Effects of oral calcium on reproduction and postpartum health in cattle: a meta-analysis and quality assessment.

Postpartum blood calcium (Ca) concentration is related to the reproduction and health of cattle. Oral calcium supplements were given to dairy cows after calving to increase blood Ca concentration and reduce the risk of hypocalcemia. However, studies have shown that oral Ca has different effects in preventing disease. The purposes of this study were (i) to conduct a meta-analysis to evaluate the expected effect of oral Ca on incidence of calving-related diseases, pregnancy risk and milk yield in dairy cows, and (ii) to make a quality assessment of these related studies. In total, 22 eligible studies were included in this review. Meta-analysis showed that oral Ca could significantly reduce the incidence of hypocalcemia (clinical hypocalcemia: relative risk (RR) = 0.67, 95% confidence interval (CI) = [0.52, 0.87]; subclinical hypocalcemia: RR = 0.81, CI = [0.72, 0.91]), and incidence of retained placenta (RR = 0.77, CI = [0.62, 0.95]), improved blood Ca concentrations: mean difference (MD) = 0.08; 95% CI = [0.04, 0.11]. For other results, the meta-analysis revealed a lack of evidence of the correlation between oral Ca and serum magnesium (Mg) / phosphorus (P) concentration (Mg: MD = -0.04; 95% CI = [-0.10, 0.02]; P: MD = 0.05; 95% CI = [-0.10, 0.21]) or incidence of other calving-related disorders (metritis: RR = 1.06, CI = [0.94, 1.19]; ketosis: RR = 1.04, CI = [0.91, 1.18]; mastitis: RR = 1.02, CI = [0.86, 1.21]; displacement of the abomasum: RR = 0.81, CI = [0.57, 1.16]) or pregnancy risk (pregnancy risk at first service: RR = 0.99, CI = [0.94, 1.05]; overall pregnancy rate: RR = 1.03, CI = [0.98, 1.08]) or milk yield (MD = 0.44; 95% CI = [-0.24, 1.13]). The distribution of the funnel plot formed by the included studies was symmetrical, and the Egger's test had a p > 0.05, indicating that there was no significant publication bias. Sensitivity analyses results suggested that the results of meta-analysis are robust. Quality assessment of the included studies revealed that the risk of bias was focused on selection bias, performance bias, detection bias and other sources of bias, and the future research should focus on these aspects.

Incidence of Post-Thyroidectomy Hypoparathyroidism and Associated Preoperative and Intraoperative Risk Factors.

INTRODUCTION: Thyroidectomy technique and extent are related to parathyroid injury and hypoparathyroidism. Total thyroidectomy is one of the most commonly performed endocrine surgeries, and the majority of patients recover completely without any complications. However, persistent hypoparathyroidism is the most prevalent long-term consequence following total thyroidectomy. While it is seldom deadly, it can cause severe morbidity for the patient and raise healthcare expenses. METHODS: This retrospective cohort study was conducted at King Abdulaziz Medical City, Jeddah, Saudi Arabia. We included all confirmed thyroid cancer cases that underwent thyroidectomy with or without neck dissection between July 2016 and August 2022. The data was collected from a chart review of the electronic medical record system (BEST-care), and a data collection sheet was utilized. SPSS version 26 was used to analyze the data. RESULTS: A total of 192 patients undergoing thyroid surgery were enrolled. One hundred forty-three (74.5%) were females and the mean age of participants was 45.29 ± 16.88 years. Most patients, 170 (88.5%), had a papillary histological type, and total thyroidectomy was performed in 150 (78.1%). A significant association was found between the type of surgery and postoperative hypoparathyroidism (p=<0.05*). In addition, hypocalcemia was seen in 147 (76.6%) of the patients. Postoperative hypoparathyroidism was significantly higher among patients who had asymptomatic postoperative hypocalcemia and those who received IV calcium gluconate (p=<0.05*). Moreover, postoperative hypocalcemia, hypomagnesemia, and hyperphosphatemia were significantly associated with postoperative hypoparathyroidism (p=<0.05*). CONCLUSION: The incidence of postoperative hypoparathyroidism is significantly higher among patients who underwent total thyroidectomy and had a normal level of preoperative parathyroid hormone (PTH) and magnesium (Mg) levels. Identifying these factors is a crucial step to minimize the occurrence of such complications.

The Diagnosis of Albright's Osteodystrophy in a Case With Respiratory Failure.

Albright's hereditary osteodystrophy is a rare hereditary disease due to a mutation of the complex guanine nucleotide-binding protein, alpha-stimulating activity polypeptide. This condition is commonly associated with type 1A and 1C pseudohypoparathyroidism and pseudo-pseudohypoparathyroidism due to resistance of parathyroid hormone. Patients present with specific characteristics such as brachydactyly, short stature, round facies, subcutaneous ossifications, developmental delay, and obesity, associated with hypocalcemia and hyperphosphatemia. This case presents a 55-year-old woman with short stature and neurocognitive impairment, who was admitted to the emergency department with acute decompensated heart and respiratory failure. On admission, hypocalcemia and hyperphosphatemia were noted, which in combination with the patient's clinical history led to an etiological investigation. This case stresses the importance of not only treating the acute disease but also looking at the patient and their clinical and analytical features to diagnose this disease and prevent its complications.

A Study of Incidence and Management of Postoperative Hypocalcemia in Patients Undergoing Near-Total and Total Thyroidectomy.

To study the incidence and management of postoperative hypocalcemia in participants undergoing near-total (NTT) and total thyroidectomy (TT) at a tertiary health care center. This is an observational prospective study. Patients posted for NTT and TT in our institute and meeting the inclusion criteria were included. A total of 45 participants were enrolled. The serum calcium was measured on postoperative day 2, at the time of discharge and on 3 months follow-up. A combination of injectable and oral calcium supplements with or without vitamin D sachet was used for the treatment of hypocalcemia. Hypocalcemia was observed in 49% cases. Women were observed to develop hypocalcemia at a higher rate than men. Incidence of hypocalcemia was more in TT patients than NTT patients. Cases with malignant pathology were more susceptible to develop hypocalcemia than those with benign pathology. Operated TT with concomitant neck dissection were at higher risk for development of hypocalcemia. There was no significant association between age and incidence of hypocalcemia. Serum calcium measured on postoperative day 2 was a reliable indicator of risk of hypocalcemia. The early measurement of serum calcium level is a reliable indicator of the risk of hypocalcemia. Standardized treatment of hypocalcemic patients with calcium and vitamin D supplements can reduce the incidence and morbidity associated with postoperative hypocalcemia.

Hypomagnesemia with Secondary Hypoparathyroidism and Hypocalcemia due to Novel Variants in the Transient Receptor Potential Cation Channel Subfamily M Member 6 ( TRPM6 ) Gene.

HOMG1 (hypomagnesemia 1, intestinal) or hypomagnesemia with secondary hypocalcemia is a rare autosomal recessive disorder of magnesium metabolism, characterized by impaired magnesium absorption. This disorder may mimic other conditions presenting with neonatal seizures. Here, we report an infant diagnosed to have hypomagnesemia with secondary hypocalcemia due to novel variants in TRPM6 gene.

Treatment of Hypoparathyroidism by Re-Establishing the Effects of Parathyroid Hormone.

The conventional treatment of hypoparathyroidism (HypoPT) includes active vitamin D and calcium. Despite normalization of calcium levels, the conventional treatment is associated with fluctuations in calcium levels, hypercalciuria, renal impairment, and decreased quality of life (QoL). Replacement therapy with parathyroid hormone (PTH)(1-84) is an option in some countries. However, convincing beneficial effects have not been demonstrated, which may be due to the short duration of action of this treatment. Recently, palopegteriparatide (also known as TransCon PTH) has been marketed in Europe and is expected also to be approved in other countries. Palopegteriparatide is a prodrug with sustained release of PTH(1-34) designed to provide stable physiological PTH levels for 24 hours/day. A phase 3 study demonstrated maintenance of normocalcemia in patients with chronic HypoPT, with no need for conventional therapy. Furthermore, this treatment lowers urinary calcium and improves QoL. Another long-acting PTH analog with effects on the parathyroid hormone receptor (eneboparatide) is currently being tested in a phase 3 trial. Furthermore, the treatment of autosomal dominant hypocalcemia type 1 with a calcilytic (encaleret) is also being tested. All in all, improved treatment options are on the way that will likely take the treatment of HypoPT to the next level.

A prospective cross-sectional study on hypocalcemia after total thyroidectomy in patients with Graves' disease: insights on secondary hyperparathyroidism.

PURPOSE: To investigate the parathyroid function and calcium (Ca) levels in the secondary hyperparathyroidism (SHPT) state in patients with Graves' disease. METHODS: We examined 31 consecutive patients with Graves' disease without chronic kidney disease, who were treated with total thyroidectomy. The patients were divided into a normal parathyroid hormone (PTH) group (NPTH group; n = 19) with a PTH level ≤ 65 pg/mL, and a secondary hyperparathyroidism group (SHPT group; n = 12), with a PTH level > 65 pg/mL. The PTH and Ca-related parameters were examined and the risk factors for postoperative hypocalcemia were analyzed. RESULTS: The preoperative Ca level was significantly lower (2.24 ± 0.06 vs. 2.31 ± 0.07 mmol/L, p < 0.05) in the SHPT group than in the NPTH group. The reduction in PTH, 1,25-dihydroxyvitamin D (1,25(OH)2D), and Ca levels from the preoperative day to the next morning was significantly greater in the SHPT group than in the NPTH group (p < 0.05). When intraoperative factors were included, the decrease in the PTH level alone was significant. SHPT was a significant factor in determining the extent of PTH reduction. CONCLUSIONS: Hyperfunctioning parathyroid glands in the SHPT state were more susceptible to postoperative PTH reduction, which, combined with low preoperative Ca levels, increased the risk of postoperative hypocalcemia in patients with Graves' disease.

Increased risk of hypocalcemia with decreased kidney function in patients prescribed bisphosphonates based on real-world data from the MID-NET® in Japan: a new-user cohort study.

BACKGROUND: In the post-marketing stage, cases of hypocalcemia associated with bisphosphonate preparations (BPs) have been reported in patients with decreased kidney function, despite warning against use of BPs in such patients in the package insert (PI) of Japan. The purpose of this study was to investigate the safety of BPs in patients with decreased kidney function. METHODS: The cohort study was conducted in patients with osteoporosis and newly prescribed bisphosphonate utilizing real-world data from MID-NET® in Japan. The adjusted hazard ratios (aHRs) for hypocalcemia (a corrected serum Ca level < 8.00 mg/dL) relative to the normal group were calculated in each decreased kidney function group (mild, moderate or severe group). RESULTS: A total of 14,551 patients were included in the analysis, comprising 2,601 (17.88%) with normal (eGFR ≥ 90 mL/min/1.73m2), 7,613 (52.32%) with mild (60 ≤ eGFR < 90 mL/min/1.73m2), 3,919 (26.93%) with moderate (30 ≤ eGFR < 60 mL/min/1.73m2), and 418 (2.87%) with severe kidney function (eGFR < 30 mL/min/1.73m2). The aHRs (95% confidence interval) for hypocalcemia were 1.85 (0.75-4.57), 2.30 (0.86-6.21), and 22.74 (8.37-61.78) in the mild, moderate, and severe groups, respectively. The increased risk of hypocalcemia depending on kidney function was also observed even when calculating the aHR for each specific BP such as alendronate sodium hydrate, minodronic acid hydrate, and sodium risedronate hydrate. Furthermore, similar results were obtained in the sensitivity analysis by altering the outcome definition to a 20% or more reduction in corrected serum Ca level from the baseline, as well as when focusing on patients with more than one laboratory test result per 30 days during the follow-up period. CONCLUSIONS: These findings suggest that the risk of hypocalcemia during BP prescription is higher in patients with decreased kidney function, particularly those with severely decreased kidney function. The quantitative real-world evidence on the safety risk of BPs obtained in this study has led to the PI revision describing a relationship between hypocalcemia risk and decreased kidney function as a regulatory action in Japan and will contribute to promoting the proper use of BPs with appropriate risk management in clinical practice.

Anaesthetic concerns of a child with symptomatic vitamin D deficiency rickets with secondary hyperparathyroidism: A case report.

Rickets is a paediatric bone disorder characterised by defective mineralisation of bony matrix due to abnormalities in calcium and phosphate metabolism. Despite being a common disease globally, literature on the anaesthetic concerns in rickets are scant. Herein, we describe the management of a 12-year-old child with symptomatic vitamin D deficiency rickets with secondary hyperparathyroidism, undergoing general anaesthesia for an urgent orthopaedic procedure. There are numerous risks involved in such a case, such as hypocalcemia, hypophosphatemia, chest and vertebral deformities, restrictive lung disease, difficult intubation and weaning, difficult regional anaesthesia, chronic bone pain, infectious complications and postoperative decreased renal function, all of which require careful preoperative assessment and risk stratification. In elective surgeries, it is important to optimise the metabolic parameters before taking up the case. However, in urgent and emergent procedures like ours, it is imperative to take up the case after informing the parents of the risks involved.

Further delineation of phenotype and genotype of Kenny-Caffey syndrome type 2 (phenotype and genotype of KCS type 2).

BACKGROUND: Kenny-Caffey syndrome type 2 (KCS2) is an extremely rare inherited disorder characterized by proportionate short stature, skeletal defects, ocular and dental abnormalities, and transient hypocalcemia. It is caused by variants in FAM111A gene. Diagnosis of KCS2 can be challenging because of its similarities to other syndromes, the absence of clear hallmarks and the deficient number of genetically confirmed cases. Here, we aimed to further delineate and summarize the genotype and phenotype of KCS2, in order to get a better understanding of this rare disorder, and promote early diagnosis and intervention. METHODS: We present clinical and genetic characteristics of eight newly affected individuals with KCS2 from six families, including one family with three individuals found to be a father-to-daughter transmission, adding to the limited literature. Furthermore, we performed a review of genetically confirmed KCS2 cases in PubMed, MEDLINE and CNKI databases. RESULTS: There were six females and two males in our cohort. All the patients presented with short stature (100.0%). Clinical manifestations included ocular defects such as hypermetropia (5/8), dental problems such as defective dentition (3/8) and dental caries (3/8), skeletal and brain anomalies such as delayed closure of anterior fontanelle (6/8), cerebral calcification (3/8), cortical thickening (3/8) and medullary stenosis (4/8) of tubular bones. Endocrinologic abnormalities included hypoparathyroidism (5/8) and hypocalcemia (3/8). One male patient had micropenis and microorchidism. All cases harboured missense variants of FAM111A, and nucleotides c.1706 arose as a mutational hotspot, with seven individuals harbouring a c.1706G>A (p.Arg569His) variant, and one child harbouring a c.1531T>C (p.Tyr511His) variant. Literature review yielded a total of 46 patients from 20 papers. Data analysis showed that short stature, hypoparathyroidism and hypocalcemia, ocular and dental defects, skeletal features including cortical thickening and medullary stenosis of tubular bones, and seizures/spasms were present in more than 70% of the reported KCS2 cases. CONCLUSION: We provide detailed characteristics of the largest KCS2 group in China and present the first genetically confirmed instance of father-to-daughter transmission of KCS2. Our study confirms that Arg569His is the hot spot variant and summarizes the typical phenotypes of KCS2, which would help early diagnosis and intervention.

Nonfebrile Seizures in Pediatrics: Key Points to Remember.

Seizures are the most common neurological disorder in pediatrics, and their initial approach aims at clinical stabilization. A thorough patient evaluation may provide important clues for the etiological diagnosis. A 12-month-old female child was observed in the emergency department after experiencing her first apyretic seizure. She had a history of congenital alopecia and, on physical examination, presented subtotal alopecia and milia. Initial investigation revealed hypocalcemia; therefore, intravenous calcium correction was started with a partial response. The analytical study was extended, revealing hypophosphatemia, elevated parathormone, and 1,25(OH)2 vitamin D with normal 25(OH) vitamin D. The genetic analysis confirmed hereditary vitamin D-resistant rickets (HVDRR). The integration of the findings was crucial to diagnostic reasoning and to guide further investigation. HVDRR is a rare disorder, with more severe clinical presentations associated with alopecia. Early diagnosis and treatment are fundamental to minimize the impact on growth and the development of other comorbidities.

Assessing Postoperative Phosphate and Calcium/Phosphate Ratio as Surrogates for Parathyroid Hormone Following Total Thyroidectomy.

OBJECTIVE: Evaluate utility of postoperative phosphate and calcium/phosphate ratio (Ca/P) as surrogates for parathyroid hormone (PTH) following total thyroidectomy. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary care hospital. METHODS: We retrospectively reviewed patients 18 years or older who underwent total thyroidectomy in a tertiary care hospital by a single surgeon from 2015 through 2021. Patients with incomplete data, pre-existing hypoparathyroidism, vitamin D deficiency, or renal failure were excluded. All patients had PTH drawn within 4 hours of surgery and serum calcium, albumin, and phosphate levels on postoperative Day 1. Corrected calcium was used to calculate a Ca/P. Receiver operating characteristic (ROC) curves were generated to compare phosphate level or Ca/P with PTH. Each possible surrogate was assessed relative to PTH cutoffs of less than 5, 10, 15, and 20 pg/mL. A good screening test was defined as having an area under the curve (AUC) greater than 0.8. RESULTS: A total of 185 patients underwent total thyroidectomy with 1 fellowship-trained otolaryngologist. Most patients were female (62%), median age 48 years. Most surgeries were performed for cancer (68%). Six (3.2%) patients required IV calcium supplementation and 2 (1.1%) required readmission for symptomatic hypocalcemia. ROC curves comparing phosphate and Ca/P to PTH at the listed cutoffs demonstrated AUC ranging from 0.55 to 0.66 and 0.61 to 0.79, respectively. None met the threshold for a good screening test. CONCLUSION: Postoperative phosphate and Ca/P ratio are not surrogates for PTH levels following total thyroidectomy. More research is needed to identify cost-effective strategies for postoperative calcium monitoring in patients undergoing total thyroidectomy. LEVEL OF EVIDENCE: Retrospective cohort study.

Lower Rates of Hypocalcemia Following Near-Infrared Autofluorescence Use in Thyroidectomy: A Meta-Analysis of RCTs.

BACKGROUND: Iatrogenic injury of the parathyroid glands is the most frequent complication after total thyroidectomy. OBJECTIVE: To determine the effectiveness of near-infrared autofluorescence (NIRAF) in reducing postoperative hypocalcemia following total thyroidectomy. METHODS: PubMed, Scopus, and Google Scholar databases were searched. Randomised trials reporting at least one hypocalcemia outcome following total thyroidectomy using NIRAF were included. RESULTS: The qualitative data synthesis comprised 1363 patients from nine randomised studies, NIRAF arm = 636 cases and non-NIRAF arm = 637 cases. There was a statistically significant difference in the overall rate of hypocalcemia log(OR) = -0.7 [(-1.01, -0.40), M-H, REM, CI = 95%] and temporary hypocalcemia log(OR) = -0.8 [(-1.01, -0.59), M-H, REM, CI = 95%] favouring the NIRAF. The difference in the rate of permanent hypocalcemia log(OR) = -1.09 [(-2.34, 0.17), M-H, REM, CI = 95%] between the two arms was lower in the NIRAF arm but was not statistically significant. CONCLUSIONS: NIRAF during total thyroidectomy helps in reducing postoperative hypocalcemia. Level of evidence-1.

Calcium trafficking and gastrointestinal physiology following an acute lipopolysaccharide challenge in pigs.

The influence of systemic immune activation on whole-body calcium (Ca) trafficking and gastrointestinal tract (GIT) physiology is not clear. Thus, the study objectives were to characterize the effects of lipopolysaccharide (LPS) on Ca pools and GIT dynamics to increase understanding of immune-induced hypocalcemia, ileus, and stomach hemorrhaging. Twelve crossbred pigs [44 ±â€…3 kg body weight (BW)] were randomly assigned to 1 of 2 intramuscular treatments: (1) control (CON; 2 mL saline; n = 6) or (2) LPS (40 µg LPS/kg BW; n = 6). Pigs were housed in metabolism stalls to collect total urine and feces for 6 h after treatment administration, at which point they were euthanized, and various tissues, organs, fluids, and digesta were weighed, and analyzed for Ca content. Data were analyzed with the MIXED procedure in SAS 9.4. Rectal temperature and respiration rate increased in LPS relative to CON pigs (1.4 °C and 32%, respectively; P ≤ 0.05). Inflammatory biomarkers such as circulating alkaline phosphatase, aspartate aminotransferase, and total bilirubin increased in LPS compared with CON pigs whereas albumin decreased (P ≤ 0.02). Plasma glucose and urea nitrogen decreased and increased, respectively, after LPS (43% and 80%, respectively; P < 0.01). Pigs administered LPS had reduced circulating ionized calcium (iCa) compared to CON (15%; P < 0.01). Considering estimations of total blood volume, LPS caused an iCa deficit of 23 mg relative to CON (P < 0.01). Adipose tissue and urine from LPS pigs had reduced Ca compared to CON (39% and 77%, respectively; P ≤ 0.05). There did not appear to be increased Ca efflux into GIT contents and no detectable increases in other organ or tissue Ca concentrations were identified. Thus, while LPS caused hypocalcemia, we were unable to determine where circulating Ca was trafficked. LPS administration markedly altered GIT dynamics including stomach hemorrhaging, diarrhea (increased fecal output and moisture), and reduced small intestine and fecal pH (P ≤ 0.06). Taken together, changes in GIT physiology suggested dyshomeostasis and alimentary pathology. Future research is required to fully elucidate the etiology of immune activation-induced hypocalcemia and GIT pathophysiology.

Lipopolysaccharide (LPS) activates the immune system and this is accompanied with hypocalcemia and altered gastrointestinal tract (GIT) physiology. The study objectives were to characterize whole-body calcium (Ca) trafficking and evaluate GIT dynamics during LPS-induced immune activation. Ca concentrations were analyzed after intramuscular LPS injection. Administering LPS caused marked alterations in metabolic and inflammatory biomarkers and GIT dynamics, characterized by increased lower GIT motility and stomach hemorrhaging. Circulating Ca and adipose tissue and urine Ca output were decreased after LPS. Ca concentrations in other tissues and GIT contents were not detectably different. Thus, we were unable to account for about 110 mg Ca following LPS. Where and how circulating Ca is partitioned during immune activation remains unclear.

Early parathyroid hormone (PTH) level as a predictor of post-surgical hypoparathyroidism.

INTRODUCTION: Post-operative hypocalcemia and postoperative persistent hypoparathyroidism remain the most common complications after thyroidectomy. Many approaches have been developed to prevent them, but actually, a common protocol is not yet individuated. MATERIALS AND METHODS: We retrospectively analyzed the results of a prospectively collected database. We dosed PTH preoperatively and 4 h after surgery (PTH_4); calcium was evaluated preoperatively, on the first (I_POD) and on the second postoperative day (II_POD). Hypocalcemia was defined when calcium <8 mg/dl. PTH_4 and I_POD calcium serum levels are identified to predict postoperative hypocalcemia. RESULTS: Three hundred and forty-eight patients were enrolled, 37 patients resulted as hypocalcemic on I_POD and 41 on the II_POD. PTH_4 is related to I_POD (p < 0.001, r = 0.45) and II_POD (p < 0.001, r = 0.44) calcemia. PTH_4-cut-off predicting I_POD hypocalcemia was 10.50 pg/ml (sensitivity: 78.7%, specificity: 72.7%). A PTH_4 value of 11.5 pg/ml is able to predict hypocalcemia during II_POD (sensitivity: 76.5%, specificity: 69.2%). We set up a combined test to predict II_POD hypocalcemia, using PTH_4 and I_POD calcium (sensitivity: 77.8%, specificity: 89.9%). CONCLUSION: This research shows the association between PTH_4 and postoperative hypocalcemia. The PTH_4 cut-off to predict I_POD-hypocalcemia was 10.5 pg/ml. We analyzed the calcemia trend during the postoperative period and we realized a combined test using PTH_4 and I_POD-calcemia. This test improves the accuracy of the previous test. Further studies, in particular multicentric, with a larger sample are necessary to validate the combined model.

Proton pump inhibitors, bone and phosphocalcic metabolism.

Proton pump inhibitors (PPIs) are widely used for acid-related gastrointestinal disorders; however, concerns have arisen about their prolonged and inappropriate use. Although generally considered safe, recent evidence has linked PPI use with an increased risk of kidney disease, stomach cancer, pneumonia, dementia, cardiovascular events and potential bone health problems. This systematic review examines the effects of PPIs on bone health, including osteoporosis and changes in phosphocalcic and magnesium metabolism, through a comprehensive analysis of the recent literature. The relationship between PPIs, bone mineral density and fracture risk, especially in populations with comorbidities, is complex and we propose a focus based on recent data. Studies of the effect of PPI use on bone mineral density have shown mixed results and require further investigation. Observational studies have indicated an increased risk of fractures, particularly vertebral fractures, associated with PPI use. Recent meta-analyses have confirmed an association between PPI use and hip fractures with a dose-dependent effect. More recently, PPIs have been associated with serious disturbances in phosphocalcic and magnesium metabolism that require careful management and discontinuation. Proton pump inhibitor-induced hypomagnesemia (PPIH) is a well-established phenomenon. In addition, hypocalcemia secondary to severe hypomagnesemia has been described. Despite growing evidence of PPI-related risks, further research is essential to better understand the complex mechanisms, as most data are from observational studies and do not establish a causal relationship. This review emphasizes the need for judicious prescription practices, particularly in long-term use scenarios and rheumatological contexts.

Higher Doses of Calcium Associated With Survival in Trauma Patients.

INTRODUCTION: Calcium is required for coagulation, cardiac output, and peripheral vascular resistance. Between 85% and 94% of trauma patients treated with massive blood transfusion develop hypocalcemia.1 The aim of this study is to evaluate the relationship between increased intravenous calcium administration during massive transfusion and improved survival of trauma patients. METHODS: We performed a retrospective analysis of trauma patients who received massive transfusion over a 2-y period. Doses of elemental calcium administered per unit of blood product transfused were calculated by calcium to blood product ratio (CBR). Chi-square test evaluated association between coagulopathy and 30-d mortality. Two-sample t-test evaluated association between CBR and coagulopathy. Bivariate regression analysis evaluated association between CBR and blood products transfused per patient. Multivariable logistic regression analysis, controlling for age, sex, coagulopathy, and Injury Severity Score evaluated the association between CBR and mortality. RESULTS: The study included 77 patients. Coagulopathy was associated with increased 30-d mortality (P < 0.05). Patients who survived had higher CBR than those who died (P < 0.05). CBR was associated with a significant reduction in total blood products transfused per patient (P < 0.05). CBR was not associated with coagulopathy (P = 0.24). Multivariable logistic regression analysis demonstrated that Injury Severity Score ≥16, coagulopathy and decreased CBR were significant predictors of mortality (P < 0.05). CBR above 50 mg was a predictor of survival (P < 0.05). CONCLUSIONS: Higher doses of calcium given per blood product transfused were associated with improved 30-d survival and decreased blood product transfusions.

Recalcitrant Hypocalcemia: Postsurgical Hypoparathyroidism Exacerbated by a Chyle Leak Treated With Octreotide.

Background/Objective: To report a case of recalcitrant post-surgical hypocalcemia caused by hypoparathyroidism complicated by a chyle leak and octreotide use. Case Report: A man in his 60s with a 4-month history of voice changes, 10-pound weight loss, and a right-sided neck mass presented with difficulty breathing for 1 week. He had a right laryngeal/hypopharyngeal mass, which was biopsied. Pathology results were positive for invasive squamous cell carcinoma. He underwent an extensive neck surgery, including total thyroidectomy. Postsurgical laboratory results revealed serum corrected calcium of 7.6 mg/dL (ref 8.0-10.2 mg/dL) and parathyroid hormone <6.3 pg/mL (ref. 10-65). Despite treatment with calcium carbonate 12 g (elemental) daily, calcitriol and hydrochlorothiazide, his corrected serum calcium levels remained low. Patient also had a chyle leak that was treated with octreotide. Resolution of his hypocalcemia occurred after substitution of calcium carbonate with calcium citrate, cessation of octreotide, and management of the chyle leak. Discussion: Our patient likely developed recalcitrant hypocalcemia from: 1) postsurgical hypoparathyroidism, 2) a chyle leak, and 3) the use of octreotide. Administration of octreotide to seal the chyle leak most likely decreased gastric acid production and contributed to decrease in absorption of calcium carbonate. Oral calcium citrate may be better absorbed in this case. Conclusion: Postsurgical hypoparathyroidism can lead to hypocalcemia. This case is unique in that the patient's chyle leak and the use of octreotide contributed to recalcitrant hypocalcemia.

Recurrent severe hypocalcemia following chemotherapy regimen changes in advanced breast cancer: two case reports.

BACKGROUND: As an oncologic emergency related to abnormalities in calcium metabolism, hypercalcemia associated with paraneoplastic syndrome and bone metastases is well known. Meanwhile, the incidence of hypocalcemia is low, except in cases associated with bone-modifying agents used for bone metastases. Hypocalcemia induced by bone-modifying agents typically occurs early after the initial administration, and its incidence can be significantly reduced by preventive administration of calcium and vitamin D3 supplements. CASE REPORT: We report two cases of recurrent severe hypocalcemia occurring during chemotherapy for metastatic breast cancer with multiple bone metastases. Case 1: A 35-year-old Japanese woman developed metastases in the bone, liver, and ovaries during postoperative endocrine therapy for invasive lobular carcinoma of the breast. She underwent chemotherapy and treatment with denosumab. She experienced recurrent episodes of severe hypocalcemia subsequent to a change in the chemotherapy regimen. Case 2: A 65-year-old Japanese woman encountered multiple bone metastases after postoperative anti-human epidermal growth factor receptor 2 therapy and during endocrine therapy for invasive ductal carcinoma of the breast. She underwent anti-human epidermal growth factor receptor 2 therapy and treatment with denosumab. She experienced recurrent severe hypocalcemia subsequent to a change in the chemotherapy regimen to letrozole + lapatinib, trastuzumab emtansine, and lapatinib + capecitabine. CONCLUSIONS: We observed two cases of recurrent severe hypocalcemia in patients with advanced breast cancer and bone metastases after modifications to their therapy regimens. These cases differed from the typical hypocalcemia induced by bone-modifying agents. It is possible that antitumor drugs affect calcium and bone metabolism associated with bone metastases. While these cases are rare, it is crucial for oncologists to be aware of hypocalcemia not only at the initiation of bone-modifying agents but also throughout the entire antitumor therapy, as hypocalcemia can lead to fatal outcomes.

Hypoparathyroidism Revealed by Unsuccessful Anti-epileptic Therapy.

Pediatric hypoparathyroidism is an uncommon endocrine disease that can be either isolated or syndromic. It occurs when the secretion of parathormone is insufficient to maintain normal levels of ionized calcium. Patients with hypoparathyroidism can exhibit cerebral calcifications and metabolic disorders, and the severity of such features is inversely correlated with hypocalcemia. We report a case of a 13-year-old patient who was initially diagnosed with epilepsy by another medical team two years before her admission to our hospital and who was subjected to oral valproate therapy. The anti-epileptic therapy proved to be unsuccessful even with increasing doses. The diagnosis was corrected when we performed adequate biological investigations. This case is underlying the importance of the electrolytes profile, especially the serum phosphocalcic test, in the management of patients with new onset or recurrent epileptic seizures.