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BACKGROUND: This study assessed the prevalence of gastroesophageal reflux disease (GERD) in a general adult population in Iran. The association between GERD and various factors was also evaluated. METHODS: We performed a cross-sectional study on 163,018 individuals aged over 35 who were enrolled in the PERSIAN cohort. GERD was defined as the occurrence of heartburn and/or regurgitation symptoms at least several days a month. Survey design analysis for pooled data was performed and multiple regression analysis was conducted to determine the independent risk factors for GERD. RESULTS: The prevalence of GERD in our study was estimated at 21.86% (95% confidence interval:17.4%-36.4%). The mean age of the participants was 49.84 years±9.25 (35-70) and 44.75% of the participants were male. Symptoms of heartburn and regurgitation were reported in 18.65% (n: 29,170) and 6.06% (n: 9,717) of participants, respectively. In the multivariate analysis, several factors were found to be associated with a higher prevalence of GERD: female sex, age >50, current smoking, opium use, weekly consumption of fried foods, frequent consumption of hot tea, less than 6 hours of sleep per night, psychiatric disorders, usage of NSAIDs, and poor oral hygiene, were associated with a higher prevalence of GERD. Conversely, higher education levels and average physical activity were found to be less commonly associated with GERD. CONCLUSION: We found a relatively high prevalence of GERD (21.86%) in this population-based study in Iran. By identifying modifiable risk factors, this research offers opportunities for targeted interventions and lifestyle modifications to reduce the burden of GERD.
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Refluxo Gastroesofágico , Humanos , Refluxo Gastroesofágico/epidemiologia , Irã (Geográfico)/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Estudos Transversais , Adulto , Prevalência , Idoso , Estudos de CoortesRESUMO
BACKGROUND: Rectal cancer (RC) poses a significant global health challenge, causing substantial morbidity and mortality. This study aims to investigate the survival rates of RC patients and identify the factors that influence their survival. The study considers demographic characteristics, tumor features, and treatment received as the factors under consideration. METHODS: A retrospective analysis was conducted on the medical records of 593 RC patients. Data were collected through a comprehensive review of medical records and conducting telephone interviews. Survival rates were estimated using the life table method, and subgroup comparisons were performed using the log-rank test. Cox regression analysis was utilized to assess the independent associations between RC survival time and various covariates. RESULTS: The study cohort comprised 593 RC patients, with a predominantly male representation. The mean age at diagnosis was 58.18 years, and the majority of patients (78.6 %) underwent surgical interventions. The median age at symptom onset and diagnosis were 58 and 59 years, respectively. Survival rates at 1st, 3rd, 5th, and 10th years were estimated to be 85 %, 59 %, 47 %, and 36 %, respectively. Statistical analysis revealed several significant prognostic factors, including age, education, symptoms, and cancer stage. In the multivariate Cox proportional-hazards analysis, advanced regional stage (HR = 1.54, 95 % CI, 1.13-2.08), presence of metastasis (HR = 3.73, 95 % CI, 2.49-5.58), and age over 70 (HR = 1.65) were associated with a higher risk of mortality. CONCLUSION: Given the alarming prognosis of RC observed in the study area and the significant delay between symptom onset and diagnosis, it is crucial to address this issue and potentially improve the survival rates of RC patients.
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Neoplasias Retais , Humanos , Masculino , Neoplasias Retais/mortalidade , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Neoplasias Retais/diagnóstico , Estudos Retrospectivos , Pessoa de Meia-Idade , Feminino , Irã (Geográfico)/epidemiologia , Prognóstico , Idoso , Taxa de Sobrevida , Adulto , Estadiamento de Neoplasias , Modelos de Riscos ProporcionaisRESUMO
Ulcerative colitis (UC) is one of the two types of inflammatory bowel disease (IBDs), which have a pivotal role in weakening the quality of lives of suffering patients. According to some recent studies, significant changes in dietary patterns may have contributed to the increased prevalence of UC. Potential renal acid load (PRAL) is an index used to estimate dietary acid load of the diet. The aim of the current study is to investigate the association between PRAL and odds of UC. The current case-control study included 62 newly diagnosed cases of UC and 124 healthy controls. Dietary habits of participants in the last year were collected with a valid food frequency questionnaire (FFQ). Thereafter, PRAL score was calculated based on a formula containing the dietary intake of protein, phosphorus, potassium, calcium, and magnesium. Participants were categorized according to quartiles of PRAL. Multivariable logistic regression models were used to estimate the odds' ratio (OR) with 95% confidence intervals (CIs) of UC across quartiles of PRAL. The results of the current study indicated that in the crude model, participants in the fourth quartile of PRAL had 2.51 time higher odds of UC compared with those in the first quartile of the PRAL [(OR 2.51; 95% CI 1.03-6.14), (P = 0.043)]. After adjustment for age and biological gender, this positive association remained significant [(OR 2.99; 95% CI 1.16-7.72), (P = 0.023)]. In the final model, after further adjustment for BMI, current smoking, education, Helicobacter pylori infection, and dietary intakes of total energy, omega-3 fatty acids, trans-fatty acids, and total dietary fiber, the odds of UC in the highest quartile of PRAL was significantly higher compared to the lowest quartile [(OR 3.08; 95% CI 1.01-9.39), (P = 0.048)]. So, we observed that higher dietary acid load assessed by PRAL score is associated with greater odds of UC.
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Colite Ulcerativa , Infecções por Helicobacter , Helicobacter pylori , Humanos , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/etiologia , Estudos de Casos e Controles , Dieta/efeitos adversosRESUMO
Colorectal cancer (CRC) is the third most common type of cancer worldwide. Red beetroot (Beta vulgaris) contains Betanin as its major betacyanin, possessing wide proapoptotic effects. This study aimed to investigate the anticancer and pro-papoptotic effects of beetroot hydro-alcoholic extract (BHE) and betanin, on colorectal cancer cell lines. BHE and betanin were used to treat Caco-2 and HT-29 colorectal cancer cells. MTT assay, DAPI staining, and FACS-flow cytometry tests were used to determine the half-maximal inhibitory concentration (IC50) and apoptosis-inducing evaluations. Intended genes were assessed by real-time polymerase chain reaction (RT-PCR). The IC50 for HT-29 and Caco-2 cell lines were 92 µg/mL, 107 µg/mL for BHE, and 64 µg/mL, 90 µg/mL for betanin at 48 h, respectively. BHE and betanin significantly inhibited the growth of both cancer cell lines time and dose-dependently. DAPI staining and flow cytometry results revealed significant apoptosis symptoms in treated cancerous cell lines. The expression level of proapoptotic genes (BAD, Caspase-3, Caspase-8, Caspase-9, and Fas-R) in treated HT-29 and Caco-2 cells was higher than in untreated and normal cells. In contrast, the anti-apoptotic gene (Bcl-2) was significantly downregulated. BHE and betanin effectively inhibited cancer cell proliferation and induced apoptosis via the modification of effective genes.
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Betacianinas , Neoplasias Colorretais , Humanos , Betacianinas/farmacologia , Células CACO-2 , Apoptose , Neoplasias Colorretais/tratamento farmacológicoRESUMO
BACKGROUND: Multiple primary cancers (MPC) present many coding difficulties, while a distinction should be made between new cases and those with metastasis and/or extension and recurrence of the primary ones. We aimed to reflect on the experiences and results of data quality control of the East Azerbaijan/Iran Population-Based Cancer Registry and present our suggested rules for reporting, recording and registering multiple primary cancer. METHODS: Comparability, validity, timeliness, and completeness of data assessment were performed. As a result, we created a consulting team including expert oncologists, pathologists, and gastroenterologists to discuss for multiple primary tumors recording, identifying, coding and registering. RESULTS: In case of confirmed Blood malignancies with definite BMB results, Brain and/or Bone involvements are always metastatic. In most cases of multiple cancers with the same morphological types, the earlier should be registered as primary tumor. In most of the synchronous multiple cancers, familial cancer syndromes should be considered and rules out. In case of two tumors diagnosed at the same time in colon and rectum, primary site should be detected by T stage or tumor sizes. In case of multiple tumors in Recto-sigmoid, Colon , and Rectum the earlier history of tumor should be considered as primary site. This rule was applied for Female Genital tumors, as earlier site is always the Primary cancer and other tumors should be registered as metastatic sites. Conclusion: Given the complexity of coding MPCs, we suggested some additional rules for identifying, recording, coding, and registering multiple primary cancers in the context of the EA-PBCR program.
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Neoplasias dos Genitais Femininos , Neoplasias Primárias Múltiplas , Síndromes Neoplásicas Hereditárias , Humanos , Feminino , Sistema de Registros , Confiabilidade dos DadosRESUMO
OBJECTIVES: Hyperinsulinaemia and insulin resistance are proposed as contributors to the incidence of cardiometabolic phenotypes (CMPs) with unhealthy metabolic status. This study analysed the association between dietary insulin load (DIL) and Dietary Insulin Index (DII) with CMPs in the AZAR cohort population. DESIGN: This study was a cross-sectional analysis of the AZAR Cohort Study, beginning in 2014 and continuing to this date. SETTING: The AZAR cohort is a part of an Iranian screening programme named the Persian cohort and involves participants living in the Shabestar region, Iran for at least 9 months. PARTICIPANTS: A total of 15 006 participants agreed to partake in the study. We excluded participants with missing data (n=15), daily energy intake lower than 800 kcal (n=7) or higher than 8000 kcal (n=17), and cancer (n=85). Finally, 14 882 individuals remained. PRIMARY AND SECONDARY OUTCOME MEASURES: The gathered information included the participants' demographic, dietary, anthropometric and physical activity data. RESULTS: The frequency of DIL and DII significantly decreased from the first to fourth quartiles in metabolically unhealthy participants (p≤0.001). The mean values of DIL and DII were greater in metabolically healthy participants than in unhealthy ones (p<0.001). The results of the unadjusted model showed that the risks of unhealthy phenotypes in the fourth DIL quartile decreased by 0.21 (0.14-0.32) and 0.37 (0.33-0.43), respectively, compared with the first quartile. The same model showed the same risks for DII decreased by 0.18 (0.11-0.28) and 0.39 (0.34-0.45), respectively. The results in both genders were the same as all participants combined. CONCLUSIONS: DII and DIL were correlated with a decreased OR of unhealthy phenotypes. We suggest the reason may be either a lifestyle change in metabolically unhealthy participants or elevated insulin secretion not being as detrimental as previously thought. Further studies can confirm these speculations.
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Doenças Cardiovasculares , Insulina , Masculino , Feminino , Humanos , Irã (Geográfico)/epidemiologia , Estudos de Coortes , Estudos Transversais , Dieta , Fenótipo , Doenças Cardiovasculares/epidemiologia , Índice de Massa Corporal , Fatores de RiscoRESUMO
Background: Colorectal cancer (CRC) is the third most common cancer and the second leading cause of death worldwide. However, CRC is considered as one of the most preventable cancers by which the mortality rates reduce about 60% through implementing the screening programmes. The present study aimed to evaluate the main barriers of CRC screening in a defined population. Method: Healthy individuals from all regions of the state were invited to participate in different healthcare centres. They were assessed by a provided online risk assessment tool, which was completed for all recruited subjects, and has been developed to assess the CRC risk based on personal and family history of adenoma, CRC, and other high-risk diseases. Research team staff assessed all individuals by this tool and then eligible people according to their lifetime risk of CRC were included in the study. There was not any age restriction in this study. Colonoscopy and three stool-based tests including faecal occult blood test, faecal immunochemical test and stool DNA tests were performed. Results: Overall, 725 cases including 425 (58.6%) males and 300 (41.4%) females participated in the study. Lack of knowledge and attitude about screening programmes was the most common barrier, especially among women (68% for women versus 58% for men) and those from rural areas (88% in rural versus 55% in urban areas). Fear of colonoscopy and procedure complications and pain (48%), discomfort and anxiety from inserting a tube into the bowel (65% among females versus 43% among males) were reported commonly. Embarrassment and dignity were other complaints, especially in women (62% in females versus 35% in males). Conclusion: Increasing knowledge and attitude about the aims and benefits of screening programmes, acceptable and convenient communication of health systems with the general population are considered to be the key elements in the success and implementation of any screening programme.
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INTRODUCTION: There are limited prospective studies assessing the post-diagnosis nutritional status of patients with gastric cancer (GC). This study aimed to assess the association between nutritional status and three-year survival of patients with GC. METHODS: In this prospective study, we included all histologically confirmed GC patients admitted to the Imam Reza Hospital in Tabriz, Iran from September 2016 to October 2019. The nutritional status of patients was assessed using the Patient-Generated Subjective Global Assessment (PG-SGA) form. All patients were followed up every six months for three years. The overall survival (OS) was calculated from the diagnosis date to the date of death or last visit. RESULTS: In this study, 302 patients (mean age: 67.39 ± 12.04 years) with GC were included. The median OS was 11.00 mo, (95% CI: 80.03, 13.96). Only 28.4% of patients were well-nourished, and survived significantly longer than malnourished patients (20.5 vs. 8 mo, P = 0.01). The mortality hazard rate in patients with moderate and severe malnutrition was 2.04 times higher than well-nourished patients. CONCLUSION: According to our results, the nutrition status of GC patients at the time of diagnosis was independently associated with their survival rate.
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Desnutrição , Neoplasias Gástricas , Idoso , Humanos , Desnutrição/diagnóstico , Pessoa de Meia-Idade , Avaliação Nutricional , Estado Nutricional , Prognóstico , Estudos Prospectivos , Neoplasias Gástricas/complicações , Redução de PesoRESUMO
Background: Globally, colorectal cancer (CRC) is the third most common cancer and the second leading cause of death from cancer. Incidence and mortality from CRCboth can be reduced and prevented using screening and early detection programs. The current study aimed to assess the feasibility of the colorectal cancer screening program in Northwest of Iran. Methods: The study designed as a cross-cultural analytic study, to evaluate the diagnostic accuracy of stool-based tests compared with colonoscopy, during 2016-2020. All individuals first were assessed with our CRC risk assessment tool, then eligible volunteers entered the study. Colonoscopy was performed on all participants, also stool-based tests including traditional guaiac, high-sensitivity guaiac-based, fecal immunochemical test (FIT), and multitarget stool DNA (Mt-sDNA) panel tests were performed. Results: Mt-sDNA test panel had a sensitivity of 77.8% (95% CI: 40-97.2)for detecting colorectal cancer with a specificity of 91.2% (95% CI:85.4-95.2). The FIT test alone had a lower sensitivity (66.7%; 95% CI:29.9-92.5) and almost the same specificity of 93.9% (95% CI: 88.7-97.2) for cancer detection. Mt-sDNA test had better diagnostic accuracy than the FIT (AUC = 0.85 vs 0.80), and is a more useful screening test. Positive and negative predictive values for cancer detection for both Mt-sDNA and FIT tests were almost the same results, however Mt-sDNA test had better NPV results than the FIT test alone. Conclusion: Our results showed that both Mt-sDNA panel and the FIT test had acceptable cut-off points for cancer detection, however, Mt-sDNA test had better diagnostic accuracy.
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INTRODUCTION: This study aimed to collect and summarize test data and conduct a meta-analysis, with respect to the Multitarget Stool DNA test sensitivity and specificity, compared to colonoscopy. MATERIAL AND METHODS: All manuscripts were screened for eligibility according to inclusion criteria. Participants were a normal population at an average risk of developing CRC. Intervention was Stool based and DNA panel tests compared with colonoscopy, and outcome was detection of CRC and any pre-cancerous lesions. Inter-study and inconsistency (using the I-squared test) were assessed. RESULTS: Meta-analyses of the Mt-sDNA test showed a combined sensitivity of 89%, 51%, and 76% for the detection of CRC, advanced adenoma (AA), and combined CRC and AA, respectively. The overall specificity was 91%, 89%, and 90% for the detection of CRC, AA, and combined CRC and AA, respectively. CONCLUSION: Mt-sDNA had significantly acceptable diagnostic accuracy for CRC and AA diagnosis, but still has lower sensitivity and specificity than colonoscopy.
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Adenoma , Neoplasias Colorretais , Humanos , Detecção Precoce de Câncer/métodos , Programas de Rastreamento/métodos , Sangue Oculto , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Adenoma/diagnóstico , Adenoma/genética , DNA/análiseRESUMO
INTRODUCTION: In the present study, we evaluated the association of nutritional status and quality of life (QoL) in patients with gastric cancer (GC). MATERIALS AND METHODS: In the present cross-sectional study, the study sample consisted of 299 patients with GC. The assessment of the nutritional status and QoL of patients was done after diagnosis and before initiation of any treatment. The nutritional status was assessed using Patient-Generated Subjective Global Assessment (PG-SGA). The 30-item European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTCQLQ-C30) was used for the assessment of QoL score. Statistical significance was reported at the p < 0.05 level. RESULTS: The mean age of participants was 67.39 ± 12.04 years and 65.5% of them were males. According to the PG-SGA, 28.5% of patients were in good nutritional condition. The patients with better nutrition status had significantly better global and functional categories scores (p < 0.001) except social functioning. Moreover, they had significantly lower scores in symptoms severity except for dyspnea, constipation, and diarrhea. The result of regression analysis indicated that after adjusting to confounders, nutrition status was significantly associated with global score and functional categories score except for social and emotional functioning scores. Moreover, in terms of symptom categories, there was a significant association between PG-SGA score and all symptoms except diarrhea and dyspnea. CONCLUSION: The results of the present study showed the significant association between nutrition status and functioning and symptom categories of QoL in patients with GC.
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Qualidade de Vida , Neoplasias Gástricas , Idoso , Estudos Transversais , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Estado Nutricional , Neoplasias Gástricas/complicaçõesRESUMO
Background: With a global prevalence of about 10%, gastric cancer is among the most prevalent cancers. Currently, there has been an ongoing trend toward investigating genetic disruptions in different cancers because they can be used as a target-specific therapy. We aimed to systemically review some gene expression patterns in gastric cancer. Methods: The current systematic review was designed and executed in 2020. Scopus, PubMed, Cochrane Library, Google Scholar, web of knowledge, and Science Direct were searched for relevant studies. A manual search of articles (hand searching), reference exploring, checking for grey literature, and seeking expert opinion were also done. Results: In this review, 65 studies were included, and the expression pattern of HER2/ ERBB2, ER1/Erb1/EGFR, PIK3CA, APC, KRAS, ARID1A, TP53, FGFR2 and MET was investigated. TP53, APC, KRAS, and PIK3CA mutation cumulative frequency were 24.8 (I2=95.05, Q value=525.53, df=26, P<0.001), 7.2 (I2=89.79, Q value=48.99, df=5, P<0.001), 7.8 (I2=93.60, Q value=140.71, df=9, P=0.001) and 8.6 (I2=80.78, Q value=525.53, df=9, P<0.001) percent, respectively. Overexpression was investigated for HER1/ Erb1/EGFR, PIK3CA, APC, KRAS, ARID1A, TP53, CCND1, FGFR2, MET and MYC. The frequency of TP53 and HER2/ERBB2 were 43.1 (I2=84.06, Q value=58.09, df=9, P<0.001) and 20.8 (I2=93.61, Q value=234.89, df=15, P<0.001) percent, respectively. Conclusion: More research is encouraged to investigate the genes for which we could not perform a meta-analysis.
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The outbreak of coronavirus disease 2019 (COVID-19) has posed a serious threat to public health. There is an urgent need for discovery methods for the prevention and treatment of COVID-19 infection. Understanding immunogenicity together with immune responses are expected to provide further information about this virus. We hope that this narrative review article may create new insights for researchers to take great strides toward designing vaccines and novel therapies in the near future. The functional properties of the immune system in COVID-19 infection is not exactly clarified yet. This is compounded by the many gaps in our understanding of the SARS-CoV-2 immunogenicity properties. Possible immune responses according to current literature are discussed as the first line of defense and acquired immunity. Here, we focus on proposed modern preventive immunotherapy methods in COVID-19 infection.
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COVID-19 , Imunidade Adaptativa , Vacinas contra COVID-19 , Humanos , SARS-CoV-2RESUMO
Helicobacter pylori (H. pylori) infection is the most common cause of gastric cancer (GC). This microorganism is genetically diverse; GC is caused by several genetic deregulations in addition to environmental factors and bacterial virulence factors. lncRNAs (long noncoding RNAs) are significant biological macromolecules in GC, have specific functions in diseases, and could be therapeutic targets. Altered lncRNAs can lead to the abnormal expression of adjacent protein-coding genes, which may be important in cancer development. Their mechanisms have not been well understood, so we are going to investigate the risk of GC in a population with both high lncRNA and H. pylori infection.
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Regulação Neoplásica da Expressão Gênica , Infecções por Helicobacter/genética , Infecções por Helicobacter/microbiologia , Helicobacter pylori/fisiologia , RNA Longo não Codificante/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/microbiologia , Impressão Genômica , Infecções por Helicobacter/imunologia , Humanos , RNA Longo não Codificante/metabolismo , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/patologiaRESUMO
ABSTRACT Objective: Globally developing metabolic syndrome (MetS) prevalence as a major health problem can be related to multiple factors of genetic and environmental. Dimethylaminohydrolase 2 (DDAH2) is the main enzyme implicated in the cardiovascular system, which regulates the nitric oxide pathway. This study investigated the association of DDAH2 polymorphism −499C/G (rs805305) with the risk of MetS among the Azar-Cohort population. Subjects and methods: The occurrence of SNP rs805305 in the DDAH2 gene was tested using the PCR-RFLP method in 332 MetS cases and 294 healthy controls. Afterward, the association of the allele and genotypes with the risk of MetS and its components were examined. Results: The G allele and GC genotype were significantly associated with a reduced risk of MetS (P ≤ 0.001). Also, the dominant genetic model (GG+GC) significantly decreased the risk of MetS (P = 0.001), however, in sex subtypes MetS risk was significantly reduced in males before and in females after adjustment for age (P ≤ 0.02). Conclusion: The −499C/G polymorphism of DDAH2 may play a protective role and reduce MetS risk among the Azar-Cohort population.
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Humanos , Masculino , Feminino , Síndrome Metabólica/genética , Amidoidrolases/genética , Polimorfismo Genético , Estudos de Casos e Controles , Regiões Promotoras Genéticas , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Fatores de Proteção , GenótipoRESUMO
BACKGROUND: The current recommendation for treating hepatitis C virus (HCV) in HIV patients includes the combination of sofosbuvir (SOF) and daclatasvir (DCV). DCV should be used at different doses to compensate for interactions with antiretroviral therapy (ART). Up to three pills a day might be required which will significantly add to the pill burden of these patients. In this study, we have used a single-tablet approach to treating HCV-HIV coinfection. METHODS: Patients coinfected with HIV and HCV were prospectively enrolled from 10 centers throughout the country. Patients received a single once-daily fixed dose combination (FDC) pill containing 400 mg SOF and 30, 60 or 90 mg DCV depending on the type of ART they were receiving for 12 or 24 weeks. (ClinicalTrials.gov ID: NCT03369327). RESULTS: Two hundred thirty-three patients were enrolled from 10 centers. Twenty-three patients were lost to follow-up and two patients died from causes unrelated to treatment. Two hundred eight patients completed the treatment course of which 201 achieved SVR (96.6%). CONCLUSION: Single-tablet combination of DCV and SOF is an effective and safe treatment for patients coinfected with HIV and HCV. The combination works well in patients on ART in which dose adjustment is required. Patients with cirrhosis, previous treatment failure and various genotypes respond identically. The expenses of genotyping can be saved.
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Coinfecção , Infecções por HIV , Hepatite C Crônica , Antivirais/uso terapêutico , Carbamatos , Coinfecção/tratamento farmacológico , Quimioterapia Combinada , Genótipo , HIV , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Imidazóis , Pirrolidinas , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Resultado do Tratamento , Valina/análogos & derivadosRESUMO
[This corrects the article DOI: 10.1155/2020/1963814.].
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Lipid metabolism rewiring in gastric adenocarcinoma (GA) pathogenesis is still not clearly elucidated. This study aimed to describe the role of lipid catabolism in GA patient outcomes and possible therapeutic targets by analyzing the effect of hypoxia-inducible factor-1α (HIF-1α) on fatty acid oxidation (FAO). AGS cell line was cultured in normoxic and hypoxic conditions, and FAO-related genes were analyzed by real-time-PCR and Western-blot. The study group comprised 108 newly diagnosed GA patients and 152 control cases. Serum concentrations of medium and long-chain acyl-CoA dehydrogenases (MCAD and LCAD) proteins were measured using ELISA, and local expression of HIF-1α, carnitine palmitoyl transferase 1 (CPT1A) and peroxisome proliferator-activated receptor γ (PPARγ) was evaluated by immunohistochemistry. In addition, gene expression of PPARγ, CPT1A, LCAD, and MCAD was assessed by real-time-PCR. In vitro findings indicate HIF-1α upregulation and FAO-related genes and proteins reduction in the hypoxic culture of AGS cells. GA patients had significantly lower circulating levels of LCAD compared to controls. Higher protein expression of HIF-1α and downregulated CPT1A and PPARγ were observed in GA tissues versus controls. Gene expression of CPT1A, PPARγ, LCAD, and MCAD were repressed in GA tissues compared to controls. Moreover, reduced expression of CPT1A, PPARγ, and MCAD were correlated with HIF-1α upregulation in GA. Poor patient outcome was associated with lower PPARγ and LCAD expression in GA. HIF-1α upregulation in human GA patients and AGS cells was paralleled by downregulation of lipid catabolism genes potentially via reduced PPARγ-mediated FAO. This metabolic adaptation to hypoxic condition may play a role in GA pathogenesis and might have clinical and therapeutic value in GA patients.
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Acil-CoA Desidrogenase de Cadeia Longa/genética , Acil-CoA Desidrogenase/genética , Adenocarcinoma/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , PPAR gama/genética , Neoplasias Gástricas/genética , Acil-CoA Desidrogenase/metabolismo , Acil-CoA Desidrogenase de Cadeia Longa/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Carnitina O-Palmitoiltransferase/genética , Carnitina O-Palmitoiltransferase/metabolismo , Estudos de Casos e Controles , Hipóxia Celular , Linhagem Celular Tumoral , Ácidos Graxos/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Metabolismo dos Lipídeos/genética , Masculino , Pessoa de Meia-Idade , Oxirredução , PPAR gama/metabolismo , Transdução de Sinais , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise de SobrevidaRESUMO
BACKGROUND: There are limited number of studies with controversial findings regarding the association between anemia at admission and coronavirus disease 2019 (COVID-19) outcomes. Therefore, in this research, we aimed to investigate the prospective association between anemia and COVID-19 outcomes in hospitalized patients in Iran. METHODS: In this prospective study, the data of 1274 consecutive patients hospitalized due to COVID-19 were statistically analyzed. All biomarkers, including hemoglobin and high-sensitivity C-reactive protein (hs-CRP) levels were measured using standard methods. Anemia was defined as a hemoglobin (Hb) concentration of less than 13 g/dL and 12 g/dL in males and females, respectively. Assessing the association between anemia and COVID-19 survival in hospitalized patients was our primary endpoint. RESULTS: The mean age of the participants was 64.43 ± 17.16 years, out of whom 615 (48.27%) were anemic subjects. Patients with anemia were significantly older (P = 0.02) and had a higher frequency of cardiovascular diseases, hypertension, kidney disease, diabetes, and cancer (P < 0.05). The frequency of death (anemic: 23.9% vs. nonanemic: 13.8%), ICU admission (anemic: 27.8% vs. nonanemic:14.71%), and ventilator requirement (anemic: 35.93% vs. nonanemic: 20.63%) were significantly higher in anemic patients than in nonanemic patients (P < 0.001). According to the results of regression analysis, after adjusting for significant covariate in the univariable model, anemia was independently associated with mortality (OR: 1.68, 95% CI: 1.10, 2.57, P = 0.01), ventilator requirement (OR: 1.74, 95% CI: 1.19, 2.54, P = 0.004), and the risk of ICU admission (OR: 2.06, 95% CI: 1.46, 2.90, P < 0.001). CONCLUSION: The prevalence of anemia in hospitalized patients with COVID-19 was high and was associated with poor outcomes of COVID-19.
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Anemia/complicações , COVID-19/complicações , COVID-19/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/epidemiologia , Feminino , Hemoglobinas/análise , Hospitalização , Humanos , Unidades de Terapia Intensiva , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Respiração Artificial , Índice de Gravidade de Doença , Taxa de SobrevidaRESUMO
Introduction: Early-activated RAS/RAF mutation status is a key molecular finding in colorectal cancer (CRC), while these mutations have been proposed as predictive and prognostic biomarkers. The present study has been designed as a longitudinal study to evaluate and summarize the different genotypes of metastatic CRC (mCRC), and assessing any association with the disease prognosis and clinicopathological characteristics. This study was performed in two main referral hospitals of Tabriz University of Medical Sciences, over three years (2016-2018). Methods: Mutations were detected by Idylla tests of KRAS/NRAS/BRAF among a total of 173 mCRCs, using surgically-resected specimens or biopsied samples. To evaluate the factors associated with overall survival (OS) and prognosis, the Cox proportional hazards model was used in two steps to estimate the outcome measures (hazard ratio, or HR) with a 95% confidence interval (CI). Results: The nominal 1 to 5-year OS rates were 78%, 65%, 55%, 46%, and 42%, respectively. KRAS mutations in codon 12 was an independent significant prognostic factor, as the patients with codon 12 mutations had a significantly lower OS (P Log-rank=0.049) and a higher hazard of mortality (HR=2.30; 95% CI: 0.95-5.58; P =0.066). Also, the mCRC patients with liver metastasis (HR=2.49; 95% CI: 1.49-12.52; P =0.002) and tumors of the distal colon (HR=3.36; 95% CI: 1.07-10.49; P =0.037) had a significantly worse prognosis. Conclusion: KRAS mutation in codon 12 was an independent significant poor prognostic factor, and patients with liver metastasis had a significantly worse prognosis. Routinely performing specific oncogenic tests may help improve the patients' prognosis and life expectancy.