-
1.
Repurposing metformin to manage idiopathic or long COVID Tinnitus: self-report adopting a pathophysiological and pharmacological approach.
Kelleni, MT
Inflammopharmacology. 2024;(2):945-948
Abstract
Chronic tinnitus is a common neurological disorder that affects millions of patients globally with no available successful pharmacotherapy. It can be extremely bothersome to some patients to the extent that it occasionally qualifies as a disability that can hinder them from leading a normal life. In this short communication, the author discusses how he suffered from idiopathic tinnitus and how he managed to adopt a combined pathophysiological and pharmacological approach to the reason for the first time in the medical literature that low-dose metformin might be safely and effectively repurposed to manage at least a subset of tinnitus patients while discussing the potential role of adenosine receptor agonists as potential future tinnitus therapeutics.
-
2.
Risk of flare or relapse in patients with immune-mediated diseases following SARS-CoV-2 vaccination: a systematic review and meta-analysis.
Shabani, M, Shobeiri, P, Nouri, S, Moradi, Z, Amenu, RA, Mehrabi Nejad, MM, Rezaei, N
European journal of medical research. 2024;(1):55
Abstract
BACKGROUND Patients with autoimmune and immune-mediated diseases (AI-IMD) are at greater risk of COVID-19 infection; therefore, they should be prioritized in vaccination programs. However, there are concerns regarding the safety of COVID-19 vaccines in terms of disease relapse, flare, or exacerbation. In this study, we aimed to provide a more precise and reliable vision using systematic review and meta-analysis. METHODS PubMed-MEDLINE, Embase, and Web of Science were searched for original articles reporting the relapse/flare in adult patients with AI-IMD between June 1, 2020 and September 25, 2022. Subgroup analysis and sensitivity analysis were conducted to investigate the sources of heterogeneity. Statistical analysis was performed using R software. RESULTS A total of 134 observations of various AI-IMDs across 74 studies assessed the rate of relapse, flare, or exacerbation in AI-IMD patients. Accordingly, the crude overall prevalence of relapse, flare, or exacerbation was 6.28% (95% CI [4.78%; 7.95%], I2 = 97.6%), changing from 6.28% (I2 = 97.6%) to 6.24% (I2 = 65.1%) after removing the outliers. AI-IMD patients administering mRNA, vector-based, and inactive vaccines showed 8.13% ([5.6%; 11.03%], I2 = 98.1%), 0.32% ([0.0%; 4.03%], I2 = 93.5%), and 3.07% ([1.09%; 5.9%], I2 = 96.2%) relapse, flare, or exacerbation, respectively (p-value = 0.0086). In terms of disease category, nephrologic (26.66%) and hematologic (14.12%) disorders had the highest and dermatologic (4.81%) and neurologic (2.62%) disorders exhibited to have the lowest crude prevalence of relapse, flare, or exacerbation (p-value < 0.0001). CONCLUSION The risk of flare/relapse/exacerbation in AI-IMD patients is found to be minimal, especially with vector-based vaccines. Vaccination against COVID-19 is recommended in this population.
-
3.
COVID-19 mRNA Vaccines: Lessons Learned from the Registrational Trials and Global Vaccination Campaign.
Mead, MN, Seneff, S, Wolfinger, R, Rose, J, Denhaerynck, K, Kirsch, S, McCullough, PA
Cureus. 2024;(1):e52876
Abstract
Our understanding of COVID-19 vaccinations and their impact on health and mortality has evolved substantially since the first vaccine rollouts. Published reports from the original randomized phase 3 trials concluded that the COVID-19 mRNA vaccines could greatly reduce COVID-19 symptoms. In the interim, problems with the methods, execution, and reporting of these pivotal trials have emerged. Re-analysis of the Pfizer trial data identified statistically significant increases in serious adverse events (SAEs) in the vaccine group. Numerous SAEs were identified following the Emergency Use Authorization (EUA), including death, cancer, cardiac events, and various autoimmune, hematological, reproductive, and neurological disorders. Furthermore, these products never underwent adequate safety and toxicological testing in accordance with previously established scientific standards. Among the other major topics addressed in this narrative review are the published analyses of serious harms to humans, quality control issues and process-related impurities, mechanisms underlying adverse events (AEs), the immunologic basis for vaccine inefficacy, and concerning mortality trends based on the registrational trial data. The risk-benefit imbalance substantiated by the evidence to date contraindicates further booster injections and suggests that, at a minimum, the mRNA injections should be removed from the childhood immunization program until proper safety and toxicological studies are conducted. Federal agency approval of the COVID-19 mRNA vaccines on a blanket-coverage population-wide basis had no support from an honest assessment of all relevant registrational data and commensurate consideration of risks versus benefits. Given the extensive, well-documented SAEs and unacceptably high harm-to-reward ratio, we urge governments to endorse a global moratorium on the modified mRNA products until all relevant questions pertaining to causality, residual DNA, and aberrant protein production are answered.
-
4.
Ramen noodle neuropathy: an atypical case of partial paralysis from malnutrition.
Lalley, A, Bawa, S, Harmouche, E
The American journal of emergency medicine. 2024;:198.e7-198.e10
Abstract
INTRODUCTION Due to a COVID-related job loss resulting in financial and food insecurity, a 28-year-old woman initiated a diet consisting solely of one cup of ramen noodles daily for twenty-two months, leading to 27 kg of weight loss. Ramen noodles are low in calories and lack key nutrients, including potassium, chloride, and vitamin B12. CASE DESCRIPTION The patient presented to the emergency department with acute, worsening weakness and paresthesias in her left wrist and hand. Exam revealed no other abnormalities aside from a cachectic appearance. Labs revealed marked hypokalemia, hypochloremia, lactic acidosis, a mixed metabolic alkalosis with respiratory acidosis, and low levels of zinc and copper. An EKG revealed a prolonged QT interval. After a neurology and psychiatry consult, the patient was admitted for failure to thrive with malnutrition, peripheral neuropathy, hypokalemia, and an acid-base disorder. An MRI of the brain was unremarkable. Studies of other nutritional deficiencies, autoimmune conditions, and sexually transmitted infections were unremarkable. The patient received food and vitamin supplementation, was monitored for re-feeding syndrome, and had a significant recovery. DISCUSSION After stroke, spinal injury, multiple sclerosis, and the most common focal mononeuropathies were ruled out, the clinical focus turned to nutritional deficiencies, the most significant of which was hypokalemia. Prior research has shown that severe hypokalemia can lead to weakness. It has also shown that chronically insufficient dietary intake is a common cause of hypokalemia. This case, with its partial paralysis of a unilateral upper extremity, may add to the known clinical manifestations of hypokalemia. We review the role of hypokalemia and hypochloremia in acid-base dynamics. Etiologies and clinical manifestations of cobalamin, thiamine, pyridoxine, and copper deficiencies, along with lead toxicity, are also discussed. Diagnostic clarity of mononeuropathies in the context of malnutrition and hypokalemia can be aided by urine potassium levels prior to repletion, neuroimaging that includes the cervical spine, and follow-up electromyography.
-
5.
Possible Role of Cannabis in the Management of Neuroinflammation in Patients with Post-COVID Condition.
Cárdenas-Rodríguez, N, Ignacio-Mejía, I, Correa-Basurto, J, Carrasco-Vargas, H, Vargas-Hernández, MA, Albores-Méndez, EM, Mayen-Quinto, RD, De La Paz-Valente, R, Bandala, C
International journal of molecular sciences. 2024;(7)
Abstract
The post-COVID condition (PCC) is a pathology stemming from COVID-19, and studying its pathophysiology, diagnosis, and treatment is crucial. Neuroinflammation causes the most common manifestations of this disease including headaches, fatigue, insomnia, depression, anxiety, among others. Currently, there are no specific management proposals; however, given that the inflammatory component involves cytokines and free radicals, these conditions must be treated to reduce the current symptoms and provide neuroprotection to reduce the risk of a long-term neurodegenerative disease. It has been shown that cannabis has compounds with immunomodulatory and antioxidant functions in other pathologies. Therefore, exploring this approach could provide a viable therapeutic option for PCC, which is the purpose of this review. This review involved an exhaustive search in specialized databases including PubMed, PubChem, ProQuest, EBSCO, Scopus, Science Direct, Web of Science, and Clinical Trials. Phytocannabinoids, including cannabidiol (CBD), cannabigerol (CBG), and Delta-9-tetrahydrocannabinol (THC), exhibit significant antioxidative and anti-inflammatory properties and have been shown to be an effective treatment for neuroinflammatory conditions. These compounds could be promising adjuvants for PCC alone or in combination with other antioxidants or therapies. PCC presents significant challenges to neurological health, and neuroinflammation and oxidative stress play central roles in its pathogenesis. Antioxidant therapy and cannabinoid-based approaches represent promising areas of research and treatment for mitigating adverse effects, but further studies are needed.
-
6.
Association of SARS-CoV-2 infection with neurological impairments in pediatric population: A systematic review.
Kwan, ATH, Portnoff, JS, Al-Kassimi, K, Singh, G, Hanafimosalman, M, Tesla, M, Gharibi, N, Ni, T, Guo, Z, Sonfack, DJN, et al
Journal of psychiatric research. 2024;:90-110
Abstract
Neurological manifestations have been widely reported in adults with COVID-19, yet the extent of involvement among the pediatric population is currently poorly characterized. The objective of our systematic review is to evaluate the association of SARS-CoV-2 infection with neurological symptoms and neuroimaging manifestations in the pediatric population. A literature search of Cochrane Library; EBSCO CINAHL; Global Index Medicus; OVID AMED, Embase, Medline, PsychINFO; and Scopus was conducted in accordance with the Peer Review of Electronic Search Strategies form (October 1, 2019 to March 15, 2022). Studies were included if they reported (1) COVID-19-associated neurological symptoms and neuroimaging manifestations in individuals aged <18 years with a confirmed, first SARS-CoV-2 infection and were (2) peer-reviewed. Full-text reviews of 222 retrieved articles were performed, along with subsequent reference searches. A total of 843 no-duplicate records were retrieved. Of the 19 identified studies, there were ten retrospective observational studies, seven case series, one case report, and one prospective cohort study. A total of 6985 individuals were included, where 12.8% (n = 892) of hospitalized patients experienced neurocognitive impairments which includes: 1) neurological symptoms (n = 294 of 892, 33.0%), 2) neurological syndromes and neuroimaging abnormalities (n = 223 of 892, 25.0%), and 3) other phenomena (n = 233 of 892, 26.1%). Based on pediatric-specific cohorts, children experienced more drowsiness (7.3% vs. 1.3%) and muscle weakness (7.3% vs. 6.3%) as opposed to adolescents. Agitation or irritability was observed more in children (7.3%) than infants (1.3%). Our findings revealed a high prevalence of immune-mediated patterns of disease among COVID-19 positive pediatric patients with neurocognitive abnormalities.
-
7.
COVID-19 related neurological manifestations in Parkinson's disease: has ferroptosis been a suspect?
Jia, F, Han, J
Cell death discovery. 2024;(1):146
Abstract
A rising number of patient cases point to a probable link between SARS-CoV-2 infection and Parkinson's disease (PD), yet the mechanisms by which SARS-CoV-2 affects the brain and generates neuropsychiatric symptoms in COVID-19 patients remain unknown. Ferroptosis, a distinct iron-dependent non-apoptotic type of cell death characterized by lipid peroxidation and glutathione depletion, a key factor in neurological disorders. Ferroptosis may have a pathogenic role in COVID-19, according to recent findings, however its potential contributions to COVID-19-related PD have not yet been investigated. This review covers potential paths for SARS-CoV-2 infection of the brain. Among these putative processes, ferroptosis may contribute to the etiology of COVID-19-associated PD, potentially providing therapeutic methods.
-
8.
A randomized double-blind pilot study to evaluate the efficacy, safety, and tolerability of intravenous iron versus oral iron for the treatment of restless legs syndrome in patients with iron deficiency anemia.
Short, V, Allen, R, Earley, CJ, Bahrain, H, Rineer, S, Kashi, K, Gerb, J, Auerbach, M
American journal of hematology. 2024
Abstract
Restless legs syndrome (RLS) is a neurological disorder that can have a profound effect on sleep and quality of life. Idiopathic RLS is associated with brain iron insufficiency despite normal peripheral iron stores. There is, however, a five- to six-fold increase in prevalence of RLS in patients with iron deficiency anemia (IDA). Several open-label trials have demonstrated symptomatic improvement in RLS following treatment of IDA using oral or intravenous iron supplementation. To date, there have been no randomized double-blind controlled trials of intravenous iron compared with oral iron for the treatment of RLS patients with IDA. In the current study, oral ferrous sulfate and ferumoxytol were compared for efficacy and speed of response for treatment of RLS occurring in patients with IDA. The planned recruitment for this study was 70 patients with RLS and IDA, to be randomly assigned 1:1 to oral or intravenous iron, using double-blind, double-dummy procedures. At Week 6, the primary outcomes of Clinical Global Impression-Improvement score and change from baseline in the International Restless Legs Syndrome Study Group rating scale score were assessed. Due to challenges, performing the clinical trial during the COVID-19 pandemic, final-week data were found missing for 30 patients. As a result, in order to maintain the prespecified statistical analysis, an additional 30 patients were recruited. Both IV and oral iron were associated with a marked improvement in RLS symptoms, with no statistically significant difference between treatment groups. No serious adverse events were observed in either treatment group.
-
9.
Mechanisms of Ferritinophagy and Ferroptosis in Diseases.
Li, S, Huang, P, Lai, F, Zhang, T, Guan, J, Wan, H, He, Y
Molecular neurobiology. 2024;(3):1605-1626
Abstract
The discovery of the role of autophagy, particularly the selective form like ferritinophagy, in promoting cells to undergo ferroptosis has inspired us to investigate functional connections between diseases and cell death. Ferroptosis is a novel model of procedural cell death characterized by the accumulation of iron-dependent reactive oxygen species (ROS), mitochondrial dysfunction, and neuroinflammatory response. Based on ferroptosis, the study of ferritinophagy is particularly important. In recent years, extensive research has elucidated the role of ferroptosis and ferritinophagy in neurological diseases and anemia, suggesting their potential as therapeutic targets. Besides, the global emergence and rapid transmission of COVID-19, which is caused by SARS-CoV-2, represents a considerable risk to public health worldwide. The potential involvement of ferroptosis in the pathophysiology of brain injury associated with COVID-19 is still unclear. This review summarizes the pathophysiological changes of ferroptosis and ferritinophagy in neurological diseases, anemia, and COVID-19, and hypothesizes that ferritinophagy may be a potential mechanism of ferroptosis. Advancements in these fields will enhance our comprehension of methods to prevent and address neurological disorders, anemia, and COVID-19.
-
10.
Protein profile pattern analysis: A multifarious, in vitro diagnosis technique for universal screening.
Kumar Barik, A, Mathew, C, Sanoop, PM, John, RV, Adigal, SS, Bhat, S, Pai, KM, Bhandary, SV, Devasia, T, Upadhya, R, et al
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences. 2024;:123944
Abstract
Universal health care is attracting increased attention nowadays, because of the large increase in population all over the world, and a similar increase in life expectancy, leading to an increase in the incidence of non-communicable (various cancers, coronary diseases, neurological and old-age-related diseases) and communicable diseases/pandemics like SARS-COVID 19. This has led to an immediate need for a healthcare technology that should be cost-effective and accessible to all. A technology being considered as a possible one at present is liquid biopsy, which looks for markers in readily available samples like body fluids which can be accessed non- or minimally- invasive manner. Two approaches are being tried now towards this objective. The first involves the identification of suitable, specific markers for each condition, using established methods like various Mass Spectroscopy techniques (Surface-Enhanced Laser Desorption/Ionization Mass Spectroscopy (SELDI-MS), Matrix-Assisted Laser Desorption/Ionization (MALDI-MS), etc., immunoassays (Enzyme-Linked Immunoassay (ELISA), Proximity Extension Assays, etc.) and separation methods like 2-Dimensional Polyacrylamide Gel Electrophoresis (2-D PAGE), Sodium Dodecyl-Sulfate Polyacrylamide Gel Electrophoresis (SDS-PAGE), Capillary Electrophoresis (CE), etc. In the second approach, no attempt is made the identification of specific markers; rather an efficient separation method like High-Performance Liquid Chromatography/ Ultra-High-Performance Liquid Chromatography (HPLC/UPLC) is used to separate the protein markers, and a profile of the protein pattern is recorded, which is analysed by Artificial Intelligence (AI)/Machine Learning (MI) methods to derive characteristic patterns and use them for identifying the disease condition. The present report gives a summary of the current status of these two approaches and compares the two in the use of their suitability for universal healthcare.