Immune checkpoint inhibitors in advanced cutaneous melanoma: a systematic review and meta-analysis of efficacy and review of characteristics.

OBJECTIVES: Immune checkpoint inhibitors (ICIs) are one of the most promising approaches toward advanced melanoma. Here, we aimed to perform a meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of all studied ICIs. METHODS: We conducted a comprehensive search to identify the relevant publications (PROSPERO registration ID: CRD42023470649). Then we performed a meta-analysis to evaluate the efficacy of different ICIs for metastatic melanoma. We used Cochrane's tool to assess the quality of studies. The outcome measures were overall survival (OS), progression-free survival (PFS), and recurrence-free survival (RFS). RESULTS: Twenty reports of RCTs entered our systematic review, 18 of which were included in our data analysis. ICIs showed improved survival compared with control group (hazard ratio (HR) = 0.57; 95% CI: 0.43-0.71; P<0.001). Using a meta-regression, we found a significant relation between patients' mean age and their OS (P<0.001, R2 = 100.00%). Also, our analysis revealed greater HR for CTLA-4 inhibitors than PD-1/PD-L1 inhibitors (HR = 0.71, 95%CI: 0.63-0.79, P<0.001 vs. HR = 0.63, 95%CI: 0.46-0.79, P<0.001). The effect sizes of different types of PD-1/PD-L1 inhibitors were comparable. CONCLUSION: Our results suggest that ICI-based immunotherapy is associated with enhanced OS, PFS, and RFS (P < 0.001) and will assist clinicians in choosing the optimal approach toward treating metastatic melanoma.

Effects of Smoking on COVID-19 Management and Mortality: An Umbrella Review.

Introduction: Smoking status appears to lead to a poor prognosis in COVID-19 patients. However, findings from the studies conducted on this topic have not been consistent, and further exploration is required. Methods: The objective of this umbrella review was to examine the effects of smoking on COVID-19 management and mortality. Online databases that included PubMed, Embase, Scopus, and Web of Science were searched using relevant keywords up to July 27, 2022. Articles were restricted to the English language, and the PRISMA protocol was followed. Results: A total of 27 systematic reviews, published from 2020 to 2022, were included. Individual studies included in the systematic reviews ranged from 8 to 186, with various population sizes. The consensus from the majority of systematic reviews was that COVID-19 smoker patients experience greater disease severity, disease progression, hospitalization rate, hospital admission duration, mechanical ventilation, ICU admission, and mortality rate. Conclusions: COVID-19 patients with a history of smoking (current and former) are vulnerable to adverse hospital outcomes and worse COVID-19 progression. Effective preventive and supportive approaches are required to decrease the risk of COVID-19 morbidity and mortality in patients with a history of smoking.

Immunological aspects of COVID-19-related skin manifestations: Revisiting pathogenic mechanism in the light of new evidence.

The newly emerged coronavirus disease 2019 (COVID-19), induced by a novel strain of the coronavirus family, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a rapidly spreading global threat. This virus affects a fair number of tissues in the human body by availing itself of potential target receptors like Angiotensin-Converting Enzyme 2 (ACE2). Presenting with diverse clinical manifestations, COVID-19 has raised the urge for extensive research in different medical fields, including dermatology. Developing a comprehensive knowledge of cutaneous manifestations is highly important as it can help us in early diagnosis and better management of the ongoing pandemic. The dermatological presentations of COVID-19 are classified into main categories of vascular and non-vascular (exanthematous) patterns. Though not yet fully confirmed, the pathogenesis of these cutaneous presentations has been suggested to be more related to the overactivation of the immune system. In this review, we discuss in detail the clinical features of the diverse skin lesions in COVID-19 patients and the imperative role of the immune system in their pathogenesis and development. Furthermore, we will discuss the reasons behind the accentuation of skin lesions in COVID-19 compared to the same virus family predecessors.

Anaphylaxis and allergic reactions to COVID-19 vaccines: A narrative review of characteristics and potential obstacles on achieving herd immunity.

Background and Aims: Coronavirus disease 2019 (COVID-19) is a highly contagious infection, and new variants of its causative virus continue to emerge all around the world. Meanwhile, mass vaccination represents a highly effective measure to reduce the disease burden. Not only do vaccines immunize individuals, but they also protect the entire population through achieving herd immunity. They are composed of various ingredients, some of which may induce hypersensitivity reactions, namely anaphylaxis and cutaneous allergic reactions. This review aims to provide an explicit overview of the pathophysiology, suspected responsible components, and management of COVID-19 vaccine-induced allergic reactions, and their effect on acquiring herd immunity. Methods: To perform this narrative review, a comprehensive literature search based on our selected terms was conducted in online databases of PubMed/Medline and Google Scholar for finding the relevant studies published from 2019 to 2022. Results: COVID-19 vaccines introduce several advantages that outweigh their potential risks, such as allergic reactions. Allergic reactions are mainly attributed to polyethylene glycol and polysorbate excipients that can provoke IgE-mediated reactions and hypersensitivity reactions. These reactions should be managed properly to avoid having serious sequelae. Conclusion: It is of great importance to immediately recognize and manage vaccine hypersensitivity reactions, especially anaphylaxis, to avoid allergic patients being excluded from the vaccination program, and more importantly, to stop the spreading of unfounded vaccine hesitancy leading to delayed herd immunity.

COVID-19 Vaccines' Protection Over Time and the Need for Booster Doses; a Systematic Review.

Introduction: Controversies existed regarding the duration of COVID-19 vaccines' protection and whether receiving the usual vaccine doses would be sufficient for long-term immunity. Therefore, we aimed to systematically review the studies regarding the COVID-19 vaccines' protection three months after getting fully vaccinated and assess the need for vaccine booster doses. Methods: The relevant literature was searched using a combination of keywords on the online databases of PubMed, Scopus, Web of Science, and Cochrane on September 17th, 2021. The records were downloaded and the duplicates were removed. Then, the records were evaluated in a two-step process, consisting of title/abstract and full-text screening processes, and the eligible records were selected for the qualitative synthesis. We only included original studies that evaluated the efficacy and immunity of COVID-19 vaccines three months after full vaccination. This review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement to ensure the reliability of results. Results: Out of the 797 retrieved records, 12 studies were included, 10 on mRNA-based vaccines and two on inactivated vaccines. The majority of included studies observed acceptable antibody titers in most of the participants even after 6 months; however,it appeared that the titers could also decrease in a considerable portion of people. Due to the reduction in antibody titers and vaccine protection, several studies suggested administering the booster dose, especially for older patients and those with underlying conditions, such as patients with immunodeficiencies. Conclusion: Studies indicated that vaccine immunity decreases over time, making people more susceptible to contracting the disease. Besides, new variants are emerging, and the omicron variant is continuing to spread and escape from the immune system, indicating the importance of a booster dose.

COVID-19 mortality and its predictors in the elderly: A systematic review.

Background and Aims: Older people have higher rates of comorbidities and may experience more severe inflammatory responses; therefore, are at higher risk of death. Herein, we aimed to systematically review the mortality in coronavirus disease 2019 (COVID-19) patients and its predictors in this age group. Methods: We searched PubMed, Web of Science, and Science Direct using relevant keywords. Retrieved records underwent a two-step screening process consisting of title/abstract and full-text screenings to identify the eligible studies. Results: Summarizing findings of 35 studies demonstrated that older patients have higher mortality rates compared to the younger population. A review of articles revealed that increasing age, body mass index, a male gender, dementia, impairment or dependency in daily activities, presence of consolidations on chest X-ray, hypoxemic respiratory failure, and lower oxygen saturation at admission were risk factors for death. High d-dimer levels, 25-hydroxy vitamin D serum deficiencies, high C-reactive protein (≥5 mg/L) levels plus any other abnormalities of lymphocyte, higher blood urea nitrogen or lactate dehydrogenase, and higher platelet count were predictors of poor prognosis and mortality in the elderly. Studies have also shown that previous treatment with renin-angiotensin-aldosterone system inhibitors, pharmacological treatments of respiratory disorders, antibiotics, corticosteroids, vitamin K antagonist, antihistamines, azithromycin, Itolizumab (an anti-CD6 monoclonal antibody) in combination with other antivirals reduces COVID-19 worsening and mortality. Vaccination against seasonal influenza might also reduce COVID-19 mortality. Conclusion: Overall, a critical consideration is necessary for the care and management of COVID-19 in the aged population considering the drastic contrasts in manifestation and prognosis compared to other age groups. Mortality from COVID-19 is independently associated with the patient's age. Elderly patients with COVID-19 are more vulnerable to poor outcomes. Thus, strict preventive measures, timely diagnosis, and aggressive therapeutic/nontherapeutic care are of great importance to reduce acute respiratory distress syndrome and severe complications in older people.

Public acceptability of COVID-19 vaccines and its predictors in Middle Eastern/North African (MENA) countries: a systematic review .

INTRODUCTION: COVID-19 vaccines emerged as a worldwide hope to contain the pandemic. However, many people are still hesitant to receive these vaccines. We aimed to systematically review the public knowledge, perception, and acceptability of COVID-19 vaccines in the Middle East and North Africa (MENA) countries and the predictors of vaccine acceptability in this region. METHODS: We systematically searched databases of PubMed, Scopus, Web of Science, and Cochrane and retrieved all relevant studies by 5 August 2021. RESULTS: There was a considerable variation in the COVID-19 vaccine acceptance rates, from 12% in a study from Israel to 83.3% in Kuwait, although two other studies from Israel mentioned 75% and 82.2% acceptability rates. Concerns about the side effects and safety of the vaccine were the main reasons for the lack of acceptability of taking the vaccine, which was reported in 19 studies. . CONCLUSION: Several factors, such as age, gender, education level, and comorbidities, are worthy of attention as they could expand vaccine coverage in the target population. .

Impact of COVID-19 pandemic on routine vaccination coverage of children and adolescents: A systematic review.

BACKGROUND AND AIMS: Scientists and healthcare workers have expressed their concerns on the impacts of the COVID-19 pandemic on vaccination coverage in children and adolescents. Therefore, we aimed to systematically review the studies addressing this issue worldwide. METHODS: We conducted a systematic search of relevant studies using the keywords on databases of PubMed, Web of Science, and Cochrane on May 22, 2021. The identified records were imported into EndNote software and underwent a two-phase screening process consisting of title/abstract and full-text screenings against inclusion criteria. The data of the included studies were summarized into a table and the findings were analyzed in a systematic approach. RESULTS: From 26 eligible studies, 21 studies demonstrated decreased vaccination rates in the children during the COVID-19 pandemic, while three studies found increased or no significant changes only in influenza vaccination. The two remaining studies from Brazil and Sweden also showed no significant changes in vaccination rates in the children during the pandemic. CONCLUSION: Most of the reports worldwide reported a decline or delay in vaccination at the time of the COVID-19 pandemic. A sustained catch-up program seems to be necessary, especially in low-income countries, to avoid any vaccine dose missing. Facilitating the vaccination process is recommended, such as decreasing the waiting time for vaccination at the health center, addressing the fear and concerns related to COVID infection for parents, and enhancing vaccine availability, and promoting access in remote areas. Countries should ensure proper vaccination to prevent future pandemics related to vaccine-preventable diseases.

Immune modulations and immunotherapies for Alzheimer's disease: a comprehensive review.

Alzheimer's disease (AD), the most common cause of dementia, is characterized by progressive cognitive and memory impairment ensued from neuronal dysfunction and eventual death. Intraneuronal deposition of tau proteins and extracellular senile amyloid-ß plaques have ruled as the supreme postulations of AD for a relatively long time, and accordingly, a wide range of therapeutics, especially immunotherapies have been implemented. However, none of them resulted in significant positive cognitive outcomes. Especially, the repetitive failure of anti-amyloid therapies proves the inefficiency of the amyloid cascade hypothesis, suggesting that it is time to reconsider this hypothesis. Thus, for the time being, the focus is being shifted to neuroinflammation as a third core pathology in AD. Neuroinflammation was previously considered a result of the two aforementioned phenomena, but new studies suggest that it might play a causal role in the pathogenesis of AD. Neuroinflammation can act as a double-edged sword in the pathogenesis of AD, and the activation of glial cells is indispensable for mediating such attenuating or detrimental effects. The association of immune-related genes polymorphisms with the clinical phenotype of AD as well as the protective effect of anti-inflammatory drugs like nonsteroidal anti-inflammatory drugs supports the possible causal role of neuroinflammation in AD. Here, we comprehensively review immune-based therapeutic approaches toward AD, including monoclonal antibodies and vaccines. We also discuss their efficacy and underlying reasons for shortcomings. Lastly, we highlight the capacity of modulating the neuroimmune interactions and targeting neuroinflammation as a promising opportunity for finding optimal treatments for AD.