusscher-Panfilov dynamics. [K+] and [Ca2+] were varied individually and in combination. Twelve-lead ECGs were simulated and the width, amplitude and morphological variability of T waves and QRS complexes were quantified. Results were compared to measurements from 29 end-stage renal disease (ESRD) patients undergoing hemodialysis (HD). Results: Both simulations and patients data showed that most of the analyzed T wave and QRS complex markers correlated strongly with [K+] (absolute median Pearson correlation coefficients, r, ranging from 0.68 to 0.98) and [Ca2+] (ranging from 0.70 to 0.98). The same sign and similar magnitude of median r was observed in the simulations and the patients. Different cell type distributions in the ventricular wall led to variability in ECG markers that was accentuated at high [K+] and low [Ca2+], in agreement with the larger variability between patients measured at the onset of HD. The simulated ECG variability explained part of the measured inter-patient variability. Conclusion: Changes in ECG markers were similarly related to [K+] and [Ca2+] variations in our models and in the ESRD patients. The high inter-patient ECG variability may be explained by variations in cell type distribution across the ventricular wall, with high sensitivity to variations in the proportion of epicardial cells. Significance: Differences in ventricular wall composition help to explain inter-patient variability in ECG response to [K+] and [Ca2+]. This finding can be used to improve serum electrolyte monitoring in ESRD patients.

Efficacy and Safety of Ferric Citrate on Hyperphosphatemia among Chinese Patients with Chronic Kidney Disease Undergoing Hemodialysis: A Phase III Multicenter Randomized Open-Label Active-Drug-Controlled Study

Introduction: Hyperphosphatemia in chronic kidney disease (CKD) patients is positively associated with mortality. Ferric citrate is a potent phosphorus binder that lowers serum phosphorus level and improves iron metabolism. We compared its efficacy and safety with active drugs in Chinese CKD patients with hemodialysis. Methods: Chinese patients undergoing hemodialysis were randomized into two treatment groups in a 1:1 ratio, receiving either ferric citrate or sevelamer carbonate, respectively, for 12 weeks. Serum phosphorus levels, calcium concentration, and iron metabolism parameters were evaluated every 2 weeks. Frequency and severity of adverse events were recorded. Results: 217 (90.4%) patients completed the study with balanced demographic and baseline characteristics between two groups. Ferric citrate decreased the serum phosphorus level to 0.59 ± 0.54 mmol/L, comparable to 0.56 ± 0.62 mmol/L by sevelamer carbonate. There was no significant difference between two groups (p > 0.05) in the proportion of patients with serum phosphorus levels reaching the target range, the response rate to the study drug, and the changes of corrected serum calcium concentrations, and intact-PTH levels at the end of treatment. The change of iron metabolism indicators in the ferric citrate group was significantly higher than those in the sevelamer carbonate group. There are 47 (40.5%) patients in the ferric citrate group, and 26 (21.3%) patients in the sevelamer carbonate group experienced drug-related treatment emergent adverse events (TEAEs); most were mild and tolerable. Common drug-related TEAEs were gastrointestinal disorders, including diarrhea (12.9 vs. 2.5%), fecal discoloration (14.7 vs. 0%), and constipation (1.7 vs. 7.4%) in ferric citrate and sevelamer carbonate group. Conclusion: Ferric citrate capsules have good efficacy and safety in the control of hyperphosphatemia in adult patients with CKD undergoing hemodialysis. Efficacy is not inferior to sevelamer carbonate. The TEAEs were mostly mild and tolerated by the patients.

SAT257 Efficacy Of Oral Cinacalcet In Non-PTH Non-Malignant Hypercalcemia From Excess 1,25 Dihydroxyvitamin D

Abstract Disclosure: S. Mohan: None. M.T. Sheehan: None. P.J. Tebben: None. R.A. Wermers: None. Introduction: Elevated 1,25-dihydroxyvitamin D (1,25(OH)2D) is a rare cause of non-parathyroid hormone (PTH) mediated hypercalcemia. An increase in the activating enzyme 1-alpha hydroxylase is seen in granulomatous diseases and lymphoma, while mutations in the CYP24A1 gene leads to reduced catabolism of 1,25(OH)2D. Cinacalcet has been shown to successfully treat 1,25(OH)2D-mediated hypercalcemia of malignancy. Extrapolating this, we report 3 patients with non-malignant 1,25(OH)2D-mediated hypercalcemia treated with cinacalcet. Case Series: The patients (2 male and 1 female) were 55-71 years old. At presentation to our clinic, all had hypercalcemia with serum calcium concentrations between 10.6-11.5 mg/dL (normal, 8.8-10.2 mg/dL). PTH ranged between 16-35 pg/ml (normal 15-65 pg/ml), PTH-related peptide was normal in all patients, 25-hydroxyvitamin D was 32-51 ng/ml, and 1,25(OH)2D was inappropriately normal between 31-77 pg/ml (normal 18-78 pg/mL) in the setting of hypercalcemia and chronic kidney disease in 2 patients with estimated glomerular filtration rates 35-42 ml/min. Other causes of hypercalcemia including sarcoidosis, tuberculosis and malignancy were ruled out. The female patient had hypercalciuria (288 mg/24 hours) without nephrolithiasis and both male patients had severe hypercalciuria (400-660 mg/24 hours) with recurrent nephrolithiasis. One male patient had biallelic variants in the CYP24A1 gene, while the other male patient was suspected to have similar mutations, but not identified on genetic testing. The female patient with a PTH of 35 pg/mL on our initial measurement had documented 1,25(OH)2D level of 82 pg/mL with PTH &amp;lt;20 pg/mL while previously hypercalcemic. Upon cinacalcet initiation all patients demonstrated normalization of calcium levels (8.6-9.5 mg/dl) with doses between 30-90 mg daily. The patient with CYP24A1 gene mutations experienced symptomatic hypocalcemia with calcium of 8.1 mg/dL requiring dose reduction and eventual discontinuation of cinacalcet due to limited clinical benefit. There were no consistent changes in 24-hour urine calcium or fractional excretion of calcium. Levels of 1,25(OH)2D increased and PTH decreased on cinacalcet while serum calcium levels were maintained within normal range, including 2 subjects with continued normocalcemia after 2 years of therapy. Conclusion: Cinacalcet may be a therapeutic option in non-malignant 1,25(OH)2D-mediated hypercalcemia. Further evaluation is needed to confirm efficacy, understand risks and benefits, and elucidate potential mechanisms of action. Mild decrease in PTH may lead to reduced skeletal calcium efflux while the maintenance of normocalcemia despite rising 1,25(OH)2D, which was also seen in our reported patients with malignant 1,25(OH)2D-mediated hypercalcemia, suggests cinacalcet may decrease intestinal calcium absorption. Presentation: Saturday, June 17, 2023

Central Adiposity Increases Risk of Kidney Stone Disease through Effects on Serum Calcium Concentrations.

Kidney stone disease is a common disorder with poorly understood pathophysiology. Observational and genetic studies indicate that adiposity is associated with an increased risk of kidney stone disease. However, the relative contribution of general and central adipose depots and the mechanisms by which effects of adiposity on kidney stone disease are mediated have not been defined. Using conventional and genetic epidemiological techniques, we demonstrate that general and central adiposity are independently associated with kidney stone disease. In addition, one mechanism by which central adiposity increases risk of kidney stone disease is by increasing serum calcium concentration. Therapies targeting adipose depots may affect calcium homeostasis and help to prevent kidney stone disease. Kidney stone disease affects approximately 10% of individuals in their lifetime and is frequently recurrent. The disease is linked to obesity, but the mechanisms mediating this association are uncertain. Associations of adiposity and incident kidney stone disease were assessed in the UK Biobank over a mean of 11.6 years/person. Genome-wide association studies and Mendelian randomization (MR) analyses were undertaken in the UK Biobank, FinnGen, and in meta-analyzed cohorts to identify factors that affect kidney stone disease risk. Observational analyses on UK Biobank data demonstrated that increasing central and general adiposity is independently associated with incident kidney stone formation. Multivariable MR, using meta-analyzed UK Biobank and FinnGen data, established that risk of kidney stone disease increases by approximately 21% per one standard deviation increase in body mass index (BMI, a marker of general adiposity) independent of waist-to-hip ratio (WHR, a marker of central adiposity) and approximately 24% per one standard deviation increase of WHR independent of BMI. Genetic analyses indicate that higher WHR, but not higher BMI, increases risk of kidney stone disease by elevating adjusted serum calcium concentrations (β=0.12 mmol/L); WHR mediates 12%-15% of its effect on kidney stone risk in this way. Our study indicates that visceral adipose depots elevate serum calcium concentrations, resulting in increased risk of kidney stone disease. These findings highlight the importance of weight loss in individuals with recurrent kidney stones and suggest that therapies targeting adipose depots may affect calcium homeostasis and contribute to prevention of kidney stone disease.

Effect of low-calcium and standard-calcium dialysate on serum calcium, phosphorus and full-segment parathyroid hormone in patients on peritoneal dialysis: A retrospective observational study.

To investigate the effects of low-calcium and standard-calcium dialysate in patients with chronic kidney disease on peritoneal dialysis, and find out which dialysate has less vascular calcification effect. A total of 141 patients who had undergone peritoneal dialysis (PD) for 2 years in the PD centre from January 2012 to December 2017 were included and divided into two groups according to the calcium concentration of the PD fluid used. There were 79 cases in the low-calcium group, with a dialysate calcium concentration of 1.25 mmol/L and 62 cases in the standard-calcium group, with a dialysate calcium concentration of 1.75 mmol/L. The demographic characteristics and clinical information before initiation of PD were collected and compared between the two groups. Information on the serum calcium, phosphorus and PTH, systolic and diastolic blood pressures and the use of antihypertensive and phosphate-lowering drugs in the second year of dialysis was also collected and compared between the two groups. Vascular calcification was assessed in patients on PD treatment. The mean serum calcium concentrations before initiation of PD in the low- and standard-calcium groups were 1.94 ± 0.27 and 1.89 ± 0.28 mmol/L, respectively. The serum calcium concentrations after PD were 2.30 ± 0.21 and 2.41 ± 0.23 mmol/L, respectively. After PD, the serum calcium concentration in both groups was significantly increased (p < 0.05). The serum calcium concentration in the low-calcium group after PD treatment was lower than that in the standard-calcium group, and the difference was statistically significant (p < 0.05). Compared with the standard-calcium group, patients in the low-calcium group had significantly higher parathyroid hormone concentrations (p < 0.05). More types of phosphate-lowering drugs were used (59.49%) in the low-calcium group than that in the standard-calcium group (35.48%; p < 0.05). The number of antihypertensive drug usage were also higher in the low-calcium group, and the difference was statistically significant (p < 0.05). As for the vascular calcification effect, the two groups have shown no statistical difference in abdominal aortic calcification rate, carotid arteriosclerosis rate and aortic arch calcification rate (p < 0.05). We found that low-calcium PD fluid may increase the PTH level and the proportion of CKD patients using antihypertensive drug and phosphorus-lowering drug, but the vascular calcification effect of the low and standard calcium PD fluid needs further exploration. This paper provides new evidence for the choice of dialysate for PD, low-calcium dialysate has no outstanding advantages for long term dialysis.

A genetic study of a Brazilian cohort of patients with X-linked hypophosphatemia reveals no correlation between genotype and phenotype.

X-linked hypophosphatemia (XLH) is the most common inherited form of rickets, and it is caused by pathogenic inactivating variants of the phosphate-regulating endopeptidase homolog X-linked (PHEX) gene. The main purpose of this study is to identify the presence of a genotype-phenotype correlation in a cohort of XLH patients. This is a retrospective study including patients diagnosed with hypophosphatemic rickets, confirmed by clinical, radiological, and laboratory findings. Medical records were reviewed for phenotypic analyses. Genomic DNA was extracted from the peripheral blood lymphocytes, and PHEX sequencing was performed by exomic NGS sequencing. The Wilcoxon rank-sum test and the two-tailed Fisher's exact test were employed for the statistical analyses of this study. A total of 41 patients were included in this study, and 63.41% (26/41) of the patients were female. The mutation analyses identified 29.27% missense variants and 29.72% nonsense variants, most of them were considered deleterious (66.41%). Six novel deleterious variants in the PHEX gene were detected in seven patients. The median concentrations of pretreatment serum calcium, phosphorus, and parathyroid hormone (PTH) were not significantly different among patients with different genotypes. An orthopedic surgery due to bone deformity was required in 57.69%. Our analysis did not identify any specific genotype as a predictor. No significant genotype-phenotype correlation was found, suggesting that the recognition of subjacent pathogenic mutation in the PHEX gene may have limited prognostic value. Despite this finding, genetic testing may be useful for identifying affected individuals early and providing appropriate treatment.

Are Twin Pregnancies at Higher Risk for Iron and Calcium Deficiency than Singleton Pregnancies?

The aim of this study was to compare the iron and calcium status in singleton and twin pregnancies and to assess whether there is an increased risk for iron and calcium deficiency in twin gestation. The study included 105 singleton and 9 twin pregnancies at or above 35 weeks of gestation. Information on prenatal supplementation with iron or calcium was acquired, and adverse perinatal outcomes were recorded. Biosamples from all 114 mothers and 73 newborns (61 singleton and 12 twin newborns) were finally analyzed. Total iron and calcium concentrations in serum were measured through total reflection X-ray fluorescence analysis. The results indicated no significant differences in maternal serum iron and calcium concentrations between singleton and twin pregnancies. Similarly, iron and calcium concentrations in newborn umbilical cord serum samples were not different between singleton and twin pregnancies. The comparison of total iron and calcium between mothers and umbilical cord serum indicated significantly lower concentrations in the mothers, with the differences being not homogenous but rather pair-specific. A significant positive correlation between maternal serum and umbilical cord serum calcium concentration was noticed. Prenatal iron supplementation was associated with higher iron concentrations in both mothers and newborns, supporting the efficiency of supplementation and the quality of the study methods. Collectively, the data indicate no significant differences in serum iron and calcium concentrations with regard to singleton or twin pregnancies and the efficiency of iron supplementation during pregnancy for increasing iron status.

Circulating parathyroid hormone and serotonin in multiparous cows with differing postparturient serum calcium concentrations

Many multiparous dairy cows experience subclinical hypocalcemia (SCH) in the immediate postpartum period as they adapt to the demands of lactation. Furthermore, differing dynamics of SCH in the days following parturition are associated with varied health and production outcomes, with cows experiencing transient SCH producing more milk and facing fewer negative health events than cows with delayed or persistent SCH. Our objectives were to describe differences in mediators of calcium (Ca) homeostasis between cows experiencing differing Ca dynamics postpartum. A prospective cohort of 89 multiparous Holstein cows from 2 herds in New York were classified into 1 of 4 SCH groups based on mean serum total Ca (tCa) at 1 and 4 d in milk (DIM): normocalcemic (NC; [tCa] >1.89 mmol/L at 1 DIM and >2.25 mmol/L at 4 DIM, n = 30); transient SCH (tSCH; [tCa] ≤1.89 mmol/L at 1 DIM and >2.25 mmol/L at 4 DIM, n = 12); delayed SCH (dSCH; [tCa] >1.89 mmol/L at 1 DIM and ≤2.25 mmol/L at 4 DIM, n = 23); and persistent SCH (pSCH; [tCa] ≤1.89 mmol at 1 DIM and ≤2.25 mmol/L at 4 DIM, n = 24). Blood samples were collected at -5, -1, 1 through 5, 7, and 10 DIM and analyzed for tCa, parathyroid hormone (PTH), and serotonin. Repeated measures ANOVA models were used to analyze differences between SCH groups and changes over time for tCa, PTH, and serotonin. During the prepartum period, tCa was greater in the NC, tSCH, and dSCH cows as compared with the pSCH cows and there was marginal evidence for a difference in PTH between SCH groups. Postpartum tCa varied over time between SCH groups. Mean postpartum (95% confidence interval) tCa for respective SCH groups were NC = 2.32 (2.28, 2.35) mmol/L; tSCH = 2.20 (2.14, 2.25) mmol/L; dSCH = 2.17 (2.13, 2.21) mmol/L; and pSCH = 2.03 (1.99, 2.07) mmol/L. Mean concentrations of PTH in the postpartum period were NC = 70.1 (66.2, 74.4) pmol/L; tSCH = 72.1 (66.1, 79.2); dSCH = 75.8 (70.8, 81.5) pmol/L; and pSCH = 77.7 (72.4, 83.9) pmol/L. Serotonin was similar between SCH groups pre- and postpartum and followed a cyclical pattern from 1 to 10 DIM. Our results agreed with our hypothesis that differences in postpartum PTH might exist between cows experiencing different dynamics of SCH in the early lactation period; however, further studies are needed to confirm this difference. If true, this would suggest that Ca homeostasis may be disrupted in cows with dSCH and pSCH. Gaining a better understanding of these modulatory differences may aid in the prevention, management, and treatment of SCH.

Smartphone-Interfaced Serum Calcium-Level Quantification on a Simple Paper Strip Assay for Diagnostics at Extreme Point of Care

Due to its pivotal role in many physiological processes and calcium-depleting diseases like osteoporosis, accurate quantification of the concentration of calcium in blood serum is imperative in monitoring multifarious facets of human health and disease. Established laboratory-based protocols for serum calcium level detection are expensive, resource-intensive and functionally dependent on skilled technicians. Circumventing these constraints, here we innovate a novel adaptation of the Bradford’s assay as a decisive pre-processing step of a highly specific diagnostic test for serum calcium level detection. This ensures the binding of protein molecules to Coomassie dye under acidic conditions with a resulting alteration in its colour so as to quench out the possibilities of unwarranted side reactions with excess proteins abundantly present in patient samples. This specific adaptation renders the test to be implemented on a simple paper strip without deploying controlled laboratory-based procedure, obviating any adverse interference in the subsequent reaction of calcium in the serum with Arsenazo III, a metallochromic dye used for the final colorimetric detection step. The method is affordable, user-friendly and can be deployed by minimally trained personnel at the point of use in extreme harsh environments. By mapping the resulting colorimetric information quantitatively with the serum concentration level from a panel of training dataset pre-standardized via established laboratory-based gold standard examination, a simple smartphone-based readout system may be developed, bearing the potential of replacing the currently existing expensive, time-consuming and environmentally-restrictive diagnostic solutions.

Preoperative Serum Calcium Level Predicts Postoperative Mortality in Older Adult Patients with Hip Fracture: A Prospective Cohort Study of 2333 Patients

ObjectivesHip fractures are a significant cause of mortality among older adults. However, predictive markers for an unfavorable prognosis are still lacking. Serum calcium is an essential element in several biochemical reactions in the body. This study investigated the role of the preoperative serum calcium level as a prognostic parameter for postoperative mortality in older adult patients with hip fractures. DesignWe conducted a prospective cohort study at the trauma center in our hospital, from January 1, 2015, to September 30, 2019. A total of 2333 older patients with hip fractures were recruited. This prospective cohort study was conducted in accordance with the criteria of STROCSS. Setting and ParticipantsOlder adult patients with hip fractures were screened between January 2015 and September 2019 at the trauma center of our hospital. MethodsDemographic and clinical characteristics of the patients were collected. Linear and nonlinear multivariate Cox regression models were used to identify the association between preoperative serum calcium level and all-cause mortality. All analyses were performed using EmpowerStats and the R software. ResultsA total of 2333 older adult patients with hip fractures were included in the study. The mean follow-up was 37.5 months. Overall, 770 patients (33%) died of all causes. The preoperative serum calcium concentrations were 2.18 ± 0.13 mmol/L. Linear multivariate Cox regression models showed that preoperative serum calcium levels were associated with mortality [hazard ratio (HR) 0.37, 95% CI 0.21-0.67; P = .0009] after adjusting for confounders. However, the linear association was unstable, and nonlinearity was identified. A preoperative serum calcium level of 2.3 mmol/L was an inflection point for prediction. When the preoperative serum calcium concentration was below 2.3 mmol/L, serum calcium concentration increased by 1 mmol/L, and mortality risk decreased by 77% (HR 0.23, 95% CI 0.13-0.43, P < .0001). In contrast, when the preoperative serum calcium concentration was more significant than 2.3 mmol/L, the mortality risk increased with serum calcium concentration (HR 6.27, 95% CI 1.65-23.74, P = .0069). Conclusions and ImplicationsThe preoperative serum calcium level is nonlinearly associated with mortality in older adults with hip fractures, with a U-shaped association, and could be used as a potential predictor of prognosis.

Dietary vitamin D3 requirement of magang goslings from 1–21 days of age

The present study was conducted to investigate the effect of dietary vitamin D3 levels (0, 200, 400, 800, 1600, and 3200 IU/kg) on growth performance, calcium-phosphorus metabolism, and tibia development of goslings from 1 to 21 days of age. A total of 720 one-day-old Magang male goslings with similar initial body weight were randomly divided into 6 treatments with 6 replicates per treatment and 20 geese per replicate. The goslings fed with 400 IU vitamin D3/kg of diet obtained the maximum average daily gain, while vitamin D3 supplementation significantly improved the feed/gain of goslings aged from 1 to 21 days (P < 0.05). The vitamin D3 requirement of gosling aged from 1 to 21 days for optimal feed/gain ratio and average daily gain were estimated from three regression models (one-slope straight, two-slope straight, and quadratic broken-line model) to be 246–352 IU/kg diet and 400–518 IU/kg diet, respectively. Serum calcium and phosphorus contents, parathyroid hormone level, and 25-hydroxycholecalciferol level responded to increasing dietary vitamin D3 levels (P < 0.05) and reached a plateau at 800, 0, and 200 IU vitamin D3/kg diet, respectively. The mRNA expressions of target genes related to calcium homeostasis such as vitamin D3 receptor, Na+/Ca2+ exchanger 1, and plasma membrane calcium ATPase 1b in the duodenum and kidney (P < 0.05) and parathyroid hormone receptor mRNA expression in the kidney (P < 0.05) were increased linearly and quadratically with the increasing dietary vitamin D3 levels, respectively. Graded doses of dietary vitamin D3 from 0 to 3200 IU/kg produced linear responses in tibial density (P < 0.05). The vitamin D3 requirement of gosling aged from 1 to 21 days ranged from 519 to 698 IU/kg diet when tibial density as an evaluation criterion. In conclusion, the vitamin D3 requirement of gosling aged from 1 to 21 days for optimal growth performance (feed/gain and average daily gain) and tibial density was estimated to be 246–352 IU/kg of diet, 400–518 IU/kg of diet, and 519–698 IU/kg of diet based on three regression models (one-slope straight, two-slope straight, and quadratic broken-line model), respectively. The most appropriate vitamin D3 requirement was recommended at 602 IU/kg of diet of young geese based on the mean estimated values of three regression models for the tibial density with the highest coefficient of determination and lowest mean square error.

Elevated Calcium after Acute Ischemic Stroke Predicts Severity and Prognosis.

The aim of this study is to investigate whether there is a correlation between serum calcium levels and clinical severity or functional outcome at discharge in Chinese patients with acute ischemic stroke. Data from 339 patients admitted to our hospital between July 2020 and July 2021 were analyzed. Baseline demographic and clinical information was collected within 24h of admission, including serum calcium levels, stroke severity (measured by the National Institutes of Health Stroke Scale [NIHSS] score), and lesion volumes. The modified Rankin Scale [mRS] assessed functional outcomes at discharge. Our analysis showed that the median age of patients included in the study was 65 years (interquartile range [IQR], 60-70), and 60.8% were men. We found a positive correlation between serum calcium levels and stroke severity (r[spearman] = 0.266, P < 0.001), with calcium levels increasing as stroke severity increased. In a subgroup of 188 patients with available MRI data, serum calcium concentrations positively correlated with infarct size. Furthermore, in multivariate analysis, a calcium serum level in the highest quartile was associated with a higher risk of unfavorable outcome (odds ratios [OR] = 3.27; 95% confidence intervals [CI] = 1.91-5.59; P < 0.001). In conclusion, our study indicates that higher calcium serum levels are associated with stroke severity and early neurologic outcome after acute ischemic stroke, indicating that calcium may serve as a prognostic biomarker for stroke in Chinese patients.

Stunting and wasting in neurological Wilson disease: Role of copper, zinc, and insulin-like growth factor-I.

Copper (Cu) and zinc (Zn) are important trace elements for the growth and development of children. In Wilson disease (WD), impaired Cu metabolism may affect growth. This study was conducted to evaluate the height and weight of children with neurological WD and correlate these with serum Cu, Zn, and insulin-like growth factor-I (IGF-I). This prospective cohort study was conducted in a tertiary care teaching institute. Children with neurologic WD were included. The height, weight, and body-mass index of each child were measured and categorized according to the revised national growth chart. Serum Cu, Zn, calcium, alkaline phosphatase, albumin, thyroid-stimulating hormone, and urinary-Cu were measured. Serum IGF-1 was measured by enzyme-linked immunosorbent assay. The relationship between height and weight with trace elements and IGF was analyzed using parametric or non-parametric tests. There were 52 children (5-18 years) with neurologic WD. Thirty-six (69.2%) children had normal height, 12 (23.1%) were tall, and 4 (7.7%) were stunted. Forty-six (88.5%) children had normal weight and six (11.5%) children were underweight. IGF-1 correlated with height, weight, duration of treatment, and serum Zn level. About 15.4% of children had stunting and/or wasting, which was associated with low levels of serum IGF-I, Zn, and calcium. Stunting and/or wasting occurs in 15.4% of children with neurologic WD and is associated with reduced serum IGF-I, Zn, and calcium concentration. Adjunctive Zn and calcium treatment may help in achieving normal growth.

Association of Serum Calcium with the Risk of Chronic Obstructive Pulmonary Disease: A Prospective Study from UK Biobank.

Although intracellular calcium had been demonstrated to involve in the pathogenesis of chronic obstructive pulmonary disease (COPD), the association between serum calcium and COPD risk remains unclear. We included 386,844 participants with serum calcium measurements and without airway obstruction at the baseline from UK Biobank. The restricted cubic splines were used to assess the dose-response relationship. Multivariable cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of albumin-corrected calcium concentrations with the risk of COPD incidence and mortality. During a median of 12.3 years of follow-up, 10,582 incident COPD cases were documented. A linear positive association was observed between serum calcium concentrations and the risk of COPD incidence. Compared to participants with normal serum calcium (2.19-2.56 mmol/L), a 14% higher risk of COPD was observed in hypercalcemic participants (≥2.56 mmol/L, HR = 1.14; 95% CI: 1.02-1.27). No significant effect modifications were observed in stratified variables. In survival analysis, 215 COPD-specific deaths were documented after a median survival time of 3.8 years. Compared to participants with normal serum calcium, hypercalcemic participants had a 109% (HR = 2.09, 95% CI: 1.15-3.81) increased risk for COPD-specific mortality. Our study indicated that hypercalcemia was associated with an elevated risk of COPD incidence and mortality in the European population, and suggested that serum calcium may have a potential impact on the progression of COPD.

Establishment of a reference interval for 12-hour fasted serum gastrin concentration in adult dogs.

Adherence to traditional 24-h fasting periods for serum gastrin concentration in dogs can be challenging and may delay the institution of therapies for suspected hypergastrinemia. Peer-reviewed publications regarding serum gastrin reference intervals (RI) are lacking. Hypercalcemia is associated with hypergastrinemia in people; limited data exist in dogs. The objective of the study was to generate a RI for a 12-h fasted serum gastrin concentration in dogs and to investigate whether correlations exist with age, weight, sex, and total calcium concentration. Fifty-five healthy adult dogs (>1 year of age). The screening included: medical history, physical examination, CBC (15 dogs), and serum chemistry (55 dogs). Gastrin was measured via a commercial radioimmunoassay. The RI for 12-h fasted serum gastrin concentration was calculated according to the recommendations of the American Society for Veterinary Clinical Pathology. Additionally, data were evaluated for correlation with selected variables. The RI for serum gastrin following a 12-h fasting period was 15.1-78.9 ng/L with 90% confidence intervals for the lower and upper limits of 14.0-22.9 and 68.3-83.0 ng/L, respectively. A generalized linear model did not detect significant relationships between gastrin and age (P = 0.48), sex (P = 0.30), weight (P = 0.93), or total calcium concentration (P = 0.84). A 12-h fasted serum gastrin concentration RI has been established. Given the limited range of serum calcium concentrations in our healthy study population, additional investigations are needed to determine the effects of hypercalcemia on serum gastrin concentrations in dogs and for any potential clinical consequences thereof.

Cystic Parathyroid Adenomas as a Risk Factor for Severe Hypercalcemia.

(1) Background: Parathyroid cystic adenomas (PCA) are rare entities representing only 0.5-1% of parathyroid adenomas, accounting for 1-2% of cases of primary hyperparathyroidism (PHPT). The purpose of this study was to compare classical and functional/secreting cystic parathyroid lesions and identify risk factors for severe hypercalcemia; (2) Methods: A total of 17 patients with PHPT and parathyroid cysts (study group) were compared with the group of 100 patients with hyperparathyroidism caused by adenoma or hyperplasia (control group). In both groups the majority were women (88% vs. 12%, with gender ratio 7, 3:1). The patients were examined preoperatively and postoperatively: PTH, creatine, calcium and phosphate serum and urine concentrations and calcidiol serum levels were assessed; (3) Results: Patients with parathyroid cyst had statistically higher PTH and calcium serum concentration, higher calciuria and lower serum phosphate concentration. There were no statistically significant differences in the concentration of creatine in serum and urine and tubular reabsorption of phosphorus (TRP); (4) Conclusions: Due to higher PTH and calcium levels, cystic parathyroid adenomas could be one of the rare risk factors for severe hypercalcemia and hypercalcemic crisis which can be life threatening.