The effect of supplementation with vitamins A, B, C, D, and E on disease severity and inflammatory responses in patients with COVID-19: a randomized clinical trial.

BACKGROUND AND OBJECTIVE: Because of the effect of vitamins on modulating the immune system function, we have evaluated the effect of supplementation with vitamins A, B, C, D, and E in ICU-admitted patients with COVID-19. METHODS: This study was a randomized and single-blinded clinical trial in which 60 subjects were randomly assigned to two groups. The intervention group (n=30) received vitamins, and the control group did not receive any vitamin or placebo. The intervention was included 25,000 IU daily of vitamins A, 600,000 IU once during the study of D, 300 IU twice daily of E, 500 mg four times daily of C, and one amp daily of B complex for 7 days. At baseline and after the 7-day intervention, the serum levels of inflammatory markers, vitamins, and the SOFA score were assessed. In addition, the mortality rate and duration of hospitalization were evaluated after the intervention (IRCT registration number: IRCT20200319046819N1/registration date: 2020-04-04, https://www.irct.ir/trial/46838 ). RESULTS: Significant changes were detected in serum levels of vitamins (p < 0.001 for all vitamins), ESR (p < 0.001), CRP (p = 0.001), IL6 (p = 0.003), TNF-a (p = 0.001), and SOFA score (p < 0.001) after intervention compared with the control group. The effect of vitamins on the mortality rate was not statistically significant (p=0.112). The prolonged hospitalization rate to more than 7 days was significantly lower in the intervention group than the control group (p=0.001). Regarding the effect size, there was a significant and inverse association between receiving the intervention and prolonged hospitalization (OR = 0.135, 95% CI 0.038-0.481; p=0.002); however, after adjusting for confounders, it was not significant (OR=0.402, 95% CI 0.086-1.883; p=0.247). CONCLUSION: Supplementation with vitamins A, B, C, D, and E could improve the inflammatory response and decrease the severity of disease in ICU-admitted patients with COVID-19.

Impact of vitamins A, B, C, D, and E supplementation on improvement and mortality rate in ICU patients with coronavirus-19: a structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: This study will evaluate the main hypothesis that supplementation with vitamins A, B, C, D, and E significantly improves the severity and mortality rate in ICU patients with COVID-19. TRIAL DESIGN: This study is a randomized, single-blinded, two-arm (1:1 ratio) parallel group clinical trial. PARTICIPANTS: We are conducting this study in patients with COVID-19 admitted to intensive care units at the Imam Khomeini Hospital Complex in Tehran, Iran. The inclusion criteria are as follows: (1) aged between 20 and 60 years, (2) both male and female patients with COVID-19, (3) clinical or definitive diagnosis (using polymerase chain reaction (PCR) test), (4) patients have not participated in other clinical trials, and (5) no renal or hepatic abnormalities. The exclusion criteria are as follows: (1) patients with specific and rare viral diseases such as HIV and (2) patients who have been undergoing chemotherapy for the past month. INTERVENTION AND COMPARATOR: Duration of intervention: 7 days from randomization Intervention in the treatment group: Vitamin A 25,000 IU daily Vitamin D 600,000 IU once during study Vitamin E 300 IU twice daily Vitamin C is taken four times per day B vitamins are taken as a daily Soluvit [which included thiamine nitrate 3.1 mg, sodium riboflavin phosphate 4.9 mg (corresponding to vitamin B2 3.6 mg), nicotinamide 40 mg, pyridoxine hydrochloride 4.9 mg (corresponding to vitamin B6 4.0 mg), sodium pantothenate 16.5 mg (corresponding to pantothenic acid 15 mg), sodium ascorbate 113 mg (corresponding to vitamin C 100 mg), biotin 60 µg, folic acid 400 µg, and cyanocobalamin 5 µg] The control group will not receive any supplements or placebo. All supplements are made in Iran except for Soluvit (from Fresenius Kabi, New Zealand). MAIN OUTCOMES: 1. Weight, height, and BMI 2. Severity of pulmonary involvement according to CT scan 3. Respiratory support (invasive or non-invasive) 4. Percentage of oxygen saturation (SpO2 level) 5. Serum levels of WBC, CRP, ESR, IL6, IFN-G, and TNF-α 6. The patient's body temperature 7. The presence or absence of involvement of organs other than the lungs (e.g., heart, liver, kidneys) 8. Duration of hospitalization 9. Mortality rate RANDOMIZATION: At baseline, eligible patients were randomly assigned to a 1:1 ratio to one of two groups: intervention and control. Block randomization is used based on the gender of patients. BLINDING (MASKING): Patients are unaware of being placed in the intervention or control groups after signing consent. All treatment staff will be aware of which group each of the patients is in due to the specific conditions of the ICU and the absence of placebo for the control group. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): The researchers plan to include 60 patients in total, with 30 patients in each group. TRIAL STATUS: This is the first version of the protocol which started on April 2, 2020. Recruitment began April 2, 2020, and is expected to be complete by July 4, 2020. TRIAL REGISTRATION: The Iranian Registry of Clinical Trials IRCT20200319046819N1 . Registered on April 4, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol (Fig. 1, Table 1).

Effect of magnesium supplementation on lactate clearance in critically ill patients with severe sepsis: a randomized clinical trial.

OBJECTIVES: In this study, changes in lactate clearance following magnesium supplementation were evaluated in critically ill patients with severe sepsis. METHODS: Fifty-eight patients with severe sepsis were randomly assigned to receive either magnesium (n = 30) or placebo (n = 28). Patients in the magnesium group received intravenous magnesium sulfate to maintain serum magnesium level around 3 mg/dL for 3 days. The placebo group received the same volume of normal saline. Change in lactate clearance was considered primary outcome of the study. RESULTS: Mean increase in the lactate clearance in the magnesium group was significantly higher than the placebo group on day 2 (27.53% vs. 23.79% respectively, p < 0.001) and day 3 (49.83% vs. 37.02% respectively, p < 0.001). Time to lactate clearance was also significantly shorter in the magnesium group than the placebo group (47.28 ± 20.59 vs. 61.20 ± 24.31 h respectively, p = 0.03). Sepsis-related mortality was not significantly different but median length of ICU stay was significantly shorter in the magnesium group than the placebo group (8 vs. 15 days respectively, p < 0.01). CONCLUSIONS: Magnesium supplementation increased lactate clearance in critically ill patients with severe sepsis. Optimizing serum magnesium level near the upper limit of the normal range may improve severe sepsis outcomes.

Effect of Magnesium Loading Dose on Insulin Resistance in Patients With Stress-Induced Hyperglycemia: A Randomized Clinical Trial.

OBJECTIVES: There is currently no evidence that whether magnesium supplementation would improve stress-induced hyperglycemia (SIH) in critically ill patients. In this study, effects of magnesium loading dose on insulin resistance (IR) indices were evaluated in critically ill patients without diabetes having SIH. METHODS: Seventy critically ill patients with SIH were assigned to receive a loading dose of magnesium (7.5 g of magnesium sulfate in 500 mL normal saline as intravenous infusion over an 8-hour period) or placebo. Changes in baseline of serum and intracellular magnesium and serum adiponectin (AD) levels, homeostasis model assessment of IR (HOMA-IR), and HOMA-AD ratio were assessed in this study. RESULTS: Serum and intracellular magnesium levels increased significantly in patients in the magnesium group (P < .001). At day 3, there were significant differences between the magnesium group and the placebo group in the mean changes from baseline in the HOMA (between-group difference: -0.11; 95% confidence interval [CI]: -0.19 to -0.01; P = .02), the AD (between-group difference: 0.94; 95% CI: 0.41-1.48; P = .04), and the HOMA-AD ratio (between-group difference: -0.03; 95% CI: -0.04 to -0.01; P < .001). CONCLUSION: In the present study, a single-loading dose of intravenous magnesium improved IR indices in critically ill patients with SIH.

Adjuvant potential of selegiline in treating acute toxicity of aluminium phosphide in rats.

Aluminium phosphide (AlP) is a highly toxic substance with a high mortality rate and no effective antidote. Once exposed to the moisture and acidic conditions of the stomach, AlP releases toxic phosphine (PH3 ) gas, which results in severe toxicity in poisoned subjects. Selegiline is a monoamine oxidase inhibitor with antioxidant and anti-apoptotic properties, which is mostly prescribed for the treatment of mood disorders and Parkinson's disease. Since AlP has detrimental effects on cardiac physiology and mitochondrial function, we tested the protective effects of acute selegiline treatment on cardiac mitochondrial function, redox status and electrocardiographic parameters in rats after AlP poisoning. To do this, AlP was given to rats by gavage to induce toxicity. Selegiline was injected intraperitoneally in the treatment groups 1 hour after AlP poisoning. Selegiline treatment after AlP intoxication was not associated with a significant difference in the mortality rate of animals. However, selegiline reduced oxidative stress (decreased the reactive oxygen species and malondialdehyde) and increased glutathione in the cardiac tissue of rats exposed to AlP. Further, the mitochondrial membrane potential (ΔΨm) collapse reversed after treatment with selegiline. Selegiline also improved the electrocardiographic (ECG) parameters and enhanced heart rate. The histopathological evaluation revealed that selegiline eliminated the inflammation and injuries induced by AlP in the stomach and duodenum, as well as cardiac tissue. In conclusion, selegiline treatment can ameliorate the AlP-induced cardiac and gastrointestinal injuries in rats via boosting redox status and mitochondrial function with no significant effect on survival. We suggest that using selegiline, apart from other clinical treatments, may improve the quality of treatment process for AlP toxicity.

Molecular Epidemiology and Drug Resistance Pattern of Carbapenem-Resistant Klebsiella pneumoniae Isolates from Iran.

The emergence and dissemination of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates and their involvement in several nosocomial outbreaks are of high concern. This study was conducted to investigate the genetic relatedness and molecular determinants of carbapenem resistance in 100 CRKP isolates. Susceptibility to carbapenems as well as other antibiotics was determined by using disk diffusion method. The Modified Hodge test was performed for detection of carbapenemase production. The minimum inhibitory concentrations of selected antibiotics were determined by broth microdilution method. The presence of blaOXA-48, blaKPC, blaNDM, and blaVIM carbapenemase genes was examined by PCR, and clonal relatedness of CRKP isolates was investigated by pulsed-field gel electrophoresis (PFGE) analysis. blaOXA-48 was the most frequent carbapenemase gene (72%), followed by blaNDM (31%). None of the isolates harbored blaKPC and blaVIM genes. PFGE separated the majority of isolates into 10 clusters, including the major clusters A and B, carrying blaOXA-48, and clusters C and D, carrying blaNDM, and 4 isolates had a unique PFGE pattern. An increased rate of colistin resistance (50%) was detected among the isolates. Tigecycline was found to be the most active agent against CRKP isolates. Our results revealed that high prevalence of blaOXA-48 and blaNDM carbapenamses and resistance to colistin are alarming threats, necessitating an immediate action to prevent the spread of carbapenem-colistin-resistant K. pneumoniae isolates in Iran.

Protective Effects of L-Carnitine Against Delayed Graft Function in Kidney Transplant Recipients: A Pilot, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial.

OBJECTIVE: Delayed graft function (DGF) is an early complication after deceased donor kidney transplantation with significant adverse effects on graft outcomes. Ischemia-reperfusion injury during transplantation is a major cause of DGF. Tissue concentrations of carnitine, an antioxidant and regulator of cellular energy supply, decrease in the kidney following ischemia-reperfusion insult. Based on promising animal data, this study evaluated the possible protective effect of L-carnitine against DGF. DESIGN: This study is a pilot, randomized, double-blind, placebo-controlled clinical trial that was conducted on kidney transplantation patients in kidney transplant ward of Imam Khomeini hospital complex affiliated to Tehran University of Medical Sciences, Tehran, Iran. SUBJECTS: Patients older than 14 years old undergoing their first kidney transplantation from a deceased donor were evaluated for eligibility to take part in this study. Fifty-six patients were randomly assigned to L-carnitine or placebo groups. INTERVENTION: During this trial, 3 g of oral L-carnitine or placebo was administered in 3 divided doses each day for 4 consecutive days starting the day before kidney transplantation (i.e., days -1, 0, 1, and 2). MAIN OUTCOME MEASURE: The need for dialysis within the first week after transplantation, serum creatinine and urine output were assessed daily. After hospital discharge, patients were followed for 3 months regarding organ function. RESULTS: DGF incidence did not differ between the L-carnitine and placebo groups (18.51% vs. 23.8%, respectively; P = .68). Total allograft failure within 3 months after kidney transplantation happened in 6 patients in the placebo and 1 patient in the L-carnitine group (P = .05). CONCLUSION: This study showed no protective effects of oral L-carnitine supplementation against DGF occurrence recipients; however, 3-month graft loss was lower in the L-carnitine supplemented group.

Effect of Silymarin Administration on Cisplatin Nephrotoxicity: Report from A Pilot, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial.

Despite several introduced preventive modalities, cisplatin nephrotoxicity remains a clinical problem. Some in vitro and in vivo studies have addressed the protective effects of silymarin against cisplatin nephrotoxicity. This study evaluated the effects of silymarin administration on cisplatin nephrotoxicity as the first human study. During this pilot, randomized, double-blinded, placebo-controlled clinical trial, the effect of oral silymarin 420 mg daily in three divided doses starting 24-48 h before the initiation of cisplatin infusion and continuing to the end of three 21-day cisplatin-containing chemotherapy courses on cisplatin-induced renal electrolytes wasting and kidney function were assessed. Cisplatin-associated acute kidney injury (AKI) occurred in 8% of the patients. Urine neutrophil gelatinase-associated lipocalin to urine creatinine ratio (NGAL/Cr) and urinary magnesium and potassium wasting increased significantly after cisplatin infusion in both groups. Significant positive correlation was found between cumulative dose of cisplatin and urine NGAL/Cr after three courses of cisplatin infusion. Incidence of AKI and the magnitude of urinary magnesium and potassium wasting did not differ between silymarin and placebo groups. No adverse reaction was reported by silymarin administration. Prophylactic administration of conventional form of silymarin tablets could not prevent cisplatin-induced urine electrolyte wasting or renal function impairment.

Evaluation of antimicrobial resistance pattern of nosocomial and community bacterial pathogens at a teaching hospital in Tehran,Iran.

Antimicrobial resistance in pathogens not only in hospitals but also in the community has become an important public health problem. The aim of this study was to determine the antimicrobial resistance patterns of predominant pathogens from hospitalized and outpatients in a university hospital in Tehran, Iran. A total of 820 samples of common Gram-negative and Gram-positive bacteria were collected from a major referral and teaching hospital affiliated to Tehran University of Medical Sciences in Iran during April 2010 to February 2011. The pattern of antibiotic resistance was determined by disk diffusion test as recommended by the Clinical Laboratory and Standards Institute (CLSI). Gram-negative bacilli were the most isolated pathogens. Acinetobacter spp. and Pseudomonas aeruginosa (P. aeruginosa) was the most antibiotic-resistant pathogens. Imipenem and piperacillin/tazobactam were the most active antimicrobials against gram-negative bacilli whereas vancomycin was the antimicrobial agent most consistently active against the Gram-positive cocci. Community-acquired organisms were more susceptible to antimicrobial drugs tested than nosocomial isolates. The rates of antibiotic resistance among isolated pathogens in this study were approximately similar to other studies. However, high rates of antibiotic resistance among Acinetobacter spp and P. aeruginosa, the most isolated pathogens, indicating that antibiotic policy is urgently needed to prevent the resistance development ago.

Effects of oral supplementation with omega-3 fatty acids on nutritional state and inflammatory markers in maintenance hemodialysis patients.

OBJECTIVE: The objective was to determine the effects of omega-3 supplementation on nutritional state and inflammatory markers of hemodialysis patients. DESIGN AND METHODS: This was a randomized, placebo-controlled trial. Adult patients undergoing maintenance hemodialysis were included. Patients with malignancy, pregnancy, concurrent inflammatory or infectious diseases, or concomitant use of any medication affecting inflammation status were excluded. The omega-3 group received 6 soft-gel capsules of fish oil (180 mg eicosapentaenoic acid and 120 mg docosahexaenoic acid in each) daily for 4 months, and the placebo group received corresponding paraffin oil capsules.Nutrition indices including body mass index; mid-arm muscle circumference; serum concentrations of albumin, prealbumin, and transferrin; and serum levels of inflammatory/anti-inflammatory markers including interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, C-reactive protein, ferritin, parathyroid hormone, and ratios of IL-10 to TNF-α and IL-10 to IL-6 were measured before and after 4 months of intervention. RESULTS: Twenty patients in the placebo and 25 patients in the omega-3 group completed the study. There were no significant changes in nutritional markers between the omega-3 and placebo groups after 4 months of intervention. Regression analysis adjusting post-treatment values of nutrition markers for baseline values, omega-3 treatment, and patients' baseline demographic and clinical data revealed that omega-3 treatment was a significant independent predictor of increased serum prealbumin level (182.53; 95% confidence interval 21.14, 511.18; P = .11). Although slight reduction of inflammatory state was observed in the omega-3 group, no significant differences were evident in the mean changes of inflammatory and anti-inflammatory markers between the 2 groups with the exception of serum ferritin level and the IL-10 to IL-6 ratio, which significantly changed in favor of omega-3 supplementation (P < .001 and P = .003, respectively). CONCLUSIONS: Omega-3 supplementation in hemodialysis patients produced a slight attenuation in systemic inflammation without any remarkable effects on nutritional markers.

Carnitine deficiency and its possible risk factors in TB patients: first report.

AIM: To assess carnitine serum levels and possible risk factors of its deficiency in patients with TB. PATIENTS & METHODS: All newly diagnosed TB patients admitted to an infectious diseases ward were recruited. Demographic, clinical and paraclinical characteristics of the patients were collected. Total carnitine serum concentrations were measured. To investigate factors that can predict carnitine deficiency, logistic regression analysis with odds ratio and 95% CI was performed. RESULTS: The mean ± standard deviation of carnitine serum levels of patients was 43.77 ± 32.92 µmol/l. Carnitine deficiency was detected in 47.7% of the study population. According to the final model of multivariate logistic regression analysis, increased serum triglyceride levels and hypoalbuminemia were identified as predictive factors of carnitine deficiency in TB patients aged over 35 years old. CONCLUSION: Nearly half of Iranian patients with TB were carnitine-deficient. Increased serum triglyceride levels and hypoalbuminemia were identified as independent risk factors of carnitine deficiency in patients aged over 35 years. Considering malnutrition as a major risk factor of TB and the safety of carnitine supplementation, use of carnitine as an adjunctive modality instead of other standard interventions may show beneficial effects in patients with TB.

Association between serum magnesium and risk factors of cardiovascular disease in hemodialysis patients.

INTRODUCTION: There are associations between serum magnesium level and some risk factors of cardiovascular disease and atherosclerosis, such as lipid profile, serum albumin, C-reactive protein, serum phosphorus, parathyroid hormone, and diabetes mellitus in hemodialysis patients. The aim of this study was to examine these associations. MATERIALS AND METHODS: This study was conducted on 103 patients with end-stage renal disease on maintenance hemodialysis. Laboratory assessment was performed before hemodialysis session in a 12-hour fasting state. Patients were divided into two groups according to their serum magnesium concentration < 2.6 mg/dL, n = 34 and >= 2.6 mg/dL, n = 69). RESULTS: The mean age of the patients was 57.4 +/- 15.4 years. The mean serum magnesium was 2.80 +/- 0.55 mg/dL (range, 1.7 mg/dL to 7 mg/dL). There were no significant differences in serum magnesium between patients with low and high values of high-density lipoprotein cholesterol, triglycerides, low-density lipoprotein cholesterol, and blood pressure. Of the 103 patients, 1 (1%) had hypomagnesemia, 41 (39.8%) had magnesium levels within normal range, and 61 (59.2%) had hypermagnesemia. Serum magnesium significantly correlated with plasma phosphorus level (r = 0.35, P < .001) and albumin (r = 0.24, P = .01). There were no correlations between serum magnesium level and age, body mass index, systolic blood pressure before dialysis, serum calcium, lipid profile, and apoprotein(a). CONCLUSIONS: In our cohort of hemodialysis patients, there were no correlations between serum magnesium levels and atherogenic lipids, serum calcium, or parathyroid hormone.

Effects of vitamin D supplementation on the bone specific biomarkers in HIV infected individuals under treatment with efavirenz.

BACKGROUND: It was reported that antiretroviral drugs such as efavirenz can increase the catabolism of vitamin D in HIV infected individuals. We have not found any study that evaluated effects of vitamin D supplementation on the bone specific biomarkers in HIV positive patients under treatment with antiretroviral regimen containing efavirenz. FINDINGS: Vitamin D deficiency was detected in 88.4 % of included patients. Baseline osteocalcin, but not collagen telopeptidase, serum levels were lower than normal range in all of these individuals. Both bone biomarkers' concentrations increased significantly (p < 0.001 for both of them) after supplementation of vitamin D and it was more predominant for osteocalcin. CONCLUSION: In the HIV-infected patients under treatment with efavirenz, vitamin D deficiency is prevalent. After supplementation with single dose of 300,000 IU vitamin D in this population, the activation of osteoblasts and osteoclasts stimulates bone formation and resorption respectively with favorable bone formation without any adverse event. Significant percent of HIV infected individuals are vitamin d deficient that could benefit from vitamin D supplementation.