Abstract:

Study Design: A retrospective study Objective: This study aims to retrospectively present our experience in the management of frontal sinus fractures, thus understanding the entire epidemiology of fractures and guiding us in the best form of treatment. Methods: The medical records of patients with frontal sinus fractures, which occurred from 2017 to 2024 (8 years), in the city os Piracicaba (423.000 inhabitants), State od São Paulo (Brazil), involving three trauma reference hospitals in the region. These patients were diagnosed and treated by the same Oral and Maxillofacial Surgery team. Results: we obtained the number of 40 patients, with ages ranging from 1 to 89 years, and an average age of 41 years. There was a predominance of the male sex with 39 cases and only 1 case of the female. After establishing the diagnosis, 22 patients received conservative treatment, while 18 patients were treated surgically (45%). The predominant etiology of the fractures was traffic accidents, accounting for 15 patients (37.5%). Conclusions: An analysis of data relating to frontal sinus fractures revealed a higher prevalence among male patients, with an average age of 41 years. The main causal factor identified was traffic accidents, which represented the majority of cases. Not that it refers to treatment, the conservative approach was the most commonly adopted. Furthermore, case review did not indicate the occurrence of complications during follow-up, resulting in recovery without the need for additional interventions.

Abstract: Oropouche fever is caused by the Oropouche virus (OROV; Bunyaviridae, Orthobun-yavirus), one of the most frequent arboviruses that infect humans in the Brazilian Amazon. This year, an OROV outbreak was identified in Brazil, and its vertical trans-mission was reported, which was associated with fetal death and microcephaly. We describe the clinical manifestations identified in three cases of congenital OROV infec-tion with confirmed serology (OROV-IgM) in the mother-newborn binomial. One of the newborns died, and post-mortem molecular analysis using real-time RT-qPCR identified the OROV genome in several tissues. All three newborns were born in the Amazon region in Brazil, and the mothers reported fever, rash, headache, myalgia, and/or retro-orbital pain during pregnancy. The newborns presented with severe mi-crocephaly secondary to brain damage and arthrogryposis, suggestive of an em-bryo/fetal disruptive process at birth. Brain and spinal images identified overlapping sutures, cerebral atrophy, brain cysts, thinning of the spinal cord, corpus callosum, and posterior fossa abnormalities. Fundoscopic findings included macular chorioretinal scars, focal pigment mottling, and vascular attenuation. The clinical presentation of vertical OROV infection resembled congenital Zika syndrome to some extent but pre-sents some distinctive features on brain imaging and in several aspects of its neurolog-ical presentation. A recognizable syndrome with severe brain damage, neurological alterations, arthrogryposis, and fundoscopic abnormalities can be associated with in-utero OROV infection.

Abstract: Despite enormous progress in the development of therapeutic agents for persons with hemophilia A and B (HA, HB), several unmet needs persist. These are disease- and treatment-related. Prophylaxis with clotting factor replacement is the gold standard but not feasible in HA and HB with inhibitors. Whereas persons with HA with inhibitors can receive prophylaxis with a factor-mimicking agent, emicizumab, there is no recommendation on the agents to use as prophylaxis in persons with HB with inhibitors, as there are no available molecules. Concizumab is a novel, subcutaneous prophylaxis option in persons with HA or HB with inhibitors that can potentially improve long-term outcomes. Here, we review the available data on concizumab and discuss its possible positioning in the armamentarium to treat hemophilia with inhibitors.

Abstract: Background: Despite advances in treatment over the past 20 years that have significantly improved patient survival in shock conditions, septic shock continues to present numerous questions regarding long-term outcomes, primarily due to its associated metabolic changes.Objective: To evaluate hypoalbuminemia as a predictor of mortality in patients admitted with septic shock to the emergency department, through a review of clinical records from January to September 2023 at Hospital General Regional No. 1 (HGR1) in Michoacán, Mexico.Methods: A retrospective study analyzed patients diagnosed with septic shock between January and September 2023. The study examined admission albumin parameters and mortality, along with sociodemographic variables, comorbidities, mean arterial pressure, lactate levels, and vasopressor use.Results: The study included 130 patients meeting inclusion criteria, with equal gender distribution (50% male, n=65; 50% female, n=65). The predominant age group was over 68 years (35.3%, n=46), followed by 59-68 years (27.6%, n=36). Common comorbidities included systemic arterial hypertension (50.7%, n=66), diabetes mellitus (48.4%, n=63), chronic kidney disease (21.5%, n=28), and neoplasms (19.2%, n=25). Serum albumin levels were distributed as follows: ≥3.5 g/dL (13.8%, n=18), 3.4-3.0 g/dL (20%, n=26), 2.9-2.5 g/dL (24.6%, n=32), and <2.5 g/dL (41.5%, n=54). Among patients with albumin <2.5 g/dL, mortality was 92.5% (n=50), with only 7.4% (n=4) surviving to discharge. Statistical analysis using Pearson's Chi-square showed an asymptotic significance of 0.003 with a likelihood ratio of 0.346.Conclusions: This descriptive study demonstrates that hypoalbuminemia (<2.5 g/dL) is significantly associated with mortality in septic shock patients, with a mortality rate of 92.5%. The findings validate the initial hypothesis that hypoalbuminemia serves as a predictor of mortality in more than 50% of patients with septic shock.

Abstract: Epilepsy is a neurological disorder characterized by repeated convulsions. Antiepileptic drugs (AEDs) are the main course of therapy for epilepsy. These medications are given according to each patient’s personal medical history and the type of seizures they suffer. They have been employed for decades to manage epilepsy, thus delivering relief from seizures through numerous mechanisms of action. Aside from their anticonvulsant attributes, current evidence suggests that certain AEDs may display potential inhibitory effects against cancer invasion and metastasis. This review explored the complicated interactions between the modes of action of AEDs and the pathways causing cancer, and the potential impact of AEDs on the invasion and metastasis of various forms of cancer, while addressing their associated side effects. For example, valproic acid inhibits histone deacetylase, causing hyperacetylation of genes especially those regulating cell cycle, culminating in cell cycle arrest. Topiramate inhibits carbonic anhydrase, thus disrupting the acidic micrenvironment needed for cancer cells to thrive. Lacosamide increases the slow inactivation of the voltage gated Na+ channel thus inhibiting the growth, proliferation, and metastasis of many cancers. Although drug development is a complex task due to regulatory, intellectual property, and economic challenges, researchers are exploring drug repurposing tactics to overcome these challenges and to find new therapeutic alternatives for diseases like cancer. Thus, drug repurposing is considered among the most effective ways to develop drug candidates using novel properties and therapeutic characteristics, and this review also discusses these issues.

Abstract: Background: While left-bundle-branch-block-related contraction patterns as well as echocardiography derived strain are variably associated with volumetric response to cardiac resynchronization therapy (CRT), the role of CMR-derived strain parameters is unexplored. Methods: 50 patients receiving CRT implantation were retrospectively analysed, all of which had undergone CMR imaging within one year before, and echocardiography within 6 months before and 6-12 months after CRT implantation. We assessed CMR-derived morphological and functional parameters with regard to echocardiographic response, defined as reduction of left ventricular end-systolic volume ≥15%. Results: Among standard CMR parameters, indexed right ventricular volumes in end-diastole (RVEDVi) (74.5 ±19.5 vs. 94.8 ±30.2 ml/m², P=.006) and end-systole (RVESVi) (43.2 ±13.3 vs. 61.6 ±28.8 ml/m², P=.003) as well as left atrial (LA) area (24.8 ±3.5 vs. 30.4 ±9.5 cm², P=.020) differed significantly between CRT responders and non-responders. In strain analysis, CRT responders showed significantly better LA global longitudinal strain (GLS) (25.1 ±10.4 vs. 15.3 ±10.5, P=.002), LA global circumferential strain (GCS) (27.9 ±14.7 vs. 17.1 ±13.1%, P=.012), RV GLS (-25.0 ±6.5 vs. -18.9 ±7.6%, P=.004) and RV free wall strain (-31.1 ±7.9 vs. -24.9 ±9.5, P=.017). Conclusions: CMR-derived peak septal circumferential strain and RVEDVi correlated with echocardiographic volumetric response to CRT at 6-12 months.

Abstract: Minimal hepatic encephalopathy (MHE) is primarily a cognitive disorder linked to chronic liver disease that often remains underdiagnosed due to the subtlety of its clinical manifestations. These symptoms are frequently overlooked or dismissed as inconsequential in clinical practice, leading to many undiagnosed cases. The standard neurological examination is usually normal in indi-viduals with MHE. Regular and systematic screening for MHE is essential for early detection, which can improve cognitive outcomes and prevent progression to a more serious and debilitat-ing condition also known as overt hepatic encephalopathy. The pathophysiology of MHE is very complex and multifactorial, involving several interplaying mechanisms. Mainly, hyperammone-mia, system-wide inflammation, gut-derived neurotoxins, oxidative stress, and mitochondrial dysfunction are at its root. Any of these factors may interfere with the normal functioning of neu-rotransmitters, giving rise to the typical subtle cognitive impairments that are hallmarks of MHE. The Animal Naming Test and EncephalApp-Stroop tests are useful for screening for minimal en-cephalopathy in office or bedside settings. The role potentially played by emerging diagnostic technologies of advanced neuroimaging and biomarkers has been reviewed, underscoring its promise in improving early detection and diagnosis of MHE.

Abstract:

Background/Objectives: Ectopic pancreatic tissue (EPT), an infrequently documented condition within the pediatric population, is often asymptomatic. When clinical manifestations do occur, their severity is contingent upon the location, size, and involvement of the adjacent mucosa. Methods: This is a case series study, involving children aged 15 days – 13 years diagnosed with EPT from one single institution. Results: Six cases of EPT were identified. Five of the 6 cases presented with both EPT and ectopic gastric tissue, located at the site of Meckel’s diverticulum, while 1 case presented EPT exclusively and it was localized in the duodenum I. A case of Littre’s hernia was identified in a newborn. Two of the 6 cases experienced gastrointestinal bleeding. Conclusions: The identification of EPT continues to pose a diagnostic challenge, as the symptoms are nonspecific and can sometimes be life-threatening. Additionally, there are currently no specific paraclinical investigations available for this purpose.

Abstract: The major cause for blindness worldwide is age-related macular degeneration (AMD), and its incidence and prevalence are rising. There is no treatment for the early or atrophic forms of AMD. In terms of pathogenesis, the complex interaction of metabolic, functional, genetic, and environmental factors creates a stage for chronically developing changes in ocular structures of the macular region which contribute to varying degrees to the onset and final picture of AMD. Oxidative stress is a constant condition of the retina. Brown seaweed contains bioactive compounds with promising activities that make them interesting for potential use in AMD, such as the polysaccharide fucoidan, the carotenoid fucoxanthin and fucoxanthinol. Considering fucoidans, their heterogeneity requires intensive research to find suitable fucoidans for further applications. Fucoxanthin and its metabolite, fucoxanthinol, have shown antioxidant activities attributed to free radical scavenging and singlet oxygen inactivation in vitro. Fucoxanthin has greater antioxidant activity and is considered a potential protective agent against oxidative stress. This review gives an overview of the recent studies regarding their potential and challenges.

Abstract:

Immune-mediated inflammatory diseases (IMIDs) are characterized by chronic systemic inflammation and multiorgan involvement. Fibrosis formation in IMIDs can cause tissue destruction and subsequently organ malfunction. Fibroblast activation protein inhibitor positron emission tomography/computed tomography (FAPi PET/CT) represents a novel imaging technique that holds great potential to visualize in vivo fibrosis. We here provide an overview of available evidence on FAPi PET/CT imaging to visualize fibrosis in var-ious IMIDs, including interstitial lung diseases, Immunoglobulin G4-related diseases, cardiovascular diseases, kidney diseases and gastrointestinal diseases. FAPi PET/CT imaging demonstrates high sensitivity in detecting early fibrosis, correlating with dis-ease severity, across different IMIDs, showing superiority compared to conventional imaging modalities. Although FAPi PET/CT might be a useful tool to assess fibrosis formation, thereby aiding in grading disease severity and staging, future studies should include larger sample sizes in a broad variety of IMIDs with emphasis on the optimiza-tion of imaging protocols to further validate its diagnostic value.

Abstract: Background: Returning to and sustaining employment after cancer presents significant challenges for individuals touched by cancer (ITBC). While vocational rehabilitation and workplace accommodations are critical, existing return to work (RTW) assessments lack cancer-specific considerations, limiting their clinical and occupational utility. Purpose: This study aimed to develop and validate the Cancer and Work Scale (CAWSE), a psychometrically robust tool designed to assess RTW likelihood and employment sustainability among ITBC, while also providing avenues for targeted interventions. Methods: A two-phase cross-sectional study was conducted. Study I (n = 130) assessed content validity and construct development, leading to a refined 43-item CAWSE. Study II (n = 216) employed exploratory and confirmatory factor analyses to establish structural validity, reliability, and responsiveness. Additional validation included correlations with fatigue, cognitive difficulties, depression, and anxiety. Results: Factor analysis supported a seven-factor structure with 31 final items. The CAWSE demonstrated strong internal consistency (α = 0.787), construct validity, and moderate responsiveness (AUC = 0.659). High sensitivity allowed for accurate identification of RTW difficulties, with an established cut-off score of 123.5 on the total CAWSE scale. Implications: The CAWSE fills a critical gap in oncology-specific vocational rehabilitation, offering healthcare providers a validated tool for targeted interventions to enhance RTW outcomes and long-term employment sustainability for ITBC.

Abstract:

This study examines the impact of SI-based treatments on neuroplastic alterations and functional recovery in persons with acquired neurological disorders. We quantify cortical remodeling following organized sensory-based therapies using standardized functional evaluations and functional magnetic resonance imaging (fMRI). Proprioceptive, vestibular, and tactile inputs are used in designed SI activities to integrate sensory-motor skills. Changes in sensorimotor network activation, enhancements in activities of daily living (ADLs), and general functional independence are examples of outcome measures. The function of SI in adult neurological rehabilitation has not been thoroughly investigated, despite its extensive usage in developmental disorders. In diseases including multiple sclerosis (MS), traumatic brain injury (TBI), and stroke, neuroplasticity—the brain's capacity to rearrange itself in response to experience or injury—is a crucial rehabilitation process. The objective of this research is to develop a novel method of neurological rehabilitation by fusing SI concepts with contemporary neuroscience. The results will strengthen the body of evidence supporting sensory-based therapies to promote functional neuroplasticity. Additionally, the study will give doctors a foundation for using SI in adult rehabilitation settings. This effort will demonstrate the potential of SI to enhance recovery trajectories for individuals with stroke, TBI, and MS, bridging the gap between occupational therapy and neuroscience. Long-term impacts and the integration of SI into multimodal rehabilitation programs should be the focus of future research.

Abstract: Background: The long-term effects of COVID-19 infection represent an emerging area of research that explores the relationships between a history of COVID-19 infection and its consequential sequelae. This study investigates the potential associations among the duration since infection, the severity of the acute phase of the disease, and sex, while controlling for age, in relation to mental health.; Methods: A total of 305 university students participated in this cross-sectional study, during which data were collected using the SCL-90-R questionnaire. The analysis of the collected data was conducted using MANCOVA, ANCOVA, and partial Kendall tau methods. Results: The findings indicated that factors such as sex—specifically being female—, longer time elapsed since infection, and disease severity significantly influenced multiple scales of the SCL-90-R. Conclusions: Based on these findings, it is recommended that investigations into mental health issues consider biological sex, COVID-19 severity, and the duration since infection as potential risk factors among young adults with a history of COVID-19 infection.

Abstract:

Cystic fibrosis (CF) patients experience higher risks of colorectal cancer, but pathogenesis is unclear. In the general population, polyketide synthase-positive (pks+) E. coli is impli-cated in intestinal carcinogenesis via production of colibactin, however relevance in CF is unknown. We investigated pks+ E. coli prevalence in CF at baseline and longitudinally, performing PCR on stool DNA extracts. Potential associations between pks+ E. coli and gastrointestinal inflammation or microbiome dynamics were analysed using faecal calprotectin and 16SrRNA gene taxonomic data. At baseline, no difference in pks+ E. coli carriage was identified between CF and healthy controls, 21/55(38%) vs 26/55(47%), p=0.32. Pks+ E. coli was not associated with significant differences in mean (SD) calpro-tectin concentration (124(154) vs 158(268) mg/kg; p=0.60), microbial richness (159(76.5) vs 147(70.4); p=0.50) or Shannon diversity index (2.78(0.77) vs 2.65(0.74); p=0.50) in CF. Lon-gitudinally, subjects demonstrated intra-individual variation in pks+ E. coli presence, however no significant difference in overall prevalence was observed. Thus, intesti-nal pks+ E. coli prevalence was not different between CF and healthy controls, nor associ-ated with differences in gut microbial profile or inflammation. Investigating effects of re-peat exposure on risk profile and analysis of older CF cohorts is necessary to identify if associations with colorectal cancer exist.

Abstract: Post-COVID-19 syndrome (PCS), also known as Long COVID, is a multifaceted condition characterized by persistent fatigue, cognitive dysfunction, sleep disturbances, and mood disorders. Emerging evidence suggests that serotonergic system disruption plays a central role in PCS pathophysiology, with reduced serotonin levels linked to chronic inflammation, platelet hyperactivity, and altered tryptophan metabolism. This review explores the potential therapeutic role of mirtazapine, a tetracyclic antidepressant that antagonizes 5-HT₂ and 5-HT₃ receptors while blocking α₂-adrenergic autoreceptors, leading to enhanced serotonin and norepinephrine release. Mirtazapine’s pharmacological properties extend beyond mood stabilization, encompassing sleep regulation, neuroplasticity promotion, and anti-inflammatory effects. By modulating serotonergic and noradrenergic transmission, it may alleviate key PCS symptoms such as cognitive impairment, chronic fatigue, and sleep disturbances. Furthermore, its neuroprotective role in preventing neuronal apoptosis and mitigating neuroinflammation makes it a promising candidate for addressing the long-term neurological consequences of PCS. Despite its potential, clinical trials evaluating mirtazapine in PCS are lacking, necessitating well-designed studies to assess its efficacy and safety. This review synthesizes current knowledge on mirtazapine’s mechanisms of action, its impact on neuroimmune interactions, and its potential advantages over conventional selective serotonin reuptake inhibitors (SSRIs) in the context of PCS. Future research should focus on randomized controlled trials and longitudinal studies to establish mirtazapine as a viable therapeutic option for PCS management.

Abstract:

The mRNA- and DNA-based “genetic” COVID-19 vaccines can induce a broad range of adverse events (AEs), with statistics showing significant variation depending on timing and data analysis methods. Focusing only on lipid nanoparticle-enclosed mRNA (mRNA-LNP) vaccines, this review traces the evolution of statistical conclusions on AE prevalence and incidence associated with these vaccines, from initial underestimation of atypical, severe toxicities to recent claims suggesting the possible contribution of Covid-19 vaccinations to the excess deaths observed in many countries over the past few years. Among hundreds of different AEs listed in Pfizer’s pharmacovigilance survey, the present analysis categorizes the main symptoms according to organ systems, nearly all being affected. Using data from the US Vaccine Adverse Event Reporting System and a global vaccination dataset, a comparison of the prevalence and incidence rates of AEs induced by genetic versus flu vaccines revealed an average 26-fold increase in AEs with genetic vaccines. The difference is especially pronounced in the case of severe ‘Brighton-listed’ AEs, which are also observed in COVID-19 and post-COVID conditions. Among these, the increases of incidence rates relative to flu vaccines, given as x-fold rises, were 1,152x, 455x, 226x, 218x, 162x, 152x; and 131x, for myocarditis, thrombosis, death, myocardial infarction, tachycardia, dyspnea, and hypertension, respectively. The review delineates the concepts that genetic vaccines can be regarded as prophylactic immuno-gene therapies, and that the chronic disabling AEs might be categorized as iatrogenic orphan diseases. It also examines the unique vaccine characteristics that could be causally related to abnormal immune responses potentially leading to adverse events and complications. These new insights may contribute to improving the safety of this platform technology and assessing the risk-benefit balance of various products.

Abstract: Iron represents a vital element needed for normal physiologic functions across the body. A vast network of transporters is involved not only in uptake but in processing, oxidation and recycling to maintain this element in a tight balance to avoid excess storage. This complex network of transporters including heme and ferroportin among many others are responsible for facilitating inter-organ and tissue iron exchange, contributing to systemic heme homeostasis. Patients with genetic diseases such as sickle disease suffer from a chronic anemia due to the presence of an abnormal hemoglobin that requires, in most instances, a lifetime of red blood cell transfusions to overcome disease crises. These transfusions over time lead to a high iron exposure that results in a profound change to the physiology of organ systems at the cellular level requiring aggressive chelation. This exposure unfortunately leads to irreversible changes to these organs from the cardiovascular system and bone marrow, to the central nervous system. In the bone marrow, heme is synthesized, mainly within developing red blood cells, iron excess leads to impairments in cell production and differentiation due to processes needing a balanced intracellular heme concentration to prevent toxicity. In light of the extensive role of iron in the body, the aim of this review is to summarize the important metabolic pathways involved in iron homeostasis across a number of cell types and organ systems while contrasting these against effects caused by iron overload.

Abstract: Background: Dandruff and related scalp disorders, often caused by Malassezia furfur, pose significant dermatological challenges. This study evaluates FERMENZA®, a novel, patented formulation derived from pomegranate and beetroot fermented extracts, as a natural alternative to synthetic agents like ketoconazole and zinc pyrithione. Methodology and Results: In this study, mixed substrate fermentation was utilized for synergistic effect on bioactivity of natural fruits and vegetable extracts. The pomegranate-beetroot fermented extract demonstrated impressive antifungal efficacy against Malassezia furfur MTCC 1374, with percent inhibition of 96% and 86.7% compared to active pharmaceutical ingredients ketoconazole and zinc pyrithione, respectively. The investigational formulation FERMENZA® derived from pomegranate and beetroot fermented extract exhibited the highest zone of inhibition (ZOI) of 28 ± 0.12 mm, outperforming marketed products A and B lotions by achieving 93 ± 0.04% and 60 ± 0.09% inhibition, respectively. Minimum inhibitory concentration (MIC) studies revealed potent activity of the formulation at 8mg/ml. The MIC90 value was observed at 20µg/mL achieving 92 ± 0.01% inhibition compared to ketoconazole. A time-kill assay highlighted the superior antifungal potency of FERMENZA® against M. furfur, significantly reducing fungal growth intensity within 48 hours, starting from 6 hours of incubation. The mechanism of fungicidal action is attributed to gallic acid, a key active component of pomegranate and beetroot fermented extract which disrupts fungal cell structures.Conclusion: Efficacy and sensory evaluation confirmed FERMENZA®’s ability to alleviate dandruff, itching, flaking, and scaling within 10 days, with moderate benefits in reducing hairfall. These results underscore FERMENZA®'s potential as a comprehensive, natural solution for managing dandruff and scalp disorders, providing a safer alternative to synthetic antifungal agents.

Abstract: Abstract: Background/Objectives: The current staging of non-small cell lung cancer (NSCLC) relies on conventional imaging, which lacks sensitivity to detect micrometa-static disease. Functional assessment of NSCLC progression may provide independent information to enhance prediction of metastatic risk.. The objective of this study was to determine if we could identify a metabolomic signature predictive of metastasis in pa-tients with NSCLC treated with definitive radiation. Methods: Plasma samples were collected prospectively from patients enrolled in a clinical trial with non-metastatic NSCLC treated with definitive radiation. Metabolites were extracted and mass spec-trometry-based analysis was performed using a flow injection electrospray (FIE) Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) method. Early metastasis was defined as metastasis within 1 year of radiation treatment. Results: The study cohort included 28 patients. FIE-FITCR produced highly reproducible profiles in technical replicates A total of 48 metabolic features were identified to be different in patients with early metastasis compared to patients without early metastasis (all ad-justed p values < 0.05, Welch’s t-test), including glycerophospholipids, sphingolipids, and fatty acyls. In follow up samples collected after initiation of chemotherapy and radiation treatment, a total of 154 metabolic features were significantly altered in patients who developed early metastasis compared to those who did not. Conclusions: We identified several distinct changes in the metabolic profiles of patients with NSCLC who developed metastatic disease within 1 year of definitive radiation. These findings highlight the potential of metabolomic profiling as a predictive tool for assessing met-astatic risk in NSCLC.

Abstract: Epilepsy, particularly early-onset and drug-resistant forms, presents a significant challenge in pediatric neurology. Inborn errors of metabolism are increasingly recognized as important contributors to these types of epilepsy. Timely diagnosis and treatment are crucial, as they can prevent irreversible metabolic damage and improve clinical outcomes and. Biallelic deleterious variants in CAD gene led CAD deficiency, progressive and severe metabolic disorder characterized by long seizures, psychomotor regression, and dyserythropoietic anemia. In this paper, we present four new cases of EIEE-50, emphasizing the importance of early, specific therapeutic interventions. Oral uridine 100 mg/kg/day was administrated with improvement of motor and cognitive function as well as immediate seizures control. Our findings underscore the potential for improved outcomes of EIEE-50 with timely and targeted treatment strategies.