Efficacy of teplizumab for treatment of type 1 diabetes: A meta-analysis of randomized controlled trials.

BACKGROUND: The management of Type 1 Diabetes Mellitus (T1DM) is a significant clinical challenge. This study evaluated the efficacy of teplizumab, an immunomodulatory drug, in patients with T1DM, using a systematic review and meta-analysis approach. METHODS: We systematically searched multiple databases including Medline, Scopus, and others up to 10 January 2024, without language or regional restrictions. We included randomized controlled trials (RCTs) comparing teplizumab with placebo in T1DM patients. RESULTS: Our analysis incorporated 8 RCTs, predominantly involving participants aged 7-35 years, diagnosed with T1DM and treated with 14-day courses of teplizumab. The primary outcomes included insulin use, C-peptide levels, and HbA1c levels. We observed a significant reduction in insulin use in the teplizumab group standardised mean difference of -0.50 (95% Confidence Interval [CI]: -0.76 to -0.23, p < 0.001; I2 = 49%). C-peptide levels were consistently higher in the teplizumab group, indicating improved endogenous insulin production. However, no significant change was noted in HbA1c levels between the groups. Quality assessment indicated a low risk of bias in most studies. CONCLUSIONS: Teplizumab has a significant impact on reducing insulin dependence and enhancing endogenous insulin production in T1DM patients. However, its effect on long-term glycaemic control, as indicated by HbA1c levels, remains inconclusive.

Reactivation of herpesviruses during COVID-19: A systematic review and meta-analysis.

To provide a comprehensive systematic review and meta-analysis regarding the cumulative incidence (incidence proportion) of human herpesvirus (HHV) reactivation among patients with coronavirus disease 2019 (COVID-19), we searched PubMed/MEDLINE, Web of Science, and EMBASE up to 25 September 2022, with no language restrictions. All interventional and observational studies enrolling patients with confirmed COVID-19 and providing data regarding HHV reactivation were included. The random-effects model was used in the meta-analyses. We included information from 32 studies. HHV reactivation was considered a positive polymerase chain reaction result taken at the time of COVID-19 infection. Most of the included patients were severe COVID-19 cases. The pooled cumulative incidence estimate was 38% (95% Confidence Intervals [CI], 28%-50%, I2  = 86%) for herpes simplex virus (HSV), 19% (95% CI, 13%-28%, I2  = 87%) for cytomegalovirus (CMV), 45% (95% CI, 28%-63%, I2  = 96%) for Epstein-Barr virus (EBV), 18% (95% CI, 8%-35%) for human herpesvirus 6 (HHV-6), 44% (95% CI, 32%-56%) for human herpesvirus 7 (HHV-7), and 19% (95% CI, 14%-26%) for human herpesvirus 8 (HHV-8). There was no evidence of funnel plot asymmetry based on visual inspection and Egger's regression test for the results of HSV (p = 0.84), CMV (p = 0.82), and EBV (p = 0.27) reactivation. In conclusion, the identification of HHV reactivation in severe COVID-19 patients is helpful in the management of patients as well as the prevention of complications. Further research is required to elucidate the interaction between HHVs and COVID-19. Systematic review registration: PROSPERO CRD42022321973.

The global prevalence of depression, anxiety, and sleep disorder among patients coping with Post COVID-19 syndrome (long COVID): a systematic review and meta-analysis.

BACKGROUND: Post COVID-19 syndrome, also known as "Long COVID," is a complex and multifaceted condition that affects individuals who have recovered from SARS-CoV-2 infection. This systematic review and meta-analysis aim to comprehensively assess the global prevalence of depression, anxiety, and sleep disorder in individuals coping with Post COVID-19 syndrome. METHODS: A rigorous search of electronic databases was conducted to identify original studies until 24 January 2023. The inclusion criteria comprised studies employing previously validated assessment tools for depression, anxiety, and sleep disorders, reporting prevalence rates, and encompassing patients of all age groups and geographical regions for subgroup analysis Random effects model was utilized for the meta-analysis. Meta-regression analysis was done. RESULTS: The pooled prevalence of depression and anxiety among patients coping with Post COVID-19 syndrome was estimated to be 23% (95% CI: 20%-26%; I2 = 99.9%) based on data from 143 studies with 7,782,124 participants and 132 studies with 9,320,687 participants, respectively. The pooled prevalence of sleep disorder among these patients, derived from 27 studies with 15,362 participants, was estimated to be 45% (95% CI: 37%-53%; I2 = 98.7%). Subgroup analyses based on geographical regions and assessment scales revealed significant variations in prevalence rates. Meta-regression analysis showed significant correlations between the prevalence and total sample size of studies, the age of participants, and the percentage of male participants. Publication bias was assessed using Doi plot visualization and the Peters test, revealing a potential source of publication bias for depression (p = 0.0085) and sleep disorder (p = 0.02). However, no evidence of publication bias was found for anxiety (p = 0.11). CONCLUSION: This systematic review and meta-analysis demonstrate a considerable burden of mental health issues, including depression, anxiety, and sleep disorders, among individuals recovering from COVID-19. The findings emphasize the need for comprehensive mental health support and tailored interventions for patients experiencing persistent symptoms after COVID-19 recovery.

Brain-derived neurotrophic factor (BDNF) as a potential marker of endometriosis: a systematic review and meta-analysis.

BACKGROUND: The existing literature on the association between BDNF protein levels and endometriosis presents inconsistent findings. This systematic review and meta-analysis aim to synthesize the available evidence and evaluate the possible relationship between BDNF protein levels and endometriosis. METHODS: Electronic databases (PubMed, Embase, Scopus, PsycINFO, and Web of Science) were used to conduct a comprehensive literature search from inception to June 2023. The search strategy included relevant keywords and medical subject headings (MeSH) terms related to BDNF, endometriosis, and protein levels. A random-effects model was used for the meta-analysis, and to explore heterogeneity subgroup analyses were performed. funnel plots and statistical tests were used for assessing the publication bias. RESULTS: A total of 12 studies were included. The pooled standardized mean difference (SMD) of BDNF levels between women with endometriosis and controls was 0.87 (95% confidence interval [CI] 0.34 to 1.39, p = 0.001; I2 = 93%). The results showed that blood levels of BDNF are significantly higher in endometriosis patients (SMD: 1.13 95% CI 0.54 to 1.73, p = 0.0002; I2 = 93%). No significant publication bias was observed based on the results of Egger's regression test ((p = 0.15). CONCLUSION: This study revealed a significant difference between patients diagnosed with endometriosis and healthy control in the level of BDNF. The results indicate that women with endometriosis have higher levels of BDNF. Further studies are needed to be undertaken to investigate the role of BDNF in endometriosis pathophysiology and the diagnostic value of BDNF in endometriosis.

Global prevalence of obesity and overweight among medical students: a systematic review and meta-analysis.

BACKGROUND: Obesity is a global health concern, and understanding its prevalence among medical students is crucial for shaping targeted interventions. This systematic review and meta-analysis aim to comprehensively assess the prevalence of obesity and overweight among medical students. METHODS: A systematic literature search was conducted across major databases, including PubMed, Scopus, and Web of Science, in order to identify relevant studies that evaluated obesity and overweight among medical students. Inclusion criteria encompassed published and peer-reviewed studies reporting the prevalence of obesity among medical students. RESULTS: A total of 1245 studies were screened based on their titles and abstracts, and 99 studies comprised a total sample size of 47,455 medical students across diverse geographical regions were included in this study. The overall pooled prevalence of overweight among medical students was estimated at 18% (95% CI: 17%-20%), with obesity at 9% (95% CI: 7%-11%). The combined prevalence of excess weight (overweight and obesity) was calculated to be 24% (95% CI: 22%-27%). Meta-regression results indicated a significant correlation between study year and overweight/obesity prevalence (p < 0.05), with a trend towards increasing prevalence over time. Male medical students exhibited a higher pooled prevalence, increasing with the percentage of male participants. CONCLUSION: This systematic review and meta-analysis provide a comprehensive overview of the prevalence of obesity among medical students globally. In summary, obesity and overweight present a substantial worldwide health concern, especially among susceptible groups such as medical students, whose prevalence is on the rise. It is crucial to grasp the extent and contributing factors of obesity among medical students to formulate precise interventions aimed at fostering healthier habits and alleviating the adverse impacts of obesity on both physical and mental health.

Dexmedetomidine administration as a possible cognitive enhancer through increasing the level of brain-derived neurotrophic factors in surgical patients: a systematic review and meta-analysis.

OBJECTIVE: This meta-analysis aimed to investigate the effect of dexmedetomidine on brain-derived neurotrophic factor (BDNF) levels in individuals undergoing various medical procedures. We systematically searched electronic databases and manually identified relevant articles to assess the impact of dexmedetomidine on BDNF levels in surgical patients. METHODS: A comprehensive literature search was conducted in PubMed, Scopus, Embase, and Web of Science databases with no language restrictions. Studies that examined the effects of dexmedetomidine administration on BDNF levels in surgical patients were included. RESULTS: The overall analysis revealed a statistically significant increase in BDNF levels in individuals receiving dexmedetomidine compared to controls (Standardized Mean Difference SMD = 1.65, 95% CI: 1.02 to 2.28; I2: 89%). Subgroup analyses based on the anesthesia method (p < 0.01), and the type of surgery (p < 0.01) showed significant between-group differences (Fig. 3). The results of the sensitivity analyses indicated that individual studies did not significantly affect the overall results. CONCLUSION: This meta-analysis indicates that dexmedetomidine administration is associated with a significant increase in BDNF levels in individuals undergoing surgical procedures. These findings highlight the potential role of dexmedetomidine in modulating BDNF levels, which may have implications for optimizing perioperative neuroprotective strategies and improving patient outcomes.

Brain-derived neurotrophic factor levels in perinatal depression: A systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis aim to synthesize the available evidence and determine the overall brain-derived neurotrophic factor (BDNF) levels in individuals diagnosed with perinatal depression (PND). METHODS: We performed a thorough search of electronic databases, including PubMed, Embase, PsycINFO, and Web of Science, from their start until April 30, 2023. Our search strategy involved using specific keywords and medical subject headings (MeSH) terms related to BDNF, perinatal, post-partum, and antepartum depression. In the meta-analysis, we employed a random-effects model, and subgroup analyses were conducted to investigate any variations in the results. RESULTS: A total of 15 studies met the inclusion criteria, of which 10 were used in the quantitative analysis. The meta-analysis demonstrated a significant decrease in BDNF levels in both individuals with antepartum depression (SMD: -0.31; 95% CI: -0.48 to -0.13; p-value = 0.0008; I2 = 71%), and post-partum depression (SMD: -0.61; 95% CI: -0.99 to -0.22; p-value = 0.0002 I2 = 77%). Furthermore, a significantly higher rate of PND among individuals in the lowest BDNF quartile (OR: 2.64; 95% CI: 1.01 to 6.89; p-value = 0.05; I2 = 90%) was seen. The results of subgroup analyses showed a statistically significant effect of the depression assessment tool on overall heterogeneity between studies. CONCLUSION: This systematic review and meta-analysis provide evidence of lower BDNF protein levels in individuals diagnosed with PND. The results indicate that BDNF dysregulation may play a part in the development of PND. More research is needed to understand the mechanisms behind this and explore potential therapeutic applications.

Frailty as a predictor of adverse outcomes in burn patients: a systematic review.

BACKGROUND: The identification of new prognostic tools for the prediction of burn patients' morbidity outcomes is necessary. Considering the feasibility of frailty assessment in the clinical setting, we aim to systematically review the literature on the associations between frailty and adverse outcomes in burn patients. METHODS: Studies were retrieved from MEDLINE (through PubMed), Web of Science, Scopus, and Embase from their inception up to 8 September 2022. Included studies were those that used frailty indices to predict adverse outcomes in burn patients. The quality assessment was done using the National, Heart, Lung, and Blood Institute (NHLBI) checklist. The results were synthesized narratively. RESULTS: We included 18 studies. The sample size among the included studies varied between 42-1615 patients. There were 12 research articles and 6 conference abstracts. Most of the studies were recently published in 2021 and 2022. Seven different frailty measures were evaluated. The following frailty measures were used: Canadian Study for Health and Ageing (CSHA) Clinical Frailty score (CFS), Modified frailty index-11 (mFI-11), Hospital frailty index, FRAIL scale, Emergency General Surgery Frailty Index (EGSFI), and Burn frailty index (BFI). There was only one report regarding a specific frailty index designed for the burn population (BFI). Except for one study (which used mFI-11), all included studies have shown a significant effect between assessing frailty and predicting worse outcomes. The CFS was an independent predictor of mortality among the burn population with high certainty of evidence. We found a significant association for other frailty indices as a predictor of mortality, however, the certainty of evidence regarding those was not high. Eight studies found a positive association between assessing frailty and unfavorable discharge location. There was no association between frailty and increased length of stay. CONCLUSION: In conclusion, the postadmission assessment of frailty can be a reliable tool for predicting unfavorable outcomes and mortalities among patients with burn injuries. In addition, future studies with various populations from other countries are required to evaluate the efficacy of frailty indices measurement in order to strengthen the available evidence.

Investigating oral health among US adults with sleep disorder: a cross-sectional study.

BACKGROUND: This study aims to investigate the relationship between sleep disorders and oral health outcomes among a representative sample of the United States population. METHODS: The study sample comprised 6,161 participants who participated in the NHANES 2017-2018, representing a population of 255,939,599. Oral health outcomes were assessed using the Oral Health Questionnaire (OHQ), covering dental pain, periodontal disease, bone loss, emotional perceptions of oral health, and impact on daily life. Sleep disorders were evaluated using questions related to sleep trouble and daytime sleepiness. RESULTS: Analysis of the NHANES 2017-2018 dataset, revealed notable associations between sleep disorders and oral health outcomes. Individuals with sleep disorders were more likely to report dental pain (19.79% vs. 11.8%), periodontal issues (19.5% vs. 12.25%), and feeling bad or embarrassed about their oral health (21% vs. 12%), compared to those without sleep disorders. Difficulty due to oral health issues was also more prevalent among participants with sleep disorders (32.6% vs. 12.9%). Adjusted models demonstrated that individuals with sleep disorders had a significantly higher likelihood of experiencing oral aches [adjusted odds ratio (aOR) = 1.58 (1.22-2.22)], reporting negative emotions about oral health [aOR = 1.59 (1.06-2.37)], and encountering challenges in school or job performance [aOR = 2.27 (1.47-3.51)], compared to individuals without sleep disorders (refer to Table 3). Other significant covariates affecting oral health outcomes included smoking, income, and education level. CONCLUSIONS: This study reveals a compelling association between sleep disorders and adverse oral health outcomes in the U.S.

Alkalinization Using Sodium Bicarbonate for COVID-19 Treatment: A Systematic Review and Meta-Analysis.

BACKGROUND: A systematic review and meta-analysis have been conducted to evaluate the efficacy of alkalinization for COVID-19 patients based on current evidence to determine the impact of alkalinization on COVID-19 outcomes. METHODS: We searched MEDLINE (Pubmed), Web of Science, Cochrane Library, and Clinicaltrials.gov for studies evaluating the efficacy of alkalinization up to 30 April 2023. Based on the PRISMA 2020 statement criteria a systematic review and meta-analysis of studies were performed. RESULTS: The results of our meta-analysis showed a significant reduction in mortality rate in the alkalinization group compared to controls (RR 0.73, 95% CI: 0.56-0.95; I2 = 0%). However, our subgroup analysis showed no significant improvement in RCT-only studies (RR 0.78, 95% CI: 0.59-1.05; I2 = 0%), the recovery rate was significantly higher in the alkalinization group (RR 2.13, 95% CI: 1.39-3.26; I2 = 0%), duration of recovery also has improved in alkalinization group (SMD 0.76, 95% CI: 0.33-1.18; I2 = 0%). The results of our meta-analysis showed a significant reduction in the duration of hospitalization in the alkalinization group compared to controls with very low certainty of evidence (SMD -0.66, 95% CI: -0.97 to -0.35; I2 = 36%). CONCLUSION: With low certainty of evidence, alkalinization (by sodium bicarbonate) can be an efficient and safe adjuvant treatment for COVID-19 patients. Future randomized controlled trials are needed to strengthen the available evidence.

Adjunctive antidepressants for the treatment of bipolar depression: An updated meta-analysis of randomized clinical trials.

This updated meta-analysis aims to evaluate the efficacy of adjunctive antidepressants in the treatment of bipolar depression. The antidepressant group exhibited a significant increase in response rate (RR: 1.12; 95 % CI 1.01-1.25; p = 0.04; I2 =55 %). The pooled results demonstrated a significant increase in response rate in the antidepressant group (RR: 1.12 95 % CI 1.01-1.25, p = 0.04; I2 =55 %). Depression score was significantly lower in the antidepressant group (SMD: -0.20 95 % CI -0.31 to -0.09, p < 0.001; I2 =14 %). Egger's regression test and funnel plot inspection did not suggest publication bias. Adjunctive antidepressants appear to enhance response rates and reduce depressive scores in bipolar depression, though potential biases and study heterogeneity warrant future randomized trials on this topic.

The effect of psychedelics on the level of brain-derived neurotrophic factor: A systematic review and meta-analysis.

BACKGROUND: Recent interest in the potential therapeutic effects of psychedelics has led to investigations into their influence on molecular signaling pathways within the brain. AIMS: Integrated review and analysis of different studies in this field. METHODS: A systematic search was conducted across international databases including Embase, Scopus, Web of Science, and PubMed from inception to 9 July 2023. Eligibility criteria encompassed published and peer-reviewed studies evaluating changes in brain-derived neurotrophic factor (BDNF) levels after psychedelic consumption. OUTCOMES: A total of nine studies were included in our study. The meta-analysis demonstrated significantly higher BDNF levels in psychedelic consumers compared to healthy controls, with a pooled standardized mean difference of 0.26 (95% CI: 0.10-0.42, I2 = 38.51%, p < 0.001). Leave-one-out analysis indicated robustness in results upon removal of individual psychedelics. No significant publication bias was observed. The results highlight the potential influence of psychedelics on neuroplasticity by altering BDNF levels. CONCLUSIONS: More precisely, the documented rise in BDNF levels indicates a neurobiological mechanism by which psychedelics could enhance synaptic plasticity and foster the growth of neurons. Given the limited data available on this topic, the conclusions remain uncertain. Consequently, we highly recommend additional research with more extensive sample sizes to yield more reliable evidence in this field.

The prevalence of depression, anxiety, and sleep disorder among dental students: A systematic review and meta-analysis.

BACKGROUND: Despite the increasing concern, the literature lacks a comprehensive synthesis of the prevalence of depression, anxiety, and sleep disturbances among dental students. METHODS: We conducted a systematic review following Cochrane Manual for Systematic Reviews of Interventions and PRISMA guidelines. Our search, spanning databases like Medline, Web of Science, and Scopus, covered data until June 5, 2023. A random effect model was utilized for the meta-analysis. RESULTS: From 508 initially identified articles, 45 studies met eligibility criteria. The pooled prevalence of depression, anxiety, and sleep disorders among dental students was estimated as follows: depression [38%, 95% confidence interval (CI): 32%-44%; I2 = 98%], anxiety [48%, 95% CI: 41%-55%; I2 = 97.7%], and sleep disorders [31%, 95% CI: 24%-38%; I2 = 85.7%]. Subgroup analyses based on geographical regions and assessment scales revealed significant between-subgroup differences. Meta-regression identified associations between the prevalence of depression and the year of publication and between the prevalence of anxiety and total sample size, participant age, and year of publication. Publication bias assessments demonstrated a lack of significant bias, strengthening the validity of the findings. CONCLUSIONS: The prevalence of depression, anxiety, and sleep disturbances in dental students is significant. This study highlighted the need for targeted interventions and support systems within dental education to alleviate the mental health challenges students face, ultimately ensuring their well-being and competence as future healthcare providers. Further research should explore the effectiveness of interventions in this population.

Effect of cannabis use on blood levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF): A systematic review and meta-analysis.

BACKGROUND: The impact of cannabis uses on blood levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) remains uncertain, with conflicting findings reported in the literature. BDNF and NGF both are essential proteins for neuron's growth, and their dysregulation is seen in various mental disorders. This study aims to evaluate the relationship between cannabis usage and BDNF and NGF levels due to their potential implications for mental health. METHODS: A comprehensive search of electronic databases was performed using appropriate MeSH terms and keywords. Inclusion criteria comprised human studies investigating the relationship between cannabis use and BDNF and NGF levels. RESULTS: A total of 11 studies met the inclusion criteria and were included. The pooled analysis revealed a nonsignificant association between cannabis use and dysregulated blood levels of BDNF (random-effects model, standardized mean differences [SMD] = .26, 95% CI -.34 to .76, p = .40). The results of our subgroup analysis based on BDNF source showed a nonsignificant between-group difference. For NGF levels, four studies were included, the pooled analysis revealed a nonsignificant association between cannabis use and dysregulated blood levels of NGF (random-effects model, SMD = -.60, 95% CI -1.43 to -.23, p = .16). In both analyses, high heterogeneity was observed among the included studies which is a notable limitation to current meta-analysis. CONCLUSION: This systematic review highlights the need for further research to elucidate the relationship between cannabis use and these neurotrophic factors. A better understanding of these associations can contribute to our knowledge of the neurobiological effects of cannabis and inform potential implications for mental health, cognitive function, and neurodegenerative disorders.

The prevalence of depression, anxiety, and sleep disturbances among medical students and resident physicians in Iran: A systematic review and meta-analysis.

BACKGROUND: We sought to conduct this comprehensive systematic review and meta-analysis to assess the prevalence of depression, anxiety, and sleep disturbance in Iranian medical students and resident physicians. METHODS: A systematic search was conducted on 23 December 2023 in PubMed/MEDLINE, Web of Science, Scopus, and Iranian national databases. We pooled the prevalence of individual studies using the random effect model. RESULTS: Our systematic search showed 36 articles that meet the eligibility criteria. Most included studies were cross-sectional. The most used questionnaire to assess depression, anxiety, and sleep disturbance were Beck Depression Inventory (BDI), The Depression, Anxiety and Stress Scale-21 Items (DASS-21), and The Pittsburgh Sleep Quality Index (PSQI), respectively. The overall prevalence of depression, anxiety, and sleep disturbance among Iranian medical students were 43% (95%CI: 33%-53%%, I2 = 98%), 44% (95%CI: 31%-58%%, I2 = 99%), 48% (95%CI: 39%-56%%, I2 = 97%), respectively. The results of subgroup and meta-regression analyses showed questionnaires used and the place of the medical school were significantly associated with the prevalence of aforementioned outcomes. Funnel plot and Begg's regression test did not show a significant source of funnel plot asymmetry for depression, anxiety, and sleep disturbance. CONCLUSION: In conclusion, our study showed that nearly half of the medical students had some type of depression, anxiety, and sleep disturbance problems. To address this serious national public health issue, efficient preventive measures, routine screenings, and prompt interventions are required.

The Worldwide Prevalence of Herpes Simplex Virus Encephalitis and Meningitis: A Systematic Review and Meta-Analysis.

Given the relatively high frequency of central nervous system infections and considerable mor- tality and morbidity reported to be caused by herpes simplex viruses among the other viral agents, having a clear knowledge about their epidemiological profile seems necessary. This systematic review and meta-analysis aimed to determine the relative frequency and preva- lence of herpes simplex encephalitis and meningitis in patients tested for viral etiologies. A comprehensive systematic review was performed in PubMed, Scopus, and Web of Science databases, searching for studies on the prevalence and relative frequency of herpes sim- plex virus 1 and herpes simplex virus 2 encephalitis and meningitis. Seventy-one studies were included. Overall, the prevalence of herpes simplex virus encephalitis among patients tested was 8% (95% confidence interval, 6%-11%; I2 = 98%) and the prevalence of herpes simplex virus meningitis among aseptic patients tested was 4% (95% confidence interval, 3%-7%; I2 = 95%), and a significant difference was observed by region. The results of our subgroup analysis for herpes simplex virus encephalitis revealed a prevalence of 8% for pediatric patients and ado- lescents and 12% for adults. The results for herpes simplex virus meningitis showed a prevalence of 4% for pediatric patients and adolescents and 9% for adults. We observed significant differ- ences in the frequency of herpes simplex virus 1 and herpes simplex virus 2 detection rates by region. Having high rates of missed cases due to inadequate, highly sensitive paraclinical tests performed on patients with suspected viral central nervous system infection is one of the pos- sible factors. More studies are needed to detect the possible flaws in the process of diagnosis in different regions.

Efficacy of Rituximab on Refractory Organ Involvements in Granulomatosis with Polyangiitis: A Systematic Review of Case Reports.

INTRODUCTION: Granulomatosis with polyangiitis (GPA) is a type of Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) characterized by necrotizing vasculitis affecting small and medium-sized blood vessels. GPA affects various organs, with respiratory tract, vasculitis and glomerulonephritis being the most common triad. Remission induction and maintenance therapy for GPA traditionally involves corticosteroids and cyclophosphamide. However, treatment with rituximab, a monoclonal antibody that depletes B-cells involved in autoimmune disease, has been successful in inducing remission in several studies. The purpose of this systematic review was to investigate the efficacy of rituximab in treating various clinical manifestations of GPA. METHODS: In adherence to PRISMA guidelines for systematic reviews and meta-analyses, we carried out a comprehensive review to investigate the effectiveness of rituximab on particular organ involvement in GPA. We searched three databases (PubMed, Scopus, and Embase) up until November 6, 2022, for case reports on the topic. To ensure all relevant studies were included, we manually screened the first 50 pages of Google Scholar's search results. RESULTS: The review identified a total of 64 case reports and a case series of 113 cases, highlighting the effectiveness of rituximab in treating refractory organ involvement in GPA. The review also analyzed the effectiveness of rituximab in treating ocular, CNS, cardiac, pulmonary, cutaneous, gastrointestinal, renal, and other organ involvements in GPA. CONCLUSIONS: Our results indicated that rituximab can be a promising therapy for treating specific clinical manifestations of several organ involvements. However, more research is needed to determine the long-term efficacy of rituximab in treating GPA.

Herpesviruses reactivation following COVID-19 vaccination: a systematic review and meta-analysis.

BACKGROUND: The reactivation of herpesviruses (HHV) in COVID-19 patients is evident in the literature. Several reports have been published regarding the reactivation of these viruses (HSV, VZV, EBV, and CMV) among those who got COVID-19 vaccines. In this study, we aimed to review the current evidence to assess whether HHVs reactivation has any association with the prior administration of COVID-19 vaccines. METHODS: A systematic search was conducted on 25 September 2022 in PubMed/MEDLINE, Web of Science, and EMBASE. We included all observational studies, case reports, and case series which reported the reactivation of human herpesviruses following administration of COVID-19 vaccines. RESULTS: Our systematic search showed 80 articles that meet the eligibility criteria. Among the evaluated COVID-19 vaccines, most of the vaccines were mRNA based. Evidence from observational studies showed the possible relation between COVID-19 vaccine administration and VZV and HSV reactivation. The results of our proportion meta-analysis showed that the rate of VZV reactivation among those who received the COVID-19 vaccine was 14 persons per 1000 vaccinations (95% CI 2.97-32.80). Moreover, our meta-analysis for HSV reactivation showed the rate of 16 persons per 1000 vaccinations (95% CI 1.06-46.4). Furthermore, the evidence from case reports/series showed 149 cases of HHV reactivation. There were several vaccines that caused reactivation including BNT162b2 mRNA or Pfizer-BioNTech (n = 76), Oxford-AstraZeneca (n = 22), mRNA-1273 or Moderna (n = 17), Sinovac (n = 4), BBIBP-CorV or Sinopharm (n = 3), Covaxin (n = 3), Covishield (n = 3), and Johnson and Johnson (n = 1). Reactivated HHVs included varicella-zoster virus (VZV) (n = 114), cytomegalovirus (CMV) (n = 15), herpes simplex virus (HSV) (n = 14), Epstein-Barr virus (EBV) (n = 6), and HHV-6 (n = 2). Most cases reported their disease after the first dose of the vaccine. Many patients reported having comorbidities, of which hypertension, diabetes mellitus, dyslipidemia, chicken pox, and atrial fibrillation were common. CONCLUSION: In conclusion, our study showed the possible association between COVID-19 vaccination and herpesvirus reactivation. The evidence for VZV and HSV was supported by observational studies. However, regarding other herpesviruses (EBV and CMV), further research especially from observational studies and clinical trials is required to elucidate the interaction between COVID-19 vaccination and their reactivation.