Immunogenicity, clinical efficacy and safety of additional second COVID-19 booster vaccines against Omicron and its subvariants: A systematic review.

The Omicron variant of severe acute respiratory syndrome coronavirus 2 is a new variant of concern (VOC) and an emerging subvariant that exhibits heightened infectivity, transmissibility, and immune evasion, escalating the incidence of moderate to severe coronavirus disease 2019 (COVID-19). It resists monoclonal antibodies and diminishes vaccine efficacy. Notably, new sublineages have outpaced earlier predominant sublineages. Although the primary vaccination series and initial boosters were robust against previous VOCs, their efficacy waned against Omicron and its subvariants. In this systematic review, we assessed real-world evidence on the immunogenicity, clinical efficacy, and safety of a second booster or fourth COVID-19 vaccine dose against the Omicron VOC and its subvariants. A comprehensive literature search was conducted in Medline/PubMed, Google Scholar, bioRxiv, and medRxiv, and relevant studies published between 2022 and 30 May 2023 were reviewed. We found a total of 40 relevant articles focusing on a second booster dose for COVID-19, including clinical trials and observational studies, involving 3,972,856 patients. The results consistently revealed that an additional second booster dose restored and prolonged waning immunity, activating both humoral and cellular responses against Omicron and its subvariants. A second booster treatment correlated with enduring protection against COVID-19, notably preventing substantial symptomatic disease and mortality associated with severe Omicron infection. Both monovalent messenger RNA (mRNA) and nonmRNA vaccines demonstrated similar efficacy and safety, with bivalent mRNA vaccines exhibiting broader protection against emerging subvariants of Omicron. The safety profiles of second booster were favourable with only mild systemic and local symptoms reported in some recipients. In conclusion, this systematic review underscores the additional COVID-19 vaccine boosters, particularly with bivalent or multivalent mRNA vaccines, for countering the highly infectious emerging subvariants of Omicron.

IL-18 Gene Promoter Polymorphisms are Involved in Periodontal Disease: A Meta-Analysis.

Microbial plaque that builds up in the gingival crevice area causes inflammation and leads to periodontal disease. Previous research has shown an association between interleukins with periodontitis. The association between interleukin-18 (IL-18) gene polymorphism and periodontitis risk was studied extensively, but the results are contradictory. The aim of this study is to find the association of two IL-18 promoter variants namely -607 C > A (rs1946518) and -137 G > C (rs187238), and the risk of chronic and aggressive periodontal disease by meta-analysis. The databases of PubMed, Medline, Web of Science, and Google Scholar were all explored to find the appropriate studies. The MetaGenyo software was used to calculate each analysis. Outcomes of the pooled analyses revealed significantly elevated risk for periodontitis for both polymorphisms. There is no significant heterogeneity between studies. No significant publication bias was observed. This meta-analysis provided the evidence of a link between IL-18 gene polymorphism in periodontitis.

Role of CD4+ T Cells in Parkinson's Disease.

Parkinson's disease (PD) is a progressive condition that affects both the central nervous system and other body parts that are controlled by the nervous system. PD is characterized by brain dopaminergic neurons loss and, at present, there are only symptomatic treatments available to alleviate the effects of the disease. With extensive research, new insights have led to defining PD as a multi-system disorder with immune dysfunction playing a dominant part in the disease pathogenesis as well as its progression. Neuroinflammation in PD leads to neurodegeneration, which is, in turn, regulated by the peripheral adaptive immunity, with CD4+ T cells being a significant player. Patients with PD have diverse CD4+ T cell phenotypes and functional profiles. These phenotypes vary, from being proinflammatory (Th1 and Th17) to anti-inflammatory (Th2 and Tregs). This report focuses on reviewing the expression of CD4+ T cells in PD and its role in the prognosis and treatment of PD.

A systematic review to identify novel clinical characteristics of monkeypox virus infection and therapeutic and preventive strategies to combat the virus.

Since May 2022, there has been a global increase in the number of Mpox virus (MPXV) cases in countries that were previously considered non-endemic. In July 2022, the World Health Organization (WHO) declared this outbreak a public health emergency of international concern. The objective of this systematic review is to examine the novel clinical features of Mpox and to assess the available treatment options for managing the disease in patients who are afflicted with it. We conducted a systematic search in several databases, including PubMed, Google Scholar, Cochrane Library, and the grey literature, from May 2022 to February 2023. We identified 21 eligible studies, which included 18,275 Mpox cases, for final qualitative analysis. The majority of cases were reported in men who have sex with men (MSM) and immunocompromised individuals with HIV (36.1%). The median incubation period was 7 days (IQR: 3-21). The novel clinical manifestations include severe skin lesions on the palms, oral and anogenital regions, as well as proctitis, penile edema, tonsillitis, ocular disease, myalgia, lethargy, and sore throat, without any preceding prodromal symptoms or systemic illness. In addition, fully asymptomatic cases were documented, and various complications, including encephalomyelitis and angina, were noted. Clinicians must be familiar with these novel clinical characteristics, as they can aid in testing and tracing such patients, as well as asymptomatic high-risk populations such as heterosexuals and MSM. In addition to supportive care, currently, there are several effective prophylactic and treatment strategies available to combat Mpox, including the vaccines ACAM2000 and MVA-BN7, as well as the immunoglobulin VIGIV and the antivirals tecovirimat, brincidofovir, and cidofovir against severe Mpox infection.

Association and Mechanisms of Proton Pump Inhibitors Use with Type-2 Diabetes Mellitus Incidence in Adults: A Systemic Review and Metaanalysis.

BACKGROUND: Proton pump inhibitors (PPIs) are an extensively prescribed class of anti-ulcer drugs. This systematic review aimed to investigate the association between PPI use and the risk of new-onset diabetes mellitus or type 2 diabetes (T2DM) incidence. METHODS: A comprehensive literature search was conducted in PubMed, Scopus, Cochrane Library, and ClinicalTrials.gov using the search terms "proton pump inhibitor," "proton pump inhibitors," "PPIs," "diabetes mellitus," and "type 2 diabetes" from inception to February 2023. Statistical analyses were performed using the "Review Manager 5.4" version, and a statistically highly significant P value <0.05 was set. RESULTS: This systematic review identified 12 studies (8 cohort, 1 RCT, and 3 case-control) with a total of 12, 64, 816 population, and the median age ranged from ≥18 yrs to ≤ 75 yrs. The pooled relative risk (RR) observations of a random-effects meta-analysis model showed that chronic exposure to PPI use has a significant association with T2DM risk incidence (RR, 2.44; 95% confidence interval, 1.31-4.54; I 2 = 99%, P < 0.00001). The systematic review findings of the three case-control studies also supported an association of dose-dependent and chronic use of PPIs with an incidence of T2DM among chronic users. CONCLUSION: The systematic review concludes that chronic PPI exposure increases the risk of T2DM incidence. The authors recommend the shortest possible duration of PPI use and not prescribing PPIs to high-risk prediabetics and those without a compelling indication for PPI use. Regular education to patients regarding adverse reactions with prolonged use may decrease the risk of adverse effects associated with PPIs. The authors suggest that gut dysbiosis, hypergastrinemia, hypomagnesemia, decreased pancreatic secretions and IGF-1 levels, and PXR activation associated with chronic acid suppression among chronic PPI users and the potency of PPIs might explain the association between abnormal glucose metabolism and T2DM incidence. Finally, the authors recommend further randomized controlled trials to investigate the association between PPIs and the risk of new-onset T2DM incidence.

Clinical virology and effect of Covid-19 vaccination and monoclonal antibodies against highly infectious SARS- CoV-2 omicron sub variant BF.7 (BA.5.2.1.7): A systematic review.

Over time, the SARS-CoV-2 virus has acquired several genetic mutations, particularly on the receptor-binding domain (RBD) spike glycoprotein. The Omicron variant is highly infectious, with enhanced immune escape activity, and has given rise to various sub-lineages due to mutations. However, there has been a sudden increase in COVID-19 reports of the Omicron subvariant BF.7 (BA.2.75.2), which has the highest number of reported cases, accounting for 76.2% of all cases worldwide. Hence, the present systematic review aimed to understand the viral mutations and factors associated with the increase in the reports of COVID-19 cases and to assess the effectiveness of vaccines and mAbs against the novel Omicron variant BF.7. The R346T mutation on the spike glycoprotein RBD might be associated with increased infection rates, severity, and resistance to vaccines and mAbs. Booster doses of COVID-19 vaccination with bivalent mRNA booster vaccine shots are effective in curtailing infections and decreasing the severity and mortality by enhancing the neutralizing antibodies (Abs) against the emerging Omicron subvariants of SARS-CoV-2, including BF.7 and future VOCs.

Global prevalence and effect of comorbidities and smoking status on severity and mortality of COVID-19 in association with age and gender: a systematic review, meta-analysis and meta-regression.

A COVID-19 patient often presents with multiple comorbidities and is associated with adverse outcomes. A comprehensive assessment of the prevalence of comorbidities in patients with COVID-19 is essential. This study aimed to assess the prevalence of comorbidities, severity and mortality with regard to geographic region, age, gender and smoking status in patients with COVID-19. A systematic review and multistage meta-analyses were reported using PRISMA guidelines. PubMed/MEDLINE, SCOPUS, Google Scholar and EMBASE were searched from January 2020 to October 2022. Cross-sectional studies, cohort studies, case series studies, and case-control studies on comorbidities reporting among the COVID-19 populations that were published in English were included. The pooled prevalence of various medical conditions in COVID-19 patients was calculated based on regional population size weights. Stratified analyses were performed to understand the variations in the medical conditions based on age, gender, and geographic region. A total of 190 studies comprising 105 million COVID-19 patients were included. Statistical analyses were performed using STATA software, version 16 MP (StataCorp, College Station, TX). Meta-analysis of proportion was performed to obtain pooled values of the prevalence of medical comorbidities: hypertension (39%, 95% CI 36-42, n = 170 studies), obesity (27%, 95% CI 25-30%, n = 169 studies), diabetes (27%, 95% CI 25-30%, n = 175), and asthma (8%, 95% CI 7-9%, n = 112). Moreover, the prevalence of hospitalization was 35% (95% CI 29-41%, n = 61), intensive care admissions 17% (95% CI 14-21, n = 106), and mortality 18% (95% CI 16-21%, n = 145). The prevalence of hypertension was highest in Europe at 44% (95% CI 39-47%, n = 68), obesity and diabetes at 30% (95% CI, 26-34, n = 79) and 27% (95%CI, 24-30, n = 80) in North America, and asthma in Europe at 9% (95% CI 8-11, n = 41). Obesity was high among the ≥ 50 years (30%, n = 112) age group, diabetes among Men (26%, n = 124) and observational studies reported higher mortality than case-control studies (19% vs. 14%). Random effects meta-regression found a significant association between age and diabetes (p < 0.001), hypertension (p < 0.001), asthma (p < 0.05), ICU admission (p < 0.05) and mortality (p < 0.001). Overall, a higher global prevalence of hypertension (39%) and a lower prevalence of asthma (8%), and 18% of mortality were found in patients with COVID-19. Hence, geographical regions with respective chronic medical comorbidities should accelerate regular booster dose vaccination, preferably to those patients with chronic comorbidities, to prevent and lower the severity and mortality of COVID-19 disease with novel SARS-CoV-2 variants of concern (VOC).

Views on artificial intelligence (AI) assisted clinical trials.

It is of interest to document the views of medical professionals on the application of artificial intelligence (using known data for the prediction of unknown events) in clinical trials using a web survery with a structured questionnaire from 377 subjects. The questionnaire contained 17 statements which were categorised into awareness (1,2 statements), perception (3-10 statements) and opinion (11-17 statements). The data obtained was compared between the subjects using two tailed Fisher's exact test with p-value <0.05 for data significance analysis. Data shows that majority of professionals have possitive views on the application of artificial intelligence in clinical trials. This will accelarrate the drug evaluation process. However, the use of emerging tools such as AI will not replace human subjects in this context.

A Review on Hematopoietic Stem Cell Treatment for Epilepsy.

Epilepsy responds to pharmacotherapy in its initial stages. The response of some forms of epilepsy, like the refractory epilepsy, is extremely low. Surgical management of epilepsy is associated with complications, which necessitates the search for novel and modern strategies for the treatment of epilepsy. Neuroprotection and neuronal regeneration are the major targets that must be accomplished by the new strategies. Hematopoietic Stem Cell (HSCs) therapy for epilepsy has shown promising results in pre-clinical studies with marginal clinical effects. This review explores the characteristics, mechanism of action, and clinical significance of HSCs therapy for the treatment of epilepsy.

Association of hypercoagulation with severe acute respiratory syndrome coronavirus 2 infection.

The coronavirus disease 2019 (COVID-19) pandemic has emerged as a major threat to all healthcare systems across the globe, and it was declared a public health emergency of international concern by the World Health Organization (WHO). The novel coronavirus affects the respiratory system, producing symptoms such as fever, cough, dyspnea, and pneumonia. The association between COVID-19 and coagulation has been previously reported. Due to several inflammatory changes that occur in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections such as alterations in the levels of clotting factors, platelet activation leads to thrombus formation in coronary and cerebral vessels, leading to myocardial infarction and cerebrovascular accidents, respectively. Unfortunately, the progression of hypercoagulability in COVID-19 is rapid in patients with and without comorbidities. Hence, the proper monitoring of thrombotic complications in patients with COVID-19 is essential to avoid further complications. The implementation of guidelines for antithrombotic treatments based on the presentation of the disease is recommended. This review discusses the symptoms and mechanisms of upregulated coagulation in patients with COVID-19.

Diagnostic and Prognostic Implications of Cardiac Markers for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HC) is a malignant primary liver cancer which has poor treatment outcomes in advanced stages, and many of the HC patients present with advanced stages. The incidence of death due to HC increase as a result of ineffective treatments for advanced stage disease. Early diagnosis and management has proven benefits in both survival and quality of life. Currently very few biomarkers are available to provide diagnostic and prognostic benefits in HC patients. The present review elaborates the association of cardiac markers in HC disease. The HC disease pathology includes many cardiovascular events like hypoxia and other parameters discussed in this review which have a role in disease advancement, and also may help as diagnostic and / or prognostic markers. The scientific lacuna in association / role of cardiac markers in HC disease is also stated in this review which may be helpful for future research studies and develop cost effective biomarker for early diagnosis of HC.