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Background: Pregnancies complicated by gestational diabetes are associated with an increased risk of adverse maternal and fetal outcomes.Objectives: This trial aimed to compare maternal and fetal outcomes in Iranian women with gestational diabetes treated with either metformin or insulin.Methods: In this open-label randomized clinical trial, eligible Iranian women referred to Shohada-e-Tajrish Hospital (Tehran, Iran) between January and September 2022 were enrolled through simple random sampling. Participants were randomly assigned to two groups: one receiving metformin (n=50) and the other receiving insulin (n=49). We measured HbA1c, fasting plasma glucose (FPG), and 2-hour plasma glucose (2 hrPG) in all participants. Maternal outcomes, including preeclampsia and cesarean delivery rates, were compared alongside neonatal outcomes such as respiratory distress, congenital disorders, small for gestational age (SGA), macrosomia, birth weight, gestational age at birth, shoulder dystocia, hypocalcemia, hypoglycemia, Apgar scores at 5 minutes, and neonatal intensive care unit (NICU) admissions. Data analysis was performed using SPSS 16 with t-tests, Mann-Whitney U tests, Chi-square tests, or Fisher's exact tests as appropriate.Results: Both metformin and insulin demonstrated similar efficacy in controlling FPG, 2-hrPG, and HbA1c levels in women with gestational diabetes (P>0.05). In the metformin group, there were slightly more cases of respiratory distress (P=0.73) and cesarean deliveries (P=0.35), although these differences were not statistically significant. Conversely, the insulin group showed higher, yet not statistically significant, rates of preeclampsia (P=0.70), congenital disorders (P=0.07), small for gestational age (SGA) infants (P=0.48), shoulder dystocia (P=0.31), hypocalcemia (P=0.31), hypoglycemia (P=0.31), and NICU admissions (P=0.21). Macrosomia, average birth weight, and gestational age at birth were similar between the two groups (P>0.05). The only significant finding was that the average Apgar score at 5 minutes was significantly higher in the metformin group compared to the insulin group (P=0.003). No mortality was reported in either group.Conclusion: The findings of this study indicate that metformin has effects comparable to those of insulin regarding maternal and neonatal outcomes in Iranian women with gestational diabetes.

Dengue fever, an arboviral disease primarily transmitted by Aedes mosquitoes, poses a significant public health concern globally. Key vectors, such as Aedes aegypti, Aedes albopictus and Aedes cinereus, are widely distributed in tropical and subtropical regions, affecting over 140 countries. These species are also found in Iran, particularly in the southern, southeastern, and northern regions. Diagnosing dengue fever presents challenges, including differentiating it from other febrile illnesses and recognizing early warning signs of severe dengue. Symptoms typically include acute fever, warning signs of severe illness, and potential complications. The clinical progression of dengue includes three phases: the febrile phase, critical phase, and recovery phase. A comprehensive understanding of clinical manifestations, prognostic indicators, diagnostic algorithms, and laboratory methods is crucial for accurate diagnosis, risk assessment, and effective disease management. Given the absence of specific antiviral treatments or vaccines for dengue, supportive care and symptomatic treatment remain essential. This narrative review discusses the management of dengue fever, focusing on supportive care, fluid management, antipyretic and analgesic medications, and antiviral treatments. Additionally, it reviews potential future treatment strategies and emphasizes the importance of early diagnosis and prompt medical intervention in improving patient outcomes. The study also explores immunological targets, vaccine platforms, clinical trials, and future prospects for dengue vaccination. Furthermore, it presents prevention strategies targeting Aedes mosquitoes and outlines the challenges that lie ahead. By adopting a comprehensive and interdisciplinary approach, we can pave the way for advancements in the prevention and control of dengue fever related to Aedes mosquito transmission. Continued research efforts, innovative collaborations, and public health training are vital to combat dengue fever and reduce its burden on affected populations worldwide.

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality worldwide, characterized by a complex cascade of pathophysiological events that can result in diverse clinical outcomes ranging from mild cognitive impairments to severe disability. The pathophysiology of TBI involves a complex interplay of cellular and molecular events that contribute to secondary brain injury and neurodegeneration. Predicting neurological outcomes in TBI patients is crucial for guiding treatment decisions and enhancing patient care. Traditional methods of assessing TBI severity and prognosis have limitations in accurately predicting long-term outcomes. In recent years, microRNAs (miRNAs) have emerged as promising biomarkers for evaluating TBI severity and prognosis. MicroRNAs are small non-coding RNA molecules that regulate gene expression and have been implicated in various physiological and pathological processes, including neurodevelopment, neuronal function, and neurodegeneration. Several studies have identified specific miRNAs as potential biomarkers for assessing TBI severity and predicting patient outcomes. MiR-21, miR-155, miR-146a, and miR-124 are among the most studied miRNAs in the context of TBI biomarkers. Elevated levels of these miRNAs in blood, cerebrospinal fluid, and brain tissue have been associated with TBI severity, neuroinflammation, and poor neurological outcomes. Understanding the role of miRNAs in TBI pathophysiology can provide valuable insights into the mechanisms underlying neuroinflammation and neurodegeneration. Furthermore, miRNA signatures have shown promise in distinguishing between different TBI phenotypes, such as mild, moderate, and severe TBI, and predicting long-term cognitive deficits and functional impairments in TBI survivors. This suggests that miRNAs could serve as valuable tools for improving TBI patient care and outcomes.[1,2] Role of miRNAs in TBI PathophysiologyMicroRNAs play a crucial role in modulating neuroinflammatory responses and neurodegenerative processes in traumatic brain injury. Dysregulated expression of specific miRNAs contributes to secondary brain injury, neuronal apoptosis, neuroinflammation, blood-brain barrier disruption, neurodegeneration, and cognitive impairments following TBI.[2]Neuroinflammation is a hallmark feature of TBI, characterized by the activation of microglia, astrocytes, and peripheral immune cells in response to brain injury. Dysregulated expression of specific miRNAs has been implicated in modulating neuroinflammatory responses following TBI. For example, miR-155 has been shown to promote microglial activation and pro-inflammatory cytokine production, exacerbating neuroinflammation and neuronal damage. In contrast, miR-146a acts as a negative regulator of inflammatory signaling pathways, attenuating neuroinflammatory responses and promoting neuroprotection in TBI models. The dynamic interplay between miRNAs and inflammatory mediators in the injured brain highlights the intricate regulatory mechanisms underlying neuroinflammation in TBI.[3]Neuronal cell death and neurodegeneration are other common pathological features of TBI, contributing to long-term cognitive impairments and functional deficits. Dysregulated expression of miRNAs has been associated with apoptotic cell death, synaptic dysfunction, and axonal injury in TBI. MiR-21, for instance, has been shown to promote neuronal apoptosis and glial scar formation following brain injury, exacerbating neurodegenerative processes. In contrast, miR-124 plays a neuroprotective role by regulating neuronal differentiation, synaptic plasticity, and axonal regeneration in response to TBI. The complex interplay between miRNAs and neurodegenerative pathways underscores their potential as therapeutic targets for mitigating neuronal damage and promoting recovery after TBI.[3]Targeting dysregulated miRNAs represents a promising therapeutic strategy for modulating neuroinflammation and neurodegeneration in TBI. MiRNA-based interventions, such as antagomirs or mimics, offer potential avenues for restoring miRNA homeostasis and promoting neuroprotective effects in the injured brain. Future research efforts should focus on identifying specific miRNA targets involved in TBI pathophysiology, elucidating their functional roles in neuroinflammation and neurodegeneration, and exploring innovative therapeutic approaches for TBI management. Collaborative initiatives between researchers, clinicians, and pharmaceutical companies are essential for translating miRNA research into clinical applications and improving outcomes for TBI patients.[4] MiRNA Biomarkers for Predicting Neurological RecoveryThe utilization of miRNA biomarkers in clinical practice holds the potential to revolutionize prognostication and treatment decision-making in TBI. By pinpointing specific miRNA signatures linked to neurological outcomes, clinicians can categorize patients based on their likelihood of developing complications, cognitive impairments, or disability post-TBI. Numerous studies have documented distinct expression patterns of miRNAs in TBI patients with varying levels of cognitive impairment, functional disability, and neurobehavioral deficits. MiR-21, miR-146a, and miR-132 have emerged as promising biomarkers for forecasting neurological recovery and functional outcomes in TBI. The integration of miRNA profiles with clinical evaluations and neuroimaging data has the potential to enhance the precision of outcome predictions and facilitate personalized treatment approaches for TBI patients. Further research is imperative to validate miRNA signatures, establish standardized protocols for miRNA profiling, and implement predictive models that amalgamate clinical, imaging, and molecular data to enhance prognostication and treatment strategies for TBI patients. Future research endeavors should prioritize the validation of miRNA biomarkers in extensive prospective cohorts, elucidate their mechanistic roles in TBI pathophysiology, and incorporate them into multidimensional prognostic models for tailored patient care. Collaborative initiatives involving researchers, clinicians, and industry partners are paramount for translating miRNA research into clinical applications and enhancing outcomes for TBI patients.[5,6] Challenges and Opportunities for Advancing MiRNA Biomarker in TBIDespite the growing interest in miRNA biomarkers for TBI, several challenges need to be addressed before their clinical implementation. Standardization of sample collection and processing protocols, validation of miRNA signatures in large patient cohorts, and integration of miRNA data with other clinical variables are critical steps towards translating miRNA research into clinical practice. Additionally, the lack of standardized protocols for miRNA profiling and validation poses obstacles to comparing results across different studies. The heterogeneity of TBI phenotypes and patient populations further complicates the identification of robust miRNA signatures predictive of neurological outcomes.[4,5] Despite the challenges, there are promising opportunities for advancing miRNA biomarker research in TBI. Technological advancements in high-throughput sequencing and bioinformatics tools enable comprehensive profiling of miRNA expression patterns in TBI patients. Collaborative efforts among researchers, clinicians, and industry partners can facilitate the validation of miRNA biomarkers in large multicenter cohorts, enhancing their clinical utility. Integrating miRNA profiles with other omics data, neuroimaging findings, and clinical assessments holds potential for developing multidimensional prognostic models for personalized TBI management.[6] ConclusionFuture research directions should focus on standardizing methodologies for miRNA biomarker discovery, validation, and implementation in TBI clinical practice. Large-scale prospective studies are needed to validate miRNA signatures associated with specific TBI outcomes and refine predictive models for patient stratification. Incorporating miRNA biomarkers into existing prognostic tools and treatment algorithms may improve risk assessment, therapeutic decision-making, and long-term outcomes for TBI patients. Collaborative initiatives aimed at translating miRNA research findings into actionable clinical insights are essential for realizing the full potential of miRNA biomarkers in TBI management.

Letter to the Editor

Letter

Dear Editor We wish to draw attention to the recent study by Fazeli et al.,1 which investigates the efficacy of early high-titer convalescent plasma therapy in patients with moderate and severe COVID-19. The authors conclude that this therapy is beneficial for Iranian patients with moderate COVID-19 in the early stages of the disease. However, we have identified several critical limitations in the study design and findings that merit careful consideration when assessing the effectiveness of convalescent plasma therapy.A primary concern is the notably high mortality rate observed among the study participants. The investigation focused on patients with severe and moderate COVID-19 who received only convalescent plasma therapy, without any adjunct or standard treatment. Specifically, the mortality rates were reported as 13.7% for the moderate group and a staggering 86.3% for the severe group, culminating in an overall death rate of 29.7%.1 In contrast, a previous study by the same research group in 2020 reported a mortality rate of 24.3% in a control group that did not receive convalescent plasma but was treated with standard care.2 The similarities in the study settings for both investigations suggest that convalescent plasma therapy may have had no significant impact on mortality rates, potentially even contributing to higher mortality among Iranian patients.The lack of a control group receiving standard treatment in Fazeli et al.'s study1 significantly limits the ability to draw definitive conclusions regarding the efficacy of convalescent plasma therapy. Furthermore, a recent systematic review and meta-analysis encompassing 39 studies reported an overall pooled case fatality rate of 10% among COVID-19 patients.3 Other studies have indicated in-hospital mortality rates ranging from 4.5% to 8.8% among Iranian patients,4,5 while the mortality rate in intensive care units was found to be as high as 67.6%.6 Investigations conducted in other Asian populations have demonstrated mortality rates of 5-7.2% for patients with mild to moderate COVID-19.7,8 These findings are particularly relevant, as they suggest lower fatality rates than those observed in the study by Fazeli et al.,1 among Iranian patients treated with convalescent plasma therapy.Fazeli et al. conducted a multivariate logistic regression analysis to assess the effectiveness of high-titer convalescent plasma therapy in patients with moderate COVID-19. The analysis indicated a death rate of 6.9% when therapy was administered within five days of hospital admission, compared to 12.3% for those receiving treatment after five days.1 Consequently, the authors concluded that convalescent plasma therapy is beneficial for patients with moderate COVID-19 in the early stages of the disease.However, it is crucial to note that the authors did not account for the total length of hospital stay in their analysis, a factor that could significantly influence outcomes. Furthermore, it remains unclear whether patients who received high-titer convalescent plasma therapy later than five days post-admission had a similar length of hospital stay compared to those who began therapy earlier. It is plausible that patients receiving therapy later experienced longer hospital stays, which may have contributed to poorer outcomes, as previous research has shown a correlation between extended hospital stays and increased mortality risk in COVID-19 patients.9 Therefore, the authors' assertion regarding the efficacy of high-titer convalescent plasma therapy as a therapeutic option for patients with moderate COVID-19 during the early stages of the disease should be interpreted with caution.Additionally, the authors emphasize that "The use of COVID-19 convalescent plasma (CCP) has been approved by the Food and Drug Administration (FDA)." However, it is important to highlight that clinical trials adhering to the FDA's convalescent plasma treatment protocol have yielded concerning results. Specifically, 88% of patients experienced cardiac events, and 66% encountered thrombotic events while undergoing convalescent plasma treatment for COVID-19.10 Moreover, some studies reporting positive outcomes associated with convalescent plasma therapy did not utilize this treatment in isolation but rather as an adjunct to standard therapies.11Among studies that employed convalescent plasma therapy alone, Agarwal et al.,12 noted minor improvements in shortness of breath and fatigue; however, the evaluators were not blinded to subject data, which raises concerns about the reliability of their findings. Furthermore, while Maor et al.,13 suggested that convalescent plasma with higher antibody levels may benefit patients with moderate to severe COVID-19, this study did not report mortality outcomes and indicated that a longer follow-up period would be necessary to assess mortality rates adequately.It is also worth mentioning that convalescent plasma therapy is prohibited for COVID-19 patients in Iran,14 and the World Health Organization (WHO) has deemed this therapy ineffective.15 This body of evidence challenges the claims made by Fazeli et al.,1 regarding the efficacy of convalescent plasma therapy in treating Iranian patients with COVID-19.In conclusion, while Fazeli et al.'s findings contribute to the ongoing discourse on COVID-19 treatments, further rigorous studies are needed to validate the efficacy and safety of high-titer convalescent plasma therapy, particularly considering the limitations discussed herein.1One significant concern within the research community is the potential for conflicts of interest that may arise during the ethical approval process for investigations. In the present study, it is noteworthy that Dr. Eshghi, who chaired the ethics committee, is also listed as one of the corresponding authors of the article.16 Detailed information regarding Dr. Eshghi's role can be found in the "Credit Authorship Contribution Statement" section.1 This dual role raises important questions about potential conflicts of interest, which could lead to a biased review of the research proposal and ultimately undermine the credibility of the findings in the eyes of the public.Given these considerations, the assertion that convalescent plasma therapy is beneficial for Iranian patients with moderate COVID-19 is, at the very least, questionable. Future research should build upon the work of Fazeli et al.,1 considering the concerns we have raised. Until more robust evidence becomes available, we recommend that this critical topic remains open for further discussion.

Background: Trauma is a leading cause of morbidity and mortality worldwide. The frequency of trauma-related deaths depends on various factors such as the severity and mechanism of the trauma.Objectives: This study aimed to determine the frequency, causes, and outcomes of trauma in patients referred to the emergency department of Ali Ibn Abitaleb Hospital, Rafsanjan, Iran, in 2021.Methods: A case-series study was conducted, examining the medical files of 4689 trauma patients referred to the emergency department of Ali Ibn Abitaleb Hospital in 2021. Data on age, gender, marital status, place of residence, mode of transportation to the hospital, reasons for admission (extremity trauma, head and neck trauma, thorax trauma, abdominal trauma, spine trauma, multiple trauma), type of trauma (blunt or penetrating), and mechanisms of trauma (traffic accidents, falls, fights, burns, electrocutions, work-related accidents) were recorded. The mortality rate and factors influencing it were also evaluated.Results: Among 4,689 trauma patients, the most common reasons for admission were organ trauma (46.4%), multiple trauma (23.5%), and cervical spine trauma (21.7%). The most common mechanisms of trauma were traffic accidents (68.3%) and fights (17.2%). Most patients (3506, 74.8%) had penetrating trauma. A total of 68 patients (1.5%) died from trauma. Significant factors related to mortality included old age (p