The relationship between liver enzymes, prehypertension and hypertension in the Azar cohort population.

BACKGROUND: The incidence of hypertension (HTN) as a worldwide health problem is rising rapidly. Early identification and management of pre-HTN before HTN development can help reduce its related complications. We evaluated the relationship between liver enzymes levels and pre-HTN/HTN in the Azar cohort population. METHOD: This cross-sectional study was based on data from the large Azar cohort study and a total of 14,184 participants were included. Pre-HTN and HTN were defined based on the American Heart Association guideline. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) levels were measured by Pars Azmoon kits. The relationship between pre-HTN/HTN and liver enzyme levels was evaluated by logistic regression. RESULTS: Of 14,184 participants, 5.7% and 39.6% had pre-HTN and HTN, respectively. In the adjusted model, AST levels of 19-23 IU/l were associated with an elevated risk of pre-HTN (OR [95% CI]: 1.24 [1.04-1.48]). A dose-response increase was seen in pre-HTN in relation to ALT, with the highest OR in the third tertile (1.34 [1.09-1.63]). The odds of pre-HTN also increased with GGT in the third tertile (1.25[1.03-1.52]). In addition, the odds of HTN increased with increased levels of AST, ALT, ALP, and GGT, such that the highest ORs were recorded in the third tertile (OR 1.22 [1.09-1.37], 1.51 [1.35-1.70], 1.19 [1.07-1.34], and 1.68 [1.49-1.89], respectively). Among these enzymes, GGT had the highest OR regarding HTN. CONCLUSION: This study indicates that AST, ALT, ALP and GGT levels were associated with pre-HTN (except for ALP) and HTN, independent of known risk factors. Hence, it may be possible to use liver enzymes to predict the incidence of pre-HTN and HTN, empowering primary care providers to make the necessary interventions promptly.

Sleep and cognitive outcomes in multiple sclerosis; a systematic review.

BACKGROUND: Multiple sclerosis (MS) is a disabling disease of the central nervous system. People living with MS often have co-existing sleep disorders and cognitive dysfunction. The objective of this study was to scrutinize the relationship between cognitive outcomes and sleep conditions in MS. METHODS: This study followed the Joanna Briggs Institute's (JBI) and PRISMA guidelines. PubMed, Scopus, Embase, and Web of Science databases were searched and original studies delineating the relationship between sleep status and cognitive findings in MS patients| were included. The risk of bias was assessed using the JBI critical appraisal tools. RESULTS: In the final review, out of 1635 screened records, 35 studies with 5321 participants were included. Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and polysomnography were the most common assessment tools for evaluation of sleep condition, and cognitive evaluations were conducted using the tests including Paced Auditory Serial Addition Test (PASAT), California Verbal Learning Test (CVLT), Symbol Digit Modalities Test (SDMT) and Brief Visuospatial Memory Test (BVMT). Assessing the quality of studies showed no significant bias in most of the included articles. A link between sleep condition and cognitive abilities was suggested in the literature, especially with objective measurement of sleep condition; however, current evidence did not support a substantial association between self-reported sleep quality and processing speed and working memory in patients with MS. DISCUSSION: Evidence proposes sleep is an independent factor associated with cognitive outcomes in MS. Given the limitations of the evidence such as the lack of well-designed prospective studies, these findings need to be interpreted with caution.

Glycemic control and associated factors among type 2 diabetes mellitus patients: a cross-sectional study of Azar cohort population.

BACKGROUND: Despite the growing prevalence of diabetes and its complications, there is a dearth of data regarding factors associated with glycemic control. Therefore, in this cross-sectional study, we aimed to identify factors influencing glycemic control in patients with type 2 diabetes mellitus (T2DM) in the Iranian population. METHODS: This cross-sectional study was conducted among the Azar cohort population and the glycemic control status of patients with T2DM was investigated. Possible risk factors including age, sex, marital status, educational level, smoking status, sleep duration, family history of diabetes and hypertension, socioeconomic status, physical activity level, and co-existence of other chronic diseases and their relationship with glycemic control status were also assessed. Multivariate logistic regression analysis was used to identify determinants of glycemic control. RESULTS: Among 1,710 T2DM patients (60.2% female), the overall prevalence of poor glycemic control was 56.8%. In the unadjusted logistic regression analysis model, a low wealth score index significantly increased the risk of poor glycemic control (OR: 1.49;1.10-2.02). Variables significantly associated with poor glycemic control even after adjusting for confounding factors were first-degree family history of diabetes (OR: 1.34; 1.08-1.65), and sleep duration (OR: 1.29 ;1.02-1.62 for 6.6-8 h/d; OR:1.42;1.10-1.88 for > 8 h/d). Interestingly, we found that the co-existence of ≥ 3 chronic diseases with diabetes decreased the risk of poor glycemic control. CONCLUSIONS: In the current study, most of the patients with T2DM had uncontrolled glycemic control. Due to the individual and social costs of diabetes complications, it is necessary to suggest tailored and effective interventions for controlling blood glucose levels in people with diabetes.

The association of parity number with multimorbidity and polypharmacy among Iranian women in the Azarcohort: a cross-sectional study.

OBJECTIVE: We aimed to study the association of parity number with multimorbidity (MM) and polypharmacy among women in the Azar cohort population. PATIENTS & METHODS: This cross-sectional investigation was based on data from the Azar Cohort Study. Information regarding demographics, personal habits, physical activity level, medical and reproductive history, and anthropometric measurements of 8,290 females (35-70 years) were evaluated. Ordinal logistic and logistic regression analyses were conducted to assess for associations of parity number with multimorbidity (MM), polypharmacy, chronic disease, and abdominal obesity. RESULTS: More educated participants and people in the fifth quintile of the Wealth Score Index were less likely to have a higher parity number. With increasing parity numbers, the prevalence of MM, polypharmacy, hypertension, cardiovascular disease, fatty liver disease, stroke, rheumatoid diseases, chronic obstructive pulmonary disease, and cancers tended to rise. Moreover, we found that increasing parity numbers (especially when ≥ 5) enhanced the odds of abdominal obesity, waist-to-hip ratio ≥ 0.85, and waist-to-height ratio ≥ 0.5; these significant associations were more obvious in parity numbers ≥ 9 and WHtR ≥ 0.5. CONCLUSION: The parity number is associated with MM and polypharmacy in Iranian women enrolled in the Azar Cohort Study. Further studies exploring the pathways (biological, social, and environmental) underlying these relationships will provide clues for preventing morbidity and premature mortality among susceptible andhighly parous women.

Prognostic values of modified NUTRIC score to assess outcomes in critically ill patients admitted to the intensive care units: prospective observational study.

PURPOSE: Modified Nutrition Risk in the Critically Ill (NUTRIC) score (mNUTRIC score) have been validated as screening tool for quantifying risk of adverse outcome critically ill patients admitted to the intensive care units (ICUs). The aim of this study was to evaluate the prognostic value of mNUTRIC score to assess outcomes in this population. MATERIALS AND METHODS: This prospective, observational study was conducted on adult patients admitted to the general ICUs of two university affiliated hospital in northwest of Iran. The association between the mNUTRIC score and outcomes was assessed using the univariate and multivariate binary logistic regression. The performance of mNUTRIC score to predict outcomes was assessed using the receiver operating characteristic (ROC)-curve. RESULTS: In total 445 ICU patients were enrolled. Based on mNUTRIC score, 62 (13.9%) and 383 (86.1%) individuals were identified at high and low nutritional risk, respectively. The area under the curve (AUC) for predicting ICU mortality, using vasopressor, duration of vasopressor, and mechanical ventilation (MV) duration were (AUC: 0.973, 95% CI: 0.954-0.986, P < 0.001), (AUC: 0.807, 95% CI: 0.767-0.843, P < 0.001), (AUC: 0.726, 95% CI: 0.680-0.769, P < 0.001) and (AUC: 0.710, 95% CI: 0.666-0.752, P < 0.001), respectively. CONCLUSIONS: An excellent and good predictive performance of the mNUTRIC score was found regarding ICU mortality and using vasopressor, respectively. However, this predictive was fair for MV and vasopressor duration and poor for ICU and hospital length of stay.

Saffron as a promising therapy for diabetes and Alzheimer's disease: mechanistic insights.

The prevalence of both Alzheimer's disease (AD) and diabetes mellitus is increasing with the societies' aging and has become an essential social concern worldwide. Accumulation of amyloid plaques and neurofibrillary tangles (NFTs) of tau proteins in the brain are hallmarks of AD. Diabetes is an underlying risk factor for AD. Insulin resistance has been proposed to be involved in amyloid-beta (Aß) aggregation in the brain. It seems that diabetic conditions can result in AD pathology by setting off a cascade of processes, including inflammation, mitochondrial dysfunction, and ROS and advanced glycation end products (AGEs) synthesis. Due to the several side effects of chemical drugs and their high cost, using herbal medicine has recently attracted attention for the treatment of diabetes and AD. Saffron and its active ingredients have been used for its anti-inflammatory, anti-oxidant, anti-diabetic, and anti-AD properties. Therefore, in the present review paper, we take account of the clinical, in vivo and in vitro evidence regarding the anti-diabetic and anti-AD effects of saffron and discuss the preventive or postponing properties of saffron or its components on AD development via its anti-diabetic effects.

Association between cannabis use and risk of diabetes mellitus type 2: A systematic review and meta-analysis.

BACKGROUND: Cannabis consumption exerts multiple effects on metabolism via various pathways, including glucose regulation and insulin secretion. Studies concerning the association between cannabis use and diabetes mellitus type 2 are discrepant. OBJECTIVE: This study was conducted to evaluate the association between cannabis use and type 2 diabetes mellitus (T2DM). SEARCH METHODS: We searched PubMed, Scopus, Embase, Proquest, Web of Science, and Cochrane Library with no time, language or study types restriction until July 1, 2022, using various forms of "cannabis" and "diabetes mellitus" search terms. SELECTION CRITERIA: Randomized control trials, cohort, and case-control studies investigating the relationship between cannabis consumption and diabetes mellitus type 2 were included. DATA COLLECTION AND ANALYSIS: The Newcastle-Ottawa scale was used to assess the quality of studies. We pooled odds ratio (OR) with 95% confidence interval (CI) using the random-effects model, generic inverse variance method, DerSimonian and Laird approach. MAIN RESULTS: A meta-analysis of seven studies, containing 11 surveys and 4 cohorts, revealed that the odds of developing T2DM in individuals exposed to cannabis was 0.48 times (95% CI: 0.39 to 0.59) lower than in those without cannabis exposure. CONCLUSIONS: A protective effect of cannabis consumption on the odds of diabetes mellitus type 2 development has been suggested. Yet given the considerable interstudy heterogeneity, the upward trend of cannabis consumption and cannabis legalization is recommended to conduct studies with higher levels of evidence.

A comprehensive insight into the molecular and cellular mechanisms of action of resveratrol on complications of sepsis a systematic review.

Sepsis and septic shock are still one of the most important medical challenges. Sepsis is an extreme and uncontrolled response of the innate immune system to invading pathogenesis. Resveratrol (3,5,4'-trihydroxytrans-stilbene), is a phenolic and non-flavonoid compound naturally produced by some plants and fruits. The object of the current study is to systematically review the impacts of resveratrol and its mechanisms of function in the management of sepsis and its related complications. The guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statements were applied to perform the study (PROSPERO: CRD42021289357). We searched Embase, Web of Science, Google Scholar, Science Direct, PubMed, ProQuest, and Scopus databases up to January 2023 by using the relevant keywords. Study criteria were met by 72 out of 1415 articles screened. The results of this systematic review depict that resveratrol can reduces the complications of sepsis by affecting inflammatory pathways, oxidative stress, and modulating immune responses. Future human randomized clinical trials are necessary due to the promising therapeutic effects of resveratrol on sepsis complications and the lack of clinical trials in this regard.

Clinical efficacy and safety of melatonin supplementation in multiple sclerosis: a systematic review.

BACKGROUND: Melatonin is a neurohormone secreted predominantly by the pineal gland that is demonstrated to be associated with the pathogenesis of multiple sclerosis (MS). This research desires to evaluate the tolerability and beneficial effects of exogenous melatonin supplementations in patients with MS. METHODS: This study was executed following the PRISMA 2020 statement. Both observational and interventional studies which reported the clinical effectiveness and/or safety of melatonin supplementation in patients with MS were included in this systematic review. Ovid, PubMed, Scopus, Embase, and Web of Science databases were searched and the risk of bias in included studies was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools based on study design. RESULTS: Out of 1304 results of database searches, finally, 14 articles, including 7 randomized controlled trials (RCTs), 6 case-control studies, and one quasi-experimental study, were included based on the full-text review. Included phenotypes of MS were mostly relapsing-remitting MS (RRMS) (in 11 studies); it was secondary progressive MS (SPMS) in only one study, and two other studies had a mixture of the different phenotypes. The course of treatment with melatonin supplementation was between 2 weeks and 12 months. There were no substantial safety issues. Although melatonin was associated with enhanced oxidative stress and inflammation status, concerning the clinical benefits, limited studies suggested improvements in sleep conditions, cognitive outcomes, and fatigue in MS. DISCUSSION: There are insufficient data to support the regular melatonin prescription in MS. Limitations such as the small number of included studies, the diversity of the dosage, route, and duration of melatonin administration, and the diversity of assessment tests lead to unconvincing findings in this study. There is a need for future studies to achieve a comprehensive judgment on this subject.

Effects of probiotic supplementation on cognitive function in elderly: A systematic review and Meta-analysis.

OBJECTIVES: Probiotic supplementation has been linked to changes in cognitive function via the gut-brain axis (GBA). However, the current literature lacks a comprehensive review regarding this matter in the elderly population. METHOD: Electronic databases including Medline (PubMed), Scopus, Embase, Web of Science, and Google Scholar were comprehensively searched for identifying studies that assessed the effects of probiotics on the cognitive function of the elderly published until July 2020. Articles were critically reviewed and if met the inclusion criteria, entered the study. RESULTS: Among a total of 1374 studies, 10 were eligible for meta-analysis. No significant alteration was found in the cognition of the elderly (SMD=-0.04; 95% CI [- 1.07,0.98]; P = 0.93). There was a nonsignificant increase in the level of brain-derived neurotrophic factor (SMD = 0.58; 95% CI [-1.40,2.56]; P = 0.56) and a nonsignificant reduction in malondialdehyde levels (SMD=-0.44; 95% CI [-1.07,0.19]; P = 0.17). Levels of total antioxidant capacity (SMD = 39.93; 95% CI [2.92,76.95]; P = 0.03) and total glutathione (SMD = 61.51; 95% CI [12.39,110.62]; P = 0.01) significantly increased. A significant reduction was also noted in total cholesterol levels (SMD=-4.23; 95% CI [-8.32, -0.14]; P = 0.04). CONCLUSION: Our study did not support the hypothesis of the positive effect of probiotics on cognitive function in the elderly population; which might be due to the heterogeneity across the studies.

Dichotomous effects of autophagy on infarct volume in experimental permanent/transient ischemic stroke model: a systematic review and meta-analysis.

According to the recent findings, autophagy modulation is being a potential therapeutic target in the management of ischemic stroke in a pre-clinical setting. However, the pros and cons of autophagic response strongly depend on the activation time of autophagy after injury. In this systematic review, we aimed to explore the impacts of pharmacological modulation of autophagy on infarct size in experimental ischemic stroke models. Based on our preliminary search, 3551 publications were identified. Of twenty-nine publications that met the inclusion criteria, twenty studies reported infarct volume reduction by percentage (%) with no evidence of any publication bias while nine studies reported by mm3, which had publication bias (39.25 units, standardized mean differences (SMD) = 41.92, 95% confidence interval (CI): 30.33 to 53.51). Based on a meta-analysis, the point estimate (pooled mean difference) for improvement of infarct volume during autophagy modulation according to the mm3 and percentage were 35.64 (mean differences (MD) = 35.64, 95% CI: 26.43 to 44.85, z-value = 7.58, p-value < 0.001) and 14.38 (MD = 14.38, 95% CI = 10.50 to 18.26, z-value = 7.26, p < 0.001) units, respectively. Despite the undeniable role of autophagy in ischemic stroke, the dichotomous effects of autophagy regarding infarct volume reduction should be taken into account. Based on our findings, the studies included in this meta-analysis mostly reported a negative relation between autophagy induction and stroke volume development due to over-activity of autophagy upon the severe ischemic stroke; therefore, further pre-clinical studies are also recommended to establish adjusted autophagy with considering a time-dependent effect as a promising therapeutic target.

Effects of saffron (Crocus sativus L.) on anthropometric and cardiometabolic indices in overweight and obese patients: A systematic review and meta-analysis of randomized controlled trials.

The worldwide prevalence of obesity is approximately tripled between 1975 and 2016 according to World Health Organization; therefore, obesity is now considered a global pandemic that needs academic and clinical focus. In search of antiobesity agents, Crocus sativus, known widely as saffron, has been praised for its beneficial effects. Several randomized controlled trials (RCTs) have been conducted to investigate the weight lowering effect of saffron. Following PRISMA guidelines, several medical databases were comprehensively searched for RCTs with a population consisting of obese individuals. A random-effects meta-analysis was used to pool estimates across studies, and standardized mean difference (SMD) was used to synthesize quantitative results. Twenty-five RCTs met the inclusion criteria. Meta-analysis showed a nonsignificant decrease for weight (-0.32 kg; CI: -3.15, 2.51; p = 0.82), BMI (-0.06 kg/m2 ;CI:-1.04,0.93; p = .91), waist circumference (-1.23 cm; CI: -4.14, 1.68; p = .41), and hip circumference (-0.38 cm; CI: -5.99, 5.23; p = .89) and a significant decrease of waist-to-hip ratio (SMD = -0.41; CI: -0.73, -0.09; p = .01; I2  = 0%). The mean difference in fasting blood sugar showed a significant reduction in patients with metabolic syndrome (SMD = -0.30; 95% CI: -0.63, 0.03; p = .07; I2  = 0.37%) but a nonsignificant change in the HbA1C level (WMD = 0.05; 95% CI: 0.32, 0.41; p = .79). Despite bearing several limitations, mainly as a result of heterogeneity among included studies, the available evidence indicates saffron supplementation shows promising effects on some cardiometabolic factors among overweight to obese patients; however, further investigations and high-quality evidence are required for more generalizable and comprehensive results.

The effect of saffron supplementation on glycemic parameters: An overview of systematic reviews.

Due to the widespread use of herbal medicine and evidence pointing to the health benefits of saffron supplementation, this review was performed to evaluate the effects of saffron supplementation on glycemic parameters and lipid profiles based on previous reviews. Relevant articles were retrieved from various databases, which included PubMed, Scopus, ProQuest, Web of Science, Embase, and Cochrane until 2020, with no date restrictions. The quality of the included reviews was assessed using the Assessment of Multiple Systematic Reviews (AMSTAR) checklist. Finally, of 877 obtained articles, eight reviews meeting the inclusion criteria were included for analysis. Among the eight included reviews, seven articles were meta-analyses. In addition, one review had an average quality while seven had a good quality. A narrative description of the included reviews was performed, while a network meta-analysis was not conducted. A brief review of the results was reported according to the weighted mean difference and mean difference. Seven included reviews assessed the effects of saffron or crocin supplementation on glycemic parameters, and six examined these effects on lipid profile parameters. Almost half of the articles reported significant effects of these supplements on glycemic parameters and lipid profiles. Taken together, results suggest that saffron supplementation may improve glycemic and lipid profile parameters; however, further high-quality studies are needed to confirm the clinical efficacy of saffron on glycemic parameters and lipid profiles.

Probiotics in Critically Ill Patients: An Umbrella Review.

Objectives: Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. Because of the wide usage of antibiotics, acute changes in diet, and the stress of illness, critically ill patients' homeostasis of the gut microbiome can be disrupted during intensive care unit (ICU) confinement; probiotics are suggested as a beneficial intervention in critically ill patients. We tried to give an overview of the effects of probiotic supplements in critically ill patients based on published systematic reviews (SRs) and meta-analyses (MAs). Data sources: A systematic search was performed in four databases as well as hand searching. Study selection: The results were independently screened in two title/abstracts and full-text stages. Data extraction: Any reported outcomes in each study were extracted, using a data extraction table. Data synthesis: A wide range of outcomes of using probiotic supplements in critically ill patients have been reported in 20 included studies. Based on the current knowledge, we can say that probiotics may reduce the rate of ventilator-associated pneumonia, nosocomial pneumonia, the overall infection rate, duration of mechanical ventilation, and antibiotic use in critically ill patients, but there is not a significant association between using the probiotics and mortality, length of hospitalization, and incidence of diarrhea. Conclusion: Despite the various beneficial effects of probiotics in critically ill patients, there is not yet much evidence supporting the routine use of these supplements and further well-designed multicenter trials are needed to provide "evidence-based" recommendations. How to cite this article: Naseri A, Seyedi-Sahebari S, Mahmoodpoor A, Sanaie S. Probiotics in Critically Ill Patients: An Umbrella Review. Indian J Crit Care Med 2022;26(3):339-360.

Comparison of Closed vs Open Suction in Prevention of Ventilator-associated Pneumonia: A Systematic Review and Meta-analysis.

Introduction: Ventilator-associated events (VAEs) are one of the main sources of concern in critically ill patients due to the high frequency and mortality. We conducted this analysis to compare the effects of open endotracheal suctioning system with closed one on the incidences of VAEs in adult patients receiving mechanical ventilation (MV). Materials and methods: A comprehensive literature search was performed in PubMed, Scopus, Cochrane Library, and hand searching bibliographies of retrieved articles. The search was confined to randomized controlled trials with human adults comparing closed tracheal suction systems (CTSS) vs open tracheal suction systems (OTSS) in prevention of ventilator-associated pneumonia (VAP). Full-text articles were used in order to extract the data. Data extraction was only started after completing the quality assessment. Results: The search resulted in 59 publications. Among them, 10 were identified as eligible for meta-analysis. There was a significant increase in incidence of VAP when using OTSS compared to CTSS, so that OCSS increased the incidence of VAP by 57% (OR 1.57, 95% CI 1.063-2.32, p = 0.02). Discussion: Our results showed that using CTSS can significantly decrease VAP development compared to OTSS. This conclusion does not yet mean the routine use of CTSS as a standard VAP prevention measure for all patients since individual patient's disease and cost are other factors that should be in mind when determining the choice of the suctioning system. High-quality trials with a larger sample size are highly recommended. How to cite this article: Sanaie S, Rahnemayan S, Javan S, Shadvar K, Saghaleini SH, Mahmoodpoor A. Comparison of Closed vs Open Suction in Prevention of Ventilator-associated Pneumonia: A Systematic Review and Meta-analysis. Indian J Crit Care Med 2022;26(7):839-845.

Melatonin as a promising modulator of aging related neurodegenerative disorders: Role of microRNAs.

One of the host risk factors involved in aging-related diseases is coupled with the reduction of endogenous melatonin (MLT) synthesis in the pineal gland. MLT is considered a well-known pleiotropic regulatory hormone to modulate a multitude of biological processes such as the regulation of circadian rhythm attended by potent anti-oxidant, anti-inflammatory, and anti-cancer properties. It has also been established that the microRNAs family, as non-coding mRNAs regulating post-transcriptional processes, also serve a crucial role to promote MLT-related advantageous effects in both experimental and clinical settings. Moreover, the anti-aging impact of MLT and miRNAs participation jointly are of particular interest, recently. In this review, we aimed to scrutinize recent advances concerning the therapeutic implications of MLT, particularly in the brain tissue in the face of aging. We also assessed the possible interplay between microRNAs and MLT, which could be considered a therapeutic strategy to slow down the aging process in the nervous system.

SARS-CoV-2: Unique Challenges of the Virus and Vaccines.

In November 2019, the highly infectious coronavirus SARS-CoV-2 emerged in Wuhan, China, and has since spread to almost all countries worldwide. Since its emergence, the COVID-19 infection has led to significant public health, economic and social problems. The current pandemic has inspired researchers to make every effort to design and develop an effective COVID-19 vaccine to provide sufficient protection against the virus and control the infection. In December 2020, the Pfizer vaccine was the first COVID-19 vaccine given Emergency Use Authorization (EUA), and the second FDA so-approved vaccine was the Moderna mRNA-1273 vaccine, which was introduced a week later. Both Pfizer and Moderna vaccines are mRNA-based vaccines, and are estimated to have an efficacy rate of more than 94%. The aim of this article is to provide a review of the attempts made to develop safe SARS-CoV-2 vaccines, highlighting potential challenges and concerns, such as disease enhancement, virus mutations, and public acceptance of the vaccine.

Effect of Vitamin C on mortality of critically ill patients with severe pneumonia in intensive care unit: a preliminary study.

BACKGROUND: Critically ill patients frequently suffer from vitamin C deficiency. Previous studies showed that high doses of vitamin C administration had conflicting results on clinical outcomes in patients with severe sepsis, burns, and trauma. Because of the high incidence and morbidity/mortality with severe pneumonia, we aimed to investigate the effect of administration of high dose vitamin C in critically ill patients with severe pneumonia. METHODS: Eighty critically ill patients with pneumonia were enrolled in this randomized double-blinded clinical trial. Patients with a CURB-65 score > 3, one major criterion, or ≥ 3 minor criteria were considered as severe pneumonia. Patients were randomly assigned to intervention or placebo groups receiving standard treatment plus 60 mg/kg/day vitamin C as a continuous infusion or normal saline in the same volume correspondingly for 96 h. Serum levels of vitamin C were noted at baseline and 48 h after vitamin C administration. Duration of mechanical ventilation, ICU length of stay, PaO2/FiO2, and mortality rate were noted for all patients till the 28th day. Any complications related to the vitamin C administration were recorded. RESULTS: Duration of mechanical ventilation and vasopressor use were significantly lower in the intervention group (p: < 0.001 and 0.003, respectively). Baseline levels of vitamin C in both groups did not have a significant difference but its levels increased in the intervention group and decreased in the control group during the study period. Mortality rate insignificantly decreased in the intervention group (p = 0.17). Three patients showed hypotension and tachycardia during the administration of vitamin C which was self-limited with decreasing the dose of vitamin C. Our results showed that the intravenous administration of a relatively high dose of vitamin C to critically ill patients with severe pneumonia was safe and could decrease the inflammation, duration of mechanical ventilation, and vasopressor use without any significant effect on mortality. TRIAL REGISTRATION: IRCT registration number: IRCT20190312043030N1, Registration date: 2019-08-26, Seied Hadi Saghaleini.

Non-alcoholic fatty liver diseases: from role of gut microbiota to microbial-based therapies.

Non-alcoholic fatty liver disease (NAFLD) is the well-known disease of the liver in adults and children throughout the world. The main manifestations related to NAFLD are an unusual storage of lipid in hepatocytes (hepatic steatosis) and progression of inflammation for non-alcoholic steatohepatitis (NASH). NAFLD is described as a multifactorial complication due to the genetic predisposition, metabolic functions, inflammatory, gut microbiota (GM), and environmental factors. The GM dysregulation among these factors is correlated to NAFLD development. In recent decades, advanced microbial profiling methods are continuing to shed light on the nature of the changes in the GM caused by NASH and NAFLD. In the current review, we aim to perform a literature review in different library databases and electronic searches (Science Direct, PubMed, and Google Scholar) which were randomly obtained. This will be done in order to provide an overview of the relation between GM and NAFLD, and the role of prebiotics, probiotics, and fecal microbiota transplantation (FMT), as potential therapeutic challenges for NAFLD.

Osteosarcoma: A comprehensive review of management and treatment strategies.

Osteosarcoma, a bone cancer usually seen in children and young adults, is generally a high-grade malignancy presented by extreme metastases to the lungs. Osteosarcoma has a tendency for appearing in bones with rapid growth rate. The etiology of osteosarcoma is multifaceted and poorly understood. A molecular consideration of this disease will lead to a directed tumor treatment. The present treatment for osteosarcoma comprises of an arrangement of systemic chemotherapy and wide surgical resection. Survival rate is increased by the progress of destructive systemic chemotherapies. So, the development of new treatment approaches for metastatic osteosarcoma is essential. Immunomodulation has been used in clinical settings. Through targeting surface antigens expressed on tumor cells, particular antibodies and exploitation of cellular immunotherapy against sarcomas have been confirmed to be effective as cancer therapeutics. In this article, we have reviewed epidemiology, etiology, pathogenesis, diagnosis, and treatment of osteosarcoma and we have focused on different methods of immunotherapy including vaccines, cell-based immunotherapy, cytokines, and monoclonal antibodies.