Oral calcium supplementation versus placebo in mitigating citrate reactions during apheresis: an open-label randomized control trial.

BACKGROUND: Citrate-related hypocalcemia is the most common adverse event linked with peripheral blood progenitor cell apheresis. A previous retrospective study highlighted the prophylactic effectiveness of oral calcium drinks before apheresis, supplemented with intravenous calcium gluconate. Consequently, this study is a randomized controlled trial comparing oral calcium with placebo drinks STUDY DESIGN AND METHODS: Healthy donors were randomized to receive either oral calcium (Cohort A) or placebo (Cohort B) drinks. If symptoms emerged, all donors were given calcium drinks to counteract hypocalcemia. The primary endpoint centered on the incidence of Grade 1 or higher citrate-related symptoms. Analyses were performed using the crude model and doubly robust estimation. RESULTS: Forty-two healthy donors participated from January 2021 to July 2022. Case distribution (Cohort A: Cohort B) stood at 3:7 (Grade 1), 2:2 (Grade 2), and 1:0 (Grade 3); no Grade 4 cases were identified. There was no statistical significance in the incidence of Grade 1 or higher and Grade 3 citrate-related symptoms. DISCUSSION: The cumulative incidence of citrate-related side effects was less pronounced than in the previous research. This could stem from absence of blinding, and the decision to administer calcium drinks to the untreated group upon symptom detection. Although preemptive oral calcium intake before peripheral blood progenitor cell apheresis is not wholly effective, providing calcium-rich beverages to symptomatic donors may stave off symptom intensification.

In vivo and in vitro relationship between ionized magnesium and ionized calcium.

OBJECTIVES: The objective of this study was to determine the in vivo correlation of ionized magnesium (iMg) with ionized calcium (iCa), total calcium, albumin and pH. In addition, the analytical interference of iCa on iMg measurement on the Stat Profile Prime Plus (Nova Biomedical) and vice versa was defined. METHODS: In vivo correlation of iCa, iMg and pH was studied in 238 paired blood gas samples of 109 different patients admitted to the intensive care unit. Albumin and total magnesium (tMg) were measured in heparinized plasma samples. Measurement of iMg was performed with the ion selective magnesium electrode (ISE) of the Stat Profile Prime Plus (Nova Biomedical) and iCa and pH were measured with a Rapid Point 500 blood gas analyzer (Siemens). Albumin, total calcium and total magnesium were analyzed with a Siemens Atellica CH. Analytical interference of iCa with iMg and vice versa was investigated using unbuffered saline solutions. RESULTS: In the studied patient population, no significant correlations were observed between iMg and iCa, albumin, and pH. An inverse relationship was observed between iCa and Mg-ISE. For every 0.1 mmol/L change in iCa concentration, the iMg concentration deviated by 0.01 mmol/L at an iMg concentration of 0.5 mmol/L and by 0.013 mmol/L at an iMg concentration of 1.0 mmol/L. The measurement of iCa was not affected by iMg. CONCLUSIONS: In vivo, no correlation was observed between iMg with iCa, albumin and pH. Interference of iCa on iMg measurement was noted, with a maximum deviation of ±0.02 mmol/L iMg across the reference range of iCa (1.15-1.32 mmol/L). Additionally, the iCa measurement was not affected by the iMg concentration.

Effect of general anesthesia drugs on GFAP/Iba-1 expression: a meta-analysis.

Glial fibrillary acidic protein (GFAP) is a marker associated with astrocyte activation and plays a role in various pathologic processes, including traumatic brain injury, stroke, and neurodegenerative diseases. Interacting boson approximation (Iba-1) is a marker protein for microglia, which are important in neuroinflammatory responses. This meta-analysis aimed to investigate the impact of general anesthetics on the expression of GFAP and Iba-1 in animal models. A meta-analysis was conducted using databases such as PubMed, EMBASE, Springer, and Web of Science. The quality of the selected publications was estimated using the SYRCLE guidelines to ensure credibility and consistency of the research. Continuous variables were measured using mean difference or standardized mean difference (SMD), with a 95% confidence interval (CI) calculated. Ten randomized controlled animal experiments were included in this analysis, utilizing different general anesthetics such as sevoflurane and propofol compared to untreated control groups. The results consistently demonstrated a significant increase in GFAP (SMD = 0.41, 95% CI: 0.09, 0.72, P = 0.01) and Iba-1 (SMD = 0.43, 95% CI: 0.04, 0.83, P = 0.03) expression in the general anesthetic-treated groups, suggesting a neuroinflammatory response induced by these agents. Assessment of publication bias revealed no significant bias in the included studies. This meta-analysis highlights the impact of general anesthetics on GFAP expression in animal models, emphasizing the importance of understanding the neuroinflammatory response associated with anesthesia administration. Further research is warranted to elucidate the underlying molecular pathways and explore possible therapeutic interventions to mitigate adverse effects associated with anesthesia administration.

Changes in short-chain fatty acids affect brain development in mice with early life antibiotic-induced dysbacteriosis.

Background: Early enteral nutrition and the gut microbiota profoundly influence neonatal brain development, with short-chain fatty acids (SCFAs) from the microbiota playing a pivotal role. Understanding the relationship between dysbiosis, SCFAs, and brain development is crucial. In this study, we investigated the impact of antibiotics on the concentration of SCFAs in neonatal feces. Additionally, we developed a model of gut dysbiosis in neonatal mice to examine the potential relationship between this imbalance, SCFAs production, and brain function development. Methods: We measured the SCFAs content in the feces of two groups of neonates, categorized based on whether antibiotics were used, and conducted the Neonatal Behavioral Neurological Assessment (NBNA) test on all neonates. Then we evaluated fecal SCFAs levels in neonates and neonatal mice post-antibiotic treatment using liquid chromatography-mass spectrometry (LC-MS) analysis. Morris water maze (MWM) tests assessed behavioral performance, and western blot analysis examined brain tissue-related proteins-neuron-specific enolase (NSE), ionized calcium binding adaptor molecule-1 (IBA1), and myelin basic proteins (MBP). Results: The use of antibiotics did not affect the NBNA scores of the two groups of neonates, but it did reduce the SCFAs content in their feces. Antibiotic administration induced gut dysbiosis in mice, resulting in decreased IBA1 and MBP expression. Interventions to restore gut microbiota ameliorated these effects. Mice with dysbiosis displayed cognitive deficits in the MWM test. SCFAs levels decreased during dysbiosis, and increased upon microbiota recovery. Conclusions: Neonatal dysbiosis affects the microbiota-gut-brain axis, impairing cognitive function and nervous system development. Reduced SCFAs may contribute significantly to these alterations.

Human brain organoids containing microglia that have arisen innately adapt to a ß-amyloid challenge better than those in which microglia are integrated by co-culture.

BACKGROUND: Alzheimer disease (AD) is a heterogenous and multifactorial disease, and its pathology is partly driven by microglia and their activated phenotype. Brain organoids (BOs) are gaining prominence as a relevant model of the human brain for the study of AD; however, BOs are commonly devoid of microglia. To overcome this limitation, current protocols incorporate microglia through either (1) co-culture (BO co-culture), or (2) molecular manipulation at critical windows of BO development to have microglia arise innately (BO innate cultures). It is currently unclear whether the microglia incorporated into BOs by either of these two protocols differ in function. METHODS: At in vitro day 90, BO innate cultures and BO-co-cultures were challenged with the AD-related ß-amyloid peptide (Aß) for up to 72 h. After Aß challenge, BOs were collected for immunoblotting. Immunoblots compared immunodensity and protein banding of Aß and ionized calcium-binding adapter molecule 1 (IBA1, a marker of microglial activation) in BOs. The translational potential of these observations was supported using 56 human cortical samples from neurocognitively normal donors and patients with early-onset AD and late-onset AD. Statistical analyses were conducted using the Kruskal-Wallis test, a two-way ANOVA, or a simple linear regression, and where applicable, followed by Dunn's or Sidak's test. RESULTS: We show that BO co-cultures promote Aß oligomerization as early as 24 h and this coincides with a significant increase in IBA1 levels. In contrast, the Aßs do not oligomerize in BO innate cultures and the IBA1 response was modest and only emerged after 48 h. In human cortical samples, we found IBA1 levels correlated with age at onset, age at death, and the putative diagnostic Aß(1-42)/Aß(1-40) ratio (particularly in their oligomeric forms) in a sex-dependent manner. CONCLUSIONS: Our unique observations suggest that BOs with innate microglia model the response of a healthy brain to Aß, and by extension the initial stages of Aß challenge. It would be impossible to model these early stages of pathogenesis in BOs where microglia are already compromised, such as those with microglia incorporated by co-culture.

Perioperative Modulation of Left Ventricular Systolic Performance: A Retrospective Study on Ionized Calcium and Vitamin D in Cardiac Surgery Patients.

Background: The perioperative impact of calcium and vitamin D on left ventricular (LV) performance during major cardiac surgery remains unexplored. We aimed to assess the relation of calcium and vitamin D measured at different time points with the LV ejection fraction (EF), and to investigate whether changes in EF correlate with postoperative outcomes. Methods: We enrolled 83 patients, in whom ionized calcium was measured before, during, and after surgery (until discharge), vitamin D preoperatively, and EF pre- and postoperatively at 24 h. The postoperative outcomes were cardiopulmonary bypass (CPB) time, aortic cross-clamp time, mechanical ventilation time, vasoactive inotropic score (VIS) (intraoperative, day 0, day 1), and ICU stay time. Results: The mean age was 64.9 ± 8.5 years, with 21 of the patients (25%) having an EF < 50%. The median change from preoperative to postoperative EF was -2.0 (-10.0-0.0) % (p < 0.001). At the baseline, the EF < 50% group had significantly lower preoperative vitamin D levels than the EF ≥ 50% group (p = 0.048). The calcium trend did not differ across the groups. Preoperative EF was significantly associated with CPB time (r = 0.22, p = 0.044) and aortic cross-clamp time (r = 0.24, p = 0.031). Postoperative EF was significantly and inversely associated with intraoperative VIS (r = -0.28, p = 0.009), VIS day 0 (r = -0.25, p = 0.020), VIS day 1 (r = -0.23, p = 0.036), and ICU length of stay (r = -0.22, p = 0.047). Finally, the change in ejection fraction was significantly and inversely associated with CPB time (r = -0.23, p = 0.037), aortic cross-clamp time (r = -0.22, p = 0.044), intraoperative VIS (r = -0.42, p < 0.001), VIS day 0 (r = -0.25, p = 0.024), mechanical ventilation time (r = -0.22, p = 0.047), and ICU length of stay (r = -0.23, p = 0.039). Conclusions: The fluctuations in perioperative ionized calcium levels were not associated with the evolution of LVEF, although preoperative vitamin D levels may affect those with low EF. Correspondingly, a reduced EF significantly impacted all the studied postoperative outcomes. Further investigation into biomarkers affecting cardiac inotropic function is warranted to better understand their significance.

Comprehensive review of indicators and techniques for optical mapping of intracellular calcium ions.

Calcium ions (Ca2+) play crucial roles in almost every cellular process, making the detection of changes in intracellular Ca2+ essential to understanding cell function. The fluorescence indicator method has garnered widespread application due to its exceptional sensitivity, rapid analysis, cost-effectiveness, and user-friendly nature. It has successfully delineated the spatial and temporal dynamics of Ca2+ signaling across diverse cell types. However, it is vital to understand that different indicators have varying levels of accuracy, sensitivity, and stability, making choosing the right inspection method crucial. As optical detection technologies advance, they continually broaden the horizons of scientific inquiry. This primer offers a systematic synthesis of the current fluorescence indicators and optical imaging modalities utilized for the detection of intracellular Ca2+. It elucidates their practical applications and inherent limitations, serving as an essential reference for researchers seeking to identify the most suitable detection methodologies for their calcium-centric investigations.

Neurosteroid [3α,5α]3-hydroxypregnan-20-one inhibition of chemokine monocyte chemoattractant protein-1 in alcohol-preferring rat brain neurons, microglia, and astroglia.

BACKGROUND: Neuroimmune dysfunction in alcohol use disorder (AUD) is associated with activation of myeloid differentiation primary response 88 (MyD88)-dependent Toll-like receptors (TLR) resulting in overexpression of the chemokine monocyte chemoattractant protein-1 (MCP-1/CCL2). MCP-1 overexpression in the brain is linked to anxiety, higher alcohol intake, neuronal death, and activation of microglia observed in AUD. The neurosteroid [3α,5α][3-hydroxypregnan-20-one (3α,5α-THP) has been reported as an inhibitor of MyD88-dependent TLR activation and MCP-1 overexpression in mouse and human macrophages and the brain of alcohol-preferring (P) rats. METHODS: We investigated how 3α,5α-THP regulates MCP-1 expression at the cellular level in P rat nucleus accumbens (NAc) and central amygdala (CeA). We focused on neurons, microglia, and astrocytes, examining the individual voxel density of MCP-1, neuronal marker NeuN, microglial marker IBA1, astrocytic marker GFAP, and their shared voxel density, defined as intersection. Ethanol-naïve male and female P rats were perfused 1 h after IP injections of 15 mg/kg of 3α,5α-THP, or vehicle. The NAc and CeA were imaged using confocal microscopy following double-immunofluorescence staining for MCP-1 with NeuN, IBA1, and GFAP, respectively. RESULTS: MCP-1 intersected with NeuN predominantly and IBA1/GFAP negligibly. 3α,5α-THP reduced MCP-1 expression in NeuN-labeled cells by 38.27 ± 28.09% in male and 56.11 ± 21.46% in female NAc, also 37.99 ± 19.53% in male and 54.96 ± 30.58% in female CeA. In females, 3α,5α-THP reduced the MCP-1 within IBA1 and GFAP-labeled voxels in the NAc and CeA. Conversely, in males, 3α,5α-THP did not significantly alter the MCP-1 within IBA1 in NAc or with GFAP in the CeA. Furthermore, 3α,5α-THP decreased levels of IBA1 in both regions and sexes with no impact on GFAP or NeuN levels. Secondary analysis performed on data normalized to % control values indicated that no significant sex differences were present. CONCLUSIONS: These data suggest that 3α,5α-THP inhibits neuronal MCP-1 expression and decreases the proliferation of microglia in P rats. These results increase our understanding of potential mechanisms for 3α,5α-THP modulation of ethanol consumption.

Maternal Uterine Artery Adenoviral Vascular Endothelial Growth Factor (Ad.VEGF-A165) Gene Therapy Normalises Fetal Brain Growth and Microglial Activation in Nutrient Restricted Pregnant Guinea Pigs.

Fetal growth restriction (FGR) is associated with uteroplacental insufficiency, and neurodevelopmental and structural brain deficits in the infant. It is currently untreatable. We hypothesised that treating the maternal uterine artery with vascular endothelial growth factor adenoviral gene therapy (Ad.VEGF-A165) normalises offspring brain weight and prevents brain injury in a guinea pig model of FGR. Pregnant guinea pigs were fed a restricted diet before and after conception and received Ad.VEGF-A165 (1 × 1010 viral particles, n = 18) or vehicle (n = 18), delivered to the external surface of the uterine arteries, in mid-pregnancy. Pregnant, ad libitum-fed controls received vehicle only (n = 10). Offspring brain weight and histological indices of brain injury were assessed at term and 5-months postnatally. At term, maternal nutrient restriction reduced fetal brain weight and increased microglial ramification in all brain regions but did not alter indices of cell death, astrogliosis or myelination. Ad.VEGF-A165 increased brain weight and reduced microglial ramification in fetuses of nutrient restricted dams. In adult offspring, maternal nutrient restriction did not alter brain weight or markers of brain injury, whilst Ad.VEGF-A165 increased microglial ramification and astrogliosis in the hippocampus and thalamus, respectively. Ad.VEGF-A165 did not affect cell death or myelination in the fetal or offspring brain. Ad.VEGF-A165 normalises brain growth and markers of brain injury in guinea pig fetuses exposed to maternal nutrient restriction and may be a potential intervention to improve childhood neurodevelopmental outcomes in pregnancies complicated by FGR.

The Relationship Between Ionized Calcium Levels and Prognosis in Patients with Spontaneous Subarachnoid Hemorrhage.

BACKGROUND: The serum calcium plays a role as a cofactor in critical steps such as cardiac contractility, vascular tone, and the coagulation cascade. This study aimed to determine if the level of ionized calcium can predict outcomes in patients with spontaneous subarachnoid hemorrhage (SAH) in the emergency department. METHODS: The study was a retrospective cross-sectional case series. Patients aged 18 and over diagnosed with spontaneous SAH in the emergency department were included in the study. Patients' demographic characteristics, comorbidities, vital signs, laboratory parameters, World Federation of Neurosurgical Societies score, SAH grading according to the Fisher scale, needs of mechanical ventilation and inotropic treatment, administered treatments, complications, Rankin scores at discharge, and outcome were recorded in a standard data form. RESULTS: A total of 267 patients were studied, with a mean age of 55.5 ± 13.4 years, and 53.9% (n = 144) were female. Hydrocephalus was present in 16.5% of patients. The average hospital stay was 20.4 ± 19.8 days. Mortality rate was 34.8% (n = 93). Mortality was significantly higher in patients with low calcium levels upon admission (P = 0.024). Ionized calcium levels during complication development independently predicted mortality (OR: 0.945, 95% CI: 0.898-0.996, P = 0.034). Patients with poor neurologic outcomes (Rankin: 3-6) had significantly lower initial ionized calcium levels (P = 0.002). CONCLUSIONS: The ionized calcium level is a readily accessible blood gas parameter that assists clinicians in predicting functional independence and mortality at discharge in patients presenting to the emergency department with spontaneous SAH.

Investigating Potential Correlations between Calcium Metabolism Biomarkers and Periprocedural Clinical Events in Major Cardiovascular Surgeries: An Exploratory Study.

Background: There is emerging but conflicting evidence regarding the association between calcium biomarkers, more specifically ionized calcium and the prognosis of intensive care unit (ICU) postoperative cardiac patients. Methods: Our study investigated the relationship between ionized calcium, vitamin D, and periprocedural clinical events such as cardiac, neurologic and renal complications, major bleeding, vasoactive-inotropic score (VIS), and length of ICU and hospitalization. Results: Our study included 83 consecutive subjects undergoing elective major cardiac surgery requiring cardiopulmonary bypass. The mean age of the participants was 64.9 ± 8.5 years. The majority of procedures comprised isolated CABG (N = 26, 31.3%), aortic valve procedures (N = 26, 31.3%), and mitral valve procedures (N = 12, 14.5%). A difference in calcium levels across all time points (p < 0.001) was observed, with preoperative calcium being directly associated with intraoperative VIS (r = 0.26, p = 0.016). On day 1, calcium levels were inversely associated with the duration of mechanical ventilation (r = -0.30, p = 0.007) and the length of hospital stay (r = -0.22, p = 0.049). At discharge, calcium was inversely associated with length of hospital stay (r = -0.22, p = 0.044). All calcium levels tended to be lower in those who died during the 1-year follow-up (p = 0.054). Preoperative vitamin D levels were significantly higher in those who experienced AKI during hospitalization (median 17.5, IQR 14.5-17.7, versus median 15.3, IQR 15.6-20.5, p = 0.048) Conclusion: Fluctuations in calcium levels and vitamin D may be associated with the clinical course of patients undergoing cardiac surgery. In our study, hypocalcemic patients exhibited a greater severity of illness, as evidenced by elevated VIS scores, and experienced prolonged mechanical ventilation time and hospital stays. Additional larger-scale studies are required to gain a deeper understanding of their impact on cardiac performance and the process of weaning from cardiopulmonary bypass, as well as to distinguish between causal and associative relationships.

Web-accessible critical limits and critical values for urgent clinician notification.

OBJECTIVES: To survey the World Wide Web for critical limits/critical values, assess changes in quantitative low/high thresholds since 1990-93, streamline urgent notification practices, and promote global accessibility. METHODS: We identified Web-posted lists of critical limits/values at university hospitals. We compared 2023 to 1990-93 archived notification thresholds. RESULTS: We found critical notification lists for 26 university hospitals. Laboratory disciplines ranged widely (1-10). The median number of tests was 62 (range 21-116); several posted policies. The breadth of listings increased. Statistically significant differences in 2023 vs. 1990 critical limits were observed for blood gas (pO2, pCO2), chemistry (glucose, calcium, magnesium), and hematology (hemoglobin, platelets, PTT, WBC) tests, and for newborn glucose, potassium, pO2, and hematocrit. Twenty hospitals listed ionized calcium critical limits, which have not changed. Fourteen listed troponin (6), troponin I (3), hs-TnI (3), or troponin T (2). Qualitative critical values expanded across disciplines, encompassing anatomic/surgical pathology. Bioterrorism agents were listed frequently, as were contagious pathogens, although only three hospitals listed COVID-19. Only one notification list detailed point-of-care tests. Two children's hospital lists were Web-accessible. CONCLUSIONS: Urgent notifications should focus on life-threatening conditions. We recommend that hospital staff evaluate changes over the past three decades for clinical impact. Notification lists expanded, especially qualitative tests, suggesting that automation might improve efficiency. Sharing notification lists and policies on the Web will improve accessibility. If not dependent on the limited scope of secondary sources, artificial intelligence could enhance knowledge of urgent notification and critical care practices in the 21st Century.

Characterization of variables related to high stability of raw cow milk.

This research paper analyzes the stability of raw cow milk in the alcohol test and seeks to understand to know the factors that influence milk stability and the occurrence of unstable non-acid milk. Milk samples were collected from the cooling tanks of rural farmers in the state of Paraná twice in summer and twice in winter. The farms were classified according to the production system: pasture with supplementation and feedlot. The following variables were analyzed: stability in the alcohol test, titratable acidity, ionized calcium concentration (iCa), chemical composition of milk, somatic cell count and standard plate count. The results showed that milk stability was greater in winter vs. summer, when the milk contained higher iCa, and in the feedlot vs. pasture system. The Pearson Correlation between variables (ethanol stability, milk composition, iCa, cooling tank temperature, milk volume, number of milking, number of cows milked, fat/protein ratio, distance and travel time) were analyzed. Stability was negatively correlated with iCa concentration and positively with lactose content. Logistic regression of the risk of unstable non-acid milk at 72% alcohol (UNAM72) showed that only iCa and lactose were determinants, while evaluation of the same risk at 78% alcohol revealed iCa, titratable acidity, lactose and milk urea nitrogen as risk factors. Under the dairy farming conditions of Paraná state, the frequency of UNAM72 was low (12.16%) and was higher in summer and in pasture systems with supplementation. In conclusion, in dairy herds bred with high technological level, with adequate nutritional and health management, the frequency of UNAM is low and is related to nutritional management abnd, perhaps, heat stress, factors that alter iCa and lactose levels.

Parkinson's Disease Dementia Patients: Expression of Glia Maturation Factor in the Brain.

Parkinson's disease (PD) is the second most common progressive neurodegenerative disease characterized by the presence of dopaminergic neuronal loss and motor disorders. PD dementia (PDD) is a cognitive disorder that affects many PD patients. We have previously demonstrated the proinflammatory role of the glia maturation factor (GMF) in neuroinflammation and neurodegeneration in AD, PD, traumatic brain injury (TBI), and experimental autoimmune encephalomyelitis (EAE) in human brains and animal models. The purpose of this study was to investigate the expression of the GMF in the human PDD brain. We analyzed the expression pattern of the GMF protein in conjunction with amyloid plaques (APs) and neurofibrillary tangles (NFTs) in the substantia nigra (SN) and striatum of PDD brains using immunostaining. We detected a large number of GMF-positive glial fibrillary acidic protein (GFAP) reactive astrocytes, especially abundant in areas with degenerating dopaminergic neurons within the SN and striatum in PDD. Additionally, we observed excess levels of GMF in glial cells in the vicinity of APs, and NFTs in the SN and striatum of PDD and non-PDD patients. We found that the majority of GMF-positive immunoreactive glial cells were co-localized with GFAP-reactive astrocytes. Our findings suggest that the GMF may be involved in the pathogenesis of PDD.

Predictors of blood ionized calcium concentration in sick adult cattle.

BACKGROUND: Data on the factors affecting blood ionized calcium concentration (ciCa2+ ) and diagnostic performance of serum total calcium concentration (ctCa) measurements to detect abnormal blood iCa2+ status are lacking in sick adult cattle. OBJECTIVE: Assess the association of ciCa2+ with venous blood pH, plasma concentrations of chloride (cCl), sodium (cNa), and potassium (cK), and ctCa, and total protein, albumin, and globulin concentrations in sick adult cattle. ANIMALS: Two-hundred and sixty-five adult cattle (≥1-year-old) with different diseases. METHODS: Prospective study. Whole blood pH, ciCa2+ , cNa, cK, and cCl were measured using a blood gas and electrolyte analyzer, whereas ctCa, and total protein, and albumin concentrations were determined using an autoanalyzer. The relationship between ciCa2+ and venous blood pH, plasma cCl, cNa, cK, and ctCa, and total protein, albumin, and globulin concentrations was investigated. Sensitivity and specificity were calculated for ctCa for diagnosis of abnormal ciCa2+ . RESULTS: Sensitivity of ctCa measurements to detect abnormal ciCa2+ was 66.0% whereas specificity of ctCa measurements was 72.3%. Serum total calcium concentration measurements accounted for 42% of adjusted blood ionized calcium (iCa2+ 7.40 ) concentration variance. Plasma cCl, and cK had explanatory power of ciCa2+ 7.40 , accounting for an additional 21% and 9% of the variance, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Serum tCa measurements failed to accurately predict blood iCa2+ status in ill adult cattle. Serum tCa concentrations and plasma cCl were the strongest predictors of ciCa2+ in sick adult cattle.

Normal Levels of Ionized Calcium Despite Persistent Increase in Total Calcium in a Patient With IgA Paraproteinemia.

Approximately half of the calcium in the blood circulates in the ionized, free form; which is critical for cellular function. As a result, its levels are tightly regulated by homeostatic mechanisms dependent on hormones such as PTH, vitamin D, and fibroblast growth factor-23. The other half of the total calcium is in a complex with anions, predominantly albumin. Clinically, the levels of albumin are known to influence the relationship of total calcium to free calcium. However, the relevance of changes in other serum proteins on calcium homeostasis is less appreciated. We present the case of a 70-year-old woman who was followed over 5 years with persistently elevated total calcium levels but with normal ionized calcium levels. Her evaluation was notable for IgA paraprotein, which paralleled her history of elevated total serum calcium. Extensive clinical investigations did not reveal hyperparathyroidism or cancer-mediated hypercalcemia. Additional in vitro analyses comparing the plasma containing the IgA paraprotein against a healthy control revealed that a high-molecular-weight IgA paraprotein in the patient has increased capacity to reduce the amount of free calcium in solution, thus providing a direct mechanistic explanation for the clinical findings.

Prognostic value of initial routine laboratory blood tests in patients with aneurysmal subarachnoid hemorrhage requiring mechanical ventilation: a retrospective cohort study.

Background: Aneurysmal subarachnoid hemorrhage (aSAH) necessitating mechanical ventilation (MV) presents a serious challenge for intensivists. Laboratory blood tests reflect individual physiological and biochemical states, and provide a useful tool for identifying patients with critical condition and stratifying risk levels of death. This study aimed to determine the prognostic role of initial routine laboratory blood tests in these patients. Methods: This retrospective cohort study included 190 aSAH patients requiring MV in the neurosurgical intensive care unit from December 2019 to March 2022. Follow-up evaluation was performed in May 2022 via routine outpatient appointment or telephone interview. The primary outcomes were death occurring within 7 days after discharge (short-term mortality) or reported at time of follow-up (long-term mortality). Clinico-demographic and radiological characteristics, initial routine laboratory blood tests (e.g., metabolic panels and arterial blood gas analysis), and treatment were analyzed and compared in relation to mortality. Multivariable logistic and Cox regression analyses, with adjustment of other clinical predictors, were performed to determine independent laboratory test predictors for short- and long-term mortality, respectively. Results: The patients had a median age of 62 years, with a median World Federation of Neurosurgical Societies grade (WFNS) score of 5 and a median modified Fisher grade (mFisher) score of 4. The short- and long-term mortality of this cohort were 60.5% and 65.3%, respectively. Compared with survivors, non-survivors had more severe disease upon admission based on neurological status and imaging features and a shorter disease course, and were more likely to receive conservative treatment. Initial ionized calcium was found to be independently associate with both short-term [adjusted odds ratio (OR): 0.92; 95% confidence interval (CI): 0.86 to 0.99; P=0.020] and long-term mortality [adjusted hazard ratio (HR): 0.95; 95% CI: 0.92 to 0.99; P=0.010], after adjusting for potential confounders. Moreover, the admission glucose level was found to be associated only with short-term mortality (adjusted OR: 1.19; 95% CI: 1.06 to 1.34; P=0.004). Conclusions: Laboratory screening may provide a useful tool for the management of aSAH patients requiring MV in stratifying risk levels for mortality and for better clinical decision-making. Further study is needed to validate the effects of calcium supplementation and glucose-lowering therapy on the outcomes in this disease.

The Effect of Hyperventilation Syndrome on Ionized and Serum Calcium: A Case Presentation in the Emergency Department.

Hyperventilation syndrome is described as a constellation of symptoms that are typically benign but can become a medical emergency in the setting of severe metabolic derangement secondary to shifts in a patient's pH. A 36-year-old male with a history of intravenous (IV) drug abuse presented to the emergency department (ED) in distress, complaining of diffuse muscle cramping with tetany and peripheral vasospasm. This case report discusses his initial ED testing and treatment when ionized calcium was low and serum calcium was high.

Increased dietary vitamin D was associated with increased circulating vitamin D with no observable adverse effects in adult dogs.

Introduction: There is no consensus for the optimum concentration of vitamin D, although a minimum concentration of 100 ng/mL (250 nM) of circulating vitamin D, measured as 25(OH) D, has been suggested in order to support optimal health in dogs. Few studies have examined the relationship between dietary vitamin D3 (cholecalciferol) intake and the resulting concentrations of circulating 25(OH) D in adult dogs. Recommendations for dog foods for adult maintenance report a safe upper limit of 3,200 IU vitamin D/kg on a dry matter basis. However, these recommendations were not based on studies of adult maintenance requirements. Understanding the relationship between dietary vitamin D and circulating vitamin D is necessary to utilize dietary vitamin D to influence health in dogs. Methods: Five groups of adult dogs (each n = 8) were fed food of approximately 4,000 kcal/kg containing one of the following dry matter concentrations of vitamin D for 6 months: 795.7, 3087.3, 5510.9, 7314.0, and 9992.5 IU/kg. Body weight was recorded at baseline and measured weekly, and daily food intake was recorded. Blood samples were taken at baseline and at the end of the 26-week study period. Results: There were no clinical signs of vitamin D deficiency or excess. Serum concentrations of creatinine, blood urea nitrogen, albumin, hematocrit, hemoglobin, alkaline phosphatase, phosphorus, total calcium, ionized calcium, and parathyroid hormone were maintained within reference values in all groups. Circulating 25(OH) D increased in all groups except those that consumed food with 795.7 IU/kg vitamin D, and increased in a linear and quadratic fashion in response to dietary vitamin D concentration. All of the dogs fed food with 5510.9 IU/kg vitamin D or above met or exceeded 100 ng/mL (250 nM) circulating 25(OH) D. Discussion: Dietary vitamin D was positively associated with increased circulating concentrations in concentrations up to 9992.5 IU/kg dry matter, with no observable adverse effects. Consumption of ≥5510.9 IU/kg vitamin D resulted in all dogs with at least the 100 ng/mL (250 nM) circulating concentration.

Prevalence of baseline hypocalcemia and symptomatic hypocalcemia during leukapheresis.

Symptoms of hypocalcemia are reported in up to 50% of patients undergoing leukapheresis procedures. There is no set standard of practice for administering calcium supplementation in the prevention or treatment of hypocalcemia symptoms. The goal of this descriptive, retrospective study was to determine the prevalence of baseline hypocalcemia and symptomatic hypocalcemia during leukapheresis with acid citrate dextrose solution A and to identify patient characteristics associated with symptomatic hypocalcemia. Three percent of patients were found to have hypocalcemia before leukapheresis with 35% experiencing hypocalcemia symptoms during leukapheresis. Older age, higher albumin levels, and longer procedure time were associated with increased risk of hypocalcemia symptoms.