Diagnostic accuracy of ESR1 mutation detection by cell-free DNA in breast cancer: a systematic review and meta-analysis of diagnostic test accuracy.

BACKGROUND: Estrogen receptors express in nearly 70% of breast cancers (ER-positive). Estrogen receptor alpha plays a fundamental role as a significant factor in breast cancer progression for the early selection of therapeutic approaches. Accordingly, there has been a surge of attention to non-invasive techniques, including circulating Cell-free DNA (ccfDNA) or Cell-Free DNA (cfDNA), to detect and track ESR1 genotype. Therefore, this study aimed to examine the diagnosis accuracy of ESR1 mutation detection by cell-free DNA in breast cancer patientsthrough a systematic review and comprehensive meta-analysis. METHODS: PubMed, Embase, and Web of Science databases were searched up to 6 April 2022. Diagnostic studies on ESR1 measurement by cfDNA, which was confirmed using the tumour tissue biopsy, have been included in the study. The sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were considered to analyse the data. RESULTS: Out of 649 papers, 13 papers with 15 cohorts, including 389 participants, entered the meta-analyses. The comprehensive meta-analysis indicated a high sensitivity (75.52, 95% CI 60.19-90.85), specificity (88.20, 95% CI 80.99-95.40), and high accuracy of 88.96 (95% CI 83.23-94.69) for plasma ESR1. We also found a moderate PPV of 56.94 (95% CI 41.70-72.18) but a high NPV of 88.53 (95% CI 82.61-94.44). We also found an NLR of 0.443 (95% CI 0.09-0.79) and PLR of 1.60 (95% CI 1.20-1.99). CONCLUSION: This systematic review and comprehensive meta-analysis reveal that plasma cfDNA testing exhibits high sensitivity and specificity in detecting ESR1 mutations in breast cancer patients. This suggests that the test could be a valuable diagnostic tool. It may serve as a dependable and non-invasive technique for identifying ESR1 mutations in breast cancer patients. However, more extensive research is needed to confirm its prognostic value.

Morphological evaluation of maxillary arch in unilateral buccally and palatally impacted canines: a cone-beam computed tomography (CBCT)-based study in Northern Iran.

Purpose: This study investigated the association between the maxillary impacted canines' position and the maxilla's morphological features in an Iranian population based on cone-beam computed tomography (CBCT) images. Material and methods: In this cross-sectional descriptive-analytical study, 47 CBCT images of unilateral buccally impacted maxillary canines and 47 CBCT images of unilateral palatally impacted maxillary canines were examined. Several morphological variables were compared between the impacted and non-impacted sides, and between the buccal and palatal impaction types. Results: Gender and age were not significantly associated with the canine impaction type. The alveolar bone height at the impacted side was significantly greater in the buccally impacted group than in the palatally impacted group (p = 0.016). In a comparison of the impacted and non-impacted sides, all variables of alveolar bone thickness at depth of 2 mm, maxillary arch width, and palatal volume had significantly smaller values in the impacted side in both buccally and palatally impacted groups (p < 0.05). The alveolar bone was significantly thicker at the depth of 10 mm in the impacted side of the buccal group (p = 0.024). The maxillary arch perimeter was significantly smaller in the impacted side of the buccal group (p = 0.008). The palatal depth did not significantly differ between the groups. Conclusion: Among the studied variables, the alveolar bone thickness showed contrary results at different depths. The palatal volume and maxillary arch width were significantly smaller on the impacted side in both buccal and palatal groups, and the arch perimeter showed the same results only in the buccal group.

Opium use and risk of lung cancer: A multicenter case-control study in Iran.

Opium use was recently classified as a human carcinogen for lung cancer by the International Agency for Research on Cancer. We conducted a large, multicenter case-control study evaluating the association between opium use and the risk of lung cancer. We recruited 627 cases and 3477 controls from May 2017 to July 2020. We used unconditional logistic regression analyses to estimate the odds ratios (OR) and 95% confidence intervals (CI) and measured the association between opium use and the risk of lung cancer. The ORs were adjusted for the residential place, age, gender, socioeconomic status, cigarettes, and water pipe smoking. We found a 3.6-fold risk of lung cancer for regular opium users compared to never users (95% CI: 2.9, 4.6). There was a strong dose-response association between a cumulative count of opium use and lung cancer risk. The OR for regular opium use was higher for small cell carcinoma than in other histology (8.3, 95% CI: 4.8, 14.4). The OR of developing lung cancer among opium users was higher in females (7.4, 95% CI: 3.8, 14.5) than in males (3.3, 95% CI: 2.6, 4.2). The OR for users of both opium and tobacco was 13.4 (95% CI: 10.2, 17.7) compared to nonusers of anything. The risk of developing lung cancer is higher in regular opium users, and these results strengthen the conclusions on the carcinogenicity of opium. The association is stronger for small cell carcinoma cases than in other histology.

Opium use and risk of colorectal cancer: a multi-center case-referent study in Iran.

BACKGROUND: Opium use has been associated with an increased risk of cancers of the lung, oesophagus, and pancreas, and it was recently classified by the International Agency for Cancer Research as carcinogenic to humans. It is not clear whether opium also increases the risk of colorectal cancer (CRC). The aim of our study was to assess the association between various metrics of opium use and the risk of CRC. METHODS: This case-referent study from seven provinces in Iran comprised 848 CRC cases and 3215 referents. Data on opium use (duration, amount, frequency) and potential confounders were collected by trained interviewers. Multivariable unconditional logistic regression models were used to measure odds ratios (OR) adjusted for age, gender, province, marital status, family history of CRC-linked cancers, consumption of red meat, fruits and vegetables, body shape, occupational physical activity, and socioeconomic status. RESULTS: Regular opium consumption was not associated with the risk of CRC (OR 0.9, 95% confidence interval, CI: 0.7, 1.2) compared to subjects who never used opium. However, frequent opium use more than twice a day was associated with an increased risk of CRC compared to non-users of opium (OR: 2.0, 95% CI: 1.1, 3.8; p for quadratic trend 0.008). CONCLUSION: There seems to be no overall association between opium use and CRC, but the risk of CRC might be increased among persons who use opium many times a day.

Melatonin effects on sleep quality and outcomes of COVID-19 patients: An open-label, randomized, controlled trial.

This trial aims to evaluate the effectiveness of adding melatonin to the treatment protocol of hospitalized coronavirus disease 2019 (COVID-19) patients. This was an open-label, randomized controlled clinical trial in hospitalized COVID-19 patients. Patients were randomized into a treatment arm receiving melatonin plus standard care or a control arm receiving standard care alone. The trial's primary endpoint was sleep quality examined by the Leeds Sleep Evaluation Questionnaire (LSEQ). The trial's secondary endpoints were symptoms alleviation by Day 7, intensive care unit admission, 10-day mortality, white blood cell count, lymphocyte count, C-reactive protein status, and peripheral capillary oxygen saturation. Ninety-six patients were recruited and allocated to either the melatonin arm (n = 48) or control arm (n = 48). Baseline characteristics were similar across treatment arms. There was no significant difference in symptoms on Day 7. The mean of the LSEQ scores was significantly higher in the melatonin group (p < 0.001). There was no significant difference in laboratory data, except for blood oxygen saturation, which has improved significantly in the melatonin group compared with the control group (95.81% vs. 93.65% respectively, p = 0.003). This clinical trial study showed that the combination of oral melatonin tablets and standard treatment could substantially improve sleep quality and blood oxygen saturation in hospitalized COVID-19 patients.

The effect of immunomodulatory properties of naringenin on the inhibition of inflammation and oxidative stress in autoimmune disease models: a systematic review and meta-analysis of preclinical evidence.

BACKGROUND/OBJECTIVE: Naringenin is a member of the flavonoid family that can perform many biological processes to treat a wide range of inflammatory diseases and pathological conditions related to oxidative stress (OS). Naringenin immunomodulatory activities have been the subject of recent research as an effective alternative treatment for autoimmune disorders. The effects of naringenin on the levels of inflammatory biomarkers and OS factors in animal models of autoimmune disorders (ADs) were studied in this meta-analysis. METHODS: Up until January 2022, electronic databases such as Cochrane Library and EMBASE, PubMed, Web of Science, and Scopus were used to conduct a comprehensive literature search in English language. To evaluate the effect of naringenin on inflammatory mediators, such as TNF-α, IL-6, IL-ß, IFN-γ, NF-κB, and nitric oxide, and OS biomarkers, such as CAT, SOD, GPx, GSH and MDA, in AD models, we measured the quality assessment and heterogeneity test using the PRISMA checklist protocol and I2 statistic, respectively. A random-effects model was employed based on the heterogeneity test, and then pooled data were standardized as mean difference (SMD) with a 95% confident interval (CI). RESULTS: We excluded all clinical trials, cell experiment studies, animal studies with different parameters, non-autoimmune disease models, and an inadequate series of studies for quantitative synthesis. Finally, from 627 potentially reports, 12 eligible studies were included in the meta-analysis. Data were collected from several groups. Of these, 153 were in the naringenin group and 149 were in the control group. Our meta-analysis of the pooled data for the parameters of inflammation and OS indicated that naringenin significantly reduced the levels of NF-κB (SMD - 3.77, 95% CI [- 6.03 to - 1.51]; I2 = 80.1%, p = 0.002), IFN-γ (SMD - 6.18, 95% CI [- 8.73 to - 3.62]; I2 = 53.7%, p = 0.115), and NO (SMD - 3.97, 95% CI [- 5.50 to - 2.45]; I2 = 73.4%, p = 0.005), IL-1ß (SMD - 4.23, 95% CI [- 5.09 to - 3.37]; I2 = 0.0%, p = 0.462), IL-6 (SMD - 5.84, 95% CI [- 7.83 to - 3.85]; I2 = 86.5%, p < 0.001), and TNF-α (SMD - 5.10, 95% CI [- 6.34 to - 3.86]; I2 = 74.7%, p < 0.001). These findings also demonstrated the efficacy of naringenin on increasing the levels of CAT (SMD 4.19, 95% CI [1.33 to 7.06]; I2 = 79.9%, p = 0.007), GSH (SMD 4.58, 95% CI [1.64 to 7.51]; I2 = 90.5%, p < 0.001), and GPx (SMD 9.65, 95% CI [2.56 to 16.74]; I2 = 86.6%, p = 0.001) and decreasing the levels of MDA (SMD - 3.65, 95% CI [- 4.80 to - 2.51]; I2 = 69.4%, p = 0.001) than control groups. However, treatment with naringenin showed no statistically difference in SOD activity (SMD 1.89, 95% CI [- 1.11 to 4.89]; I2 = 93.6%, p < 0.001). CONCLUSION: Overall, our findings revealed the immunomodulatory potential of naringenin as an alternative treatment on inhibition of inflammation and OS in several autoimmune-related diseases. Nevertheless, regarding the limitation of clinical trials, strong preclinical models and clinical settings in the future are needed that address the effects of naringenin on ADs. Before large-scale clinical studies, precise human pharmacokinetic investigations are required to determine the dosage ranges and evaluate the initial safety profile of naringenin.

TFF1 gene single nucleotide polymorphism (rs3761376) and colorectal cancer risk.

INTRODUCTION: Trefoil Factor 1 (TFF1) is a secretory peptide with gastrointestinal protective functions. Abnormal TFF1 expression is reported in some cancers and functional promoter polymorphism in TFF1 is believed to be associated with risk of gastric cancer. We evaluated rs3761376 in a sample of Iranian patients with colorectal cancer. METHODS: Peripheral blood samples were taken from pathology confirmed cases of colorectal cancer and healthy volunteers. Genotyping was carried out using Restriction Fragment Length Polymorphism (RFLP) PCR. Any association with clinicopathologic data was assessed by SPSS version 19. RESULTS: A total of 245 participants, including 122 patients with cancer and 123 non-cancer subjects were enrolled. Age, body mass index, and smoking habits were not significantly different between the two groups (P > 0.05). Distribution of TFF1 genotypes was not found to be associated with colorectal cancer. However, distant metastasis was more prevalent in carriers of the mutant allele. CONCLUSION: TFF1 rs3761376 was not associated with colorectal cancer but it may be involved in metastasis. Therefore, further investigation is warranted to determine this relationship.

Pyridoxine for treatment of levetiracetam-induced behavioral adverse events: A randomized double-blind placebo-controlled trial.

BACKGROUND: Levetiracetam is a broad-spectrum antiseizure medication with known behavioral side effects. The possible beneficial effect of pyridoxine on improvement of these psychiatric problems has been suggested in few previous studies. This clinical trial aimed to investigate the effect of pyridoxine on behavioral side effects of levetiracetam in adult patients with epilepsy. METHODS: This study was a randomized double-blind placebo-controlled clinical trial on 53 adult patients with epilepsy with behavioral side effects after treatment by levetiracetam. Patients who met the study criteria were randomized to receive 40 mg/day pyridoxine or placebo. Their psychiatric state was surveyed by SCL-90-R questionnaire before and three weeks after initiation of treatment. RESULTS: There were no statistically significant differences in the behavioral adverse effects between the pyridoxine-treated group and the placebo group. CONCLUSION: Although this study showed no statistically significant beneficial effects of pyridoxine on the behavioral adverse effects of levetiracetam, placebo-controlled trials with a larger size and higher doses are needed to determine whether it is effective or not.

Immune-related adverse events (irAEs) in ankylosing spondylitis (AS) patients treated with interleukin (IL)-17 inhibitors: a systematic review and meta-analysis.

BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease characterized by immune system dysregulation and inflammation in the joints. Interleukin (IL)-17 inhibitors are new biological drugs used to treat AS. In this study, we aimed to assess the risk of immune system-related AEs due to targeting IL-17 or IL-17R. METHODS: The CENTRAL, PubMed, Scopus, Google Scholar, Clinical Trials Registry, and ICTRP were searched for randomized clinical trials (RCTs) and non-RCTs until February 2021. The risk of irAEs in patients treated with IL-17 inhibitors compared to the placebo or a drug-free control was evaluated. In studies that reported AEs of the IL-17 inhibitors at several different time points, we compared the number of cases/100 patient-year in which irAEs were reported. Subgroup analyses were also performed based on the dose and type of drugs. RESULTS: Thirteen studies of 1848 AS patients treated by IL-17 inhibitors (secukinumab, ixekizumab, bimekizumab, and netakimab) and 764 participants who received a placebo were included. The risk of some AEs related to immune function in patients under IL-17 inhibitors treatment was significantly higher than that of the placebo group, including infection and infestation (risk difference RD = 0.09, P = 0.02), nasopharyngitis (RD = 0.04, P < 0.001), opportunistic infections (RD = 0.01, P = 0.04), and neutropenia (RD = 0.04, P = 0.03). Besides, the results of the Cochran Q test showed that there were significant differences between the occurrence of some AEs over time, including infection and infestations (p < 0.001, RCTs), upper respiratory tract infections (p < 0.001, non-RCTs), urinary tract infections (p < 0.001, non-RCTs), and diarrhea (p < 0.01, RCTs). CONCLUSIONS: The most common immune system-related AEs in patients treated with IL-17 inhibitors are mucosal and opportunistic infections.

The effects of apigenin administration on the inhibition of inflammatory responses and oxidative stress in the lung injury models: a systematic review and meta-analysis of preclinical evidence.

BACKGROUND/OBJECTIVE: Apigenin is a member of the flavonoid family that can regulate various biological processes, which is characterized as a treatment of different inflammatory disorders and pathological problems associated with oxidative stress (OS). Recent research has focused on apigenin immunomodulatory properties as a potential treatment for different types of lung injuries. This meta-analysis was designed to determine the impact of apigenin treatment on inflammatory markers and OS parameters in animal models of lung injuries. METHODS: The comprehensive literature search was conducted using electronic databases such as Google Scholar, PubMed, Web of Science, Scopus, and Embase up to August 2021. To assess apigenin's effect on inflammatory mediators and OS biomarkers in lung injury animal models, we used the I2 statistic to determine the heterogeneity. We then pooled data as standardized mean difference (SMD) with a 95% confidence interval (CI). RESULTS: Our meta-analysis of the pooled data for inflammatory biomarkers demonstrated that the apigenin administration significantly decreased the NF-κB expression (SMD - 1.60, 95% CI [- 2.93 to - 0.26]; I2 = 89.0%, p < 0.001), IL-1ß (SMD - 4.30, 95% CI [- 6.24 to - 2.37]; I2 = 67.3%, p = 0.047), IL-6 (SMD - 4.10, 95% CI [- 5.04 to - 3.16]; I2 = 72.6%, p < 0.001), TNF-α (SMD - 3.74, 95% CI [- 4.67 to - 2.82]; I2 = 84.1%, p < 0.001), and TNF-α gene expression (SMD - 3.44, 95% CI [- 4.44 to - 2.43]; I2 = 0.0%, p = 0.622). This study also indicated the efficacy of apigenin in increasing the level of CAT (SMD 4.56, 95% CI [3.57 to 5.55]; I2 = 15.3%, p = 3.15), GSH (SMD 5.12, 95% CI [3.53 to 6.70]; I2 = 77.6%, p < 0.001), and SOD (SMD 3.45, 95% CI [2.50 to 4.40]; I2 = 79.2%, p < 0.001), and decreasing the level of MDA (SMD - 3.87, 95% CI [- 5.25 to - 2.49]; I2 = 80.3%, p < 0.001) and MPO (SMD - 4.02, 95% CI [- 5.64 to - 2.40]; I2 = 88.9%, p < 0.001), TGF- ß (SMD - 3.81, 95% CI [- 4.91 to - 2.70]; I2 = 73.4%, p = 0.001) and W/D level (SMD - 3.22, 95% CI [- 4.47 to - 1.97]; I2 = 82.1%, p < 0.001) than control groups. CONCLUSION: Overall, our findings showed the immunomodulatory potential of apigenin as an alternative treatment for the suppression of inflammatory responses and OS in different types of lung injury diseases. Nevertheless, due to the paucity of clinical studies, reliable preclinical models, and clinical settings, evaluating the influence of apigenin on lung injury is required in the future. Before conducting large-scale clinical trials, detailed human pharmacokinetic studies are also needed to establish dosage ranges and determine the initial safety and tolerability of apigenin.

Opium use and the risk of head and neck squamous cell carcinoma.

Scant evidence exists to support the association of opium use with head and neck cancer, limited to the larynx and oral cavity. In a multicenter case-control study-Iran Opium and Cancer study, we recruited 633 cases of head and neck squamous cell carcinoma (HNSCC) (254 lip and oral cavity, 54 pharynx, 327 larynx and 28 other subsites within the head and neck) and 3065 frequency-matched controls from April 2016 to April 2019. Odds ratios (ORs) for opium use and 95% confidence intervals (95% CIs) were obtained using mixed-effects logistic regression because of heterogeneity among centers. The adjusted OR (95% CI) for regular opium use was 3.76 (2.96-4.79) for all HNSCC combined. Strong dose-response effects were observed by frequency or amount of use, and duration of use. Regular opium uses significantly increased the risk of HNSCC of the pharynx, larynx and other subsites within the head and neck with OR (95% CI) of 2.90 (1.40-6.02), 6.55 (4.69-9.13) and 5.95 (2.41-14.71), respectively. The observed associations were significant even among never tobacco smokers (including cigarette and water-pipe smoking). Moreover, by the multiplicative interaction scale, the effect of opium use could be varied by cigarette smoking on HNSCC, 8.16 (6.20-10.74). For the first time, the current study showed opium users have an increased risk of several anatomic subsites of HNSCC.

Sofosbuvir and daclatasvir for the treatment of COVID-19 outpatients: a double-blind, randomized controlled trial.

INTRODUCTION: Effective treatments are urgently needed to tackle the novel coronavirus disease 2019 (COVID-19). This trial aims to evaluate sofosbuvir and daclatasvir versus standard care for outpatients with mild COVID-19 infection. METHODS: This was a randomized controlled clinical trial in outpatients with mild COVID-19. Patients were randomized into a treatment arm receiving sofosbuvir/daclatasvir plus hydroxychloroquine or a control arm receiving hydroxychloroquine alone. The primary endpoint of the trial was symptom alleviation after 7 days of follow-up. The secondary endpoint of the trial was hospital admission. Fatigue, dyspnoea and loss of appetite were investigated after 1 month of follow-up. This study is registered with the IRCT.ir under registration number IRCT20200403046926N1. RESULTS: Between 8 April 2020 and 19 May 2020, 55 patients were recruited and allocated to either the sofosbuvir/daclatasvir treatment arm (n = 27) or the control arm (n = 28). Baseline characteristics were similar across treatment arms. There was no significant difference in symptoms at Day 7. One patient was admitted to hospital in the sofosbuvir/daclatasvir arm and four in the control arm, but the difference was not significant. After 1 month of follow-up, two patients reported fatigue in the sofosbuvir/daclatasvir arm and 16 in the control arm; P < 0.001. CONCLUSIONS: In this study, sofosbuvir/daclatasvir did not significantly alleviate symptoms after 7 days of treatment compared with control. Although fewer hospitalizations were observed in the sofosbuvir/daclatasvir arm, this was not statistically significant. Sofosbuvir/daclatasvir significantly reduced the number of patients with fatigue and dyspnoea after 1 month. Larger, well-designed trials are warranted.

Lymphopenia and lung complications in patients with coronavirus disease-2019 (COVID-19): A retrospective study based on clinical data.

A rapid outbreak of novel coronavirus, coronavirus disease-2019 (COVID-19), has made it a global pandemic. This study focused on the possible association between lymphopenia and computed tomography (CT) scan features and COVID-19 patient mortality. The clinical data of 596 COVID-19 patients were collected from February 2020 to September 2020. The patients' serological survey and CT scan features were retrospectively explored. The median age of the patients was 56.7 ± 16.4 years old. Lung involvement was more than 50% in 214 COVID-19 patients (35.9%). The average blood lymphocyte percentage was 20.35 ± 10.16 (normal range, 20%-50%). Although the levels of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were high in more than 80% of COVID-19 patients; CRP, ESR, and platelet-to-lymphocyte ratio (PLR) may not indicate the in-hospital mortality of COVID-19. Patients with severe lung involvement and lymphopenia were found to be significantly associated with increased odds of death (odds ratio, 9.24; 95% confidence interval, 4.32-19.78). These results indicated that lymphopenia < 20% along with pulmonary involvement >50% impose a multiplicative effect on the risk of mortality. The in-hospital mortality rate of this group was significantly higher than other COVID-19 hospitalized cases. Furthermore, they meaningfully experienced a prolonged stay in the hospital (p = .00). Lymphocyte count less than 20% and chest CT scan findings with more than 50% involvement might be related to the patient's mortality. These could act as laboratory and clinical indicators of disease severity, mortality, and outcome.

Overexpression of chemokine receptor CXCR4 predicts lymph node metastatic risk in patients with melanoma: A systematic review and meta-analysis.

CXCR4 is a member of CXC-type and G protein-coupled receptors that can conduce many biological processes, including hemostasis, migration, and adhesion of different types of immune cells. Also, the contribution of CXCR4 in metastasis cascade and development of various malignancies has been addressed in previous reports. This meta-analysis was performed to explore whether the CXCR4 expression affects prognosis and clinicopathologic features in melanoma cancer. Our study involved 656 melanoma patients from 13 reports by detailed literature search from PubMed, Embase, Web of Science, and Google Scholar up to April 2021. To evaluate the association between CXCR4 expression and clinicopathological features of melanoma, we calculated odds ratios (ORs) with its 95% confidence intervals (CIs). We indicated that the CXCR4 overexpression was obviously correlated with ulceration (OR = 0.56, 95% CI: 0.38 to 0.74; I2 = 0.0%, P = 0.999), tumor thickness (OR = 0.56, 95% CI: 0.38 to 0.74; I2 = 0.0%, P = 0.999) and lymph node metastasis (OR = 8.54, 95% CI: 1.04 to 16.04; I2 = 98.9, P < 0.0001). In conclusion, our results reveal that CXCR4 is involved in enhancing the progression and metastasis of melanoma, and further clinical studies are necessary to investigate the role of CXCR4 as a diagnostic and therapeutic biomarker through the progress of melanoma cancer.

Genetic Polymorphisms of Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) and clinical outcomes post-allogeneic hematopoietic stem cell transplantation: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Although HLA matching is considered as a key genetic predictor of allo-HSCT outcomes, genetic polymorphisms in non-HLA genes, especially in genes encoding immunoregulatory proteins, have also been proposed as additional risk factors linked to the occurrence of transplant complications. This study aimed to carry out a systematic review and meta-analysis from all eligible cohort studies to determine the effect of CTLA-4 gene polymorphisms, including rs231775, rs3087243, rs4553808, rs5742909, and rs733618, on clinical outcomes in patients receiving an allo-HSCT. METHODS: A systematic literature search in PubMed, Web of Science, and Scopus was performed to identify the relevant studies, and related information was extracted. The effect size (ES) and corresponding 95% confidence intervals (CIs) were calculated to estimate the association. RESULTS: 16 studies were eligible and included in the meta-analysis. The pooled results showed that only the dominant models of rs3087243 were significantly associated with chronic GVHD (cGVHD), while other SNPs were not significantly associated with overall survival, disease-free survival, relapse, and GVHD. CONCLUSIONS: Our study represents, for the first time, a comprehensive meta-analysis on the role of CTLA-4 polymorphisms on outcomes after allo-HSCT. The results indicate that the CT60 CTLA-4 polymorphism could be a significant risk factor for cGVHD.

Oral contraceptives and hypertension in women: results of the enrolment phase of Tabari Cohort Study.

BACKGROUND: The association between oral contraceptives (OCP) and hypertension has been reported in the literature with controversial results. According to the growing use of OCPs among women in Iran, this study aims to investigate the association between the duration of the OCP consumption and risk of hypertension among Iranian women. METHODS: In the current study, the data collected during the enrolment phase of the Tabari cohort were analyzed. Of 6106 women recruited in the cohort, 133 pregnant women were excluded. Epidemiological variables were collected using pre-designed questionnaires as well as the health insurance evidences. In addition, blood pressure and anthropometric factors were measured based on the standard guidelines. Chi square and partial correlation tests as well as logistic regression models were applied for data analysis. RESULTS: Frequency of oral contraceptive use among 35-70 year-old women in Tabari cohort study (TCS) was 42.2% (2520/5973). Hypertension was observed among 25% (1793/5973) of them. The adjusted odds ratio for OCP use was 1.23 (95% confidence interval: 1.08, 1.40, p = 0.002). The corresponding odds ratios for 61-120 months and more than 120 months OCP use were 1.39 (1.12,1.73) and 1.47 (1.16,1.87) respectively. CONCLUSIONS: Oral contraceptives especially in long term use can be associated with hypertension.

Cardiovascular diseases burden in COVID-19: Systematic review and meta-analysis.

BACKGROUND: High rate of cardiovascular disease (CVD) have been reported among patients with novel coronavirus disease (COVID-19). Meanwhile there were controversies among different studies about CVD burden in COVID-19 patients. Hence, we aimed to study CVD burden among COVID-19 patients, using a systematic review and meta-analysis. METHODS: We have systematically searched databases including PubMed, Embase, Cochrane Library, Scopus, Web of Science as well as medRxiv pre-print database. Hand searched was also conducted in journal websites and Google Scholar. Meta-analyses were carried out for Odds Ratio (OR) of mortality and Intensive Care Unit (ICU) admission for different CVDs. We have also performed a descriptive meta-analysis on different CVDs. RESULTS: Fifty-six studies entered into meta-analysis for ICU admission and mortality outcome and 198 papers for descriptive outcomes, including 159,698 COVID-19 patients. Results of meta-analysis indicated that acute cardiac injury, (OR: 13.29, 95% CI 7.35-24.03), hypertension (OR: 2.60, 95% CI 2.11-3.19), heart Failure (OR: 6.72, 95% CI 3.34-13.52), arrhythmia (OR: 2.75, 95% CI 1.43-5.25), coronary artery disease (OR: 3.78, 95% CI 2.42-5.90), and cardiovascular disease (OR: 2.61, 95% CI 1.89-3.62) were significantly associated with mortality. Arrhythmia (OR: 7.03, 95% CI 2.79-17.69), acute cardiac injury (OR: 15.58, 95% CI 5.15-47.12), coronary heart disease (OR: 2.61, 95% CI 1.09-6.26), cardiovascular disease (OR: 3.11, 95% CI 1.59-6.09), and hypertension (OR: 1.95, 95% CI 1.41-2.68) were also significantly associated with ICU admission in COVID-19 patients. CONCLUSION: Findings of this study revealed a high burden of CVDs among COVID-19 patients, which was significantly associated with mortality and ICU admission. Proper management of CVD patients with COVID-19 and monitoring COVID-19 patients for acute cardiac conditions is highly recommended to prevent mortality and critical situations.

The role of vitamin D in the age of COVID-19: A systematic review and meta-analysis.

BACKGROUND: Evidence recommends that vitamin D might be a crucial supportive agent for the immune system, mainly in cytokine response regulation against COVID-19. Hence, we carried out a systematic review and meta-analysis in order to maximise the use of everything that exists about the role of vitamin D in the COVID-19. METHODS: A systematic search was performed in PubMed, Scopus, Embase and Web of Science up to December 18, 2020. Studies focused on the role of vitamin D in confirmed COVID-19 patients were entered into the systematic review. RESULTS: Twenty-three studies containing 11 901 participants entered into the meta-analysis. The meta-analysis indicated that 41% of COVID-19 patients were suffering from vitamin D deficiency (95% CI, 29%-55%), and in 42% of patients, levels of vitamin D were insufficient (95% CI, 24%-63%). The serum 25-hydroxyvitamin D concentration was 20.3 ng/mL among all COVID-19 patients (95% CI, 12.1-19.8). The odds of getting infected with SARS-CoV-2 are 3.3 times higher among individuals with vitamin D deficiency (95% CI, 2.5-4.3). The chance of developing severe COVID-19 is about five times higher in patients with vitamin D deficiency (OR: 5.1, 95% CI, 2.6-10.3). There is no significant association between vitamin D status and higher mortality rates (OR: 1.6, 95% CI, 0.5-4.4). CONCLUSION: This study found that most of the COVID-19 patients were suffering from vitamin D deficiency/insufficiency. Also, there is about three times higher chance of getting infected with SARS-CoV-2 among vitamin-D-deficient individuals and about five times higher probability of developing the severe disease in vitamin-D-deficient patients. Vitamin D deficiency showed no significant association with mortality rates in this population.

Corticosteroids in idiopathic granulomatous mastitis: a systematic review and meta-analysis.

Idiopathic granulomatous mastitis (IGM) is an inflammatory disease of the breasts with an unknown etiology. Corticosteroids are one the primary options for treating this disease, but the results of previous studies concerning their efficacy have been controversial. We, therefore, decided to assess the effectiveness of corticosteroids on IGM using a systematic review and meta-analysis. We conducted a systematic search using MeSH terms and all relevant keywords in PubMed, EMBASE, Cochrane Library and Web of Science until May 21, 2019. Data were analyzed using the Comprehensive Meta-Analysis (CMA) V.2 software program and presented as the event rate, risk ratio (RR) and risk difference (RD). Twelve studies including 559 IGM patients were entered into the meta-analysis. Our analysis showed that the RR and RD of recurrence in the steroid-only group compared with the surgery-only group were 2.99 (95% confidence interval [CI] 0.28-31.33) and 0.14 (95% CI - 0.01-0.30), respectively, showing no statistical significance. The meta-analysis of the steroid-only group and steroid + surgery group showed that the RR of recurrence was 6.13 (95% CI 0.41-81.62) with no significance. However, the meta-analysis of the RD showed that the risk of recurrence in the steroid group was significantly higher than that in the steroids + surgery group (RD: 0.28, 95% CI 0.11-0.44). This meta-analysis showed that managing IGM with only steroids may be less effective than the combination of steroids and surgery. This combination approach may result in a lower rate of recurrence and side effects in these patients.

Effects of coenzyme Q10 supplementation on inflammation, angiogenesis, and oxidative stress in breast cancer patients: a systematic review and meta-analysis of randomized controlled- trials.

BACKGROUND/OBJECTIVE: Systemic inflammation and oxidative stress (OS) are associated with breast cancer. CoQ10 as an adjuvant treatment with conventional anti-cancer chemotherapy has been demonstrated to help in the inflammatory process and OS. This systematic review and meta-analysis of randomized clinical trials (RCTs) aimed to evaluate the efficacy of CoQ10 supplementation on levels of inflammatory markers, OS parameters, and matrix metalloproteinases/tissue inhibitor of metalloproteinases (MMPs/TIMPs) in patients with breast cancer. METHODS: A systematic literature search was carried out using electronic databases, including PubMed, Web of Science, Scopus, Google Scholar, and Embase, up to December 2020 to identify eligible RCTs evaluating the effect of CoQ10 supplementation on OS biomarkers, inflammatory cytokines, and MMPs/TIMPs. From 827 potential reports, 5 eligible studies consisting of 9 trials were finally included in the current meta-analysis. Quality assessment and heterogeneity tests of the selected trials were performed using the PRISMA checklist protocol and the I2 statistic, respectively. Fixed and random-effects models were assessed based on the heterogeneity tests, and pooled data were determined as the standardized mean difference (SMD) with a 95% confidence interval (CI). RESULTS: Our meta-analysis of the pooled findings for inflammatory biomarkers of OS and MMPs showed that CoQ10 supplementation (100 mg/day for 45-90 days) significantly decreased the levels of VEGF [SMD: - 1.88, 95% CI: (- 2. 62 to - 1.13); I2 = 93.1%, p < 0.001], IL-8 [SMD: - 2.24, 95% CI: (- 2.68 to - 1.8); I2 = 79.6%, p = 0.001], MMP-2 [SMD: - 1.49, 95% CI: (- 1.85 to - 1.14); I2 = 76.3%, p = 0.005] and MMP-9 [SMD: - 1.58, 95% CI: (- 1.97 to - 1.19); I2 = 79.6%, p = 0.002], but no significant difference was observed between CoQ10 supplementation and control group on TNF-α [SMD: - 2.30, 95% CI: (- 2.50 to - 2.11); I2 = 21.8%, p = 0.280], IL-6 [SMD: - 1.56, 95% CI: (- 1.73 to - 1.39); I2 = 0.0%, p = 0.683], IL-1ß [SMD: - 3.34, 95% CI: (- 3.58 to - 3.11); I2 = 0.0%, p = 0.561], catalase (CAT) [SMD: 1.40, 95% CI: (1.15 to 1.65); I2 = 0.0%, p = 0.598], superoxide dismutase (SOD) [SMD: 2.42, 95% CI: (2.12 to 2.71); I2 = 0.0%, p = 0.986], glutathione peroxidase (GPx) [SMD: 2.80, 95% CI: (2.49 to 3.11); I2 = 0.0%, p = 0.543]], glutathione (GSH) [SMD: 4.71, 95% CI: (4.26 to 5.16); I2 = 6.1%, p = 0.302] and thiobarbituric acid reactive substances (TBARS) [SMD: - 3.20, 95% CI: (- 3.53 to - 2.86); I2 = 29.7%, p = 0.233]. CONCLUSION: Overall, the findings showed that CoQ10 supplementation reduced some of the important markers of inflammation and MMPs in patients with breast cancer. However, further studies with controlled trials for other types of cancer are needed to better understand and confirm the effect of CoQ10 on tumor therapy.