Anemia is still prevalent among low and middle-income countries,posing serious family and social burdens.However,scarce studies provided evidence for real-world exposure to polycyclic aromatic hydrocarbons(PAHs)and an...Anemia is still prevalent among low and middle-income countries,posing serious family and social burdens.However,scarce studies provided evidence for real-world exposure to polycyclic aromatic hydrocarbons(PAHs)and anemia among pregnant women,as well as involved biological mechanisms.So,we conducted this study including 1717 late pregnant women fromZunyi Birth Cohort and collected urine samples for PAHs metabolites detection.Logistic regression and restricted cubic spline regression were used to examine exposuredisease risks and dose-response relationships.We conducted Bayesian kernel machine regression,weighted quantile sum regression,and quantile g-computation regression to fit the joint impacts of multiple PAHs in the real-world scenario on hypocalcemia and anemia.Results showed single exposure to 2-OHNap,2-OHFlu,9-OHFlu,1-OHPhe,2-OHPhe,3-OHPhe,and 1-OHPyr(all P-trend<0.05)increased the risks of hypocalcemia and anemia.Moreover,PAHs mixture was significantly related to higher risks of hypocalcemia and anemia,with 3-OHPhe and 1-OHPyr identified as their major drivers,respectively.Importantly,hypocalcemia served as a significant biological mechanism responsible for PAHs and anemia.Our findings suggest that individual and joint exposure to PAHs during late pregnancy elevate the anemia risk,and calcium supplementation might be a low-cost intervention target for reducing the PAHs-related impairment on anemia for pregnant women.展开更多
BACKGROUND Hypocalcemia is highly common in hospitalized patients,especially in those with trauma,On the other hand,abnormal calcium metabolism is an important metabolic challenge;however,it is often neglected and unt...BACKGROUND Hypocalcemia is highly common in hospitalized patients,especially in those with trauma,On the other hand,abnormal calcium metabolism is an important metabolic challenge;however,it is often neglected and untreated,and certain factors may induce serious neurological and cardiovascular complications.AIM To retrospectively analyze the impact of hypocalcemia on the prognosis of patients with multiple traumas.METHODS The study was conducted from January 2020 to December 2021.Ninety-nine patients with multiple injuries were treated at the critical care medicine department of Fuyang People’s Hospital.The selected indicators included sex,age,and blood calcium and hematocrit levels.Many indicators were observed,including within 24 h of hospitalization,and the prognosis was collected after 28 d.Based on the blood calcium levels,the patients were divided into the following two groups:Normocalcemia and hypocalcemia.Of the 99 patients included,81 had normocalcemia,and 18 had hypocalcemia.Separate experiments were conducted for these two groups.RESULTS There was an association between serum calcium levels and the prognosis of patients with polytrauma.CONCLUSION Clinically,the prognosis of patients with multiple traumas can be preliminarily evaluated based on serum calcium levels.展开更多
BACKGROUND Denosumab inhibits the receptor activator of nuclear factor kappa-ligand.It markedly increases bone mineral density and has been proven to reduce the risk of fractures.However,numerous adverse effects,notab...BACKGROUND Denosumab inhibits the receptor activator of nuclear factor kappa-ligand.It markedly increases bone mineral density and has been proven to reduce the risk of fractures.However,numerous adverse effects,notably hypocalcemia,are prevalent in patients with end-stage renal disease(ESRD).AIM To analyze the incidence and predictors of hypocalcemia caused by denosumab compared to control in patients with ESRD.METHODS We conducted this study in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.PubMed,Scopus,Cochrane Central,and EMBASE were systematically searched from inception through March 2024.All original studies investigating the effects of denosumab on patients with ESRD compared to control were extracted.The primary outcomes of our study were the incidence of mild,severe,and very severe hypocalcemia.Secondary outcomes included serum levels of intact parathyroid hormone,calcium,and phosphate.The results were pooled and analyzed using a random-effects model.RESULTS Seven articles comprising 3240 patients were included in our study.Patients treated with denosumab had a significantly increased incidence of mild hypocalcemia[risk ratio(RR):2.79;95%confidence interval(CI):0.99-7.91;P=0.05;I^(2)=37%]and of very severe hypocalcemia(RR:9.58;95%CI:1.58-57.98;P=0.01;I^(2)=49%).However,an increase in the occurrence of severe hypocalcemia was non-significant(RR:4.23;95%CI:0.47-38.34;P=0.20;I^(2)=96%).Alternatively,denosumab showed a significant decrease in serum intact parathyroid hormone[mean difference(MD):-433.20,95%CI:-775.12 to-91.28,I2=98%,P=0.01],while there was a non-significant decrease in phosphate(MD:-0.47,95%CI:-1.35 to 0.41,I^(2)=88%,P=0.30)and calcium levels(MD:-0.33,95%CI:-0.95 to 0.29,I^(2)=94%,P=0.29).CONCLUSION Our study demonstrated that denosumab is significantly associated with mild and very severe hypocalcemia in patients with ESRD making it necessary to detect and prevent this side effect of treatment.展开更多
BACKGROUND Severe hypocalcemia(SH)is a dreaded complication of total parathyroidectomy(TPTX)without auto-transplantation.AIM To compare conventional and preventive calcium supplementation(CS)regimens in terms of SH oc...BACKGROUND Severe hypocalcemia(SH)is a dreaded complication of total parathyroidectomy(TPTX)without auto-transplantation.AIM To compare conventional and preventive calcium supplementation(CS)regimens in terms of SH occurrence after TPTX.METHODS This retrospective study included patients who underwent TPTX between January 2015 and May 2018 at the China-Japan Friendship Hospital.From January 2015 to May 2016,conventional CS was performed in patients who underwent TPTX,with calcium amounts adjusted according to postoperative serum calcium levels.From October 2016 to May 2018,preventive CS was performed according to preoperative alkaline phosphatase(ALP)levels.The patients were defined as lowrisk(ALP<500 U/L)and high-risk(ALP>500 U/L)for SH.All preoperative blood samples were collected in the fasting state on the day before surgery.Postoperative blood samples were obtained at 6-7 AM from the first postoperative day.RESULTS A total of 271 patients were included.These patients were 47.7±11.1 years old,and 57.6%were male.Their mean body mass index(BMI)was 22.9±3.8 kg/m^(2).There were no significant differences in sex,age,BMI,preoperative ALP,serum calcium,serum phosphorus,calcium-phosphorus ratio,and intact parathyroid hormone(iPTH)between the two CS groups.Compared with conventional CS,preventive CS led to lower occurrence rates of hypocalcemia within 48 h(46.0%vs 74.5%,P<0.001)and SH(31.7%vs 64.1%,P<0.001).Multivariable analysis showed that preoperative iPTH levelsodds ratio(OR)=1.001,95%confidence interval(CI:1.000-1.001,P=0.009),preoperative ALP amounts(OR=1.002,95%CI:1.001-1.003,P=0.002),preoperative serum phosphorus levels(OR=8.729,95%CI:1.518-50.216,P=0.015)and preventive CS(OR=0.132,95%CI:0.067-0.261,P<0.001)were independently associated with SH.In patients with preoperative ALP≥500 U/L,only preventive CS(OR=0.147,95%CI:0.038-0.562.P=0.005)was independently associated with SH.CONCLUSION This study suggests that preventive CS could reduce the occurrence of SH,indicating its critical value for hypocalcemia after TPTX.展开更多
Hypomagnesemia with secondary hypocalcemia (HSH) is a rare inherited disorder, characterized by extremely low levels of serum magesium associated with symptomatic hypocalcemia. HSH manifests in the new born period wit...Hypomagnesemia with secondary hypocalcemia (HSH) is a rare inherited disorder, characterized by extremely low levels of serum magesium associated with symptomatic hypocalcemia. HSH manifests in the new born period with neurological symptoms, including generalized seizures, which are refractory to anticonvulsant treatment. In this disorder, the basic abnormality is the defective intestinal absorption of magnesium. Mutations in TRPM6, the gene encoding the transient receptor potential cation channel subfamily member 6 have been found to be responsible for this disease. We report on a four-month-old Tunisian girl who presented with convulsions. Laboratory evaluation yielded extremely low serum magnesium levels, low calcium levels, and abnormal PTH levels. The diagnosis of HSH was confirmed by mutation analysis which identified the novel mutation c.1307A >G in exon 11 of TRPM6 (Lys436Arg). Our patient was homozygous for this mutation. Prenatal diagnosis was done during second pregnancy. DNA from trophoblast biopsy showed the same mutation as the proband.展开更多
We present this rare occurrence of a 17 yr old boy,a known case of congenital hypoparathyroidism, who presented with fever and jaundice for 8 days and 2 episodes of generalised tonic-clonic seizures.Premorbidly patien...We present this rare occurrence of a 17 yr old boy,a known case of congenital hypoparathyroidism, who presented with fever and jaundice for 8 days and 2 episodes of generalised tonic-clonic seizures.Premorbidly patient was on regular oral calcium supplementations with normal serum calcium levels.Investigations revealed severe hypocalcaemia(3.2 mg/dL),low 25 hydroxyvitamin D levels and hypomagnesacmia.The marked elevation of serum bilirubin was accompanied by derangement of liver enzymes.Microbiological investigations were confirmatory for both hepatitis A and typhoid fever.In spite of the aggressive management with intravenous calcium gluconate infusion,refractory hypocalcaemia persisted with recovery only after gradual decline in the bilirubin levels.We inferred that the cholestatic process produced by both acute viral hepatitis A and typhoid fever precipitated this state of refractory hypocalcaemia in the previously well preserved patient.展开更多
Autosomal dominant hypocalcemia(ADH)type 1 and 2 are disorders of calcium homeostasis caused by gain of function variants.The calcium-sensing receptor(CaSR)is a class C GPCR that responds to elevated extracellular cal...Autosomal dominant hypocalcemia(ADH)type 1 and 2 are disorders of calcium homeostasis caused by gain of function variants.The calcium-sensing receptor(CaSR)is a class C GPCR that responds to elevated extracellular calcium(Ca^(2+)o)by inhibiting parathyroid hormone(PTH)secretion and promoting renal excretion of Ca^(2+)and other salts to restore physiologically normal Ca^(2+)o concentrations.CaSR negative allosteric modulators(NAMs)transiently raise PTH levels in individuals with ADH1,restoring Ca^(2+)o concentration to a physiological normal range.Herein we disclose the discovery of a chemoreactive NAM(ATF936-NCS,4)for the CaSR that(i)is wash-resistant indicative of irreversible receptor binding and(ii)stimulates prolonged PTH release in vivo.This‘first-in-class’chemical probe will provide invaluable insight towards the development of longer acting NAMs for the treatment of ADH.展开更多
Background Parathyroid hormone deficiency or resistance may cause hypocalcemia with related symptoms and signs. Lifelong treatment of calcium combined with vitamin D or its metabolites is always necessary for these pa...Background Parathyroid hormone deficiency or resistance may cause hypocalcemia with related symptoms and signs. Lifelong treatment of calcium combined with vitamin D or its metabolites is always necessary for these patients. Here we reported a prospective and open-label trial to investigate the efficacy and safety of domestic-made calcitriol in treatment of hypocalcemia caused by hypoparathyroidism or pseudohypoparathyroidism. Methods Twenty-four patients with confirmed hypoparathyroidism or pseudohypoparathyroidism aged （36.5±11.0） years old were studied. Among them, 16 patients had idiopathic hypoparathyroidism, 2 had pseudohypoparathyroidism and 6 had hypoparathyroidism secondary to cervical surgery. Serum calcium levels were lower than 1.88 mmol/L. Oral calcitriol was administered twice or three times with elemental calcium 1.2 g per day. All patients were followed every 4 weeks throughout the 12-week period. Dose adjustments of calcitriol were based on serum and urinary calcium levels and symptoms of hypocalcemia. Results Twenty patients were included by the end of this study. Muscular weakness, cramps, extremity paresthesia, Chovestek＇s sign and Trousseau＇s sign were relieved in 76.9%, 100%, 94.4%, 93.3% and 78.9% of patients, respectively. Serum calcium, plasma ionized calcium and serum phosphorus levels were （1.54±0.25） mmol/L, （0.64±0.10） mmol/L and （2.00±0,46） mmol/L at baseline, and reached （2.20±0.20） mmol/L, （0.95±0.06） mmol/L and （1.68±0.25） mmol/L （P 〈0.01） at the 12th week of treatment, respectively. Eighty percent of patients were assessed as effective and 20% as partly effective. Three, four and eight patients had hypercalciuria at the 4th, 8th and 12th week of treatment, respectively, which were reduced by thiazide diuretics. The final dose of calcitriol was （1.09±0.50） ug/d. Conclusions Calcitriol combined with calcium can be used in treatment of hypocalcemia caused by hypoparathyroidism or pseudohypoparathyroidism effectively and safely. Serum and urinary calcium levels should be monitored during the course of the therapy.展开更多
基金supported by the Science&Technology Program of Guizhou Province(Nos.QKHPTRC-GCC[2022]039-1,QKHPTRC-CXTD[2022]014,and QKHHBZ[2020]3002)the Scientific Research Programof Guizhou Provincial Department of Education(No.QJJ[2023]019).
文摘Anemia is still prevalent among low and middle-income countries,posing serious family and social burdens.However,scarce studies provided evidence for real-world exposure to polycyclic aromatic hydrocarbons(PAHs)and anemia among pregnant women,as well as involved biological mechanisms.So,we conducted this study including 1717 late pregnant women fromZunyi Birth Cohort and collected urine samples for PAHs metabolites detection.Logistic regression and restricted cubic spline regression were used to examine exposuredisease risks and dose-response relationships.We conducted Bayesian kernel machine regression,weighted quantile sum regression,and quantile g-computation regression to fit the joint impacts of multiple PAHs in the real-world scenario on hypocalcemia and anemia.Results showed single exposure to 2-OHNap,2-OHFlu,9-OHFlu,1-OHPhe,2-OHPhe,3-OHPhe,and 1-OHPyr(all P-trend<0.05)increased the risks of hypocalcemia and anemia.Moreover,PAHs mixture was significantly related to higher risks of hypocalcemia and anemia,with 3-OHPhe and 1-OHPyr identified as their major drivers,respectively.Importantly,hypocalcemia served as a significant biological mechanism responsible for PAHs and anemia.Our findings suggest that individual and joint exposure to PAHs during late pregnancy elevate the anemia risk,and calcium supplementation might be a low-cost intervention target for reducing the PAHs-related impairment on anemia for pregnant women.
文摘BACKGROUND Hypocalcemia is highly common in hospitalized patients,especially in those with trauma,On the other hand,abnormal calcium metabolism is an important metabolic challenge;however,it is often neglected and untreated,and certain factors may induce serious neurological and cardiovascular complications.AIM To retrospectively analyze the impact of hypocalcemia on the prognosis of patients with multiple traumas.METHODS The study was conducted from January 2020 to December 2021.Ninety-nine patients with multiple injuries were treated at the critical care medicine department of Fuyang People’s Hospital.The selected indicators included sex,age,and blood calcium and hematocrit levels.Many indicators were observed,including within 24 h of hospitalization,and the prognosis was collected after 28 d.Based on the blood calcium levels,the patients were divided into the following two groups:Normocalcemia and hypocalcemia.Of the 99 patients included,81 had normocalcemia,and 18 had hypocalcemia.Separate experiments were conducted for these two groups.RESULTS There was an association between serum calcium levels and the prognosis of patients with polytrauma.CONCLUSION Clinically,the prognosis of patients with multiple traumas can be preliminarily evaluated based on serum calcium levels.
文摘BACKGROUND Denosumab inhibits the receptor activator of nuclear factor kappa-ligand.It markedly increases bone mineral density and has been proven to reduce the risk of fractures.However,numerous adverse effects,notably hypocalcemia,are prevalent in patients with end-stage renal disease(ESRD).AIM To analyze the incidence and predictors of hypocalcemia caused by denosumab compared to control in patients with ESRD.METHODS We conducted this study in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.PubMed,Scopus,Cochrane Central,and EMBASE were systematically searched from inception through March 2024.All original studies investigating the effects of denosumab on patients with ESRD compared to control were extracted.The primary outcomes of our study were the incidence of mild,severe,and very severe hypocalcemia.Secondary outcomes included serum levels of intact parathyroid hormone,calcium,and phosphate.The results were pooled and analyzed using a random-effects model.RESULTS Seven articles comprising 3240 patients were included in our study.Patients treated with denosumab had a significantly increased incidence of mild hypocalcemia[risk ratio(RR):2.79;95%confidence interval(CI):0.99-7.91;P=0.05;I^(2)=37%]and of very severe hypocalcemia(RR:9.58;95%CI:1.58-57.98;P=0.01;I^(2)=49%).However,an increase in the occurrence of severe hypocalcemia was non-significant(RR:4.23;95%CI:0.47-38.34;P=0.20;I^(2)=96%).Alternatively,denosumab showed a significant decrease in serum intact parathyroid hormone[mean difference(MD):-433.20,95%CI:-775.12 to-91.28,I2=98%,P=0.01],while there was a non-significant decrease in phosphate(MD:-0.47,95%CI:-1.35 to 0.41,I^(2)=88%,P=0.30)and calcium levels(MD:-0.33,95%CI:-0.95 to 0.29,I^(2)=94%,P=0.29).CONCLUSION Our study demonstrated that denosumab is significantly associated with mild and very severe hypocalcemia in patients with ESRD making it necessary to detect and prevent this side effect of treatment.
基金Supported by the Subject of Beijing Science and Technology Plan,No.Z191100006619014.
文摘BACKGROUND Severe hypocalcemia(SH)is a dreaded complication of total parathyroidectomy(TPTX)without auto-transplantation.AIM To compare conventional and preventive calcium supplementation(CS)regimens in terms of SH occurrence after TPTX.METHODS This retrospective study included patients who underwent TPTX between January 2015 and May 2018 at the China-Japan Friendship Hospital.From January 2015 to May 2016,conventional CS was performed in patients who underwent TPTX,with calcium amounts adjusted according to postoperative serum calcium levels.From October 2016 to May 2018,preventive CS was performed according to preoperative alkaline phosphatase(ALP)levels.The patients were defined as lowrisk(ALP<500 U/L)and high-risk(ALP>500 U/L)for SH.All preoperative blood samples were collected in the fasting state on the day before surgery.Postoperative blood samples were obtained at 6-7 AM from the first postoperative day.RESULTS A total of 271 patients were included.These patients were 47.7±11.1 years old,and 57.6%were male.Their mean body mass index(BMI)was 22.9±3.8 kg/m^(2).There were no significant differences in sex,age,BMI,preoperative ALP,serum calcium,serum phosphorus,calcium-phosphorus ratio,and intact parathyroid hormone(iPTH)between the two CS groups.Compared with conventional CS,preventive CS led to lower occurrence rates of hypocalcemia within 48 h(46.0%vs 74.5%,P<0.001)and SH(31.7%vs 64.1%,P<0.001).Multivariable analysis showed that preoperative iPTH levelsodds ratio(OR)=1.001,95%confidence interval(CI:1.000-1.001,P=0.009),preoperative ALP amounts(OR=1.002,95%CI:1.001-1.003,P=0.002),preoperative serum phosphorus levels(OR=8.729,95%CI:1.518-50.216,P=0.015)and preventive CS(OR=0.132,95%CI:0.067-0.261,P<0.001)were independently associated with SH.In patients with preoperative ALP≥500 U/L,only preventive CS(OR=0.147,95%CI:0.038-0.562.P=0.005)was independently associated with SH.CONCLUSION This study suggests that preventive CS could reduce the occurrence of SH,indicating its critical value for hypocalcemia after TPTX.
文摘Hypomagnesemia with secondary hypocalcemia (HSH) is a rare inherited disorder, characterized by extremely low levels of serum magesium associated with symptomatic hypocalcemia. HSH manifests in the new born period with neurological symptoms, including generalized seizures, which are refractory to anticonvulsant treatment. In this disorder, the basic abnormality is the defective intestinal absorption of magnesium. Mutations in TRPM6, the gene encoding the transient receptor potential cation channel subfamily member 6 have been found to be responsible for this disease. We report on a four-month-old Tunisian girl who presented with convulsions. Laboratory evaluation yielded extremely low serum magnesium levels, low calcium levels, and abnormal PTH levels. The diagnosis of HSH was confirmed by mutation analysis which identified the novel mutation c.1307A >G in exon 11 of TRPM6 (Lys436Arg). Our patient was homozygous for this mutation. Prenatal diagnosis was done during second pregnancy. DNA from trophoblast biopsy showed the same mutation as the proband.
文摘We present this rare occurrence of a 17 yr old boy,a known case of congenital hypoparathyroidism, who presented with fever and jaundice for 8 days and 2 episodes of generalised tonic-clonic seizures.Premorbidly patient was on regular oral calcium supplementations with normal serum calcium levels.Investigations revealed severe hypocalcaemia(3.2 mg/dL),low 25 hydroxyvitamin D levels and hypomagnesacmia.The marked elevation of serum bilirubin was accompanied by derangement of liver enzymes.Microbiological investigations were confirmatory for both hepatitis A and typhoid fever.In spite of the aggressive management with intravenous calcium gluconate infusion,refractory hypocalcaemia persisted with recovery only after gradual decline in the bilirubin levels.We inferred that the cholestatic process produced by both acute viral hepatitis A and typhoid fever precipitated this state of refractory hypocalcaemia in the previously well preserved patient.
基金supported by the Australian Research Council(No.DP170104228)the National Health and Medical Research Council of Australia(No.1138891)+1 种基金KL and KJG are Australian Research Council Future Fellows(fellowships FT160100075 and FT170100392,respectively)TMJ is a National Health and Medical Research Council Emerging Leader Fellow(fellowship 2008341,Australia).
文摘Autosomal dominant hypocalcemia(ADH)type 1 and 2 are disorders of calcium homeostasis caused by gain of function variants.The calcium-sensing receptor(CaSR)is a class C GPCR that responds to elevated extracellular calcium(Ca^(2+)o)by inhibiting parathyroid hormone(PTH)secretion and promoting renal excretion of Ca^(2+)and other salts to restore physiologically normal Ca^(2+)o concentrations.CaSR negative allosteric modulators(NAMs)transiently raise PTH levels in individuals with ADH1,restoring Ca^(2+)o concentration to a physiological normal range.Herein we disclose the discovery of a chemoreactive NAM(ATF936-NCS,4)for the CaSR that(i)is wash-resistant indicative of irreversible receptor binding and(ii)stimulates prolonged PTH release in vivo.This‘first-in-class’chemical probe will provide invaluable insight towards the development of longer acting NAMs for the treatment of ADH.
文摘Background Parathyroid hormone deficiency or resistance may cause hypocalcemia with related symptoms and signs. Lifelong treatment of calcium combined with vitamin D or its metabolites is always necessary for these patients. Here we reported a prospective and open-label trial to investigate the efficacy and safety of domestic-made calcitriol in treatment of hypocalcemia caused by hypoparathyroidism or pseudohypoparathyroidism. Methods Twenty-four patients with confirmed hypoparathyroidism or pseudohypoparathyroidism aged （36.5±11.0） years old were studied. Among them, 16 patients had idiopathic hypoparathyroidism, 2 had pseudohypoparathyroidism and 6 had hypoparathyroidism secondary to cervical surgery. Serum calcium levels were lower than 1.88 mmol/L. Oral calcitriol was administered twice or three times with elemental calcium 1.2 g per day. All patients were followed every 4 weeks throughout the 12-week period. Dose adjustments of calcitriol were based on serum and urinary calcium levels and symptoms of hypocalcemia. Results Twenty patients were included by the end of this study. Muscular weakness, cramps, extremity paresthesia, Chovestek＇s sign and Trousseau＇s sign were relieved in 76.9%, 100%, 94.4%, 93.3% and 78.9% of patients, respectively. Serum calcium, plasma ionized calcium and serum phosphorus levels were （1.54±0.25） mmol/L, （0.64±0.10） mmol/L and （2.00±0,46） mmol/L at baseline, and reached （2.20±0.20） mmol/L, （0.95±0.06） mmol/L and （1.68±0.25） mmol/L （P 〈0.01） at the 12th week of treatment, respectively. Eighty percent of patients were assessed as effective and 20% as partly effective. Three, four and eight patients had hypercalciuria at the 4th, 8th and 12th week of treatment, respectively, which were reduced by thiazide diuretics. The final dose of calcitriol was （1.09±0.50） ug/d. Conclusions Calcitriol combined with calcium can be used in treatment of hypocalcemia caused by hypoparathyroidism or pseudohypoparathyroidism effectively and safely. Serum and urinary calcium levels should be monitored during the course of the therapy.
