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.

A systematic review and dose‒response meta-analysis of the association between nitrate & nitrite intake and gastroesophageal cancer risk.

OBJECTIVE: The objective of this systematic review and dose‒response meta-analysis was to assess the associations between the dietary consumption of nitrate and nitrite and the risk of gastric and esophageal cancer. METHODS: MEDLINE, Scopus, Embase, Web of Science, Proquest, and Google Scholar were searched until April 1, 2024. Articles were selected by two independent researchers on the basis of the inclusion and exclusion criteria. Data regarding the study design, type of exposure and outcomes, intervals of intake of nitrate or nitrite in each layer, OR/RR/HR of the relationship for each layer of intake, total sample size, and number of cases of gastric or esophageal cancer were extracted. The certainty of the evidence was rated via the GRADE method. The pooled odds ratios, risk ratios, and dose‒response analyses were calculated via Stata version 17.0. The best-fit dose‒response model was assessed by the P value for linearity and nonlinearity. Study heterogeneity was assessed via the I2 and Q tests. RESULTS: We found 2124 nonredundant studies, 234 of which were potentially relevant. Eighteen articles met the inclusion criteria and were included in the review. The results of the meta-analysis revealed a significant positive association between nitrite intake and gastric cancer in both case‒control studies (OR = 1.29, 95 % CI = 1.09-1.52, P value = 0.001, I2 = 1.91 %) and cohort studies (RR = 1.17, 95 % CI = 1.00-1.37, P value = 0.04, I2 = 0.00 %). In addition, case‒control studies revealed a nonsignificant inverse association between nitrate intake and gastric cancer incidence (OR = 0.71, 95 % CI = 0.50-1.01, P value = 0.06, I2 = 74.89 %), and cohort studies (RR = 0.89, 95 % CI = 0.73-1.09, P value = 0.27, I2 = 0.00 %). Case‒control studies also revealed no significant correlation between nitrite intake and esophageal cancer incidence (OR = 1.48, 95 % CI = 0.91 to 2.42, P value = 0.12, I2 = 0.001 %). Nitrites correlated linearly with gastric cancer (linearity P value = 0.001). The most appropriate fit models for the relationship between nitrate and gastric cancer were both piecewise linear and natural polynomial regression (quadratic) models (P values = 0.003 and 0.005, respectively). There was no significant publication bias. CONCLUSION: According to this meta-analysis, high consumption of nitrites was associated with an increased risk of gastric cancer in case‒control and cohort studies with a linear regression model, and dietary nitrate intake was not associated with the risk of gastric cancer in either case‒control or cohort studies. These findings are inconclusive and require confirmation in future prospective studies with robust methodologies and adjustments for potential confounders.

Prevalence of anemia and related factors among Tabari cohort population: a cross-sectional study.

BACKGROUND: Anemia presents a considerable public health challenge, standing as a leading contributor to elevated rates of mortality and morbidity. Therefore, this study aimed to investigate the prevalence of anemia and related factors among Tabari cohort population. METHODS: This study involved a cross-sectional investigation carried out during the enrollment phase of the Tabari cohort. The Tabari cohort is a subset of the larger nationwide cohort study known as the "Prospective Epidemiological Research Studies in IrAN" (PERSIAN) cohort. The collected data included general information, anthropometric measurements, medical history and blood samples. Anemia was defined as a hemoglobin level less than 13 mg/dL for men and less than 12 mg/dL for women. Data were analyzed using SPSS V.16. RESULTS: Out of the 10,073 participants included in the analysis, 1,352 individuals (13.4%) were diagnosed with anemia. In the multiple regression analysis, the odds of anemia were significantly 2.31 times in females compared to males, 3.69 times in urban residents compared to rural residents, 1.41 times in social economic categories of IV and 1.35 in social economic categories of V compared to social economic categories of I, 1.70 times in drug abuse compared to non-drug abuse, 0.71 times in body mass index (BMI) categories of 25-29.9 kg/m² and 0.70 in BMI ≥ 30 kg/m² compared to BMI < 25, 0.77 times for triglycerides(TG) > 150 compared to below 150, 0.76 times for total cholesterol(TC) > 200 compared to below 200, 0.83 times for high waist-to-hip ratio (WHR) compared to low WHR, 1.33 times in low High-density Lipoprotein (HDL) compared to high HDL, 1.18 times in diabetics (DM) compared to non-DM, and 1.37 times in individuals with coronary heart diseases (CHD) compared to healthy individuals. CONCLUSION: Anemia was a prevalent condition among Tabari cohort population. Several conditions including female gender, urban residence, Social economic level of IV and V, drug abuse, low HDL, high WHR, DM, and CHD conditions were significantly associated with increased odds of anemia. Furthermore, BMI categories of 25-29.9 kg/m² and ≥ 30 kg/m², high TC and high TG were significantly associated with decreased odds of anemia among this population.

Accelerated hazard prediction based on age time-scale for women diagnosed with breast cancer using a deep learning method.

Breast cancer is the most common cancer in women. Previous studies have investigated estimating and predicting the proportional hazard rates and survival in breast cancer. This study deals with predicting accelerated hazards (AH) rate based on age categories in breast cancer patients using deep learning methods. The AH has a time-dependent structure whose rate changes according to time and variable effects. We have collected data related to 1225 female patients with breast cancer at the Mandarin University of Medical Sciences. The patients' demographic and clinical characteristics including family history, age, history of tobacco use, hysterectomy, first menstruation age, gravida, number of breastfeeding, disease grade, marital status, and survival status have been recorded. Initially, we dealt with predicting three age groups of patients: ≤ 40, 41-60, and ≥ 61 years. Then, the prediction of accelerated risk value based on age categories for each breast cancer patient through deep learning and the importance of variables using LightGBM is discussed. Improving clinical management and treatment of breast cancer requires advanced methods such as time-dependent AH calculation. When the behavioral effect is assumed as a time scale change between hazard functions, the AH model is more appropriate for randomized clinical trials. The study results demonstrate the proper performance of the proposed model for predicting AH by age categories based on breast cancer patients' demographic and clinical characteristics.

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.

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.

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.

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.