A randomized clinical trial investigating the impact of magnesium supplementation on clinical and biochemical measures in COVID-19 patients.

BACKGROUND: This study sought to examine the impact of magnesium supplementation on clinical outcomes and biochemical factors among hospitalized patients with COVID-19. METHODS: This double-blind, randomized clinical trial was conducted at Razi Hospital, Ahvaz, Iran, between September 2021 and March 2022. Participants aged 18-70 years with moderate disease severity were enrolled. Magnesium supplementation (300 mg daily) was administered to the intervention group, while the control group received a placebo. Clinical outcomes, including the need for oxygen therapy, oxygen saturation, respiratory rate, fever, hs-CRP and TNF-α levels, as well as quality of life and mental health, were assessed. Blood samples were collected to measure biochemical variables. RESULTS: The main result was the count of individuals requiring oxygen therapy. Additional outcomes comprised of oxygen saturation, respiratory rate, fever, hs-CRP and TNF-α levels, as well as quality of life and mental health. Out of 64 participants, 60 completed the study. The results showed that magnesium supplementation significantly reduced the number of patients requiring oxygen therapy (9 vs. 14; P < 0.001). Moreover, the magnesium group demonstrated improved oxygen saturation compared to the control group (4.55 ± 2.35 vs. 1.8 ± 1.67; P < 0.001). Furthermore, we observed a noteworthy enhancement in the quality of life and depression score in the magnesium group. No significant differences were observed in respiratory rate, fever, hs-CRP, and TNF-α levels (P > 0.05). CONCLUSION: The findings suggest that magnesium supplementation may have beneficial effects on clinical outcomes and arterial oxygen saturation in COVID-19 patients. More investigation is necessary to delve into its potential mechanisms and long-term effects on patient outcomes. TRIAL REGISTRATION: This study is registered on Iranian Registry of Clinical Trials (IRCT) under identifier IRCT20210413050957N1. (The registration date: May 1, 2021).

Magnesium supplementation therapy to prevent cisplatin-induced acute nephrotoxicity in pediatric cancer: a randomized phase-2 trial.

BACKGROUND: The present study aimed to examine the effect of magnesium (Mg) supplementation on cisplatin-induced nephrotoxicity (CIN) in pediatric cancer patients. METHODS: The present phase-2, open-label, multicenter, randomized controlled trial enrolled patients aged less than 20 years who were scheduled to receive cisplatin-containing chemotherapy and randomly allocated them at a ratio of 1:1 to a Mg supplementation arm with even-numbered chemotherapy courses (arm AB) or another arm with odd-numbered courses (arm BA). Analysis objects were reconstructed into two groups depending on whether the chemotherapy course had Mg supplementation (group B) or not (group A). The primary outcome was the proportion of chemotherapy courses resulting in elevated serum creatinine per chemotherapy course. The secondary outcomes included efficacies evaluated using other biomarkers and the safety of the Mg supplementation. RESULTS: Twenty-eight patients were randomly allocated to either group (16 to arm AB and 12 to arm BA). The baseline characteristics of the groups were similar. There was no significant difference in the proportion of courses with increased serum creatinine between the groups (group A: 10% vs. group B: 6%; P = 0.465) nor was any significant difference observed in other biomarkers during any chemotherapy course. The Mg value during chemotherapy was significantly higher in group B than that in group A. No adverse events related to magnesium administration were observed. CONCLUSIONS: The study design, which treated a single chemotherapy course as a study object, failed to detect a statistically significant benefit of Mg supplementation for preventing CIN in pediatric cancer patients. TRIAL REGISTRATION: JRCT ( https://jrct.niph.go.jp/ ) Identifier UMIN000029215 jRCTs031180251. UMIN-CTR ( http://www.umin.ac.jp/icdr/index.html ) Identifier UMIN000029215.

Oral magnesium supplementation does not affect insulin sensitivity in people with insulin-treated type 2 diabetes and a low serum magnesium: a randomised controlled trial.

AIMS/HYPOTHESIS: Hypomagnesaemia has been associated with insulin resistance and an increased risk of type 2 diabetes. Whether magnesium supplementation improves insulin sensitivity in people with type 2 diabetes and a low serum magnesium level is unknown. METHODS: Using a randomised, double-blind (both participants and investigators were blinded to the participants' treatment sequences), placebo-controlled, crossover study design, we compared the effect of oral magnesium supplementation (15 mmol/day) for 6 weeks with that of matched placebo in individuals with insulin-treated type 2 diabetes (age ≥18 years, BMI 18-40 kg/m2, HbA1c <100 mmol/mol [11.3%], serum magnesium ≤0.79 mmol/l). Participants were recruited from the outpatient clinic and through advertisements. Randomisation to a treatment sequence order was done using a randomisation list. We used block randomisation and the two possible treatment sequences were evenly distributed among the trial population. The primary outcome was the mean glucose infusion rate during the final 30 min of a hyperinsulinaemic-euglycaemic clamp (i.e. M value). Secondary outcomes included variables of glucose control, insulin need, BP, lipid profile and hypomagnesaemia-related symptoms during follow-up. RESULTS: We recruited 14 participants (50% women, 100% White, mean ± SD age 67±6 years, BMI 31±5 kg/m2, HbA1c 58±9 mmol/mol [7.4±0.9%]) with insulin-treated type 2 diabetes. Magnesium supplementation increased both mean ± SEM serum magnesium level (0.75±0.02 vs 0.70±0.02 mmol/l, p=0.016) and urinary magnesium excretion (magnesium/creatinine ratio, 0.23±0.02 vs 0.15±0.02, p=0.005), as compared with placebo. The M value of the glucose clamp did not differ between the magnesium and placebo study arms (4.6±0.5 vs 4.4±0.6 mg kg-1 min-1, p=0.108). During the 6 weeks of treatment, continuous glucose monitoring outcomes, HbA1c, insulin dose, lipid profile and BP also did not differ, except for a lower HDL-cholesterol concentration after magnesium compared with placebo (1.14±0.08 vs 1.20±0.09 mmol/l, p=0.026). Symptoms potentially related to hypomagnesaemia were similar for both treatment arms. CONCLUSIONS/INTERPRETATION: Despite an albeit modest increase in serum magnesium concentration, oral magnesium supplementation does not improve insulin sensitivity in people with insulin-treated type 2 diabetes and low magnesium levels. TRIAL REGISTRATION: EudraCT number 2021-001243-27. FUNDING: This study was supported by a grant from the Dutch Diabetes Research Foundation (2017-81-014).

Impact of magnesium infusion rate on serum magnesium level after magnesium replacement in hospitalized surgical patients with hypomagnesemia: A 11-year retrospective cohort study

Background: Hypomagnesemia is common for surgical patients and often requires intravenous (IV) magnesium replacement. Due to the renal handling mechanism of magnesium, prolonging the duration of an IV magnesium infusion has been postulated to improve magnesium retention by reducing the renal excretion of magnesium. However, the evidence supporting this hypothesis is limited. Objective: To determine the change in serum magnesium level after IV magnesium replacement from baseline compared between prolonged (infusion rate < 0.5 g/h) and short infusions (infusion rate < 0.5 g/h) in hospitalized surgical patients. Methods: Medical records of surgical patients with hypomagnesemia who received IV magnesium replacement for three consecutive days and admitted to a university hospital between 2012 and 2022 were reviewed. Patients were separated by the replacement rate into two cohorts: prolonged infusion and short infusion. The primary outcome was a change in serum magnesium per gram administered from the baseline. The secondary outcome was the percentage of patients who achieved an optimal serum magnesium level after IV magnesium replacement. Results: 114 participants were enrolled in the study. The short infusion cohort showed a significantly greater increase in serum magnesium change per gram administered from baseline (0.07 mg/dL/g) compared to the prolonged infusion cohort (0.05 mg/dL/g) (p = 0.04). The difference of serum magnesium level between the two cohorts was 0.013 mg/dL/g of Mg. The percentage of patients who achieved the optimal serum magnesium level after IV magnesium replacement was not different between the two cohorts (prolonged infusion 66.7% vs. short infusion 70.2%; p = 0.84). The change in serum magnesium levels was influenced by renal function and the timing of serum magnesium level measurement after IV magnesium replacement (AU)

Association between a Calcium-to-Magnesium Ratio and Osteoporosis among Puerto Rican Adults.

BACKGROUND: The ratio of calcium-to-magnesium intake (Ca:Mg) may be important for bone due to their competitive absorption. The Ca:Mg ratio has been related to health outcomes, but few studies have related it to bone. OBJECTIVES: The purpose of this analysis was to examine associations between the Ca:Mg intake with bone mineral density (BMD) and osteoporosis among Puerto Rican adults. METHODS: Adults, aged 47-79 y, from the Boston Puerto Rican Osteoporosis Study, with complete BMD and dietary data (n = 955) were included. BMD was assessed with dual-energy X-ray absorptiometry and diet by a food frequency questionnaire. Calcium and magnesium intakes from food were energy adjusted, and the Ca:Mg was calculated. Adjusted linear and logistic regression models were utilized for testing associations between Ca:Mg and bone outcomes. RESULTS: Calcium intake was greater in the highest compared with lowest tertile, whereas magnesium intake was similar across tertiles. Mean BMD at hip sites was higher in the middle, compared with the lowest, tertile. Higher odds of osteoporosis were observed for the highest and lowest tertiles, compared with the middle tertile, after adjustment (T3 compared with T2 OR: 2.79; 95% CI: 1.47, 5.3; T1 compared with T2 OR: 2.01; 95% CI: 1.03, 3.92). Repeated analyses without supplement users (n = 432) led to stronger differences and ORs, but lost significance for some comparisons. CONCLUSIONS: Dietary calcium and magnesium are important for bone, perhaps not independently. The Ca:Mg intake ratio appeared most protective within a range of 2.2-3.2, suggesting that a balance of these nutrients may be considered in recommendations for osteoporosis..

Magnesium in the treatment of alcohol withdrawal syndrome: a multicenter randomized controlled trial.

OBJECTIVE: Alcohol withdrawal syndrome (AWS) is a frequent and potentially life-threatening condition experienced in alcohol use disorder. Since hypomagnesemia is involved in AWS's severity, we conducted a multicenter double-blind randomized placebo-controlled trial to examine the efficacy of oral magnesium supplementation as an adjuvant therapy of AWS. MATERIAL AND METHODS: Inpatients were recruited in six different centers if they had a baseline score higher than eight on the Revised Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar). The experimental treatment was magnesium lactate dehydrate, administrated three times per day providing a total of 426.6 mg per day and up to 15 days. The primary endpoint was the significant between-group difference of the CIWA-Ar total score change from baseline to 3 days later. The treatment group and baseline score were introduced as covariables in an analysis of covariance. RESULTS: A total of 98 inpatients were included {71.4% of men; mean age of 49.1 years [standard deviation (SD): 10.3]}. In the intention-to-treat population, the mean reduction of the CIWA-Ar score in the experimental group between baseline and 3 days later was 10.1 (SD: 5.2), whereas it was 9.2 (SD: 3.9) in the control group. The absolute difference of the adjusted mean in the experimental group compared with the control group was -0.69 (SD: 0.72), which did not correspond to a significant between-group difference (P = 0.34). Per-protocol analysis and sensitivity analyses also supported this result. Supplementary analyses found no significant difference regarding benzodiazepine consumption, magnesium blood concentration, and satisfaction to care. CONCLUSIONS: The present study does not support the rationale of systematic oral magnesium supplementation in patients with AWS.

Síndrome de Gitelman: cuándo sospecharlo / Gitelman syndrome, when to suspect it

Las tubulopatías son un grupo heterogéneo de entidades definidas por anomalías de la función tubular renal. El síndrome de Gitelman, objeto de nuestro artículo, está causado por mutaciones inactivantes del gen SLC12A3, que codifica el cotransportador Na-Cl sensible a tiazidas del túbulo contorneado distal, produciendo así una pérdida urinaria de Cl-Na. Se exponen tres casos clínicos de síndrome de Gitelman, cada uno con una clínica de presentación. La finalidad de este artículo es sensibilizar al lector en esta tubulopatía y ayudar en su diagnóstico precoz (AU)

Tubulopathies are a heterogeneous group of entities defined by abnormalities of renal tubular function. Gitelman syndrome, the subject of our article, is caused by inactivating mutations of the SLC12A3 gene, which encodes the thiazide-sensitive Na-Cl cotransporter of the distal convoluted tubule, thus producing a urinary loss of Cl-Na.Three clinical cases of Gitelman syndrome are presented, each with a clinical presentation. The purpose of this article is to familiarize the reader with this tubulopathy and to help in its early diagnosis. (AU)

Magnesium Intake, C-Reactive Protein, and Muscle Mass in Adolescents.

Background: Adult studies have suggested that magnesium intake may regulate C-reactive protein (CRP) and muscle mass, known risk factors for cardiometabolic diseases. Given the large deficiencies in magnesium intake in adolescents, we aimed to investigate sex and race differences in dietary magnesium intake and test the hypothesis that lower magnesium intake is associated with higher CRP and lower muscle mass. Methods: A total of 766 black and white adolescents, 14 to 18 years old (51% black; 50% female) were previously recruited. Diet was assessed with four to seven independent 24-h recalls. Body composition was measured by dual-energy X-ray absorptiometry. High-sensitivity CRP (hs-CRP), leptin, resistin, and adiponectin were measured using fasting blood samples by ELISA. Results: There were sex and race differences in the daily consumption of magnesium. The average daily magnesium intakes were 200.66 ± 7.09 mg and 205.03 ± 7.05 mg for males and females, respectively, far below the recommended amounts of 410 mg for males and 360 mg for females. White subjects (217.95 ± 6.81 mg/day) consumed more than black subjects (187.75 ± 6.92 mg/day). Almost none of the adolescents met the recommendations. Adjusted multiple linear regressions revealed that lower magnesium intake was associated with higher hs-CRP and lower fat-free mass (FFM) (p-values < 0.05). Higher hs-CRP was associated with lower FFM. Moreover, an interaction between magnesium intake and hs-CRP on FFM was identified (p-value < 0.05). Lower magnesium intake amplified the inverse relationships between hs-CRP and FFM (p-values < 0.05). Conclusion: Magnesium consumption in our adolescents was far below daily recommended levels with male and black subjects consuming less than female and white subjects. Lower magnesium intake was associated with higher CRP and lower muscle mass. Low magnesium intake may also augment the inverse relationship between CRP and FFM.

Magnesium and Zinc Intake Ratio Mediates the Increase of Coronary Artery Calcification through Upregulating Interleukin 6.

The relation between dietary minerals and coronary artery calcification (CAC) has been emphasized. However, the effects of multiple dietary minerals on CAC progression remain unclear. This study Investiagetes the effect of combined dietary mineral intake on the progression of CAC. We analyzed a population-based cohort with 6814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). CAC scores were measured at baseline and subsequent follow-up examinations by Multi-detector computed tomography (MDCT) scans with Agatston scores. Then, the progression of CAC was defined through increased CAC scores in the follow-up from the baseline exam. The results revealed that the dietary intake of individual minerals did not show significant differences across CAC progression vs non progression groups. However, participants with CAC progression had an increased Magnesium (Mg):Zinc (Zn) ratio (P < 0.05). This effect was significant in logistic regression after adjusting for multiple established risk factors of CAC progression (OR 1.050; 95% CI 1.003, 1.099; P = 0.038). The increased risk of CAC associated with Mg/Zn was mediated through an increase level of IL-6, which increased with association to the Mg: Zn ratio. In conclusion, the dietary of Mg: Zn ratio, rather than individual mineral intake is associated with increased risk of CAC progression, which is mediated by pro-calcific IL-6. Therefore, the consideration of dietary intake of Zn and Mg together would play a cardio protective role among CAC patients.

Chronic magnesium deficiency causes reversible mitochondrial permeability transition pore opening and impairs hypoxia tolerance in the rat heart.

Chronic magnesium (Mg) deficiency induces and exacerbates various cardiovascular diseases. We previously investigated the mechanisms underlying decline in cardiac function caused by chronic Mg deficiency and the effectiveness of Mg supplementation on this decline using the Langendorff-perfused isolated mouse heart model. Herein, we used the Langendorff-perfused isolated rat heart model to demonstrate the chronic Mg-deficient rats (Mg-deficient group) had lower the heart rate (HR) and left ventricular pressure (LVDP) than rats with normal Mg levels (normal group). Furthermore, decline in cardiac function due to hypoxia/reoxygenation injury was significantly greater in the Mg-deficient group than in the normal group. Experiments on mitochondrial permeability transition pore (mPTP) using isolated mitochondria revealed that mitochondrial membrane was fragile in the Mg-deficient group, implying that cardiac function decline through hypoxia/reoxygenation injury is associated with mitochondrial function. Mg supplementation for chronic Mg-deficient rats not only improved hypomagnesemia but also almost completely restored cardiac and mitochondrial functions. Therefore, proactive Mg supplementation in pathological conditions induced by Mg deficiency or for those at risk of developing hypomagnesemia may suppress the development and exacerbation of certain disease states.

Magnesium sensing via LFA-1 regulates CD8+ T cell effector function.

The relevance of extracellular magnesium in cellular immunity remains largely unknown. Here, we show that the co-stimulatory cell-surface molecule LFA-1 requires magnesium to adopt its active conformation on CD8+ T cells, thereby augmenting calcium flux, signal transduction, metabolic reprogramming, immune synapse formation, and, as a consequence, specific cytotoxicity. Accordingly, magnesium-sufficiency sensed via LFA-1 translated to the superior performance of pathogen- and tumor-specific T cells, enhanced effectiveness of bi-specific T cell engaging antibodies, and improved CAR T cell function. Clinically, low serum magnesium levels were associated with more rapid disease progression and shorter overall survival in CAR T cell and immune checkpoint antibody-treated patients. LFA-1 thus directly incorporates information on the composition of the microenvironment as a determinant of outside-in signaling activity. These findings conceptually link co-stimulation and nutrient sensing and point to the magnesium-LFA-1 axis as a therapeutically amenable biologic system.

Effect of calcium and magnesium on inflammatory cytokines in accidentally multiple fracture adults: A short-term follow-up.

ABSTRACT: Calcium (Ca) and magnesium (Mg), which play an important role in several cellular processes, is essential for normal development of the skeleton and maintenance of tissue homeostasis. Deficiency of these elements might delay bone fracture recovery or accelerates bone loss. We aimed to examine whether supplementation of trace element (TE) promotes fracture healing in accidentally fracturing adults by involvement of inflammatory mechanism.A short-term follow-up in clinic was performed. Totally, 117 subjects diagnosed with multiple fractures by traffic accidents were recruited in this study. Serum Ca and Mg levels were measured by inductively coupled plasma atomic emission spectrophotometry. Short-term changes such as serum C-reactive protein, interleukin (IL)-1ß, IL-6, and tumor necrosis factor alpha in normal treatment and TE supplement groups were detected by enzyme-linked immunosorbent assay. Student t test and the Spearman correlation were performed to analyze the data.Significantly negative correlations between Ca (r = 0.7032; P < .001) and Mg (r = 0.2719; P < .05) and injury severity score were observed. Serum Ca and Mg were significantly increased at Day 5, 7, and 9 following TE supplements. After treatment, serum C-reactive protein, IL-1ß, IL-6, and tumor necrosis factor alpha were significantly reduced whereas cytokine levels of the TE supplement group were found to be lower than that of the normal treatment group after Day 3.These findings suggest that Ca and Mg levels are associated with the injury severity of multiple fractures, and the supplement could reduce the inflammation, which may be beneficial for the bone recovery and disease process.

Pharmacological and clinical implications of local anaesthetic mixtures: a narrative review.

Various techniques have been explored to prolong the duration and improve the efficacy of local anaesthetic nerve blocks. Some of these involve mixing local anaesthetics or adding adjuncts. We did a literature review of studies published between 01 May 2011 and 01 May 2021 that studied specific combinations of local anaesthetics and adjuncts. The rationale behind mixing long- and short-acting local anaesthetics to hasten onset and extend duration is flawed on pharmacokinetic principles. Most local anaesthetic adjuncts are not licensed for use in this manner and the consequences of untested admixtures and adjuncts range from making the solution ineffective to potential harm. Pharmaceutical compatibility needs to be established before administration. The compatibility of drugs from the same class cannot be inferred and each admixture requires individual review. Precipitation on mixing (steroids, non-steroidal anti-inflammatory drugs) and subsequent embolisation can lead to serious adverse events, although these are rare. The additive itself or its preservative can have neurotoxic (adrenaline, midazolam) and/or chondrotoxic properties (non-steroidal anti-inflammatory drugs). The prolongation of block may occur at the expense of motor block quality (ketamine) or block onset (magnesium). Adverse effects for some adjuncts appear to be dose-dependent and recommendations concerning optimal dosing are lacking. An important confounding factor is whether studies used systemic administration of the adjunct as a control to accurately identify an additional benefit of perineural administration. The challenge of how best to prolong block duration while minimising adverse events remains a topic of interest with further research required.

ALM Fluid Therapy Shifts Sympathetic Hyperactivity to Parasympathetic Dominance in the Rat Model of Non-Compressible Hemorrhagic Shock.

ABSTRACT: Excessive sympathetic outflow following trauma can lead to cardiac dysfunction, inflammation, coagulopathy, and poor outcomes. We previously reported that buprenorphine analgesia decreased survival after hemorrhagic trauma. Our aim is to examine the underlying mechanisms of mortality in a non-compressible hemorrhage rat model resuscitated with saline or adenosine, lidocaine, magnesium (ALM). Anesthetized adult male Sprague-Dawley rats were randomly assigned to Saline control group or ALM therapy group (both n = 10). Hemorrhage was induced by 50% liver resection. After 15 min, 0.7 mL/kg 3% NaCl ±â€ŠALM intravenous bolus was administered, and after 60 min, 0.9% NaCl ±â€ŠALM was infused for 4 h (0.5 mL/kg/h) with 72 h monitoring. Animals received 6-12-hourly buprenorphine for analgesia. Hemodynamics, heart rate variability, echocardiography, and adiponectin were measured. Cardiac tissue was analyzed for adrenergic/cholinergic receptor expression, inflammation, and histopathology. Four ALM animals and one Saline control survived to 72 h. Mortality was associated with up to 97% decreases in adrenergic (ß-1, α-1A) and cholinergic (M2) receptor expression, cardiac inflammation, myocyte Ca2+ loading, and histopathology, indicating heart ischemia/failure. ALM survivors had higher cardiac output and stroke volume, a 30-fold increase in parasympathetic/sympathetic receptor expression ratio, and higher circulating adiponectin compared to Saline controls. Paradoxically, Saline cardiac adiponectin hormone levels were higher than ALM, with no change in receptor expression, indicating intra-cardiac synthesis. Mortality appears to be a "systems failure" associated with CNS dysregulation of cardiac function. Survival involves an increased parasympathetic dominance to support cardiac pump function with reduced myocardial inflammation. Increased cardiac α-1A adrenergic receptor in ALM survivors may be significant, as this receptor is highly protective during heart dysfunction/failure.

Micro-/Nano-Structures on Biodegradable Magnesium@PLGA and Their Cytotoxicity, Photothermal, and Anti-Tumor Effects.

The size and structural control of particulate carriers for imaging agents and therapeutics are constant themes in designing smart delivery systems. This is motivated by the causal relationship between geometric parameters and functionalities of delivery vehicles. Here, both in vitro and in vivo, the controlling factors for cytotoxicity, photothermal, and anti-tumor effects of biodegradable magnesium@poly(lactic-co-glycolic acid (Mg@PLGA) particulate carriers with different sizes and shell thicknesses are investigated. Mg@PLGA microspheres fabricated by microfluidic emulsification are shown to have higher Mg encapsulation efficiency, 87%, than nanospheres by ultrasonic homogenization, 50%. The photothermal and anti-tumor effects of Mg@PLGA spheres are found to be dictated by their Mg content, irrelevant to size and structural features, as demonstrated in both in vitro cell assays and in vivo mice models. These results also provide important implications for designing and fabricating stimuli-responsive drug delivery vehicles.

Scaffold 3D-Printed from Metallic Nanoparticles-Containing Ink Simultaneously Eradicates Tumor and Repairs Tumor-Associated Bone Defects.

Bone metastasis occurs in about 70% of breast cancer patients. The surgical resection of metastatic tumors often leads to bone erosion and destruction, which greatly hinders the treatment and prognosis of breast cancer patients with bone metastasis. Herein, a bifunctional scaffold 3D-printed from nanoink is fabricated to simultaneously eliminate the tumor cells and repair the tumor-associated bone defects. The metallic polydopamine (PDA) nanoparticles (FeMg-NPs) may effectively load and sustainably release the metal ions Fe3+ and Mg2+ in situ. Fe3+ exerts a chemodynamic therapy to synergize with the photothermal therapy induced by PDA with effective photothermal conversion under NIR laser, which efficiently eliminates the bone-metastatic tumor. Meanwhile, the sustained release of osteoinductive Mg2+ from the bony porous 3D scaffold enhances the new bone formation in the bone defects. Taken together, the implantation of scaffold (FeMg-SC) 3D-printed from the FeMg-NPs-containing nanoink provides a novel strategy to simultaneously eradicate bone-metastatic tumor and repair the tumor-associated bone defects.

Comparison of intra-articular administration of adenosine, lidocaine and magnesium solution and tranexamic acid for alleviating postoperative inflammation and joint fibrosis in an experimental model of knee arthroplasty.

BACKGROUND: Dysregulated inflammatory responses are implicated in the pathogenesis of joint stiffness and arthrofibrosis following total knee arthroplasty (TKA). The purpose of this study was to compare the effects of intra-articular (IA) administration of tranexamic acid (TXA), an anti-fibrinolytic commonly used in TKA, and ALM chondroprotective solution on postoperative inflammation and joint tissue healing in a rat model of knee implant surgery. METHODS: Male Sprague-Dawley rats (n = 24) were randomly divided into TXA or ALM treatment groups. The right knee of each rat was implanted with titanium (femur) and polyethylene (tibia) implants. An IA bolus (0.1 ml) of TXA or ALM was administered after implantation and capsule closure, and before skin closure. Postoperative coagulopathy, haematology and systemic inflammatory changes were assessed. Inflammatory and fibrotic markers were assessed in joint tissue, 28 days after surgery. RESULTS: Haemostasis was comparable in animals treated with TXA or ALM after knee implant surgery. In contrast to ALM-treated animals, systemic inflammatory markers remained elevated at day 5 (IL-6, IL-12, IL-10, platelet count) and day 28 (IL-1ß, IL-10) following surgery in TXA-treated animals. At day 28 following surgery, the extension range of motion of operated knees was 1.7-fold higher for ALM-treated animals compared to the TXA group. Key inflammatory mediators (NF-κB, IL-12, IL-2), immune cell infiltration (CD68+ cells) and markers of fibrosis (α-SMA, TGF-ß) were also lower in capsular tissue of ALM-treated knees at day 28. CONCLUSION: Data suggest that IA administration of ALM is superior to TXA for reducing postoperative systemic and joint inflammation and promoting restoration of healthy joint tissue architecture in a rat model of TKA. Further studies are warranted to assess the clinical translational potential of ALM IA solution to improve patient outcomes following arthroplasty.

Oral Magnesium Supplementation for Treating Glucose Metabolism Parameters in People with or at Risk of Diabetes: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials.

There is a large and growing body of literature focusing on the use of oral magnesium (Mg) supplementation for improving glucose metabolism in people with or at risk of diabetes. We therefore aimed to investigate the effect of oral Mg supplementation on glucose and insulin-sensitivity parameters in participants with diabetes or at high risk of diabetes, compared with a placebo. Several databases were searched investigating the effect of oral Mg supplementation vs placebo in patients with diabetes or conditions at high risk of diabetes. Data were reported as standardized mean differences (SMDs) with their 95% confidence intervals (CIs) using follow-up data of glucose and insulin-sensitivity parameters. Compared with placebo, Mg supplementation reduced fasting plasma glucose in people with diabetes. In people at high risk of diabetes, Mg supplementation significantly improved plasma glucose per se, and after a 2 h oral glucose tolerance test. Furthermore, Mg supplementation demonstrated an improvement in insulin sensitivity markers. In conclusion, Mg supplementation appears to have a beneficial role and improves glucose parameters in people with diabetes. Moreover, our work indicates that Mg supplementation may improve insulin-sensitivity parameters in those at high risk of diabetes.