Global Perspective on COVID-19 Therapies, Cardiovascular Outcomes, and Implications for Long COVID: A State-of-the-Art Review.

The COVID-19 pandemic has resulted in many therapies, of which many are repurposed and used for other diseases in the last decade such in Influenza and Ebola. We intend to provide a robust foundation for cardiovascular outcomes of the therapies to better understand the rationale for the clinical trials that were conducted during the COVID-19 pandemic, and to gain more clarity on the steps moving forward should the repurposing provide clinical benefit in pandemic situations. With this state-of-the-art review, we aim to improve the understanding of the cardiovascular involvement of the therapies prior to, during, and after the COVID-19 pandemic to provide meaningful findings to the cardiovascular specialists and clinical trials for therapies, moving on from the period of pandemic urgency.

Managing Chronic Neuropathic Pain: Recent Advances and New Challenges.

Aim: Neuropathic pain affects 7-10% of the population, with most of the patients receiving inadequate and incomplete treatment. Owing to the high financial burden and the poor quality of life of the patients and their caretakers, there is a dire need to address the challenges in diagnosing and treating chronic neuropathic pain. Methods: This literature review was conducted to review novel treatments and related challenges through a systematic search from sources such as PubMed, Google Scholar with the combination of MESH words such as neuropathic pain, management of neuropathic pain. Articles from non-English literature, reports without human subjects, animal studies, and abstracts/posters were excluded. However, human studies and studies published in English were included. Result: This review article discusses novel treatment modalities while acknowledging the challenges medical workers face while encountering neuropathic pain. Despite the recent advances in diagnosis and treatment modalities, several challenges still exist. Hence, there is still a need to explore the various treatment modalities, emphasizing the cause and underlying pathophysiology of neuropathic pain. Conclusion: We recommend integrated multimodal treatment with the current treatment facility, including various medical disciplines. However, a personalized approach would work the best depending on the 'patient's medical history. Therefore, this article recommends an integrated, cause-specific, cost-effective approach to address this problem of chronic neuropathic pain.

A Case Report on Neuroleptic Malignant Syndrome (NMS): How to Approach an Early Diagnosis.

Neuroleptic malignant syndrome (NMS) is a life-threatening neurological emergency that has been observed to occur in some patients following the administration of anti-dopaminergic agents or the rapid withdrawal of dopaminergic medications. In this report, the authors present a case of a 51-year-old male patient with a known history of cocaine abuse, who was given quetiapine during his hospitalization. This precipitated an episode of NMS that eventually concluded uneventfully due to quick diagnosis and management. Prompt recognition of the condition is required to reduce significant morbidity and mortality. Ultimately, maintaining vigilance for the clinical features of NMS is crucial for timely diagnosis and intervention.

Industry 4.0 Technologies for the Manufacturing and Distribution of COVID-19 Vaccines.

BACKGROUND: The evolutionary stages of manufacturing have led us to conceptualize the use of Industry 4.0 for COVID-19 (coronavirus disease 2019), powered by Industry 4.0 technologies. Using applications of integrated process optimizations reliant on digitized data, we propose novel intelligent networks along the vaccine value chain. Vaccine 4.0 may enable maintenance processes, streamline logistics, and enable optimal production of COVID-19 vaccines. VACCINE 4.0 FRAMEWORK: The challenge in applying Vaccine 4.0 includes the requirement of large-scale technologies for digitally transforming manufacturing, producing, rolling-out, and distributing vaccines. With our framework, Vaccine 4.0 analytics will target process performance, process development, process stability, compliance, quality assessment, and optimized maintenance. The benefits of digitization during and post the COVID-19 pandemic include first, the continual assurance of process control, and second, the efficacy of big-data analytics in streamlining set parameter limits. Digitization including big data-analytics may potentially improve the quality of large-scale vaccine production, profitability, and manufacturing processes. The path to Vaccine 4.0 will enhance vaccine quality, improve efficacy, and compliance with data-regulated requirements. DISCUSSION: Fiscal and logistical barriers are prevalent across resource-limited countries worldwide. The Vaccine 4.0 framework accounts for expected barriers of manufacturing and equitably distributing COVID-19 vaccines. With amalgamating big data analytics and biometrics, we enable the identification of vulnerable populations who are at higher risk of disease transmission. Artificial intelligence powered sensors and robotics support thermostable vaccine distribution in limited capacity regions, globally. Biosensors isolate COVID-19 vaccinations with low or limited efficacy. Finally, Vaccine 4.0 blockchain systems address low- and middle-income countries with limited distribution capacities. CONCLUSION: Vaccine 4.0 is a viable framework to optimize manufacturing of vaccines during and post the COVID-19 pandemic.

Multidimensional mechanisms of metformin in cancer treatment.

Metformin has been in clinical use for more than half a century, yet its molecular mechanism of action is not entirely understood. Metformin has been shown to have antiproliferative and synergistic effects on various types of cancers. The anticancer effects of metformin are potentially applicable to both diabetic and nondiabetic patients. Areas of ongoing investigation focus on metformin's ability to activate adenosine monophosphate kinase (AMPK), in addition to its effect on Myc mRNA, monocarboxylate transporter 1 (MCT1), hypoxia-inducible factor 1 (HIF1), mammalian target of rapamycin (mTOR), and human epidermal growth factor receptor 2 (HER2). Additional anticancer effects are exhibited by acting on liver kinase B1 (LKB1), CREB-regulated transcription coactivator 2 (CRTC2), nitric oxide, and reactive oxygen species. Further investigation will be focused on elucidating metformin's metal-binding properties and how they may be harnessed for their anticancer effect. The acquired knowledge about metformin properties has expanded the number of targets for drug discovery such as microRNA, hexokinase, adenylate cyclase, transcription factors, various cyclins, and copper. In order to design anticancer drugs that mimic metformin's mechanism of action, binding assay studies must be conducted to fully understand and utilize the AMPK-dependent and independent mechanisms. Metformin's complex mechanisms that can potentially make this drug a multifaceted therapy targeting tumorigenesis in addition to information from ongoing clinical trials implicate that metformin can be a potential chemotherapeutic drug or adjuvant that could prove to be vital to future strategies against several types of cancer.

Deep Dive Into Familial Mediterranean Fever in a Child Without Fever.

This case report entails the details of a 12-year-old Egyptian boy who had recurrent episodes of shortness of breath, ascites, and pericardial effusions starting at the age of 10, returning with worsening symptoms in April of 2020. The lab findings indicated a critically elevated C-reactive protein (CRP) of 107.2 mg/L; a clinically notable inflammation process was festering. This case was all the more interesting as this boy did not present with a fever, making the diagnosis a difficult one. Nonetheless, genetic Mediterranean fever (MEFv) and polymerase chain reaction (PCR) testing confirmed the diagnosis of familial MEFv. Steroids and colchicine-salicylate decreased the frequency of the attacks and are now on half a dose of colchicine to keep his symptoms at bay. What we see here is the risk-to-benefit ratio of the therapeutic use of colchicine in children outweighs potential side effects such as nausea, vomiting, abdominal pain, diarrhea, kidney or liver failure. However, further research is needed to access better long-term treatment plans. Another key takeaway point that can be highlighted in this case is that the patient does not need to be febrile to diagnose FMF.

The Safety and Efficacy of Anakinra, an Interleukin-1 Antagonist in Severe Cases of COVID-19: A Systematic Review and Meta-Analysis.

This study aims to assess anakinra's safety and efficacy for treating severe coronavirus disease 2019 (COVID-19). Numerous electronic databases were searched and finally 15 studies with a total of 3,530 patients, 757 in the anakinra arm, 1,685 in the control arm were included. The pooled adjusted odds ratio (OR) for mortality in the treatment arm was 0.34 (95% confidence interval [CI], 0.21 - 0.54, I² = 48%), indicating a significant association between anakinra and mortality. A significant association was found regarding mechanical ventilation requirements in anakinra group compared to the control group OR, 0.68 (95% CI, 0.49 - 0.95, I² = 50%). For the safety of anakinra, we evaluated thromboembolism risk and liver transaminases elevation. Thromboembolism risk was OR, 1.59 (95% CI, 0.65 - 3.91, I² = 0%) and elevation in liver transaminases with OR was 1.35 (95% CI, 0.61 - 3.03, I² = 76%). Both were not statistically significant over the control group. Anakinra is beneficial in lowering mortality in COVID-19 patients. However, these non-significant differences in the safety profile between the anakinra and control groups may have been the result of baseline characteristics of the intervention group, and further studies are essential in evaluating anakinra's safety profile.

Bottom-up analysis of emergent properties of N-acetylcysteine as an adjuvant therapy for COVID-19.

N-acetylcysteine (NAC) is an abundantly available antioxidant with a wide range of antidotal properties currently best studied for its use in treating acetaminophen overdose. It has a robustly established safety profile with easily tolerated side effects and presents the Food and Drug Administration's approval for use in treating acetaminophen overdose patients. It has been proven efficacious in off-label uses, such as in respiratory diseases, heart disease, cancer, human immunodeficiency virus infection, and seasonal influenza. Clinical trials have recently shown that NAC's capacity to replenish glutathione stores may significantly improve coronavirus disease 2019 (COVID-19) outcomes, especially in high risk individuals. Interestingly, individuals with glucose 6-phosphate dehydrogenase deficiency have been shown to experience even greater benefit. The same study has concluded that NAC's ability to mitigate the impact of the cytokine storm and prevent elevation of liver enzymes, C-reactive protein, and ferritin is associated with higher success rates weaning from the ventilator and return to normal function in COVID-19 patients. Considering the background knowledge of biochemistry, current uses of NAC in clinical practice, and newly acquired evidence on its potential efficacy against COVID-19, it is worthwhile to investigate further whether this agent can be used as a treatment or adjuvant for COVID-19.

Thymosin alpha 1: A comprehensive review of the literature.

Thymosin alpha 1 is a peptide naturally occurring in the thymus that has long been recognized for modifying, enhancing, and restoring immune function. Thymosin alpha 1 has been utilized in the treatment of immunocompromised states and malignancies, as an enhancer of vaccine response, and as a means of curbing morbidity and mortality in sepsis and numerous infections. Studies have postulated that thymosin alpha 1 could help improve the outcome in severely ill corona virus disease 2019 patients by repairing damage caused by overactivation of lymphocytic immunity and how thymosin alpha 1 could prevent the excessive activation of T cells. In this review, we discuss key literature on the background knowledge and current clinical uses of thymosin alpha 1. Considering the known biochemical properties including antibacterial and antiviral properties, time-honored applications, and the new promising findings regarding the use of thymosin, we believe that thymosin alpha 1 deserves further investigation into its antiviral properties and possible repurposing as a treatment against severe acute respiratory syndrome coronavirus-2.