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Hypertension is a complex condition in which various actors and mechanisms combine, resulting in cardiovascular and cerebrovascular complications that today represent the most frequent causes of mortality, morbidity, disability, and health expenses worldwide. In recent decades, there has been an exceptional number of experimental, epidemiological, and clinical studies confirming a close relationship between magnesium deficit and high blood pressure. Multiple mechanisms may help to explain the bulk of evidence supporting a protective effect of magnesium against hypertension and its complications. Hypertension increases sharply with advancing age, hence older persons are those most affected by its negative consequences. They are also more frequently at risk of magnesium deficiency by multiple mechanisms, which may, at least in part, explain the higher frequency of hypertension and its long-term complications. The evidence for a favorable effect of magnesium on hypertension risk emphasizes the importance of broadly encouraging the intake of foods such as vegetables, nuts, whole cereals and legumes, optimal dietary sources of magnesium, and avoiding processed foods, which are very poor in magnesium and other fundamental nutrients, in order to prevent hypertension. In some cases, when diet is not enough to maintain an adequate magnesium status, magnesium supplementation may be of benefit and has been shown to be well tolerated.

Abstract: Magnesium deficiency is defined as a pathophysiologic factor in numerous illnesses. This study aims to define the effects of magnesium levels on patients in the intensive care unit (ICU) regarding length of stay in the ICU, length of mechanical ventilation (MV), and 28-day mortality.The following data were collected during initial assessment of patients admitted to the ICU with acute respiratory failure (ARF). Demographic data, magnesium and potassium levels, Charlson's Comorbidity Index (CCI), Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores, length of MV, length of hospital stay in the ICU, 28-day mortality, and ICU discharge status.In the initial serum analysis prior to treatment of patients in the ICU, the mortality rate of the patient group with hypermagnesemia was found to be statistically significant when compared with other magnesium levels (P = .018). Apart from renal failure, ICU mortality is higher in the hypermagnesemia group than other groups.Hypermagnesemia is an electrolyte abnormality that is generally seen in older individuals and those with serious comorbidity and it can be used in mortality prediction., Competing Interests: The authors have no funding and conflicts of interests to disclose., (Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Patients receiving chemotherapy frequently experience electrolyte imbalances. Electrolyte replacement is, therefore, a necessity as patients may experience life-threatening symptoms. Study objective: The objective of this study was to evaluate the occurrence of low serum potassium and magnesium, and identify the rate of replacement for patients with low serum potassium and magnesium levels. Based on our findings, we developed and implemented a nursing-driven electrolyte replacement protocol., Methods: Preimplementation phase - A retrospective review for serum potassium and magnesium values obtained during infusion clinic visit between 1 August and 31 October 2016 was conducted. Implementation phase - A nursing-driven electrolyte replacement protocol with medication order "smart-set" and order selection intelligence within EPIC Beacon was developed and implemented in May 2017. Postimplementation phase - The postimplementation phase data were collected from 1 August to 30 November 2017 using a similar approach as the preimplementation phase., Results: Preimplementation phase - During the preimplementation phase of the study, a total of 1495 serum potassium levels and 1193 serum magnesium levels were obtained. Among the 152 patients who needed potassium replacement, 34% ( n  = 52) were replaced and among the 118 serum magnesium levels that needed replacement, 30% ( n  = 35) were replaced. Postimplementation phase - 3979 serum potassium and 2707 magnesium levels were obtained. Among the 170 patients who needed potassium replacement, 75% ( n  = 127) were replaced. Among the 142 patients who needed magnesium replacement, 73% ( n  = 104) were replaced., Conclusion: A 121% increase in potassium replacement and a 143% increase in magnesium replacement were identified after implementing this protocol.

Background and Objectives: Lead (Pb) has been reported to disturb the metabolism of essential elements, such as calcium (Ca), magnesium (Mg), iron (Fe) and zinc (Zn) in vivo. This study focused on the relationship between various dose of Pb and the essential elements., Methods: 50 healthy male C57BL/6 mice underwent oral administration of 0.2 mL lead acetate trihydrate solution (0, 20, 100, 500, and 1000 mg Pb/day/kg body weight) for 3 days. The concentrations of Pb and four essential elements (Ca, Zn, Fe and Mg) in the blood, kidney, liver, bone and brain were quantified with inductively coupled plasma mass spectrometry., Results: Various doses of Pb led to significant increases in the contents of Ca, Fe and Zn in the liver, and decreased contents of Mg and Fe in the blood in a dose-dependent pattern. The Pb dose of 20 mg/kg reduced the concentration of bone Ca, which did not continue to show an obvious decline with continued increases in the oral Pb dose. Pb also caused alterations in the Mg distribution pattern, and decreased the correlation of Mg, Ca and Zn in the brain, both findings were dose-dependent. In addition to the changes in metallomics, the related oxidative stress was exacerbated, but no significant changes were detected in hepatic and renal histopathological lesions after a short period of Pb exposure., Conclusions: This study contributes to a thorough analysis of the Pb-poisoning mechanism, and indicates that the concentrations of essential elements could be used as sensitive toxicological indicators of Pb exposure., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Background: Dietary factors including trace elements contribute to the development of disorders including coronary artery diseases. Whether there are differences in concentrations of trace elements between on-pump and off-pump coronary artery bypass grafting (CABG) surgery remains unclear. The aim of this study was to investigate the differences in the plasma level of four trace elements Cu, Fe, Zn, magnesium (Mg), and calcium (Ca) during and after CABG between on-pump and off-pump procedure and the correlation between these trace elements and the development of postoperative AF., Methods: Fifty-three CABG patients using on-pump or off-pump methods were enrolled. The blood sample was taken before skin incision (T1), 4 h after skin incision (T2), postoperative day1 (T3), and day3 (T4) respectively. Plasma concentrations of Mg, Ca, Fe, Zn, and Cu were determined., Results: The plasma Mg concentration reached the highest level at T3 (0.94 ± 0.03 vs. 1.20 ± 0.03 mmol/L,P < 0.001) and completely recovered at T4 whereas Zn (11.28 ± 0.23 vs. 6.80 ± 0.20 mmol/L, P < 0.001) and Fe (10.97 ± 0.51 vs. 2.22 ± 0.1 μmol/L, P < 0.001) was lowest at T3 and partially recovered at T4. Cu was lowest at T2 (12.10 ± 0.33 vs. 9.62 ± 0.25 μmol/L, P < 0.001) then increased until T4. There were significant differences in Mg and Fe (P < 0.05), as well as Cu (P < 0.01) between on-pump and off-pump groups. No significant differences were detected between postoperative atrial fibrillation and sinus rhythm groups., Conclusions: In CABG, Cu and Zn are significantly reduced and Cu is recovered at postoperative Day 1 but Zn takes longer to recover. Addition of Mg and Ca during CABG are sufficient to maintain the plasma concentration. However, supplementation of Cu and Zn during and after CABG may be necessary. Further, the correlation between these trace elements and postoperative AF is to be further determined., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Aim: This study aims to determine the changes induced by a maximal exercise test until exhaustion on the serum and urinary concentrations of Magnesium (Mg), Phosphorous (P), Rubidium (Rb) and Strontium (Sr) in athletes (AG) and sedentary students (SG)., Methods: Fifty subjects participated in the study divided into two groups. In AG there were twenty-five male athletes and in SG there were twenty-five male sedentary students. Both groups performed an exercise test until exhaustion, starting at 8 or 10 km/h respectively, and increasing the speed at 1 km/h every 400 m. Serum and urine samples were obtained from all participants before and after the test., Results: Regarding the basal status, AG showed lower values of Mg in serum (p < 0.05) and urine (p < 0.01), but higher concentrations of serum P (p < 0.05) in comparison to SG. Comparing the pre and post-test values, corrected or non-corrected for hemoconcentration in serum and for creatinine in urine, AG showed a decrease in serum Mg (p < 0.05), in serum P (p < 0.01) and in urinary Sr (p < 0.01) while an increase was observed in urinary P (p < 0.05) and in urinary Rb (p < 0.05)., Conclusions: It can be concluded that a treadmill test until exhaustion leads to changes in serum and urinary concentrations of minerals in both AG and SG males. This may reflect an adaptive response of the body to overcome the physical stress and, in some cases, to avoid loss of these elements., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Background: In December 2019, the viral pandemic of respiratory illness caused by COVID-19 began sweeping its way across the globe. Several aspects of this infectious disease mimic metabolic events shown to occur during latent subclinical magnesium deficiency. Hypomagnesemia is a relatively common clinical occurrence that often goes unrecognized since magnesium levels are rarely monitored in the clinical setting. Magnesium is the second most abundant intracellular cation after potassium. It is involved in >600 enzymatic reactions in the body, including those contributing to the exaggerated immune and inflammatory responses exhibited by COVID-19 patients. Methods: A summary of experimental findings and knowledge of the biochemical role magnesium may play in the pathogenesis of COVID-19 is presented in this perspective. The National Academy of Medicine's Standards for Systematic Reviews were independently employed to identify clinical and prospective cohort studies assessing the relationship of magnesium with interleukin-6, a prominent drug target for treating COVID-19. Results: Clinical recommendations are given for prevention and treatment of COVID-19. Constant monitoring of ionized magnesium status with subsequent repletion, when appropriate, may be an effective strategy to influence disease contraction and progression. The peer-reviewed literature supports that several aspects of magnesium nutrition warrant clinical consideration. Mechanisms include its "calcium-channel blocking" effects that lead to downstream suppression of nuclear factor-Kβ, interleukin-6, c-reactive protein, and other related endocrine disrupters; its role in regulating renal potassium loss; and its ability to activate and enhance the functionality of vitamin D, among others. Conclusion: As the world awaits an effective vaccine, nutrition plays an important and safe role in helping mitigate patient morbidity and mortality. Our group is working with the Academy of Nutrition and Dietetics to collect patient-level data from intensive care units across the United States to better understand nutrition care practices that lead to better outcomes.

Case history : Two commercial pasture-based farms within the North Canterbury district of New Zealand were feeding fodder beet ( Beta vulgaris vulgaris L.) as a large proportion of the diet to cows during the dry period. On each farm 25 multiparous cows were blood sampled up to six times from 28 days before, to 21 days after calving (Day 0). Plasma samples were analysed for concentrations of β-hydroxybutyrate (BHBA), non-esterified fatty acid (NEFA), Ca, Mg and P, and aspartate aminotransferase (AST) activity. The first sampling visit was performed when cows were being fed their maximum intake of fodder beet. Clinical findings : The mean body condition score (BCS) of cows on Farm 1 was 5.4 (95% CI = 5.3-5.6) and on Farm 2, 5.4 (95% CI = 5.3-5.6) at first sampling. Mean concentrations of BHBA increased between Days -15 and Day -8 then decreased postpartum on Day 2 before increasing again on Day 21. On Farm 2, concentrations remained low (<1.2 mmol/L) on all days of sampling. Mean concentrations of NEFA in plasma remained low during the periparturient period on Farm 1, then increased on Day 2. On Farm 2, concentrations were elevated above 0.3 mmol/L between Days -28 and -17 then decreased on Day -10, before increasing on Day 2. Mean concentrations of Ca, Mg and P were higher than threshold values on both farms prepartum. However on Day 2, there were 8/23 (35%) cows on Farm 1 and 6/23 (26%) cows on Farm 2 with concentrations of Ca in plasma <2.0 mmol/L, and 10/23 (44%) cows on Farm 1 and 8/23 (35%) cows on Farm 2 with concentrations of P in plasma <1.3 mmol/L. Mean AST activities remained relatively constant and below 130 IU/L on both farms at all sampling times. Clinical relevance : On both farms, post-partum hypocalcaemia and hypophosphataemia were common after calving despite differing fodder beet feeding and mineral supplementation regimes. There was more variation in energy status, especially prior to calving. More research is required on factors affecting mineral and energy status in dry cows fed fodder beet.

Hypomagnesemia and hypermagnesemia could have serious implications and possibly lead to progress from a mild form to a severe outcome of Covid-19. Susceptibility of subjects with low magnesium status to develop and enhance this infection is possible. There is little data on the magnesium status of patients with Covid-19 with different degrees of severity. This study was conducted to evaluate prevalence of dysmagnesemia in a prospective Covid-19 cohort study according to the severity of the clinical manifestations and to identify factors associated. Serum magnesium was measured in 300 of 549 patients admitted to the hospital due to severe Covid-19. According to the WHO guidelines, patients were classified as moderate, severe, or critical. 48% patients had a magnesemia below 0.75 mmol/L (defined as magnesium deficiency) including 13% with a marked hypomagnesemia (<0.65 mmol/L). 9.6% had values equal to or higher than 0.95 mmol/L. Serum magnesium concentrations were significantly lower in female than in male (0.73 ± 0.12 vs 0.80 ± 0.13 mmol/L), whereas the sex ratio M/F was higher in severe and critical form (p<0.001). In a bivariate analysis, the risk of magnesium deficiency was significantly and negatively associated with infection severity (p<0.001), sex ratio (M/F, p<0.001), oxygenotherapy (p<0.001), stay in critical care unit (p=0.028), and positively with nephropathy (p=0.026). Logistic regression analysis revealed that the strongest predictors of magnesium deficiency were female sex (OR=2.67, p<0.001) and nephropathy (OR=2.12, p=0.032) and after exclusion of sex ratio, the severity of infection (OR=0.46, p=0.04 and OR=0.39 p=0.01), for critical and moderate forms, respectively. This transversal study reveals a high prevalence of hypomagnesemia in hospitalized patients for Covid-19, while high-level serum magnesium concentration was more prevalent in critical form.

The aim of this study was to explore the impact of prenatal Al and Mg on placental oxidative stress and inflammatory mRNA expression. A total of 2519 pregnant women from the China Ma'anshan birth cohort participated in this study. Al and Mg levels were measured by inductively coupled plasma mass spectrometry (ICP-MS). Placental stress and inflammatory mRNA expression were assessed by RT-PCR. The median Al levels in the first and second trimesters of pregnancy and in cord blood were higher than the corresponding median Mg levels. Predictors of lower Al and Mg levels included Han ethnicity and high education according to a mixed linear model. Multiple linear regression analysis revealed that Al and Al/Mg levels had a positive association with inflammatory mRNA expression and placental oxidative stress in the second trimester of pregnancy. A negative association existed between Al and Al/Mg levels and inflammatory mRNA expression and placenta oxidative stress in the cord blood, with the exception of IL-1β expression. In conclusion, prenatal Al and Mg status was associated with placental oxidative stress and inflammatory mRNA expression. More preclinical studies are needed to confirm the relevant mechanism.

Magnesium deficiency is to be expected in the population and particularly among risk groups. Magnesium deficiency can cause numerous symptoms, is per se pathological and thus requires treatment. Diagnostics is based on clinical symptoms in conjunction with anamnestic criteria and laboratory parameters. Insufficient magnesium supply is associated with an increased risk for many diseases, e. g. metabolic syndrome, type 2 diabetes and cardiovascular diseases. Magnesium deficiency often appears as comorbidity and may exacerbate diseases. Physicians should pay more attention to magnesium in order to avoid deficits as a cause for multiple symptoms and risk factor for diseases. Optimisation of magnesium status may make an important contribution to the prevention of diseases. Oral magnesium therapy is safe and cost effective., Competing Interests: Oliver Micke: Präsident der Gesellschaft für Magnesium-Forschung e. V.Jürgen Vormann: Vorstand der Gesellschaft für Magnesium-Forschung e. V.Hans-Georg Classen: Vorstand der Gesellschaft für Magnesium-Forschung e. V.Klaus Kisters: Vize-Präsident der Gesellschaft für Magnesium-Forschung e. V., (Thieme. All rights reserved.)

Background: Intravenous administration of magnesium with a short hydration regimen is recommended for patients receiving high-dose cisplatin to protect against cisplatin-induced nephrotoxicity. However, the optimal dose of magnesium supplementation has not been clarified. The aim of this trial was to investigate the safety and efficacy of a short hydration regimen with 20 mEq of magnesium supplementation for lung cancer patients receiving cisplatin-based chemotherapy., Methods: The key eligibility criteria included cytologically or histologically diagnosed lung cancer, candidacy for cisplatin-based (≥ 60 mg/m 2 ) chemotherapy or chemoradiotherapy, no prior chemotherapy, aged 20-75 years, and adequate renal function. Cisplatin was administered with pre-hydration with 20 mEq of magnesium sulfate. Mannitol was administered just before cisplatin infusion to enforce diuresis. The primary endpoint was the proportion of patients who underwent cisplatin-based chemotherapy with a short hydration regimen with 20 mEq of magnesium supplementation without a grade 2 or higher elevation in creatinine., Results: Forty patients with a median age of 66 years (range 35-74) were prospectively enrolled. Median baseline creatinine was 0.71 mg/dL. Median dose of cisplatin in the first cycle was 80 mg/m 2 . In the first cycle, no patients developed grade 2 creatinine toxicity. During the treatment period, one patient developed grade 2 creatinine elevation; thus, the proportion of patients without a grade 2 or higher elevation in creatinine was 97.5% (95% confidence interval 86.8-99.9)., Conclusion: A short hydration regimen with 20 mEq of magnesium supplementation is safe and feasible for patients with lung cancer receiving cisplatin-based chemotherapy.

In the present total diet study, the dietary intake of zinc (Zn), copper (Cu), magnesium (Mg), calcium (Ca), phosphorus (P), and sodium (Na) by healthy adults in Shiraz, Iran, was estimated from the foods as consumed. A total of 580 individual food items were collected, prepared, and pooled into 129 composite samples. The metal concentration was then evaluated using inductively coupled plasma-optical emission spectrometry. The mean intakes of Zn (12.92 mg/d), Cu (3.80 mg/d), and Mg (412.68 mg/d) exceeded the estimated average requirements (EARs), but they were well below the upper limits. A high prevalence of inadequate intake was observed for Ca (91.6%) and P (89.7%), which was mainly due to nutritionally imbalanced diets. Sodium intake for average and high consumers (97.5th percentile) was 123.6% and 237.8% of the tolerable upper intake level of 2300 mg/d, respectively, with 70% of the participants having intakes higher than this threshold value. Nutrition education, nutritional rehabilitation, Ca supplementation, food fortification, mandatory reduction of salt content in processed foods, and discretionary salt use (in home cooking or at the table) are among the possible strategies that can be adopted to combat the health problems.

Objective: This study investigates the correlation between serum apelin and galectin-3 levels with insulin resistance (IR) in women with preeclampsia (PE)., Methods: Serum apelin, galectin-3, and insulin levels were measured in 60 PE women and 30 normotensive pregnant., Results: The PE group had significantly lower apelin and higher galectin-3 levels than the control group. PE group exhibited dyslipidemia and had higher β-cell functions than the controls. Galectin-3 level correlates with insulin, glucose, and IR. High galectin-3 also is correlated positively with dyslipidemia., Conclusion: In PE, there is a possible contribution of galectin-3 to the harmful effects of IR and dyslipidemia.

The objectives of this study were to describe pharmacokinetic and pharmacodynamic changes as a result of a single intravenous administration of magnesium sulfate (MgSO 4 ) to healthy horses. MgSO 4 is a magnesium salt that has been used to calm horses in equestrian competition and is difficult to regulate because magnesium is an essential constituent of all mammals. Six healthy adult female horses were administered a single intravenous dose of MgSO 4 at 60 mg/kg of body weight over 5 min. Blood, urine, and cerebrospinal fluid (CSF) samples were collected, and cardiovascular parameters were monitored and echocardiograms performed at predetermined times. Noncompartmental pharmacokinetic analysis was applied to plasma concentrations of ionized magnesium (Mg 2+ ). Objective data were analyzed using the Wilcoxon rank-sum test with p < .05 used as a determination for significance. Plasma concentrations of Mg 2+ increased nearly fivefold, ionized calcium (Ca 2+ ) decreased by nearly 10%, and the Ca 2+ to Mg 2+ ratio declined more than 3.5-fold and remained different than baseline until 24 hr (p < .05). Significant changes were seen with urinary fractional excretion of electrolytes, cardiovascular parameters, and echocardiographic measurements. No changes were detected in CSF electrolyte concentrations. The decrease in Ca 2+ result of hypermagnesemia supports the interaction between these cations. Alterations detected in plasma electrolyte concentrations and urinary fractional excretion of electrolytes may serve as biomarkers for regulatory control for the nefarious administration of MgSO 4 ., (© 2020 John Wiley & Sons Ltd.)

Background: Few studies have investigated the association of magnesium levels with incident peripheral artery disease (PAD) despite emerging evidence of magnesium contributing to vascular calcification. Moreover, no data are available on whether the magnesium-PAD relationship is independent of or modified by kidney function., Methods: A cohort of 11 839 participants free of PAD in the Atherosclerosis Risk in Communities Study at Visit 2 (1990-92) was studied. We investigated the association of serum magnesium and other bone-mineral metabolism markers [calcium, phosphorus, intact parathyroid hormone (iPTH) and intact fibroblast growth factor-23] with incident PAD using multivariable Cox proportional hazards regression., Results: Over a median of 23 years, there were 471 cases of incident PAD. The hazard ratio for incident PAD in Quartile 1 (<1.5 mEq/L) versus Quartile 4 (>1.7 mEq/L) of magnesium was 1.96 (95% confidence interval 1.40-2.74) after adjustment for potential confounders. Lower magnesium levels were associated with greater incidence of PAD, particularly in those with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 (n = 11 606). In contrast, the association was largely flat in those with eGFR <60 mL/min/1.73 m2 (n = 233) with P-for-interaction 0.03. Among bone-mineral metabolism markers, only higher iPTH showed an interaction with kidney function (P-for-interaction 0.01) and iPTH >65 pg/mL was significantly related to PAD only in those with eGFR <60 mL/min/1.73 m2., Conclusions: Lower magnesium was independently associated with incident PAD, but this association was significantly weaker in those with reduced kidney function. In contrast, higher iPTH levels were particularly related to PAD risk in this clinical population., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

No-reflow phenomenon is a serious complication of percutaneous coronary intervention. Magnesium may play a role in pathogenesis of no-reflow phenomenon since it interacts with processes like platelet inhibition and endothelial-dependent vasodilatation. Relationship of serum magnesium concentration at admission and angiographic no-reflow phenomenon in ST elevation myocardial infarction patients undergoing primary percutaneous coronary intervention is investigated in the present study. A total of 2.248 consecutive patients with ST elevation myocardial infarction who underwent primary percutaneous coronary intervention were analyzed. After reopening of the infarct related artery, a TIMI flow rate ≤ 2 was defined as no-reflow. No-reflow phenomenon developed in 386 (17.1 %) patients. Serum magnesium concentration was significantly lower in no-reflow group (1.87 ± 0.25 vs. 2.07 ± 0.33 mg/dL, p<0.001). ROC curve analysis showed that Mg at a cut-point of 1.92 has 71.4% sensitivity and 75.2% specificity in detecting no-reflow phenomenon. In multivariate logistic regression analysis, age, serum magnesium concentration, and stent length were found as independent predictors of no-reflow phenomenon. Serum magnesium concentration is associated with no-reflow phenomenon in ST elevation myocardial infarction patients who underwent primary PCI.

Objectives: The purpose of this study was to establish age- and sex-specific pediatric reference intervals of serum potassium (K), sodium (Na), chlorine (Cl), calcium (Ca), magnesium (Mg), and phosphorus (P) using a direct sampling technique., Methods: In accordance with the a priori approach, healthy individuals (n = 6,466, aged 1 month to <18 years) were enrolled from five regions in Jilin Province, China, and all analytes were performed in the center laboratory. Reference intervals were divided according to the regression tree and Harris and Boyd's method, and then they were calculated by the nonparametric rank method. The dynamic changes of reference intervals were evaluated by the lambda-mu-sigma (LMS) method., Results: Reference intervals of serum Na and Ca were divided into three age-specific partitions. The concentrations of K, Cl, and Mg remained stable with age. However, only dramatic sex-specific changes of P were shown in those 11 to less than 13 years old and 13 to less than 15 years old, with an earlier peak time in females than in males. The correlation between Na and Cl was the strongest among all serum electrolytes (r = 0.31)., Conclusions: Serum electrolyte reference intervals for children and adolescents were established by regression tree, z test, and the LMS method, which provide a more accurate interpretation for diagnosis and prognosis evaluation of clinical pediatric diseases., (© American Society for Clinical Pathology, 2020.)

Higher serum magnesium is associated with lower risk of multiple morbidities, including diabetes, stroke, and atrial fibrillation, but its potential neuroprotective properties have also been gaining traction in cognitive function and decline research. We studied 12,040 participants presumed free of dementia in the Atherosclerosis Risk in Communities (ARIC) study. Serum magnesium was measured in fasting blood samples collected in 1990-1992. Dementia status was ascertained through cognitive examinations in 2011-2013, 2016-2017, and 2018-2019, along with informant interviews and indicators of dementia-related hospitalization events and death. Participants' cognitive functioning capabilities were assessed up to five times between 1990-1992 and 2018-2019. The cognitive function of participants who did not attend follow-up study visits was imputed to account for attrition. We identified 2519 cases of dementia over a median follow-up period of 24.2 years. The lowest quintile of serum magnesium was associated with a 24% higher rate of incident dementia compared to those in the highest quintile of magnesium (HR, 1.24; 95% CI, 1.07, 1.44). No relationship was found between serum magnesium and cognitive decline in any cognitive domain. Low midlife serum magnesium is associated with increased risk of incident dementia, but does not appear to impact rates of cognitive decline.

Curcumin exhibits antibacterial, antioxidant, and anti-inflammatory effects and has been suggested as a treatment for inflammatory diseases. The study is aimed at evaluating the effect of curcumin gel on serum levels of micronutrients (zinc, copper, and magnesium) and proinflammatory cytokines (IL-1 β and TNF- α ) in chronic periodontitis patients. Ninety subjects with an age of 25-54 were included in this study. From the total number, 30 subjects with healthy periodontium (control group) (mean age = 37.30 ± 7.08) were employed for the sole purpose of obtaining the normal mean values of clinical, chemical, and immunological parameters, and 60 with chronic periodontitis (mean age = 36.73 ± 6.22) were divided randomly into 2 groups, of which each group included 30 subjects. Group A received scaling and root planing SRP and curcumin gel injection covered by Coe pack for 7 days, and group B received SRP alone covered by Coe pack. Clinical parameters (plaque index, gingival index, bleeding on probing, pocket depth, and clinical attachment loss measurements) and blood samples were collected before and after 1 month of treatment to measure serum levels of zinc, copper, magnesium, IL-1 β , and TNF- α . The results showed significant micronutrient alteration and increase of proinflammatory cytokines in the chronic periodontitis group as compared to healthy control ( P ≤ 0.05), and curcumin gel had a significant effect on the reduction of IL-1 β , TNF- α , copper, and clinical parameters ( P ≤ 0.05) and increase of zinc and magnesium levels after 1 month as compared to baseline ( P ≤ 0.05), nearly the same pattern for group B but with nonsignificant differences for Zn ( P > 0.05). In conclusion, curcumin gel resulted in a more significant reduction in clinical parameters, inflammatory mediators, and copper and increase of zinc and magnesium levels as compared to SRP alone., Competing Interests: No conflicts of interest are reported., (Copyright © 2020 Chenar Anwar Mohammad.)

The consumption of teff ( Eragrostis tef ), a gluten-free cereal grain, has increased due to its dense nutrient composition including complex carbohydrates, unsaturated fatty acids, trace minerals (especially Fe), and phytochemicals. This study utilized the clinically-validated Gallus gallus intra amniotic feeding model to assess the effects of intra-amniotic administration of teff extracts versus controls using seven groups: (1) non-injected; (2) 18Ω H 2 O injected; (3) 5% inulin; (4) teff extract 1%; (5) teff extract 2.5%; (6) teff extract 5%; and (7) teff extract 7.5%. The treatment groups were compared to each other and to controls. Our data demonstrated a significant improvement in hepatic iron (Fe) and zinc (Zn) concentration and LA:DGLA ratio without concomitant serum concentration changes, up-regulation of various Fe and Zn brush border membrane proteins, and beneficial morphological changes to duodenal villi and goblet cells. No significant taxonomic alterations were observed using 16S rRNA sequencing of the cecal microbiota. Several important bacterial metabolic pathways were differentially enriched in the teff group, likely due to teff's high relative fiber concentration, demonstrating an important bacterial-host interaction that contributed to improvements in the physiological status of Fe and Zn. Therefore, teff appeared to represent a promising staple food crop and should be further evaluated.

Purpose: An inverse association was shown between serum magnesium levels and anemia in the general population. However, limited information is available about the association between serum magnesium level and anemia in the patient population with chronic kidney disease. We aimed to investigate the relationship between hypomagnesemia and anemia in pre-dialysis patients with chronic kidney disease stage 3-5., Methods: This cross-sectional retrospective study included 213 chronic kidney disease patients with an estimated glomerular filtration rate of 60 mL/min and below. Laboratory and demographic data of outpatients were collected in January 2018-January 2019. Patients with a magnesium level below 1.9 mg/dL were accepted as the hypomagnesemia group., Results: Serum magnesium level of 62 (29.1%) of these patients were below 1.9 mg/dL. Compared with normomagnesemic patients, hypomagnesemic patients had lower mean hemoglobin values (11.3 g/dL vs. 12.7 g/dL, P < 0.001), proton-pump inhibitor usage rates were significantly higher (33.9% vs. 17.2%, P = 0.008) and the median urine protein/creatinine ratio was found to be significantly higher (1017.5 mg/gCr vs. 536 mg/gCr, P = 0.045). In the multivariate analysis, the use of hemoglobin (OR 0.634; 95% CI 0.505-0.795; P < 0.001) and proton-pump inhibitor (OR 2.670; 95% CI 1.113-6.318; P = 0.025) were independent predictors of hypomagnesemia., Conclusions: Hypomagnesemia is a common electrolyte disorder in pre-dialysis CKD patients. In this patient group, anemia is independently associated with hypomagnesemia.

Background: Hypomagnesemia in patients with congenital anomalies of the kidneys and urinary tract or autosomal dominant tubulointerstitial kidney disease is highly suggestive of HNF1B-associated disease. Intriguingly, the frequency of low serum Mg 2+ (sMg) level varies and is lower in children than in adults with HNF1B mutations that could be partially due to application of inaccurate normal limit of sMg, irrespective of age and gender. We aimed to re-assess cross-sectionally and longitudinally the frequency of hypomagnesemia in HNF1B disease by using locally derived reference values of sMg., Methods: Fourteen children with HNF1B-associated kidney disease were included. Control group comprising 110 subjects served to generate 2.5th percentiles of sMg as the lower limits of normal., Results: In both controls and patients, sMg correlated with age, gender, and fractional excretion of Mg 2+ . In girls, sMg concentration was higher than in boys when analyzed in the entire age spectrum (p < 0.05). In HNF1B patients, mean sMg was lower than in controls as compared with respective gender- and age-specific interval (p < 0.001). Low sMg levels (< 0.7 mmol/l) were found in 21.4% of patients at diagnosis and 36.4% at last visit, which rose to 85.7% and 72.7% respectively when using the age- and gender-adjusted reference data. Similarly, in the longitudinal observation, 23% of sMg measurements were < 0.7 mmol/l versus 79.7% when applying respective references., Conclusions: Hypomagnesemia is underdiagnosed in children with HNF1B disease. sMg levels are age- and gender-dependent; thus, the use of appropriate reference data is crucial to hypomagnesemia in children.

Aim: Gitelman syndrome (GS) is a rare inherited salt-losing renal tubulopathy. Data on clinical features and the pregnancy outcome for female GS patients in a large cohort are lacking. The study was aimed to explore the phenotype and pregnant issue for female GS patients., Methods: GS cases from the National Rare Diseases Registry System of China (NRSC) were collected, and detailed clinical, laboratory and genetic data were analysed. Articles on pregnancy in GS were also systemically reviewed., Results: A total of 101 GS patients were included; among them, 42.6% were female and 79.2% showed hypomagnesaemia. A lower proportion of female patients presented before 18 years of age, with less frequently reported polyuria, higher serum potassium and less urine sodium and chloride excretions. There was no gender difference in the sodium-chloride cotransporter (NCC) dysfunction evaluated by hydrochlorothiazide test. Twelve of the 43 female GS patients delivered after disease symptom onset, and their pregnancies were generally uneventful. As a group, pregnant GS patients had lower potassium levels in the first-trimester (P = .002) requiring higher potassium supplementation. After delivery, serum potassium (P = .02) and magnesium (P = .03) increased significantly. Both caesarean section and vaginal delivery were safe., Conclusion: Female GS patients may have a less severe phenotype with generally favourable outcomes of pregnancy. Intensive monitoring and increased potassium supplementation are necessary during pregnancy, especially in the first-trimester., (© 2020 Asian Pacific Society of Nephrology.)

Robust clinical data indicate that inhibitors of the sodium/glucose cotransporter 2 (SGLT2) dramatically improve clinical outcomes in diabetes, especially heart failure and progression of kidney disease. Factors that may contribute to these findings include: 1) improved glycemic control, 2) diuresis and reduced extracellular fluid volume, 3) reduced serum uric acid levels, 3) direct myocardial effects, 4) reduction in proteinuria and preservation of kidney function, and 5) correction of diabetic magnesium deficiency. Understanding the mechanisms by which SGLT2 inhibitors improve cardiovascular outcomes has the potential to improve clinical management not only of diabetes, but also of other cardiovascular disorders such as heart failure and chronic kidney disease., (Copyright © 2020. Published by Elsevier Ltd.)

Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: Dialysis patients are at increased risk for vascular calcification and cardiovascular disease. Emerging data suggests that magnesium might be protective for the vascular system in peritoneal dialysis (PD) patients as well. However, only limited data is available on the elimination of magnesium through PD treatment. This study aims to evaluate the peritoneal magnesium elimination characteristics in comparison to other small solutes and the influence of peritoneal transport status., Materials and Methods: Peritoneal elimination of magnesium, blood-urea-nitrogen (BUN), and creatinine during a 4-hour peritoneal equilibration test (PET) was assessed in 30 stable PD patients. Absolute magnesium elimination was compared overall and between creatinine transport tertiles., Results: Median age was 61 years, 50% of patients were male, 20% were on automated PD treatment. Serum magnesium was 0.84 mmol/L, and dialysate magnesium at the end of the PET was 0.57 mmol/L in the overall cohort and did not differ significantly between tertiles. The magnesium dialysate-to-plasma ratio was significantly different between the subgroups (lower tertile: median 0.60 (minimum 0.52, maximum 0.68) vs. middle tertile: 0.64 (0.58, 0.68) vs. upper tertile: 0.69 (0.67, 0.74), p &lt; 0.001). The elimination per liter of dialysis fluid was also significantly different (8.6 (6.6, 10.4) vs. 9.4 (8.0, 10.5) vs. 10.6 (0.2, 11.8) mg/L, p = 0.002), as was the absolute removal during the 4-hour dwell (18.6 (15.8, 21.2) vs. 19.4 (13.4, 24.6) vs. 22.7 (19.6, 31.9) mg, p = 0.007, respectively)., Conclusion: Peritoneal magnesium elimination is similar to small solute transport characteristics. However, the absolute differences among patients with slower and faster transport types are small. Therefore, magnesium supplementation in PD patients should be guided by serum magnesium concentrations rather than the amount of peritoneal elimination.

Aims: Low magnesium (Mg) and high calcium (Ca) levels are linked to increased cardiovascular disease (CVD) risk in the general population. This prospective study assessed whether there are any independent associations of serum Mg levels and Ca-Mg ratios with mortality in patients with coronary artery disease (CAD)., Methods: This prospective cohort study included 3380 CAD patients. Cox regression models were used to estimate associations of serum Mg and Ca-Mg ratio with risk of mortality., Results: A total of 562 deaths (331 due to CVD) were recorded during a 7.59-year (median) follow-up. Spline plots displayed U-shaped associations between serum Mg levels and Ca-Mg ratios and risk of mortality. When compared with a moderate group, adjusted hazard ratios (95% confidence intervals) for low Mg levels and high Ca-Mg ratios were 1.59 (1.30-1.95) and 1.31 (1.06-1.61) for all-cause mortality, and 1.71 (1.32-2.22) and 1.44 (1.09-1.89) for CVD mortality, respectively. There was also a tendency to increase risk of mortality in patients with high serum Mg levels and low Ca-Mg ratios. Associations of low serum Mg and high Ca-Mg ratio with risk of mortality did not change when stratified by gender, body mass index, CAD type, estimated glomerular filtration rate, use of diuretics, or history of diabetes or hypertension., Conclusion: This study demonstrated that a moderate Ca-Mg ratio (range: 3.91-4.70) had the lowest mortality risk, and that low serum Mg and high Ca-Mg ratio were independent risk factors of mortality in CAD patients. Nevertheless, the optimal dose-response of Mg and Ca for mitigating CAD risk still requires further investigation., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background: Hemodialysis (HD) induces myocardial stunning and is associated with adverse cardiovascular outcomes. Intradialytic hypotension is a modifiable determinant of myocardial stunning. Magnesium (Mg) is reported to be valuable in maintaining intradialytic blood pressure, which potentially would protect against demand myocardial ischemia. This study aimed to compare high vs. low dialysate Mg effects on intradialytic hemodynamics and HD-induced myocardial stunning., Methods: Twenty stable prevalent HD patients entered a randomized cross-over trial of low (0.5 mmol/L) vs. high (1.0 mmol/L) dialysate Mg. Patients were studied after 2 weeks of standard HD with each Mg concentration. Serial echocardiography assessed myocardial stunning, measured by left ventricular regional wall motion abnormalities (RWMAs). Continuous intradialytic hemodynamics were measured noninvasively using thoracic bioimpedance., Findings: Median predialysis serum Mg was higher with high dialysate Mg (1.45[1.29-1.55] vs. 1.03[0.98-1.1] mmol/L, P < 0.0001). There was no significant difference in maximum intradialytic reduction in systolic BP. There was no significant difference in stroke volume, total peripheral resistance, and cardiac output. Overall ventricular global longitudinal strain (GLS) (as a sensitive marker of contractile function) was higher before dialysis in high Mg group, but there was no difference in GLS at peak stress. However, we showed a significant correlation between Mg changes and GLS changes, r = -0.47, P = 0.02. There was no difference in mean number of peak stress RWMAs per patient (4.0 ± 2.2 vs. 4.3 ± 2.9, P = 0.5). Ultrafiltration volume, a critical determinant of stunning, was not different between high and low dialysate Mg studies (1.35[0-3.3] vs. 1.5[0-2.8], P = 0.49)., Discussion: Manipulation of magnesium by altering dialysate magnesium concentration does not influence intradialytic hemodynamic response or HD-induced myocardial stunning in the short term. However, decreasing Mg changes appears to decrease GLS changes., (© 2020 International Society for Hemodialysis.)

The maintenance of magnesium (Mg2+) homeostasis is essential for human life. The Cystathionine-β-synthase (CBS)-pair domain divalent metal cation transport mediators (CNNMs) have been described to be involved in maintaining Mg2+ homeostasis. Among these CNNMs, CNNM2 is expressed in the basolateral membrane of the kidney tubules where it is involved in Mg2+ reabsorption. A total of four patients, two of them with a suspected disorder of calcium metabolism, and two patients with a clinical diagnosis of primary tubulopathy were screened for mutations by Next-Generation Sequencing (NGS). We found one novel likely pathogenic variant in the heterozygous state (c.2384C>A; p.(Ser795*)) in the CNNM2 gene in a family with a suspected disorder of calcium metabolism. In this family, hypomagnesemia was indirectly discovered. Moreover, we observed three novel variants of uncertain significance in heterozygous state in the other three patients (c.557G>C; p.(Ser186Thr), c.778A>T; p.(Ile260Phe), and c.1003G>A; p.(Asp335Asn)). Our study shows the utility of Next-Generation Sequencing in unravelling the genetic origin of rare diseases. In clinical practice, serum Mg2+ should be determined in calcium and PTH-related disorders., Competing Interests: The authors have declared that no competing interests exist.

Aim: The aim of the study was to evaluate the effects of 16 weeks of a low dose of magnesium creatine chelate supplementation on repeated sprint ability test (RAST) results in elite soccer players., Materials: Twenty well-trained soccer players participated in the study. The players were divided randomly into two groups: the supplemented group (SG = 10) and placebo group (PG = 10). Out of the 20 subjects selected for the study, 16 (SG = 8, PG = 8) completed the entire experiment. The SG ingested a single dose of 5500 mg of magnesium creatine chelate (MgCr-C), in 4 capsules per day, which was 0.07 g/kg/d. The PG received an identical 4 capsules containing corn starch. Before and after the study, the RAST was performed. In the RAST, total time (TT), first and sixth 35 m sprint length (s), average power (AP) and max power (MP) were measured. Additionally, before and after the test, lactate LA (mmol/L) and acid-base equilibrium pH (-log(H + )), bicarbonates HCO 3 - (mmol/L) were evaluated. Also, in serum at rest, creatinine (mg/dL) concentration was measured., Results: After the study, significantly better results in TT, AP and MP were observed in the SG. No significant changes in the RAST results were observed in the PG. After the study, significant changes in the first 35 m sprint, as well as the sixth 35 m sprint results were registered in the SG, while insignificant changes occurred in the PG. A significantly higher creatinine concentration was observed. Also, a higher post-RAST concentration of LA, HCO 3 - and lower values of pH were observed in April, May and June compared with baseline values., Conclusions: The long timeframe, i.e., 16 weeks, of the low dose of magnesium creatine chelate supplementation improved the RAST results in the SG. Despite the long period of MgCr-C supplementation, in the end of the study, the creatinine level in the SG reached higher but still reference values.

Background: Recent studies have found hypomagnesemia is linked to a heightened risk of cardiovascular events and mortality in hemodialysis (HD) patients; however, the level of serum magnesium (s-Mg) necessary for promoting overall health in these patients and the effects of s-Mg in diabetes HD patients remains to be clarified., Methods: HD outpatients (n = 148 under, age ≤ 70 y) were followed over a 6-y period. They were divided into four groups according to their average s-Mg during the first year (L; low level, H; high level) and if they had DM or not (non-DM). The endpoint was mortality and hospitalization for decline of Activities of Daily Living (death/hospitalization). A receiver operating characteristics curve was used in diagnostic tests to identify s-Mg associated with this endpoint. Kaplan-Meier, log-rank test, and a Cox proportional hazards model were used to evaluate prognoses. Fisher's exact test and multiple regressions examined the causes of the endpoints between the four groups and the factors predictive of s-Mg., Results: s-Mg at 2.7 mg/dL was associated with death/hospitalization. The 5-y survival rate was 38.1%, 86.7%, 73.2% and 87.5%, in the DM/Mg(L), DM/Mg(H), non-DM/Mg(L) and non-DM/Mg(H) groups, respectively (P < 0.001). The Cox proportional hazards model showed significantly lower risk in other groups compared with that in the DM/Mg(L) group [DM/Mg(H); hazard ratio (HR): 0.22, 95% confidence interval (CI): 0.05-0.97, P = 0.046, non-DM/Mg(L); HR: 0.32, 95% CI: 0.15-0.68, P = 0.003, non-DM/Mg(H); HR: 0.17, 95% CI: 0.06-0.44, P < 0.001]. The frequency of the different causes of the endpoints for each group was not significant; s-Mg only associated with age in the DM group., Conclusions: s-Mg greater than 2.7 mg/dL associated with a favorable prognosis in HD patients with DM, suggesting that s-Mg is a factor independent of diabetes., Competing Interests: We are grateful to Katsunori Shimada (STATZ Institute, Inc., Tokyo, Japan) for useful analysis and suggestion in this study. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Polycystic ovary syndrome (PCOS) is reported to be associated with certain trace elements. However, previous data are inconsistent and potentially biased due to small sample sizes. The potential utility of trace element levels for screening of PCOS remains to be established. The aim of this meta-analysis was to investigate the potential relationships between PCOS and serum levels of zinc (Zn), copper (Cu), magnesium (Mg), iron (Fe) and ferritin. We carried out a literature search of PubMed, EMBASE, and Web of Science for relevant cross-sectional/case-control studies published prior to October 2019. Random-effect models were used to estimate the overall standard mean differences (SMDs) between PCOS and healthy control subjects. The screening value of potential microelement biomarkers for PCOS was assessed using the receiver operating characteristic (ROC) curve. Twenty-one studies featuring 2,173 women with PCOS and 1,897 healthy women were selected for analysis. Our results showed that Cu and ferritin levels were significantly higher in women with PCOS than healthy controls, with SMDs of 0.52 [95% confidence interval (CI): 0.38-0.67, I 2 = 47.6%] and 1.05 (95% CI: 0.25-1.86, I 2 = 97.0%), respectively. The serum ferritin concentration was distinguished as a potential biomarker for PCOS based on the high area under ROC curve value of 0.71 (95% CI: 0.57-0.86). Although we did not identify a statistical association between serum Zn concentration and PCOS overall, the concentration of Zn in PCOS women with insulin resistance (IR) was lower than that in healthy women (SMD = -0.89, 95% CI: -1.73 to -0.06). Furthermore, the concentrations of Mg (SMD = 0.31, 95% CI: -0.32-0.94, I 2 = 95.4%) and Fe (SMD = -0.59, 95% CI: -1.29-0.12, I 2 = 97.2%) were not statistically significant between the PCOS and control groups. We generated hypothetical pathways for associations among serum Cu, ferritin and PCOS. The serum concentrations of both Cu and ferritin were significantly higher in women with PCOS, and ferritin was identified as a potential early indicator for PCOS screening. Further studies are essential to determine the specific underlying mechanisms., (Copyright © 2020 Yin, Hong, Ma, Bu and Liu.)

Objective: To evaluate total usual intakes and biomarkers of micronutrients, overall dietary quality and related health characteristics of US older adults who were overweight or obese compared with a healthy weight., Design: Cross-sectional study., Setting: Two 24-h dietary recalls, nutritional biomarkers and objective and subjective health characteristic data were analysed from the National Health and Nutrition Examination Survey 2011-2014. We used the National Cancer Institute method to estimate distributions of total usual intakes from foods and dietary supplements for eleven micronutrients of potential concern and the Healthy Eating Index (HEI)-2015 score., Participants: Older adults aged ≥60 years (n 2969) were categorised by sex and body weight status, using standard BMI categories. Underweight individuals (n 47) were excluded due to small sample size., Results: A greater percentage of obese older adults compared with their healthy-weight counterparts was at risk of inadequate Mg (both sexes), Ca, vitamin B6 and vitamin D (women only) intakes. The proportion of those with serum 25-hydroxyvitamin D < 40 nmol/l was higher in obese (12 %) than in healthy-weight older women (6 %). Mean overall HEI-2015 scores were 8·6 (men) and 7·1 (women) points lower in obese than in healthy-weight older adults. In addition, compared with healthy-weight counterparts, obese older adults were more likely to self-report fair/poor health, use ≥ 5 medications and have limitations in activities of daily living and cardio-metabolic risk factors; and obese older women were more likely to be food-insecure and have depression., Conclusions: Our findings suggest that obesity may coexist with micronutrient inadequacy in older adults, especially among women.

Magnesium wasting is a frequent side effect of epidermal growth factor receptor (EGFR)-antibody treatment as magnesium-absorption mechanisms are dependent on EGFR signaling. EGFR-inhibition results in decreased renal reabsorption. There is evidence that hypomagnesemia during cetuximab treatment correlates with response. The prognostic role of hypomagnesemia during bevacizumab treatment has not been studied yet. Here, we evaluate the prognostic value of hypomagnesemia in patients with metastatic colorectal cancer treated with FOLFIRI plus cetuximab or bevacizumab as first-line therapy. A total of 391 of 752 patients of the firstline irinotecan study population had magnesium levels measured at baseline and for the first three cycles (6 weeks) of treatment. Of those, 240 had Rat Sarkoma wildtype tumors. Overall hypomagnesemia was more common in the cetuximab compared to the bevacizumab arm (80 vs. 43%, P < 0.005). During therapy, magnesium showed a time-dependent decrease to 80% of baseline in the cetuximab and to 89% in the bevacizumab arm. Whereas magnesium continued to decrease over time in the cetuximab-treated patients, it remained stable in the bevacizumab-treated. Overall response rate (ORR) was associated with higher magnesium at week 6 (20.9 vs. 79.1%, P = 0.041). Bevacizumab-treated patients with magnesium levels below the median value at week 6 had a significantly longer progression-free survival (PFS; 11.7 vs. 9.9 months, P = 0.034; hazard ratio 0.73) and a trend towards longer overall survival (OS) (29.6 vs. 23.2 months, P = 0.089; hazard ratio 0.77). Hypomagnesemia at predefined time points and magnesium nadir had no significant effect on ORR, OS and PFS in the cetuximab arm. Our data show different magnesium kinetics in patients with metastatic colorectal cancer treated with cetuximab or bevacizumab. For patients treated with cetuximab, hypomagnesemia did not have an impact on response and survival. Hypomagnesemia might have a prognostic value in bevacizumab treatment.

Risk factors for COVID-19 patients with poorer outcomes include pre-existing conditions: obesity, type 2 diabetes mellitus, cardiovascular disease (CVD), heart failure, hypertension, low oxygen saturation capacity, cancer, elevated: ferritin, C reactive protein (CRP) and D-dimer. A common denominator, hyperinsulinaemia, provides a plausible mechanism of action, underlying CVD, hypertension and strokes, all conditions typified with thrombi. The underlying science provides a theoretical management algorithm for the frontline practitioners.Vitamin D activation requires magnesium. Hyperinsulinaemia promotes: magnesium depletion via increased renal excretion, reduced intracellular levels, lowers vitamin D status via sequestration into adipocytes and hydroxylation activation inhibition. Hyperinsulinaemia mediates thrombi development via: fibrinolysis inhibition, anticoagulation production dysregulation, increasing reactive oxygen species, decreased antioxidant capacity via nicotinamide adenine dinucleotide depletion, haem oxidation and catabolism, producing carbon monoxide, increasing deep vein thrombosis risk and pulmonary emboli. Increased haem-synthesis demand upregulates carbon dioxide production, decreasing oxygen saturation capacity. Hyperinsulinaemia decreases cholesterol sulfurylation to cholesterol sulfate, as low vitamin D regulation due to magnesium depletion and/or vitamin D sequestration and/or diminished activation capacity decreases sulfotransferase enzyme SULT2B1b activity, consequently decreasing plasma membrane negative charge between red blood cells, platelets and endothelial cells, thus increasing agglutination and thrombosis.Patients with COVID-19 admitted with hyperglycaemia and/or hyperinsulinaemia should be placed on a restricted refined carbohydrate diet, with limited use of intravenous dextrose solutions. Degree/level of restriction is determined by serial testing of blood glucose, insulin and ketones. Supplemental magnesium, vitamin D and zinc should be administered. By implementing refined carbohydrate restriction, three primary risk factors, hyperinsulinaemia, hyperglycaemia and hypertension, that increase inflammation, coagulation and thrombosis risk are rapidly managed., Competing Interests: Competing interests: JJD is Director of Scientific Affairs at Analyze. Invest. Develop. Partner., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Hypomagnesaemia in haemodialysis (HD) is associated with increased mortality risk: its relationship with dialysis fluid (DF)., Introduction: Low concentrations of magnesium (Mg) in blood have been linked to the development of diabetes, hypertension, arrhythmias, vascular calcifications and an increased risk of death in the general population and in haemodialysis patients. The composition of the dialysis fluid in terms of its magnesium concentration is one of the main determinants of magnesium in haemodialysis patients., Objective: To study magnesium concentrations in haemodialysis patients, their predictive mortality rate and what factors are associated with hypomagnesaemia and mortality in haemodialysis., Methods: Retrospective study of a cohort of prevalent haemodialysis patients followed up for two years. Serum magnesium was measured every six months. The analysis used the initial and average magnesium values for each patient, comparing patients with magnesium below the mean (2.1mg/dl) with those with magnesium above the mean. During the follow-up, three types of dialysis fluid were used: type 1, magnesium 0.5 mmol/l; type 3, magnesium 0.37 mmol/l (both with acetate); and type 2, magnesium 0.5 mmol/l with citrate., Results: We included 137 haemodialysis patients in the study, of which 72 were male and 65 were female, with a mean age of 67 (15) [26-95] years old. Of this group, 57 patients were diabetic, 70 were on online haemodiafiltration (OL-HDF) and 67 were on high-flow haemodialysis (HF-HD). The mean magnesium of the 93 patients with dialysis fluid type 1 was 2.18 (0.37) mg/dl. In the 27 patients with dialysis fluid type 3 it was 2.02 (0.42) mg/dl. And in the 17 with dialysis fluid type 2 it was 1.84 (0.24) mg/dl (p=.01). There was a pronounced direct relationship between Mg and P and albumin. After a mean follow-up of 16.6 (8.9) [3-24] months, 77 remained active, 24 had died and 36 had been transplanted or transferred. Patients with magnesium above than 2.1mg/dl had a longer survival (p=.008). The survival of patients with the three types of dialysis fluid did not differ significantly (Log-Rank, p=.424). Corrected for blood magnesium, patients with dialysis fluid with citrate have better survival (p=.009). The COX regression analysis shows how age, serum albumin, magnesium, dialysis technique and type of dialysis fluid have an independent predictive mortality rate., Conclusions: Low serum magnesium levels have a greater association with an increased risk of mortality compared to high levels. The type of dialysis fluid affects the magnesium concentration and the risk of death., (Copyright © 2020 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Classical risk factors of atherosclerosis in the general population show paradoxical effects in chronic kidney disease (CKD) patients. Thus, low low-density lipoprotein (LDL) cholesterol levels have been associated with worse cardiovascular outcomes. Magnesium (Mg) is a divalent cation whose homeostasis is altered in CKD. Furthermore, Mg levels have been associated with cardiovascular health. The present study aims to understand the relationships of Mg and lipid parameters with atherosclerosis in CKD. In this analysis, 1754 participants from the Observatorio Nacional de Atherosclerosis en Nefrologia (NEFRONA) cohort were included. Carotid intima media thickness (cIMT) was determined in six arterial territories, and associated factors were investigated by linear regression. cIMT correlated positively with being male, Caucasian, a smoker, diabetic, hypertensive, dyslipidemic and with increased age, BMI, and triglyceride levels, and negatively with levels of HDL cholesterol. First-order interactions in linear regression analysis showed that Mg was an effect modifier on the influence of lipidic parameters. Thus, cIMT predicted values were higher when triglycerides or LDL levels were high and Mg levels were low. On the contrary, when Mg levels were high, this effect disappeared. In conclusion, Mg acts as an effect modifier between lipidic parameters and atherosclerotic cardiovascular disease. Therefore, Mg levels, together with lipidic parameters, should be taken into account when assessing atherosclerotic risk.