Association of New-Onset Seizures With SARS-CoV-2 Vaccines: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Importance: Seizures have been reported as an adverse effect of the SARS-CoV-2 vaccine. However, no study has answered the question of whether there is any association between seizures in the general population and COVID-19 vaccination. Objective: To evaluate the seizure incidence among SARS-CoV-2 vaccine recipients compared with those who received a placebo. Data Sources: A systematic search of MEDLINE (via PubMed), Web of Science, Scopus, Cochrane Library, Google Scholar, review publications, editorials, letters to editors, and conference papers, along with the references of the included studies from December 2019 to July 7, 2023. Study Selection: Randomized clinical trials (RCTs) reporting seizure incidence with SARS-CoV-2 vaccination were included. Data Extraction and Synthesis: This study is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework and used the Mantel-Haenszel method with random- and common-effect models. The risk of bias of the studies was assessed using the Cochrane assessment tool for RCTs. Main Outcomes and Measures: The outcome of interest was new-onset seizure incidence proportion compared among (1) SARS-CoV-2 vaccine recipients and (2) placebo recipients. Results: Six RCTs were included in the study. Results of the pooled analysis comparing the incidence of new-onset seizure between the 63 521 vaccine and 54 919 placebo recipients in the 28-day follow-up after vaccine/placebo injection showed no statistically significant difference between the 2 groups (9 events [0.014%] in vaccine and 1 event [0.002%] in placebo recipients; odds ratio [OR], 2.70; 95% CI, 0.76-9.57; P = .12; I2 = 0%, τ2 = 0, Cochran Q P = .74). Likewise, in the entire blinded-phase period after injection, with a median of more than 43 days, no significant difference was identified between the vaccine and placebo groups regarding incident new-onset seizure (13/43 724 events [0.03%] in vaccine and 5/40 612 [0.012%] in placebo recipients; OR, 2.31; 95% CI, 0.86-3.23, P > .99, I2 = 0%, τ2 = 0, Cochran Q P = .95). Conclusions and Relevance: According to this systematic review and meta-analysis, there was no statistically significant difference in the risk of new-onset seizure incidence between vaccinated individuals and placebo recipients.

Association of seizure with COVID-19 vaccines in persons with epilepsy: A systematic review and meta-analysis.

Seizure aggravation following coronavirus disease 2019 (COVID-19) vaccines is a major cause behind vaccine hesitancy among persons with epilepsy (PwE), resulting in lower immunization rates. We systematically reviewed seizure-activity-related events in PwE following COVID-19 vaccination. We systematically searched PubMed, Web of Science, Scopus, and Cochrane Library, until January 31, 2023, and included articles reporting seizure activity-related events in PwE receiving COVID-19 vaccination. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses were followed. The protocol was registered with PROSPERO (CRD42022312475). Outcomes included pooled incidence proportions of (a) increased seizure frequency, (b) status epilepticus (SE), and (c) change in seizure type. Of the 2207 studies, 16 entered the meta-analysis. The pooled incidence proportion of increased seizure frequency (16 studies-3245 PwE) was 5% (95% CI: 3%-7%, I2 = 52%). Regarding increased seizure frequency, no significant difference was observed between mRNA and viral vector (OR: 1.11, 95% CI: 0.49-2.52, I2 = 0%), and between mRNA and inactivated virus (OR: 1.60, 95% CI: 0.27-9.37; I2 = 0%). The pooled incidence proportion of SE (15 studies-2387 PwE) was 0.08% (95% CI: 0.02%-0.33%, I2 = 0%). Ultimately, the pooled incidence proportion of change in seizure type (7 studies-1172 PwE) was 1% (95% CI: 1%-2%, I2 = 0%). The meta-analysis revealed post-COVID-19-vaccination increased seizure frequency in 5% of PwE, with no difference between mRNA and viral vector or inactivated virus vaccines. Furthermore, we found 0.08% and 1% incidence proportions for postvaccination SE and change in seizure type, respectively. While noteworthy, these values are far less than reports for COVID-19 infection, emphasizing vaccination importance in preventing COVID-19 consequences in PwE.

Superior mesenteric artery thrombosis with concomitant pancreaticoduodenal artery pseudoaneurysm in a 60-year-old male patient - A case report.

INTRODUCTION: Vascular complications like superior mesenteric artery (SMA) thrombosis and pancreaticoduodenal artery (PDA) pseudoaneurysm carry high morbidity and mortality. SMA provides the primary arterial supply to the small intestine and ascending colon. PDA aneurysms are extremely rare, accounting for only 2 % of all visceral artery aneurysms. We present a rare case of SMA thrombosis with concomitant PDA pseudoaneurysm. CASE PRESENTATION: Herein is the case of a 60-year-old male who presented with rectorrhagia, persistent generalized abdominal pain. After being diagnosed with colitis and mesenteric artery thrombosis based on a computed tomography (CT) scan, he was discharged from the hospital with rivaroxaban and mesalazin. However, he had to return to the hospital due to worsening of the symptoms. After a proper workout, SMA artery thrombosis with a concomitant PDA pseudoaneurysm was diagnosed for him. Therefore, he underwent surgery to stent the thrombosis and coil the pseudoaneurysm. His symptoms dramatically improved after the treatment. DISCUSSION: Angiography is the diagnostic and, with embolization, therapeutic procedure of choice, with surgery as a backup if embolization fails. However, even with these procedures, the mortality rate is high if the pseudoaneurysm ruptures. CONCLUSION: In order to carry out the proper choice of surgical treatment before further complications occur, SMA thrombosis and PDA pseudoaneurysms must be investigated in each patient presenting with nonspecific abdominal pain, regardless of the risk factors.

Nivolumab plus ipilimumab combination therapy in cancer: Current evidence to date.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer immunotherapy, yielding significant antitumor responses across multiple cancer types. Combination ICI therapy with anti-CTLA-4 and anti-PD-1 antibodies outperforms either antibody alone in terms of clinical efficacy. As a consequence, the U.S. Food and Drug Administration (FDA) approved ipilimumab (anti-CTLA-4) plus nivolumab (anti-PD-1) as the first-ever approved therapies for combined ICI in patients with metastatic melanoma. Despite the success of ICIs, treatment with checkpoint inhibitor combinations poses significant clinical challenges, such as increased rates of immune-related adverse events (irAEs) and drug resistance. Thus, identifying optimal prognostic biomarkers could help to monitor the safety and efficacy of ICIs and identify patients who may benefit the most from these treatments. In this review, we will first go over the fundamentals of the CTLA-4 and PD-1 pathways, as well as the mechanisms of ICI resistance. The results of clinical findings that evaluated the combination of ipilimumab and nivolumab are then summarized to support future research in the field of combination therapy. Finally, the irAEs associated with combined ICI therapy, as well as the underlying biomarkers involved in their management, are discussed.

Association of SARS-CoV-2 Vaccination or Infection With Bell Palsy: A Systematic Review and Meta-analysis.

Importance: Bell palsy (BP) has been reported as an adverse event following the SARS-CoV-2 vaccination, but neither a causative relationship nor a higher prevalence than in the general population has been established. Objective: To compare the incidence of BP in SARS-CoV-2 vaccine recipients vs unvaccinated individuals or placebo recipients. Data Sources: A systematic search of MEDLINE (via PubMed), Web of Science, Scopus, Cochrane Library, and Google Scholar from the inception of the COVID-19 report (December 2019) to August 15, 2022. Study Selection: Articles reporting BP incidence with SARS-CoV-2 vaccination were included. Data Extraction and Synthesis: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline and was conducted with the random- and fixed-effect models using the Mantel-Haenszel method. The quality of the studies was evaluated by the Newcastle-Ottawa Scale. Main Outcomes and Measures: The outcomes of interest were to compare BP incidence among (1) SARS-CoV-2 vaccine recipients, (2) nonrecipients in the placebo or unvaccinated cohorts, (3) different types of SARS-CoV-2 vaccines, and (4) SARS-CoV-2-infected vs SARS-CoV-2-vaccinated individuals. Results: Fifty studies were included, of which 17 entered the quantitative synthesis. Pooling 4 phase 3 randomized clinical trials showed significantly higher BP in recipients of SARS-CoV-2 vaccines (77 525 vaccine recipients vs 66 682 placebo recipients; odds ratio [OR], 3.00; 95% CI, 1.10-8.18; I2 = 0%). There was, however, no significant increase in BP after administration of the messenger RNA SARS-CoV-2 vaccine in pooling 8 observational studies (13 518 026 doses vs 13 510 701 unvaccinated; OR, 0.70; 95% CI, 0.42-1.16; I2 = 94%). No significant difference was found in BP among 22 978 880 first-dose recipients of the Pfizer/BioNTech vaccine compared with 22 978 880 first-dose recipients of the Oxford/AstraZeneca vaccine (OR, 0.97; 95% CI, 0.82-1.15; I2 = 0%). Bell palsy was significantly more common after SARS-CoV-2 infection (n = 2 822 072) than after SARS-CoV-2 vaccinations (n = 37 912 410) (relative risk, 3.23; 95% CI, 1.57-6.62; I2 = 95%). Conclusions and Relevance: This systematic review and meta-analysis suggests a higher incidence of BP among SARS-CoV-2-vaccinated vs placebo groups. The occurrence of BP did not differ significantly between recipients of the Pfizer/BioNTech vs Oxford/AstraZeneca vaccines. SARS-CoV-2 infection posed a significantly greater risk for BP than SARS-CoV-2 vaccination.

Fulminant psudeumonas pneumonia following coronary artery bypass grafting - Case report.

INTRODUCTION AND IMPORTANCE: Pneumonia has always been a source of complication after surgeries. Pseudomonas aeruginosa has emerged as one of the most problematic Gram-negative pathogens among nosocomial infections. Pneumonia caused by pseudomonas is usually slowly progressive allowing clinicians to detect and manage it on time. CLINICAL PRESENTATION: A 55-year-old man was hospitalized for elective CABG, complicated by fulminant pneumonia. Vancomycin and meropenem were adminestered as soon as the symptoms appeared. However, the patient died from septic shock syndrome caused by pseudomonas pneumonia on the third postoperative day, just hours after the first symptom appeared. The chest X-ray showed an extreme opacity within less than 12 h. CLINICAL DISCUSSION: This case is reported because of its rare clinical presentation of Fulminant pseudomonas pneumonia following cardiac surgery. CONCLUSION: Consider pseudomonas aeruginosa as a certain cause of pneumonia after cardiac surgery, and an organized, modified guideline is needed to determine the best option and timeline for treating this complication.

Recent advances in atezolizumab-based programmed death-ligand 1 (PD-L1) blockade therapy for breast cancer.

Breast cancer, the most common cancer in women worldwide, is curable in âˆ¼ 70-80 % of patients with early-stage, non-metastatic disorder. However, advanced breast cancer with distant organ metastases is incurable with available therapeutics. Thus, scientists have sought emerging strategies for treating metastatic breast cancers., Immune checkpoint inhibitors (ICIs) have represented a significant development in breast cancer immunotherapy. Now, targeting immune checkpoint molecules (e.g., programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1)) have attracted increasing attention in the context of breast cancer therapy, chiefly triple-negative breast cancer (TNBC). Atezolizumab, a humanized IgG1 monoclonal antibody (mAb), has been designed to interfere with the binding of the PD-L1 ligand to its receptor. Targeting PD-L1 using atezolizumab potentiates T-cell responses to the tumor and consequently boosts tumor responses. The results of the IMpassion130 trial have recently led to the approval of the combination of atezolizumab and nab-paclitaxel to treat unresectable locally advanced or metastatic patients with PD-L1-positive TNBC. Herein, we summarize the clinical efficacy of atezolizumab in treating breast cancer and briefly discuss the possible immune-related adverse events (irAEs).

Therapeutic utility of mesenchymal stromal cell (MSC)-based approaches in chronic neurodegeneration: a glimpse into underlying mechanisms, current status, and prospects.

Recently, mesenchymal stromal cell (MSC)-based therapy has become an appreciated therapeutic approach in the context of neurodegenerative disease therapy. Accordingly, a myriad of studies in animal models and also some clinical trials have evinced the safety, feasibility, and efficacy of MSC transplantation in neurodegenerative conditions, most importantly in Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). The MSC-mediated desired effect is mainly a result of secretion of immunomodulatory factors in association with release of various neurotrophic factors (NTFs), such as glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF). Thanks to the secretion of protein-degrading molecules, MSC therapy mainly brings about the degradation of pathogenic protein aggregates, which is a typical appearance of chronic neurodegenerative disease. Such molecules, in turn, diminish neuroinflammation and simultaneously enable neuroprotection, thereby alleviating disease pathological symptoms and leading to cognitive and functional recovery. Also, MSC differentiation into neural-like cells in vivo has partially been evidenced. Herein, we focus on the therapeutic merits of MSCs and also their derivative exosome as an innovative cell-free approach in AD, HD, PD, and ALS conditions. Also, we give a brief glimpse into novel approaches to potentiate MSC-induced therapeutic merits in such disorders, most importantly, administration of preconditioned MSCs.