Post-acute midterm follow-up cardiac MRI findings and clinical outcomes in patients with COVID-19 vaccine-associated myocarditis: a comprehensive systematic review and meta-analysis.

PURPOSE: Although previous investigations revealed favourable in-hospital outcomes of COVID-19 vaccine-related myocarditis, the mid-term prognosis is still unclear. Hence, we aim to summarise existing evidence on the follow-up imaging and clinical findings in patients with COVID-19 vaccine-related myocarditis. METHODS: We performed a systematic search in online databases using relevant key terms covering COVID-19 vaccine, myocarditis, follow-up, and cardiac MRI. We included all observational studies that reported cardiac MRI findings of patients with myocarditis following COVID-19 vaccination in both acute and follow-up phases. Data on clinical outcomes and cardiac MRI findings were extracted and pooled using a random-effect model. RESULTS: A total of 27 studies (126 patients) met our eligibility criteria. At the time of follow-up, myocarditis symptoms were resolved in all patients, but abnormal electrocardiography and elevated troponin levels were detected in 18.7% and 3.8% of them, respectively. Median imaging follow-up times varied from 3 to 6.3 months. On follow-up cardiac MRI, the persistence of LGE was observed in 76% (95%CI: 62 to 85%), but its extension declined compared to the baseline in almost all patients. Persistent LGE was accompanied by myocardial edoema in six patients, and it was consistent with myocardial fibrosis (LGE without edoema) in the remaining cases. Mean changes (95%CI) of cardiac MRI left ventricular ejection fraction (LVEF) (%) was +2.97 (+1.59 to +4.34) from baseline. CONCLUSION: In conclusion, although most patients likely experience favourable clinical outcomes without serious complications, cardiac MRI abnormalities, mainly LGE, may persist in a notable proportion of them beyond the acute phase.

The impact of vegetarian diet on sperm quality, sex hormone levels and fertility: a systematic review and meta-analysis.

BACKGROUND: An increasing number of people have adhered to a vegetarian diet for several years. Nowadays, the favourable effect of this dietary pattern on metabolic diseases is well established, but its impact on fertility and reproductive health as a serious health concern is not clear yet. Therefore, we aim to summarise existing evidence regarding the possible association between a vegetarian diet and fertility as measured by key indicators such as sperm quality and sex hormone levels. METHODS: We systematically searched online databases, including PubMed, ISI, Scopus and Google Scholar, up to 1 December 2022 using relevant keywords. We included observational studies that compared semen quality, sex hormone levels and infertility in people who adhered to a vegetarian diet versus an omnivore diet. Heterogeneity between studies was assessed using I2 and Q tests. Standardised mean differences (SMD) using a random/fixed model were calculated to assess outcomes between vegetarians and omnivores in included articles. RESULTS: Finally, out of 972 documents that were retrieved, 20 articles met our inclusion criteria, and 16 were eligible for quantitative synthesis. Results of meta-analyses showed that there were no significant differences between vegetarians and omnivores in terms of semen quality parameters, including total sperm count, total and progressive sperm motility, sperm morphology and sperm concentration. Seven studies on female sex hormone profiles were eligible for meta-analysis. The only significant difference was the lower level of plasma oestrone in vegetarians (pooled SMD: -0.56; 95% confidence interval [CI]: -1.08, -0.05; p-value = 0.03) compared to omnivores. Furthermore, our meta-analysis revealed significantly higher sex-hormone-binding globulin levels in vegetarian men than in omnivores (pooled SMD: 0.52; 95% CI: 0.18, 0.86; p-value = 0.002). CONCLUSION: Despite the numerous health benefits of a vegetarian diet, our review suggested that there were no conclusive positive or negative associations between vegetarian diet and semen quality, sex hormone levels and infertility. Further studies are recommended to better understand vegetarian dietary pattern effect on infertility and reproductive health.

Neuromuscular diseases associated with COVID-19 vaccines: a systematic review and pooled analysis of 258 patients.

BACKGROUND: Neuromuscular diseases (NMD) emerged as one of the main side effects of the COVID-19 vaccination. We pooled and summarized the evidence on the clinical features and outcomes of NMD associated with COVID-19 vaccination. METHODS: We comprehensively searched three databases, Medline, Embase, and Scopus, using the key terms covering "Neuromuscular disease" AND "COVID-19 vaccine", and pooled the individual patient data extracted from the included studies. RESULTS: A total of 258 NMD cases following COVID-19 have been reported globally, of which 171 cases were Guillain-Barré syndrome (GBS), 40 Parsonage-Turner syndrome (PTS), 22 Myasthenia Gravis (MG), 19 facial nerve palsy (FNP), 5 single fiber neuropathy, and 1 Tolosa-Hunt syndrome. All (100%) SFN patients and 58% of FNP patients were female; in the remaining NMDs, patients were predominantly male, including MG (82%), GBS (63%), and PTS (62.5%). The median time from vaccine to symptom was less than 2 weeks in all groups. Symptoms mainly appeared following the first dose of vector vaccine, but there was no specific pattern for mRNA-based. CONCLUSION: COVID-19 vaccines might induce some NMDs, mainly in adults. The age distribution and gender characteristics of affected patients may differ based on the NMD type. About two-thirds of the cases probably occur less than 2 weeks after vaccination.

Clinical features and outcomes of Myasthenia Gravis associated with COVID-19 vaccines: A systematic review and pooled analysis.

BACKGROUNDS: Myasthenia Gravis (MG), a chronic neuromuscular junction disorder, emerged as one of the serious side effects of the Coronavirus Disease 2019 (COVID-19) vaccination. We aimed to summarize the findings of studies on the clinical features and outcomes of COVID-19 vaccination-associated MG. METHODS: We performed a systematic search on 3 databases, Medline, Embase, and Scopus, using the query "COVID-19 vaccine" and "Myasthenia Gravis." Patients' data, including clinical data, MG subtype, vaccine type, and vaccine dose number, were extracted from the eligible studies. RESULTS: A total of 20 COVID-19 vaccination-related MGs have been reported worldwide. The median (interquartile range) age was 64 (51, 75) years; 85% (17/20) of them were male, and 70% (14/20) of patients had received messenger RNA-based vaccines. The most common symptoms, in order of frequency, were binocular diplopia (8/11) and ptosis (4/11); the median (interquartile range) time from vaccine to MG symptoms was 6 (2, 7.5) days. Repetitive nerve stimulation showed abnormal decrement in 85% (11/13) of patients, and all 4 patients getting single-fiber electromyography showed an abnormal finding. Nine out of twelve patients with data on clinical outcomes experienced partial/complete improvement of symptoms within 1 month. CONCLUSION: MG cases after the COVID-19 vaccine are more likely to occur among males and adults older than 50 years. Our pooled cohort data suggest MG symptoms appear within 2 weeks after receiving the vaccine. The presenting symptoms in MG cases associated with COVID-19 vaccine are possibly similar to non-vaccination related MGs. Most patients are expected to experience partial/complete improvement within 1 month.

Clinicopathological and prognostic value of lncRNA TPT1-AS1 in cancer: A systematic review study and meta-analysis.

INTRODUCTION: Aberrant expression of lncRNAs in cancer cells can impact their key phenotypes. We aimed to summarize available evidence on clinicopathological and prognostic value of lncRNA TPT1-AS1 in cancer. METHODS: A systematic search was performed on Medline and Embase databases using relevant key terms covering lncRNA TPT1-AS1, cancer, and clinical outcomes. The effect size estimates and their 95 % confidence interval (CI) were pooled using random-effects models. Meta- analyses were conducted using STATA 16.0 software. RESULTS: Seventeen articles met our eligibility criteria. Tumor tissue compared to normal tissue showed increased level of lncRNA TPT1-AS1 expression (pooled standardized mean difference (95 % CI): 0.65 (0.52-0.79)). Overexpression of this lncRNA was a significant predictor for poor prognosis (Pooled log-rank test P-value < 0.001); in patients with high-level of lncRNA TPT1-AS1, the risk of death at five years was 1.40 times greater than their counterparts. The pooled Odds ratios for association lncRNA TPT1-AS1 with tumor stage, tumor size, and lymph node metastasis were 1.94 (95 % CI: 0.90-4.19, 8 studies, I2 = 79.6 %), 2.33 (95 % CI: 1.31-4.14, 5 studies, I2 = 40.0 %), and 1.89 (95 % CI: 1.08-3.36, 5 studies, I2 = 61.7 %), respectively. Regarding the identified potential mechanisms, lncRNA TPT1-AS1 plays a role in cancer growth mainly by sponging miRNAs and regulating their downstream targets or controlling the expression of key cell cycle regulators. CONCLUSION: In cancer patients, elevated expression of lncRNA TPT1-AS1 might be associated with a shorter Overall Survival, advanced stages, larger tumor size, and lymph node metastasis.

A Novel Exon 2 Deletion Mutation in the GRXCR1 Gene Associated With Non-Syndromic Hearing Loss: A Case Report and Review of Literatures.

BACKGROUND: About 80% of congenital hearing loss cases have genetic causes, often autosomal recessive and non-syndromic. Autosomal Recessive Non-syndromic hearing loss is characterized by extreme genetic heterogeneity. OBJECTIVES: To report a case of congenital hearing loss with novel homozygous deletion in GRXCR1 gene. METHODS: Case reports and review of literatures. RESULTS: In this study, the proband was a 32-year-old woman seeking pre-marriage genetic counseling with non-syndromic congenital hearing loss. An owing negative test for GJB2 mutations, she underwent exome sequencing, unveiling a novel homozygous exon 2 deletion of the GRXCR1 gene. This mutation was confirmed in her affected mother and sibling by PCR and Quantitative Real-Time PCR. CONCLUSION: We identified a novel GRXCR1 gene mutation related to congenital hearing loss in a family. Our study highlights the efficiency of exome sequencing in discovering gene mutations in cases of diseases with genetic heterogeneity.

COVID-19 Associated Fulminant Myocarditis in a Fully-Vaccinated Female: A Case Report with Clinical Follow-up.

Background: Myocarditis is considered a serious adverse event after COVID-19 infection. The risk and severity of myocarditis after COVID-19 disease decreased significantly in the vaccinated population. We present a case of cardiac magnetic resonance proven fulminant myocarditis following COVID-19 disease in a young female who was previously vaccinated with 2 doses of the BIBP (Sinopharm) vaccine. Case summary: A 29-year-old female was referred to the hospital with acute chest pain, dyspnea, and nausea. Her electrocardiogram revealed ST-segment elevation in anterolateral leads with reciprocal changes in inferior leads. She was primarily diagnosed with ST-elevation myocardial infarction following spontaneous coronary artery dissection (SCAD) according to her age and gender. Her coronary angiography was normal. RT-PCR nasopharyngeal swab was positive for SARS-COV-2 infection. According to her history and excluding coronary artery diseases, she was clinically diagnosed with myocarditis and received corticosteroids, IVIG, and colchicine. She was discharged in a favorable condition after 11 days of hospitalization. Cardiac magnetic resonance imaging confirmed the diagnosis of myocarditis according to the updated lake Louise criteria. On her 4-month follow-up, she was asymptomatic, and her echocardiography showed improvement in biventricular function. Discussion: The diagnosis of myocarditis caused by COVID-19 infection may be challenging as the symptoms of myocarditis, and COVID-19 disease may overlap. It should be considered when patients have acute chest pain, palpitation, elevated cardiac biomarkers, and new abnormalities in ECG or echocardiography. Cardiac MRI is a non-invasive gold standard modality for diagnosing and follow-up of myocarditis and should be used in clinically suspected myocarditis. The long-term course of myocarditis following COVID-19 disease is still unclear, but some evidence suggests it may have a favorable mid-term outcome.

Efficacy and safety of intracoronary epinephrine for the management of the no-reflow phenomenon following percutaneous coronary interventions: a systematic-review study.

BACKGROUND: Currently, no pharmacological or device-based intervention has been fully proven to reverse the no-reflow phenomenon. OBJECTIVES: To assess the efficacy and safety of intracoronary (IC) epinephrine in the management of no-reflow phenomenon following percutaneous coronary intervention (PCI), either as first-line treatment or after the failure of conventional agents. DESIGN: Systematic review. DATA SOURCES AND METHODS: PubMed and Scopus databases were systematically searched up to 28 May 2022, with additional manual search on the Google Scholar and review of the reference lists of the relevant studies to identify all published studies. Cohort studies, case series, and interventional studies written in English which evaluated the efficacy and safety of IC epinephrine in patients with no-flow phenomenon were included in our review. RESULTS: Six of the 646 articles identified in the initial search met our inclusion criteria. IC epinephrine was used either as a first-line treatment [two randomized clinical trials (RCTs)] or after the failure of conventional agents (two cohort studies and two case series) for restoring the coronary flow, mainly after primary PCI. As first-line therapy, IC epinephrine successfully restored coronary flow in over 90% of patients in both RCTs, which significantly outperformed IC adenosine (78%) but lagged behind combination of verapamil and tirofiban (100%) in this regard. In the refractory no-flow phenomenon, successful reperfusion [thrombolysis in myocardial infarction (TIMI) flow grade = 3] was achieved in three out of four patients after the administration of IC epinephrine based on the results from both case series. Their findings were confirmed by a recent cohort study that further compared IC epinephrine with IC adenosine and found significant differences between them in terms of efficacy [% TIMI flow grade 3: (69.1% versus 52.7%, respectively; p value = 0.04)] and 1-year major adverse cardiac event (MACE) outcomes (11.3% versus 26.7%, respectively; p value ⩽ 0.01). Overall, malignant ventricular arrhythmias were reported in none of the patients treated with IC epinephrine. CONCLUSION: Results from available evidence suggest that IC epinephrine might be an effective and safe agent in managing the no-reflow phenomenon.

The role of lncRNA CERS6-AS1 in cancer and its molecular mechanisms: A systematic review and meta-analysis.

BACKGROUND: LncRNAs have the potential to play a regulatory role in different processes of cancer development and progression. We conducted a systematic review and meta-analysis of evidence on the clinical significance and prognostic value of lncRNA CERS6-AS1 in cancer. METHODS: This systematic review was conducted following PRISMA guidelines. Medline and Embase databases were searched using the relevant key terms covering lncRNA CERS6-AS1 and cancer. We pooled the estimated effect sizes and their 95 % confidence interval (CI) using random-effects models in STATA 16.0 (StataCorp, College Station, TX, USA). RESULTS: Eleven articles on pancreatic, colorectal, gastric, papillary thyroid, breast, and hepatocellular cancers fulfilled our eligibility criteria. Studies consistently found that lncRNA CERS6-AS1 expression is upregulated in all assessed cancers. Based on our meta-analysis, its aberrant expression was directly associated with unfavorable clinical outcomes, including higher stage (pooled Odds ratios (95 % CI): 3.15 (2.01-4.93; I2 = 0.0 %), tumor size (1.97 (1.27-3.05; I2 = 37.8 %), lymph node metastasis (6.48 (4.01-10.45; I2 = 0.40 %), and poor survival (Pooled log-rank test P-value < 0.001) in patients. Regarding potential mechanisms, functional studies revealed that LncRNA CERS6-AS1 is involved in cancer growth mainly by sponging miRNAs and regulating their downstream targets. CONCLUSION: Available evidence suggests that LncRNA CERS6-AS1 is upregulated in different cancers and has an oncogenic role. LncRNA CERS6-AS1 expression level might predict cancer prognosis, highlighting its potential application as a prognostic biomarker for cancer.

Utility of electrocardiogram to predict the occurrence of the no-reflow phenomenon in patients undergoing primary percutaneous coronary intervention (PPCI): a systematic review and meta-analysis.

Background: The no-reflow phenomenon affects about one out of five patients undergoing Primary Percutaneous Coronary Intervention (PPCI). As the prolonged no-reflow phenomenon is linked with unfavorable outcomes, making early recognition is crucial for effective management and improved clinical outcomes in these patients. Our review study aimed to determine whether electrocardiogram (ECG) findings before PCI could serve as predictors for the occurrence of the no-reflow phenomenon. Methods and materials: We systematically searched MEDLINE, Scopus, and Embase to identify relevant studies. The random-effect model using inverse variance and Mantel-Haenszel methods were used to pool the standardized mean differences (SMD) and odds ratios (OR), respectively. Result: Sixteen eligible articles (1,473 cases and 4,264 controls) were included in this study. Based on our meta-analysis of baseline ECG findings, the no-reflow group compared to the control group significantly had a higher frequency of fragmented QRS complexes (fQRS) (OR (95% CI): 1.35 (0.32-2.38), P-value = 0.01), and Q-waves (OR (95% CI): 1.97 (1.01-2.94), P-value <0.001). Also, a longer QRS duration (QRSD) (SMD (95% CI): 0.72 (0.21, 1.23), p-value <0.001) and R wave peak time (RWPT) (SMD (95% CI): 1.36 (0.8, 1.93), P < 0.001) were seen in the no-reflow group. The two groups had no significant difference regarding P wave peak time (PWPT), and P wave maximum duration (Pmax) on baseline ECG. Conclusion: Our findings suggest that prolonged QRSD, delayed RWPT, higher fQRS prevalence, and the presence of a Q wave on baseline ECG may predict the occurrence of the no-reflow phenomenon in patients undergoing PPCI.

Autoimmunity in monogenic combined immune deficiencies with associated or syndromic features.

Background: Combined immune deficiencies (CIDs) with associated or syndromic features are a highly heterogeneous subgroup of inherited immune disorders. These patients represent specific clinical complications with an increased risk of autoimmune conditions. Methods: We analyzed data of monogenic patients with syndromic CIDs adopted from the Iranian inborn errors of immunity registry up to January 2022. A comprehensive comparison in terms of demographic, clinical, and immunological features was performed between patients with and without autoimmunity and also among four mutation groups with the most registered cases including ATM, STAT3 (AD-LOF), DNMT3B/ZBTB24, and WAS mutations. Results: A total of 137 patients with monogenic syndromic CIDs were included. Most commonly mutated genes were the ATM [80 (58.4%)] and STAT3 (AD-LOF) [19 (13.9%)], followed by DNMT3B [11 (8%)], and WAS [11 (8%)]. More than 18% of all patients with syndromic CIDs, including most DNMT3B/ZBTB24 mutations patients, were clinically diagnosed with antibody deficiencies before genetic evaluation. Patients with ATM and WAS mutations had the latest age of onset and the lowest age of diagnosis, respectively. Autoimmune disorders were diagnosed in 24 patients at a median age of 3.5 (2.6-6.0) years, 70.6% of which were diagnosed prior to the diagnosis of immunodeficiency. Lymphoproliferation, particularly hepatosplenomegaly, was significantly higher in patients with autoimmunity (p=0.004). Syndromic CID patients with autoimmunity had significantly lower IgG levels. Hematologic autoimmunity mainly immune thrombocytopenic purpura was the most frequent autoimmunity among major groups of ATM, STAT3 (AD-LOF), DNMT3B/ZBTB24, and WAS mutations, however ATM-mutated patients present more diversified involved organs including rheumatologic, gastrointestinal and dermatologic autoimmunity. Conclusion: About 18% of patients with monogenic syndromic CIDs developed autoimmunity, mainly in the form of hematological immune diseases. Autoimmunity could be an early-onset involvement with a potential diagnostic impact on suspicious cases of syndromic CIDs.

Cardiac MRI Findings in COVID-19 Vaccine-Related Myocarditis: A Pooled Analysis of 468 Patients.

Understanding the pattern and severity of myocarditis caused by the coronavirus disease 2019 (COVID-19) vaccine is imperative for improving the care of the patients, and cardiac evaluation by MRI plays a key role in this regard. Our systematic review and meta-analysis aimed to summarize cardiac MRI findings in COVID-19 vaccine-related myocarditis. We performed a comprehensive systematic review of literature in PubMed, Scopus, and Google Scholar databases using key terms covering COVID-19 vaccine, myocarditis, and cardiac MRI. Individual-level patient data (IPD) and aggregated-level data (AD) studies were pooled through a two-stage analysis method. For this purpose, all IPD were first gathered into a single data set and reduced to AD, and then this AD (from IPD studies) was pooled with existing AD (from the AD studies) using fixed/random effect models. I2 was used to assess the degree of heterogeneity, and the prespecified level of statistical significance (P value for heterogeneity) was <0.1. Based on meta-analysis of 102 studies (n = 468 patients), 79% (95% confidence interval [CI]: 54%-97%) of patients fulfilled Lake Louise criteria (LLC) for diagnosis of myocarditis. Cardiac MRI abnormalities included elevated T2 in 72% (95% CI: 50%-90%), myocardial late gadolinium enhancement (LGE) in 93% (95% CI: 83%-99%; nearly all with a subepicardial and/or midwall pattern), impaired left ventricular ejection fraction (LVEF) (<50%) in 4% (95% CI: 1.0%-9.0%). Moreover, elevated T1 and extracellular volume fraction (ECV) (>30), reported only by some IPD studies, were detected in 74.5% (76/102) and 32% (16/50) of patients, respectively. In conclusion, our findings may suggest that over two-thirds of patients with clinically suspected myocarditis following COVID-19 vaccination meet the LLC. COVID-19 vaccine-associated myocarditis may show a similar pattern compared to other acute myocarditis entities. Notably, preserved LVEF is probably a common finding in these patients. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 3.