High-dose Calcium Research Articles

Molecular-level insights into the mitigation of magnesium-natural organic matter induced ultrafiltration membrane fouling by high-dose calcium based on DFT calculation

While magnesium cation (Mg2+) universally coexists with natural organic matter (NOM) in the water environment, influence of Mg2+ on NOM fouling in membrane filtration process is still unclear. This work was therefore performed to investigate effects of Mg2+ on NOM (sodium alginate (SA) as a model substance) fouling and role of Ca2+ in mitigating fouling from Mg2+ in the ultrafiltration (UF) water treatment process. Filtration tests showed two interesting fouling phenomena: (1) membrane fouling caused by combination of Mg2+ and SA maintained at a high value with the increased Mg2+ concentration; (2) the high fouling property of Mg2+ can be significantly improved by the prominent addition of calcium cation (Ca2+). It was found that changes of foulant morphology played essential roles through thermodynamic mechanisms represented by the Flory-Huggins lattice theory. Density functional theory (DFT) calculation showed that the combination of SA and Mg2+ tends to coordinate two terminal carboxyl groups in SA, beneficial to stretching alginate chains and forming a stable gel network at low doses. In addition, intramolecular coordination is difficult to occur between SA and Mg2+ due to the high hydration repulsion radius of Mg2+. Therefore, a dense and thick gel network remained even under high Mg2+concentration. Furthermore, due to the higher binding affinity of Ca2+ over Mg2+, high doses of Ca2+ trigger a transition of the stable SA-Mg2+ gel network to other configurations where flocculation and aggregation occur, thereby reducing the specific filtration resistance. The proposed thermodynamic mechanism satisfactorily explained the above interesting fouling behaviors, facilitating to development of new solutions to control membrane fouling.

Safety of chronic high-dose calcium channel blockers exposure in children with pulmonary arterial hypertension.

BackgroundChronic calcium channel blockers (CCBs) are indicated in children with idiopathic/heritable pulmonary arterial hypertension (IPAH/HPAH) and positive response to acute vasodilator challenge. However, minimal safety data are available on the long-term high-dose exposure to CCBs in this population.MethodsPatients aged 3 months to 18 years who were diagnosed with IPAH/HPAH and treated with CCB in the past 15 years were retrospectively reviewed. The maximum tolerated dose and the long-term safety of high-dose CCBs on the cardiovascular and noncardiovascular systems were assessed.ResultsThirty-two eligible children were enrolled in the study, with a median age of 9 (6–11) years old. Thirty-one patients were treated with diltiazem after diagnosis. The median maximum tolerated dose was 12.9 (9.8–16.8) mg/kg/day. Children younger than 7 years used higher doses than children in the older age group, 16.4 (10.5–28.5) mg/kg/day vs. 12.7 (6.6–14.4) mg/kg/day, P < 0.05. Patients were followed up for a median period of 6.2 (2.6–10.8) years. One patient died from a traffic accident, and others showed a stable or improved WHO functional class status. Thirteen (40.6%) and 10 (31.3%) patients developed arrhythmias and hypotension. Nine (28.1%) patients had sinus bradycardia, five (21.9%) had first-degree or second-degree type II atrial-ventricular blocks, and two (6.3%) had second-degree type II atrial-ventricular blocks. Most of these arrhythmias were transient and relieved after CCB dose adjustment. The most reported noncardiovascular adverse effect was gingival hyperplasia (13, 40.6%), accompanied by different degrees of dental dysplasia. No liver or kidney dysfunction was reported.ConclusionDiltiazem was used in a very high dose for eligible children with IPAH/HPAH. The toxicity of long-term CCB use on the cardiovascular system is mild and controllable. Clinicians should also monitor the noncardiovascular adverse effects associated with drug therapy.

Calcium for pre-eclampsia prevention: A systematic review and network meta-analysis to guide personalised antenatal care.

Calcium supplementation reduces the risk of pre-eclampsia, but questions remain about the dosage to prescribe and who would benefit most. To evaluate the effectiveness of high (≥1g/day) and low (<1g/day) calcium dosing for pre-eclampsia prevention, according to baseline dietary calcium, pre-eclampsia risk and co-interventions, and intervention timing. CENTRAL, PubMed, Global Index Medicus and CINAHL, from inception to 2 February 2021, clinical trial registries, reference lists and expert input (CRD42018111239). Randomised controlled trials of calcium supplementation for pre-eclampsia prevention, for women before or during pregnancy. Network meta-analysis (NMA) also included trials of different calcium doses. Two independent reviewers extracted published data. The meta-analysis employed random-effects models and the NMA, a Bayesian random-effects model, to obtain direct and indirect effect estimates. The meta-analysis included 30 trials (N=20 445 women), and the NMA to evaluate calcium dosage included 25 trials (N=15 038). Calcium supplementation prevented pre-eclampsia similarly with a high dose (RR0.49, 95%CI 0.36-0.66) or a low dose (RR0.49, 95%CI 0.36-0.65). By NMA, high-dose (vs low-dose) calcium did not differ in effect (RR0.79, 95%CI 0.43-1.40). Calcium was similarly effective regardless of baseline pre-eclampsia risk, vitamin D co-administration or timing of calcium initiation, but calcium was ineffective among women with adequate average baseline calcium intake. Low- and high-dose calcium supplementation are effective for pre-eclampsia prevention in women with low calcium intake. This has implications for population-level implementation where dietary calcium is low, and targeted implementation where average intake is adequate. A network meta-analysis of 25 trials found that low-dose calcium supplementation (<1g/day) is as effective as high-dose calcium supplementation (≥1g/day) in halving the risk of pre-eclampsia when baseline calcium intake is low.

Another case of milk–alkali syndrome or a learning opportunity?

SummaryMilk–alkali syndrome (MAS) is a triad of hypercalcaemia, metabolic alkalosis and renal insufficiency. In this study, we present a case of milk–alkali syndrome secondary to concurrent use of over-the-counter (OTC) calcium carbonate-containing antacid tablets (Rennie®) for dyspepsia and calcium carbonate with vitamin D3 (Adcal D3) for osteoporosis. A 72-year-old woman presented with a 2-day history of nausea, vomiting, epigastric pain, constipation, lethargy and mild delirium. Past medical history included osteoporosis treated with daily Adcal D3. Initial blood tests showed elevated serum-adjusted calcium of 3.77 mmol/L (normal range, 2.2–2.6) and creatinine of 292 µmol/L (45–84) from a baseline of 84. This was corrected with i.v. pamidronate and i.v. fluids. She developed asymptomatic hypocalcaemia and rebound hyperparathyroidism. Myeloma screen, vasculitis screen and serum angiotensin-converting enzyme (ACE) were normal, while the CT of the chest, abdomen and pelvis showed renal stones but no malignancy. A bone marrow biopsy showed no evidence of malignancy. Once the delirium resolved, we established that prior to admission, she had been excessively self-medicating with over-the-counter antacids (Rennie®) as required for epigastric pain. The increasing use of calcium preparations for the management of osteoporosis in addition to easily available OTC dyspepsia preparations has made MAS the third most common cause of hypercalcaemia hospitalisations. Educating patients and healthcare professionals on the risks associated with these seemingly safe medications is required. Appropriate warning labels on both calcium preparations used in the management of osteoporosis and OTC calcium-containing preparations would prevent further similar cases and unnecessary morbidity and hospital admission.Learning pointsWhat is known?An association between high-dose calcium supplementation and hypercalcaemia crisis has been seen in case studies.After as little as 1 week of excessive calcium carbonate ingestion, patients can present with symptomatic hypercalcemia, acute renal failure and metabolic alkalosis (1).Women aged 50 and younger need 1 g of calcium per day, while aged 51 and older need 1.2 g (1).Although the amount of calcium required for MAS is generally thought to be more than 4 g per day, there have been reports at intakes as low as 1.0–1.5 g per day in pre-existing risk factors including renal impairment (2).What this study adds?The danger of excessive ingestion of antacid is not adequately highlighted to prescribers and patients.Appropriate warning labels on OTC calcium-containing preparations could prevent unnecessary morbidity and hospital admission.

A case report of a 37-year-old woman with pulmonary arterial hypertension first presented during her 3rd pregnancy and favourable long-term vasoreactive response

BackgroundPulmonary arterial hypertension is a rare disease associated with high rates of mortality and can significantly complicate pregnancy posing health risks for the mother and child alike.Case summaryWe present the case of a 37-year-old female patient with World Health Organisation functional Class IV symptoms during the 34th week of her 3rd pregnancy. Initial echocardiography showed a significantly elevated estimated systolic pulmonary artery pressure of 86 mmHg + central vein pressure as well as signs of chronic pulmonary hypertension. After a successful emergent caesarean section, pulmonary hypertension was confirmed via right heart catheterization. After exclusion of secondary aetiologies of pulmonary hypertension, the diagnosis of Class 1 pulmonary artery hypertension was made. We initially treated the patient with the phosphodiesterase-5 inhibitor sildenafil (20 mg oral bid trice daily) and later extended the medication with the dual endothelin receptor antagonist Macicentan (10 mg daily). Since the patient remained symptomatic vasodilator testing was performed and showed a significant response to intravenous Epoprostenol. We initiated a high-dose calcium channel blocker (CCB) therapy with amlodipine (20 mg daily) which led to symptomatic relief, increased exercise capacity as well as reduction in mean pulmonary artery pressure and pulmonary vascular resistance as confirmed by another right heart catheterization after therapy initiation.DiscussionSince the presentation is usually non-specific, the diagnosis of pulmonary artery hypertension can be challenging and cause a delay in treatment initiation. Even though rare vasodilator testing and invasive haemodynamic measurements should be performed to identify patients with favourable long-term response to high-dose CCB.

Clinical Study of High Dose Calcium to Prevent Pregnancy Specific Hypertensive Disorders, Their Severity, Still A Research Agenda!

Background: Worldwide hypertensive disorders of pregnancy (HDsP) continue to be leading causes of maternal, perinatal severe morbidity mortality, long term disabilities. Prevention of HDsP, their severity through high dose calcium supplementation is being suggested. However, whether calcium really helps is still not established. So, research continues. Objectives: Present study was carried out to know the efficacy of high dose daily calcium from midpregnancy on reduction in occurrence of HDsP, their severity and perinatal outcome. Material Methodology: Study was done with 1200 women, (600 cases, 600 controls) of 18-39 years with, 20 + 2 weeks pregnancy, no obvious medical disorders in mothers, no ultra sonographically diagnosed anomaly in fetus at entry to study. Study cases (S) received 2 gms oral calcium daily, similar controls (C) were not given calcium. Research assistant was not part of the care providers, but kept track of everything. Women got antenatal care, clinicians not knowing which women got extra calcium. Desired information, pregnancy outcome, complications during pregnancy, birth weight, neonatal outcome, admission of baby to neonatal intensive care unit and compliance to calcium tablets in study subjects was collected by research assistant using pretested tool. Results: HDsP occurred in 7.5% S cases, 7.33% C group. Amongst group S9.43% Primigravida, 4.3% Multigravida developed HDsP (gestational hypertension 6%, preeclampsia 1.16%, eclampsia 0.33%). In group C 8.04% primigravida, 3.08% multigravida developed HDsP, (6%GH, 1% preeclampsia, 0.33% eclampsia), Total 8.8% perinatal deaths occurred in S cases who had HDsP, 2.27% in C, with HDsP and no maternal death. Conclusion: No benefit was found with high dose calcium. On the contrary, perinatal outcome was poorer. More research is needed about high dose calcium for HDsP, their severity, perinatal outcome. Keywords: Hypertensive Disorders of Pregnancy; Occurrence; Severity; Perinantal outcome

Calcium supplementation during pregnancy and long-term offspring outcome: a systematic literature review and meta-analysis.

The World Health Organization currently recommends calcium supplementation for pregnant women, especially those with low calcium intakes, to reduce the risk of hypertension and preeclampsia. We aimed to evaluate the effect of this intervention on selected offspring outcomes. A systematic search was conducted in 11 databases for published randomized controlled trials (RCTs) on the effect of maternal calcium supplementation with or without vitamin D during pregnancy on selected offspring cardiovascular, growth, and metabolic and neurodevelopmental outcomes. Screening of titles and abstracts of 3555 records and full texts of 31 records yielded six RCTs (nine reports, n = 1616). Forest plot analyses were performed if at least two studies presented comparable data on the same outcome. In one study (n = 591), high‐dose calcium supplementation during pregnancy was associated with a decreased risk of offspring high systolic blood pressure at 5–7 years of age (risk ratio = 0.59; 95% confidence interval: 0.39–0.90). The effects of the intervention on offspring growth, metabolic, and neurodevelopmental outcomes remain unknown because of conflicting or insufficient data. High risk of attrition bias decreased the quality of the evidence. Limited available data from RCTs do not provide sufficient evidence to conclude that prenatal calcium supplementation influences offspring health outcomes beyond the newborn period.

Non-inferiority of low-dose compared to standard high-dose calcium supplementation in pregnancy: study protocol for two randomized, parallel group, non-inferiority trials in India and Tanzania

BackgroundHypertensive disorders of pregnancy are important causes of maternal morbidity and mortality, as well as preterm birth, the leading cause of death for children under 5 years globally. The World Health Organization currently recommends that pregnant women receive high-dose calcium supplementation (1500–2000 mg elemental calcium) for prevention of preeclampsia in populations with low dietary calcium intake. Trials of low-dose calcium supplementation (< 1000 mg elemental calcium/day) during pregnancy have also shown similar reductions in the risk of preeclampsia; however, no trials to date have directly compared low-dose to the standard high-dose calcium supplementation. Our objective is to assess the non-inferiority of low-dose as compared to standard high-dose calcium supplementation in pregnancy.Methods/designWe will conduct two independent trials in Bangalore, India (n = 11,000 pregnancies), and Dar es Salaam, Tanzania (n = 11,000 pregnancies). The trial designs are individually randomized, parallel group, quadruple-blind, non-inferiority trials of low-dose calcium supplementation (500 mg elemental calcium/day) as compared to standard high-dose calcium supplementation (1500 mg elemental calcium/day) among nulliparous pregnant women. Pregnant women will be enrolled in the trial before 20 weeks of gestation and will receive the randomized calcium regimen from randomization until the time of delivery. The co-primary outcomes are (i) preeclampsia and (ii) preterm birth; we will test non-inferiority of the primary outcomes for low-dose as compared to the standard high-dose supplementation regimen in each trial. The trials’ secondary outcomes include gestational hypertension, severe features of preeclampsia, pregnancy-related death, third trimester severe anemia, fetal death, stillbirth, low birthweight, small-for-gestational age birth, and infant death.DiscussionThe trials will provide causal evidence on the non-inferiority of low-dose as compared to the standard high-dose supplementation in India and Tanzania. A single tablet, low-dose calcium supplementation regimen may improve individual-level adherence, reduce programmatic costs, and ultimately expand implementation of routine calcium supplementation in pregnancy in populations with low dietary calcium intake.Trial registrationClinicalTrials.gov identifier: NCT03350516; registered on 22 November 2018. Clinical Trials Registry—India identifier: CTRI/2018/02/012119; registered on 23 February 2018.Tanzania Medicines and Medical Devices Authority Trials Registry identifier: TFDA0018/CTR/0010/5; registered on 20 December 2018.

Study on Application of High-dose Atorvastatin Calcium in the Treatment of Elderly Patients with Coronary Heart Disease and Heart Failure

Study on Application of High-dose Atorvastatin Calcium in the Treatment of Elderly Patients with Coronary Heart Disease and Heart Failure

Calcium supplementation during pregnancy and maternal and offspring bone health: a systematic review and meta-analysis.

Insufficient calcium intake during pregnancy may lead to maternal bone resorption and lower bone density of offspring. We evaluated the impact of supplementary calcium with or without vitamin D during pregnancy on maternal and offspring bone mineral density (BMD) and teeth firmness of the offspring. Randomized controlled trials (RCTs) were searched systematically in 11 databases. Two researchers independently screened the titles and abstracts of 3555 records and the full texts of 31 records to examine eligibility. The search yielded seven RCTs (11 reports, n = 1566). No advantage of calcium supplementation was found on maternal BMD after delivery or during breastfeeding, or on offspring BMD, even when dietary calcium intake was low. The results were neither modified by the dose of calcium nor concomitant vitamin D administration. A suspicion of some long‐term harm of the intervention on maternal BMD and growth of female offspring was raised based on the data. One study suggested some benefit of high‐dose calcium supplementation on offspring teeth firmness at 12 years old. A low number of the studies and abundant missing data reduced the quality of the findings. The impact of calcium supplementation on maternal and offspring bone health was deemed unknown because of inconclusive research results.

Severe Hypophosphatemia and Elevated FGF23 Level Following Zoledronic Acid Infusion

Background: Severe hypophosphatemia may be seen following zoledronic acid infusion, however FGF23 elevation has not been previously reported. Clinical Case: A 67-year-old man with Crohn’s disease status post remote ileocolonic resection, malnutrition (BMI 16.7), anemia, history of hypovitaminosis D, secondary hyperparathyroidism, and severe osteoporosis, was advised to present to the emergency room for hypocalcemia and hypophosphatemia after routine lab draw. His initial ionized calcium was 0.89 mmol/L (1.09–1.29 mmol/L) and phosphorus was 0.9 mg/dL (2.3–4.4 mg/dL), with a 25-hydroxyvitamin D level of 62 ng/mL (20–50 ng/mL), PTH of 132 pg/mL (11–51 pg/mL), and normal renal function. Hemoglobin was stable between 8–9 g/dL (13.5–17.1 g/dL). He endorsed ongoing fatigue, oral ulcers, and perioral numbness, which had been attributed to Humira infusion 2 months prior. He denied other paresthesias, carpopedal spasms, seizures, bone pain, or confusion. He reported receiving his second annual infusion of zoledronic acid 10 days prior in Turkey. He was started on high-dose oral calcium, calcitriol, and phosphate, which were continued on discharge 5 days later. Several days into his hospitalization, the patient spoke with his wife in Turkey who confirmed that his calcium and phosphorus were both within normal limits immediately prior to his infusion. A 1,25-hydroxyvitamin D level obtained during his workup was normal at 42.5 pg/mL (19.9–79.3 pg/mL), however an FGF23 level, which returned 2 weeks later, was elevated at 287 RU/mL (<=180 RU/mL). Dotatate PET to rule out oncogenic osteomalacia was negative. One month later, after normalization of calcium and phosphorus levels, repeat PTH and FGF23 levels were both within normal limits. Conclusion: This case demonstrates that a transient increase in FGF23 levels may accompany and exacerbate hypophosphatemia following zoledronic acid infusion. The mechanism for this elevation is unclear, though we speculate that in the setting of acute hypocalcemia and hypophosphatemia due to zoledronic acid infusion, secondary hyperparathyroidism may upregulate FGF23 production, which further decreases phosphorus levels. If this scenario is accurate, the transient FGF23 elevation seen is not pathologic, but physiologic. Indeed, in the patient above, calcium and phosphorus repletion lead to normalization of both PTH and FGF23.

A Case of Psuedohypoparathyroidism Unmasked by COVID-19 and Rhabdomyolysis

Background: Psuedohypoparathyroidism type 1 b (PHP 1b) is a rare condition characterized by hormone resistance with PTH. It is caused by imprinting defect of the GNAS gene and is acquired as autosomal dominant. Compared with Pseudohypoparathyroidism type 1a (PHP1a), PHP1b does not have the characteristic physical features know as Albright hereditary osteodystrophy or AHO. Results: 12-year-old female with unremarkable past medical history presented with seizures. She has been complaining of leg pain for a week but on the day of presentation noted to have stiffening and shortness of breath. There was no history of cough, fever, leg trauma, headache, dysuria, hematuria or dark urine. She had no significant family history. Work up revealed severe hypocalcemia of 4.6 mg/ dL and elevated phosphorus (7.1mg/dl). There was no hypoglycemia and other electrolytes including renal function were normal. Patient also had normal inflammatory markers, normal fibrinogen, and normal ferritin. Urine was positive for trace protein and was positive for myoglobin. Alkaline phosphatase was normal. Urine toxicology screen was negative. Hand X-rays did not showed the shortening of metacarpal bones and kidney ultrasound was normal. After IV calcium bolus, calcium barely increased at 5.0. Interestingly CK was noted to be elevated at 3,794 U/L. Patient physical exam was normal and there was no signs of Albright hereditary osteodystrophy (AHO). Patient was positive for COVID19. Patient required intensive fluid therapy to correct CK which increased up to 11,223 U/L on 3rd day of admission. It eventually came down back to normal on the 6th day. Creatinine levels remained normal. Patient continued to receive high dose calcium and calcitriol supplement and discharged with calcium of 8.5 mg/dL and phosphorus of 7.8 mg/dL. Additional work up showed PTH of 885 pg/mL consistent with pseudohypoparathyroidism. Vitamin D levels and thyroid function were normal. Genetic testing for pseudohypoparathyroidism is awaited. Conclusion: Psuedohypoparathyroidism type 1 b (PHP 1b) is a rare endocrine disorder presenting with hypocalcemia, hyperphosphatemia and increased PTH values due to a variable resistance to target organs. As in our case it was unmasked by COVID 19 infection and rhabdomyolysis. Best of our knowledge there is no such unusual case reported in children. Severe hypocalcemia likely due to combination of factors including tissue calcium deposition, hyperphosphatemia, and skeletal resistance to PTH. As published in some recent reports, this case also illustrates that rhabdomyolysis could be potential complication of SARS- CoV2 infection in early stage with normal renal function, which warrants further research.

Severe hypocalcaemia in a COVID-19 female patient.

SummaryComorbidities are a risk factor for patients with COVID-19 and the mechanisms of disease remain unclear. The aim of this paper is to present a case report of an COVID-19 patient with severe hypocalcaemia. This is a report of an 81-year-old female, suffered from myalgia and fatigue for more than 3–4 weeks. Fever and cough appear 2 days before she presented to the emergency room. On physical examination, she was febrile with a temperature of 38.8°C, accompanied by cough, sore throat, headache, fatigue, and muscle ache. Her past medical history was remarkable with no chronic disease. She had lymphopenia. Laboratory test revealed moderate liver dysfunction, hypoalbuminemia, and severe hypocalcaemia (serum corrected calcium level: 5.7 mg/dL). Parathyroid hormone (PTH) was 107.9 pg/mL (range: 15–65) and 25(OH)2D levels was 4.5 ng/mL (range: 25–80). Chest CT scan detected peripheral ground-glass opacity. Throat swab for coronavirus by RT-PCRassay tested positive for the virus. She was treated with lopinavir/ritonavir, third generation cephalosporin, anticoagulant, daily high-dose calcium acetate, vitamin D3, fresh frozen plasma and oxygen therapy. She was discharged after two negative throat swab tests for coronavirus by conventional RT-PCR.Learning pointsComorbidities are a risk factor for patients with COVID-19.Laboratory findings are unspecific in COVID-19 patients; laboratory abnormalities include lymphopenia, elevated of LDH, CPK and the inflammatory markers, such as C reactive protein, ferritinemia and the erythrocyte sedimentation rate.In addition to inflammatory markers, in COVID-19 patients it is crucial to check the level of vitamin D and calcium.There may be a correlation between vitamin D deficiency and the severity of COVID-19 disease.

Role of High Dose Calcium Supplementation in Pre-eclampsia: A Pilot Study

Introduction: Pre-eclampsia is a serious condition complicating pregnancy. It is a multisystem disorder responsible for significant maternal and perinatal morbidity and mortality. Thus, prevention of pre-eclampsia may improve both maternal and foetal outcomes. It has been found that reduced serum calcium level may cause high blood pressure by stimulating parathyroid hormone, rennin release and also by producing vasoconstriction in smooth muscle. Aim: To evaluate the role of high dose (2000 mg/day) calcium compared to normal dose (1000 mg/day) calcium in preventing the incidence and severity of pre-eclampsia. Materials and Methods: This was a pilot study and this prospective interventional study conducted from January 2017 to June 2018 in Kolkata, India with 200 primigravidas. About 100 women were given 1000 mg calcium and 100 women were given 2000 mg (high dose) calcium in a day. Incidence of gestational hypertension, pre-eclampsia, severe pre-eclampsia, neonatal outcome etc were assessed in both the groups. Normally distributed data were compared with Student’s unpaired t-test. p-value was considered statistically significant when ≤0.05. Results: There was a significant reduction in the incidence of pre- eclampsia (p-value=0.03) among the cases receiving high dose calcium, without any statistically significant reduction in severity of it. There was no reduction in incidence of gestational hypertension with high dose calcium. In neonatal outcome, there was better APGAR score in the high dose group compared to control group (16% in cases and 7% in control group, p-value=0.04). Conclusion: This pilot study paves the way for larger studies to study the role of high dose of calcium which may have a significant role in reduction of pre-eclampsia.

Contemporary pharmacological treatment strategies for patients with angina and unobstructed coronary arteries (ANOCA) due to coronary microvascular dysfunction

In recent years, there has been important progress in the evolving field of coronary vasomotor disorders regarding diagnostic assessments and therapeutic strategies. It is now commonly accepted that patients with angina and unobstructed coronary arteries (ANOCA) frequently suffer from coronary vasomotor disorders. The latter can be reliably diagnosed using invasive diagnostic procedures. They comprise the detection of epicardial and/or microvascular spasm, impaired coronary vasodilatation, and enhanced microvascular resistance. As these mechanisms may overlap in one given patient, various endotypes of disease can be distinguished. Although evidence from randomized clinical trials in this setting is still sparse, it has been suggested that - in addition to strict risk factor control-targeted pharmacological therapies/treatments based on the identified mechanism of disease can improve symptoms and prognosis. In patients with coronary spasm as the predominant mechanism, first-line treatment consists of high-dose calcium channel blockers and nitrates. In patients with impaired vasodilatation or enhanced microvascular resistance, beta-blockers, angiotensin-converting enzyme inhibitors, and statins represent first-line treatment. In the group of patients with symptoms refractory to first-line medication, second-line drugs such as nicorandil, molsidomine, ranolazine, ivabradine, and others for microvascular dysfunction are available. Moreover, ongoing studies in this area are evaluating the usefulness of newer pharmacological agents such as endothelin-receptor antagonists or soluble guanylate cyclase stimulators. This article summarizes the currently available evidence for pharmacological treatment strategies in patients with ANOCA due to coronary microvascular dysfunction.

Acute vasoreactivity testing predicts outcome of idiopathic pulmonary arterial hypertension patients with a negative acute response.

BackgroundAcute vasoreactivity testing (AVT) during right heart catheterization (RHC) is performed in certain subsets of patients with pulmonary arterial hypertension (PAH) in order to identify those who benefit from calcium channel blockers. The present study aimed to investigate the prognostic value of pre-AVT, post-AVT, and changes in AVT (ΔAVT) parameters for idiopathic PAH (IPAH) patients with a negative acute response, and to identify sex differences that could be of prognostic value.MethodsA total of 487 incident IPAH patients (171 males and 316 females) with a negative acute response to AVT were recruited from Shanghai Pulmonary Hospital between 2009 and 2018. Outcomes were predicted using the Kaplan-Meier curve and univariate/multivariate Cox regression analyses. All patients were followed up till January 2020, with outcome specified as all-cause mortality.ResultsInhalation of iloprost aerosol improved the hemodynamic parameters for all patients. Post-PVR was decreased, and post-cardiac output (post-CO) and post-cardiac index (post-CI) were increased compared with pre-AVT parameters among males. Increased post- artery oxygen saturation (post-SaO2) and decreased post-mean right atrium pressure (post-mRAP) were also observed in females. For all patients, pre-CO ≥3.25 L/min, post-mPAP <53 mmHg, and post-mixed venous oxygen saturation (post-SvO2) ≤63% were parameters suggesting better prognosis. For males, patients with pre-PVR <12.47 Wood units, pre-SvO2 ≥64%, and post-mean pulmonary artery pressure (post-mPAP) <51 mmHg had a better prognosis. For females, patients with ΔmPAP ≥−4 mmHg and ΔPVR ≥−0.25 Wood units had better outcomes.ConclusionsAVT parameters, including pre-AVT, post-AVT and ΔAVT, have a more important prognostic value than currently used for identify a small subgroup of patients with PAH who are suitable for high-dose calcium channel blockers. Sex differences in AVT parameters suggest that sex should be taken into account in estimating prognosis.

The Role of Giving High Dose Calcium for Preventing Preeclampsia

AbstractObjective: Knowing the effectiveness of high doses of calcium in preventing preeclampsia.Methods: Experimental analytical study with Randomized Controlled design Single-blind trial in the form of survival analysis (survival analysis) in the period June 2018 - May 2019 in fetomaternal outpatients clinic in Mohammad Hoesin Hospital, PalembangResults: The mean hemoglobin level at the last visit found that the average hemoglobin level between the two groups was 12.81 in the high calcium group and 12.61 in the low calcium group, while the mean hematocrit level between the two groups was 35.17 in the high calcium group and 34.84 in the low calcium group and the respective calcium levels each group is 10.1. In this study, after high calcium intervention, no pregnant women with preeclampsia were found, whereas in the low-dose calcium intervention group it was found that 3 of 17 patients (17.7%) had preeclampsia. With the McNemar test it was found that there was no difference in the incidence of preeclampsia both after highdose calcium and low-dose calcium interventions (p = 0.250).Conclusions: High-dose calcium (1.5g - 2g) is effective in preventing preeclampsia and there was no difference in effectiveness between administration of high-dose calcium with low-dose calcium administration to the incidence of preeclampsia.Keywords: high dose calcium, preeclampsia, randomized control trial.&#x0D; AbstrakTujuan: Mengetahui efektivitas pemberian kalsium dosis tinggi dalam mencegah preeklamsia.Metode: Penelitian analitik eksperimental dengan desain randomized controlled trial single blind dalam bentuk ujian alias kesintasan (survival analysis) dalam kurun waktu Juni 2018 – Mei 2019 di Poliklinik Fetomaternal Rumah Sakit Umum Pendidikan Mohammad Hoesin, PalembangHasil: Rerata kadar hemoglobin pada kunjungan terakhir didapatkan rerata kadar hemoglobin antara kedua kelompok adalah 12,81 pada kelompok kalsium tinggi dan 12,61 pada kelompok kalsium rendah, sedangkan rerata kadar hematokrit antara kedua kelompok adalah 35,17 pada kelompok kalsium tinggi dan 34,84 pada kelompok kalsium rendah dan rerata kadar kalsium masing-masing kelompok adalah 10,1. Pada penelitian ini setelah intervensi kalsium tinggi tidak ditemukan ibu hamil yang mengalami preeklamsia, sedangkan pada kelompok intervensi kalsium dosis rendah ditemukan 3 dari 17 pasien (17,7%) menderita preeklamsia. Dengan uji Mc Nemar didapatkan hasil tidak terdapat perbedaan kejadian preeklamsia baik setelah intervensi kalsium dosis tinggi maupun kalsium dosis rendah (p = 0,250). Hal ini berarti kalsium dosis tinggi dan rendahefektif untuk mencegah preeklamsia.Kesimpulan: Kalsium dosis tinggi (1,5g – 2g) efektif dalam mencegah preeklamsia dan tidak ditemukan perbedaan efektivitas antara pemberian kalsium dosis tinggi dengan pemberian kalsium dosis rendah terhadap kejadian preeklamsia.Kata kunci: kalsium dosis tinggi, preeklamsia, randomized control trial.

Appropriate Phosphorus Intake by Parenteral Nutrition Prevents Metabolic Bone Disease of Prematurity in Extremely Low-Birth-Weight Infants.

Metabolic bone disease (MBD) is a common disorder in extremely low-birth-weight (ELBW) infants. However, no studies have investigated whether high-dose calcium (Ca) and phosphorus (P) supplementation by parenteral nutrition (PN) prevents MBD in ELBW infants. This study aimed to identify the effect of PN on MBD in ELBW infants. We retrospectively analyzed ELBW infants who were admitted between April 2011 and March 2017. ELBW infants were divided into the low-P group (n = 22) and the high-P group (n = 26) according to the dose of parenteral P supply. Biochemical and radiological markers of MBD and treatments were analyzed. Mean daily parenteral intake of Ca and P in the first week was significantly higher in the high-P group than in the low-P group (both P ≤ .001). Serum alkaline phosphatase (ALP) levels were significantly higher in the low-P group than in the high-P group in the first month. ELBW infants in the low-P group received alfacalcidol much more frequently than those in the high-P group. There was a trend of a higher rate of x-ray changes in the low-P group than in the high-P group. No infants developed bone fractures. Appropriate P intake by PN is required to ensure high Ca intake, reduce ALP levels in the first month, and prevent MBD from hyperparathyroidism and does not worsen x-ray findings in ELBW infants.

Effect of Xiaoji Recipe on stability of carotid artery vulnerable plaque in elderly patients with type 2 diabetes mellitus and type H hypertension

To explore the effect of Xiaoji Recipe on the stability of carotid artery vulnerable plaque in elderly patients with type 2 diabetes mellitus and type H hypertension(Qi-Yin deficiency with phlegm stagnation). From January 2017 to April 2019, in Endocrinology Department for Outpatients and Inpatients of the First Affiliated Hospital of Henan University of Chinese Medicine, 125 elderly patients with type 2 diabetes mellitus and type H hypertension with carotid artery vulnerable plaque(Qi-Yin deficiency with phlegm stagnation) were selected. According to the numerical table method, the patients were randomly divided into the control group(63 cases, including 56 cases completed) and Xiaoji group(62 cases, including 58 cases completed). Both groups were given control diet, hypoglycemic, hypotensive and symptomatic therapies. The control group was given Rosuvastatin Calcium Tablets 20 mg·d~(-1) before sleep. The Xiaojie group were given Ruisuvastatin Calcium Tablets 10 mg·d~(-1) before sleep, plus Xiaoji Recipe at the same time. Both groups were treated for 6 months. The number of vulnerable plaques, carotid intima-media thickness(IMT) and plaque thickness were detected by color Doppler ultrasound before and after treatment, in order to calculate IMT integral and improved Crouse integral. Meanwhile, lipid metabolism indexes, including total cholesterol(TC), triacylglycerol(TG), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C) and lipoprotein a(LPa). And plaque stability indexes, including hypersensitive c-reactive protein(hs-CRP), matrix metalloproteinase-9(MMP-9), oxidized low-density lipoprotein(ox-LDL), Ⅰ type platelet depolymerization protein binding protein base sequence of metalloproteinases(ADAMTS-Ⅰ) and homocysteine(Hcy) were detected. To evaluate the 6-month curative effect on TCM syndrome, the patients were followed up for 6 months for adverse cardiovascular and cerebrovascular events and adverse drug reactions. After 6 months of treatment, the efficacy on Xiaoji group was better than that of the control group(Z=-2.600, P=0.009). The significant efficiency of the Xiaoji group was higher than that of the control group(χ~2=6.039, P=0.014). The total effective rate of the Xiaoji group was higher than that of the control group(χ~2=4.564, P=0.033). The number of vulnerable plaques form indexes(IMT, IMT integral, plaque thickness, improved Crouse integral), blood lipid metabolism indexes(TC, TG, LDL-C, HDL-C, LPa) and plaque stability indexes(hs-CRP, MMP-9, ox-LDL, ADAMTS-Ⅰ, Hcy) were significantly improved than before treatment in both groups of patients(P&lt;0.01). Compared with the control group, the Xiaoji group showed more obvious improvement(P&lt;0.01). The incidence of adverse cardiovascular and cerebrovascular events in the Xiaoji group was lower than that in the control group within 6 months after treatment(χ~2=4.566, P=0.033). The incidence of adverse drug reactions in the Xiaoji group was lower than that in the control group(χ~2=4.465, P=0.035). This indicated that Xiaoji Recipe combined with small-dose Rosuvastatin Calcium(10 mg·d~(-1)) was safe and effective in the treatment of elderly patients of type 2 diabetes mellitus with type H hypertension and vulnerable carotid artery plaque(Qi-Yin deficiency with phlegm stagnation), and superior to the single high-dose Risovastatin Calcium(20 mg·d~(-1)) regimen. It can reverse carotid plaque, and reduce the activity of vulnerable plaque and the incidence of adverse cardiovascular and cerebrovascular events and adverse drug reactions.

A New Therapeutic Approach Using a Calcilytic (AXT914) for Postsurgical Hypoparathyroidism in Female Rats.

Postsurgical hypoparathyroidism is the most common complication of thyroid surgery. Conventional therapy with high-dose calcium and vitamin D can correct hypocalcemia but can increase the risk of hypercalciuria, renal stones, or ectopic calcification. The aim of the present study was to investigate the efficacy of a calcium-sensing receptor antagonist, also called a calcilytic (AXT914), in rat models of postsurgical hypoparathyroidism. Two postsurgical hypoparathyroidism rat models were made by hemi-parathyroidectomy or total parathyroidectomy with autotransplantation in 10-week-old female Wistar rats. AXT914 or vehicle was administered orally for 2 to 3 weeks. Serum PTH, calcium, and phosphorus levels, and the urinary excretion of calcium were measured. Autotransplanted parathyroid tissues were collected and examined histologically. In the hemi-parathyroidectomy model, the oral administration of the calcilytic AXT914 (5 and 10 mg/kg) for 2 weeks increased serum PTH and calcium levels and decreased serum phosphorus levels and urinary calcium excretion. In the total parathyroidectomy with autotransplantation model, the oral administration of AXT914 (10 mg/kg) for 3 weeks increased serum PTH and calcium levels and decreased serum phosphorus levels. The serum PTH and calcium levels increased by AXT914 were maintained for 1 week, even after discontinuation of the drug. In conclusion, AXT914 increased PTH secretion in rat models of postsurgical hypoparathyroidism, thereby correcting abnormal calcium and phosphorus homeostasis. Furthermore, AXT914 improved the functional recovery of autotransplanted parathyroid tissues.