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1.
Calcium-phosphate homeostasis in secondary progressive multiple sclerosis patients during mitoxantrone therapy.
Lis, M, Niedziela, N, Nowak-Kiczmer, M, Kubicka-Bączyk, K, Adamczyk-Sowa, M
Neurological research. 2021;(12):1050-1055
Abstract
OBJECTIVES To assess calcium-phosphate parameters in SPMS patients treated with mitoxantrone (MTX). METHODS Thirty eight SPMS patients eligible for MTX therapy in the Department of Neurology in Zabrze, Poland were enrolled in a prospective study from March 2016 to November 2019. The parameters of serum calcium-phosphate metabolism and the neurological status according to the Expanded Disability Status Scale (EDSS) were assessed. In patients with hypovitaminosis D, vitamin D (VitD) supplementation was introduced (4000 IU/day for 1 month and later 2000 IU /day). RESULTS Most patients were women [57.89%]. The mean age [years] was 56.11 (±7.74). The median time from diagnosis to inclusion day (ID) was 7.50 [4.00-14.00] [years]. Due to VitD supplementation, an increase in serum VitD was observed during the study. 84.21% of patients presented with hypovitaminosis D before MTX treatment compared to 47.37% after treatment. Before MTX therapy, none of the patients underwent surgical repair of the fracture compared to 42.11% of patients after MTX treatment (p < 0.01). DISCUSSION Deficiency of VitD was observed at the baseline in most SPMS patients eligible for MTX therapy. Due to adverse reactions to MTX treatment, this therapy requires patient compliance, cautious drug administration and monitoring during the therapy.
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Low serum calcium is associated with higher long-term mortality in myocardial infarction patients from a population-based registry.
Schmitz, T, Thilo, C, Linseisen, J, Heier, M, Peters, A, Kuch, B, Meisinger, C
Scientific reports. 2021;(1):2476
Abstract
Calcium plays an essential role in physiology of the cardiovascular system. Aberrations from normal serum calcium levels are known to be associated with several cardiovascular diseases. Its possible role as a predictor for long-term mortality after acute myocardial infarction (AMI) is still uncertain. In this study, a total of 3732 patients (aged 25-74 years) with incident AMI surviving at least 28 days after AMI was included. The median follow-up time was 6.0 years. Admission total serum calcium levels were divided into quartiles. The Kaplan-Meier-Curve suggested a division of the follow up time in two different time periods. So, Cox regression models were calculated to assess association between admission serum calcium levels and all-cause long-term mortality with two observation periods: 28-2500 days and > 2500 days. The final model was adjusted for various comorbidities, clinical characteristics, in-hospital treatment and medication. The third quartile (normal-high Calcium levels) served as the reference group. The fully adjusted Cox-regression model shows significantly higher mortality risk for low serum calcium (quartile 1) within the timeframe 28-2500 days after the event (OR 1.53 [1.19-1.98]). The other groups did not differ significantly from each other. In the later observation period (from 2500 days until death or censoring) no more significant differences were seen between the four calcium quartiles. In summary, low serum calcium is an independent predictor of adverse outcome in the first 2500 days (about 7 years) after AMI. On later points in time this effect attenuates, so that no more significant differences can be observed.
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Genetically Determined Serum Calcium Levels and Markers of Ventricular Repolarization: A Mendelian Randomization Study in the UK Biobank.
Young, WJ, Warren, HR, Mook-Kanamori, DO, Ramírez, J, van Duijvenboden, S, Orini, M, Tinker, A, van Heemst, D, Lambiase, PD, Jukema, JW, et al
Circulation. Genomic and precision medicine. 2021;(3):e003231
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Abstract
BACKGROUND ECG markers of ventricular depolarization and repolarization are associated with an increased risk of arrhythmia and sudden cardiac death. Our prior work indicated lower serum calcium concentrations are associated with longer QT and JT intervals in the general population. Here, we investigate whether serum calcium is a causal risk factor for changes in ECG measures using Mendelian randomization (MR). METHODS Independent lead variants from a newly performed genome-wide association study for serum calcium in >300 000 European-ancestry participants from UK Biobank were used as instrumental variables. Two-sample MR analyses were performed to approximate the causal effect of serum calcium on QT, JT, and QRS intervals using an inverse-weighted method in 76 226 participants not contributing to the serum calcium genome-wide association study. Sensitivity analyses including MR-Egger, weighted-median estimator, and MR pleiotropy residual sum and outlier were performed to test for the presence of horizontal pleiotropy. RESULTS Two hundred five independent lead calcium-associated variants were used as instrumental variables for MR. A decrease of 0.1 mmol/L serum calcium was associated with longer QT (3.01 ms [95% CI, 2.03 to 3.99]) and JT (2.89 ms [1.91 to 3.87]) intervals. A weak association was observed for QRS duration (secondary analyses only). Results were concordant in all sensitivity analyses. CONCLUSIONS These analyses support a causal effect of serum calcium levels on ventricular repolarization, in a middle-aged population of European-ancestry where serum calcium concentrations are likely stable and chronic. Modulation of calcium concentration may, therefore, directly influence cardiovascular disease risk.
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The effect of lanthanum carbonate on calciprotein particles in hemodialysis patients.
Nakamura, K, Nagata, Y, Hiroyoshi, T, Isoyama, N, Fujikawa, K, Miura, Y, Matsuyama, H, Kuro-O, M
Clinical and experimental nephrology. 2020;(4):323-329
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Abstract
BACKGROUND Aggregation of solid-phase calcium-phosphate and fetuin-A form nanoparticles called calciprotein particles (CPP). Serum CPP levels are increased in CKD patients and correlated with vascular stiffness and calcification. In this study, we evaluated effects of lanthanum carbonate (LC) and calcium carbonate (CC) on serum CPP levels in hemodialysis (HD) patients. METHODS Twenty-four (24) HD patients (50% men, age; 68 ± 12 years, dialysis period; 6.2 ± 4.8 years, Kt/v; 1.74 ± 0.34) were treated with CC during 0-8 weeks and then switched to LC during 9-16 weeks. Blood samples were obtained at 0, 8, 16 weeks. Serum CPP levels (TCPP) were measured by the gel-filtration method. Low-density CPP (LCPP) levels were determined by centrifuging the serum samples at 16,000 g for 2 h and measuring CPP levels in the supernatant. The difference between TCPP and LCPP was defined as the high-density CPP (HCPP) level. We evaluated association of TCPP, LCPP, and HCPP with serum calcium (Ca), phosphorus (P), intact PTH, FGF23, Klotho, fetuin-A, aortic calcification index (ACI), LDL cholesterol, and hs-CRP. RESULTS TCPP and LCPP levels were significantly decreased after switching CC to LC, whereas Ca and P levels were not changed. HCPP levels were below the lower limit quantification in all patients. The changes in P, Ca × P, LDL cholesterol, but not ACI and the changes in hs-CRP, were correlated with the change in TCPP levels. CONCLUSION The TCPP levels were significantly decreased after switching CC to LC. Non-calcium-containing phosphate binders may be preferable for lowering CPP levels.
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Calcium chelation: a novel approach to reduce cryopreservation-induced damage to frozen platelets.
Waters, L, Padula, MP, Marks, DC, Johnson, L
Transfusion. 2020;(7):1552-1563
Abstract
BACKGROUND Cryopreserved platelets are phenotypically and functionally different to conventionally stored platelets. Calcium may be released from internal stores during the freeze-thaw process, initiating signaling events which lead to these alterations. It was hypothesized that the addition of a calcium chelator prior to cryopreservation may mitigate some of these changes. METHODS Buffy coat-derived platelets that had been pooled and split were tested fresh and following cryopreservation (n = 8 per group). Platelets were cryopreserved using 5%-6% dimethylsulfoxide (DMSO) or were supplemented with increasing concentrations of the internal calcium chelator, BAPTA-AM (100 μM, 200 μM, or 400 μM), prior to storage at -80°C. RESULTS Supplementation of platelets with BAPTA-AM prior to freezing improved platelet recovery in a dose response manner (400 μM: 84 ± 2%) compared to standard DMSO cryopreserved platelets (70 ± 4%). There was a loss of GPIbα, GPVI, and GPIIb/IIIa receptors on platelets following cryopreservation, which was rescued when platelets were supplemented with BAPTA-AM (400 μM: p < 0.0001 for all). Platelet activation markers, such as phosphatidylserine and P-selectin, were externalized on platelets following cryopreservation. However, the addition of BAPTA-AM significantly reduced the increase of these activation markers on cryopreserved platelets (400 μM: p < 0.0001 for both). Both cryopreserved platelet groups exhibited similar functionality as assessed by thromboelastography, forming clots at a faster rate than fresh platelets. CONCLUSIONS This study demonstrates that calcium plays a crucial role in mediating cryopreservation-induced damage to frozen platelets. The addition of the calcium chelator, BAPTA-AM, prior to cryopreservation reduces this damage.
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Ionized calcium level at emergency department arrival is associated with return of spontaneous circulation in out-of-hospital cardiac arrest.
Kim, SJ, Kim, HS, Hwang, SO, Jung, WJ, Roh, YI, Cha, KC, Shin, SD, Song, KJ, ,
PloS one. 2020;(10):e0240420
Abstract
BACKGROUND Calcium level is associated with sudden cardiac death based on several cohort studies. However, there is limited evidence on the association between ionized calcium, active form of calcium, and resuscitation outcome. This study aimed to evaluate the potential role of ionized calcium in predicting resuscitation outcome in patients with out-of-hospital cardiac arrest. METHODS We analyzed the Korean Cardiac Arrest Research Consortium data (KoCARC) registry, a web-based multicenter registry that included 65 participating hospitals throughout the Republic of Korea. The patients with out-of-hospital cardiac arrest over 19 years old and acquired laboratory data including calcium, ionized calcium, potassium, phosphorus, creatinine, albumin at emergency department (ED) arrival were included. The primary outcome was successful rate of return of spontaneous circulation (ROSC) and the secondary outcomes were survival hospital discharge and favorable neurological outcome (cerebral performance category 1 or 2) at hospital discharge. RESULTS Eight-hundred and eighty-three patients were enrolled in the final analysis and 448 cases (54%) had ROSC. In multivariable logistic regression analysis, ionized calcium level was associated with ROSC (odds ratio, 1.77; 95% CI1.28-2.45; p = 0.001) even though calcium level was not associated with ROSC (odds ratio, 0.87; 95% CI 0.70-1.08; p = 0.199). However, ionized calcium level was not associated with survival discharge (odds ratio, 0.99; 95% CI 0.72-1.36; p = 0.948) or favorable neurologic outcome (odds ratio, 0.45; 95% CI 0.03-6.55, p = 0.560). CONCLUSION A high ionized calcium level measured during cardiopulmonary resuscitation was associated with an increased likelihood of ROSC.
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Differential expression of genes participating in cardiomyocyte electrophysiological remodeling via membrane ionic mechanisms and Ca2+-handling in human heart failure.
Kepenek, ES, Ozcinar, E, Tuncay, E, Akcali, KC, Akar, AR, Turan, B
Molecular and cellular biochemistry. 2020;(1-2):33-44
Abstract
Excitation-contraction coupling in normal cardiac function is performed with well balanced and coordinated functioning but with complex dynamic interactions between functionally connected membrane ionic currents. However, their genomic investigations provide essential information on the regulation of diseases by their transcripts. Therefore, we examined the gene expression levels of the most important voltage-gated ionic channels such as Na+-channels (SCN5A), Ca2+-channels (CACNA1C and CACNA1H), and K+-channels, including transient outward (KCND2, KCNA2, KCNA5, KCNA8), inward rectifier (KCNJ2, KCNJ12, KCNJ4), and delayed rectifier (KCNB1) in left ventricular tissues from either ischemic or dilated cardiomyopathy (ICM or DCM). We also examined the mRNA levels of ATP-dependent K+-channels (KCNJ11, ABCC9) and ERG-family channels (KCNH2). We further determined the mRNA levels of ryanodine receptors (RyR2; ARVC2), phospholamban (PLB or PLN), SR Ca2+-pump (SERCA2; ATP2A1), an accessory protein FKBP12 (PPIASE), protein kinase A (PPNAD4), and Ca2+/calmodulin-dependent protein kinase II (CAMK2G). The mRNA levels of SCN5A, CACNA1C, and CACNA1H in both groups decreased markedly in the heart samples with similar significance, while KvLQT1 genes were high with depressed Kv4.2. The KCNJ11 and KCNJ12 in both groups were depressed, while the KCNJ4 level was significantly high. More importantly, the KCNA5 gene was downregulated only in the ICM, while the KCNJ2 was upregulated only in the DCM. Besides, mRNA levels of ARVC2 and PLB were significantly high compared to the controls, whereas others (ATP2A1, PPIASE, PPNAD4, and CAMK2G) were decreased. Importantly, the increases of KCNB1 and KCNJ11 were more prominent in the ICM than DCM, while the decreases in ATP2A1 and FKBP1A were more prominent in DCM compared to ICM. Overall, this study was the first to demonstrate that the different levels of changes in gene profiles via different types of cardiomyopathy are prominent particularly in some K+-channels, which provide further information about our knowledge of how remodeling processes can be differentiated in HF originated from different pathological conditions.
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Reliability of calcium-phosphorus (Ca/P) ratio as a new, accurate and inexpensive tool in the diagnosis of some Ca-P disorders.
Madeo, B, De Vincentis, S, Kara, E, Vescini, F, Trenti, T, Guaraldi, G, Rochira, V
Journal of endocrinological investigation. 2019;(9):1041-1049
Abstract
PURPOSE The serum calcium/phosphorus (Ca/P) ratio is an accurate tool to differentiate patients with primary hyperparathyroidism (PHPT) from healthy subjects. However, other disorders of the Ca-P metabolism might impair the Ca/P ratio, such as hypophosphatemia (HypoP) not PHPT related. The aim of this study is to examine the diagnostic value of Ca/P ratio in the diagnosis of PHPT and HypoP not PHPT related. METHODS Single-center, retrospective, case-control study, including 150 patients with PHPT and 306 patients with HypoP, compared with 150 controls. HypoP patients were enrolled among HIV-infected patients by selecting those with Fanconi-like syndrome due to antiretroviral treatment. Parameters which were measured were serum Ca, P, parathyroid hormone (PTH), 25-OH vitamin D, albumin and creatinine). RESULTS The Ca/P ratio was significantly higher in PHPT and HypoP patients, compared to controls (p < 0.0001). At receiver operator characteristic (ROC) curve analysis, the cut-off of 3.56 (2.75 SI) for Ca/P ratio was able to identify patients with PHPT and HypoP (sensitivity 95%; specificity 93%). Among patients with Ca/P ratio above 3.56, the thresholds of 10.3 mg/dL (2.6 mmol/L) for serum Ca (sensitivity 93%; specificity 98%) and 80.5 pg/mL for PTH (sensitivity 91%; specificity 91%) were defined for the specific diagnosis of PHPT. CONCLUSIONS The Ca/P ratio above 3.56 (2.75 SI) is a highly accurate tool to identify PHPT and HypoP not PHPT-related patients. Thanks to its simplicity, this index can be proposed as a screening and first-line examination in the diagnostic work-up when a disorder of Ca-P metabolism is suspected or should be ruled out.
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Relationship between Serum Vitamin D and Calcium Levels and Vitamin D Receptor Gene Polymorphisms in Colorectal Cancer.
Al-Ghafari, AB, Balamash, KS, Al Doghaither, HA
BioMed research international. 2019;:8571541
Abstract
BACKGROUND Many epidemiological studies have shown that vitamin D deficiency is associated with various types of human cancers. The biological action of vitamin D and its metabolites is mediated by the transcription factor vitamin D receptor (VDR). The VDR gene is highly expressed in the colon and is involved in many biological functions. The aim of the current study was to assess the relationship between serum vitamin D metabolite and calcium levels with VDR polymorphisms in normal and colorectal cancer (CRC) patients. METHODS Fifty Saudi CRC patients and fifty controls were enrolled in the study. The levels of total vitamin D, 25(OH)D3, and calcium were measured in serum. RESULTS The homozygous genotype (aa) of the ApaI VDR polymorphism (rs7975232) was found to correlate with total serum vitamin D levels of CRC patients, while the heterozygous (Tt) TaqI VDR polymorphism (rs731236) was associated with serum calcium levels. In contrast, the BsmI and FokI VDR polymorphisms (rs1544410 and rs2228570, resp.) did not affect the serum levels of total vitamin D, 25-hydroxyvitamin D3, and calcium. CONCLUSION Appropriate vitamin D levels were shown to be important in preventing the onset of CRC.
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Do Symptoms and Serum Calcium Levels Affect the Results of Surgical Treatment of Primary Hyperparathyroidism?
Yu, Q, Liu, K, Ma, D, Xie, C, Wu, Y, Dai, W, Jiang, H
BioMed research international. 2019;:2150159
Abstract
INTRODUCTION The purpose of this study was to investigate the difference in surgical outcomes between symptomatic and asymptomatic patients with primary hyperparathyroidism (PHPT) and between patients with high serum calcium and those with normal blood calcium, as well as to explore the epidemiological trend of PHPT in northern China. METHODS Clinicopathologic data of 197 patients (50 men and 147 women) with PHPT who underwent surgery at the First Affiliated Hospital of Harbin Medical University from 2008 to 2017 were analyzed. Changes in clinicopathology were compared among different subgroups of patients. Patients were categorized into subgroups based on serum calcium levels, whether or not they presented with symptoms, and admission time. RESULTS Of the total patients, 82.23% had hypercalcemic primary hyperparathyroidism (HCPHPT), 17.77% had normocalcemic primary hyperparathyroidism (NCPHPT), 45.18% had symptomatic primary hyperparathyroidism (SPHPT), and 54.82% had asymptomatic primary hyperparathyroidism (ASPHPT). Seventy-seven cases of PHPT involved thyroid nodules, with 22 confirmed as papillary thyroid carcinoma, and 29 confirmed as nodular goiter. There was no significant difference in the success rate of surgery, postoperative recurrence rate, and the symptoms of temporary hypocalcemia between the HCPHPT and NCPHPT groups, and between the SPHPT and ASPHPT groups. The incidence of PHPT has increased threefold since 2013. CONCLUSIONS Symptoms and serum calcium levels did not affect the results of surgical treatment for PHPT. The incidence of PHPT in northern China is increasing. Moreover, PHPT manifestation has shifted from the symptomatic to the asymptomatic form. Thyroid surgery should be performed in PHPT patients with thyroid nodules.