The triglyceride-glucose index as a clinical useful marker for metabolic associated fatty liver disease (MAFLD): a population-based study among Iranian adults.

Background and aims: There is a bi-directional association between non-alcoholic fatty liver disease (NAFLD) and insulin resistance in type 2 diabetes mellitus (T2DM) and metabolic syndrome. The triglyceride-glucose (TyG) index is a novel surrogate marker of insulin resistance. In this population-based study, we aimed firstly to investigate the association of the TyG-index with metabolic-associated fatty liver disease (MAFLD) risk. Methods: This case-control study used the data from the first phase of the Persian Cohort Study in Sabzevar. Of 4,241 participants aged 35 to 70 years, we identified and recruited 968 MAFLD cases and 964 age- and sex-adjusted controls. Demographic, lifestyle, anthropometric, and biochemical information were collected. We calculated TyG and a new index combined of TyG and alanine aminotransferase (TyG-ALT). We used the multivariable unconditional logistic regression model to calculate the odds ratios (ORs) of the TyG and TyG-ALT for having MAFLD. Results: Among those in the highest relative to the lowest TyG and TyG-ALT tertiles, the multivariable-adjusted ORs were 12.01 (95% CI [confidence interval] 9.03 - 15.98; P trend < 0.001) and 10.89 (95% CI 7.66 - 15.48; P trend = 0.001), respectively. The area under the curves (AUC) for the TyG-index to predict MAFLD was 8.62, resulting in a cut-off value of 8.62 with a sensitivity of 81.66% and specificity of 75.36%. Conclusions: The higher TyG and TyG-ALT scores were significantly positively associated with higher MAFLD risk in the Iranian population.

Dietary and Lifestyle Inflammation Scores Are Inversely Associated with Metabolic-Associated Fatty Liver Disease among Iranian Adults: A Nested Case-Control Study.

BACKGROUND: Diet and lifestyle may affect risk for metabolic-associated fatty liver disease (MAFLD) by chronically elevating systemic inflammation. OBJECTIVES: In this study we investigated the separate and joint associations of dietary and lifestyle inflammation scores (DIS and LIS, respectively) with MAFLD risk. METHODS: For this nested case-control study we identified and recruited 968 patients with MAFLD (defined as having a fatty liver index ≥60 plus ≥1 of the following conditions: overweight or obese, type II diabetes mellitus, evidence of metabolic dysregulation) and 964 controls from among 35-70-y-old men and women in the baseline phase of the Sabzevar Persian Cohort Study. We collected demographic, lifestyle, anthropometric, biochemical, and dietary intake information (via a validated FFQ) from which we calculated a circulating inflammation biomarker-weighted, predominantly whole foods and beverages-based, 19-component DIS and a 3-component LIS. We estimated DIS- and LIS-MAFLD associations using multivariable unconditional logistic regression. We also calculated equal-weight DIS and LIS to capture all potential mechanisms (inflammation plus other mechanisms) for associations of diet and lifestyle with MAFLD risk. RESULTS: Among those in the highest relative to the lowest DIS and LIS tertiles, the multivariable-adjusted ORs and their 95% CIs were OR: 1.84; 95% CI: 1.61, 2.07; Ptrend < 0.001, and OR: 1.96; 95% CI: 1.69, 2.21; Ptrend < 0.001, respectively. For those in the highest relative to the lowest joint DIS and LIS tertile, the values were OR: 2.56; 95% CI: 2.19, 2.93; Pinteraction < 0.001. The findings were similar by sex. The third tertile values for the equal-weight DIS- and LIS-MAFLD associations were OR: 1.87; 95% CI: 1.41, 2.34; and OR: 2.16; 95% CI: 1.85, 2.46, respectively. CONCLUSIONS: Our results suggest that higher balances of pro- relative to anti-inflammatory dietary and lifestyle exposures, separately and especially jointly, may be associated with higher MAFLD risk among adults. Also, inflammation may be the primary mechanism through which diet affects MAFLD risk.

Predictors of metabolic-associated fatty liver disease (MAFLD) in adults: a population-based study in Northeastern Iran.

AIM: This study aimed to identify the risk factors of metabolic (dysfunction)-associated fatty liver disease (MAFLD) among adults in northeastern Iran. BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and hepatic manifestation of metabolic syndrome that threatens global public health. Recently, MAFLD has been proposed as a new terminology updated from NAFLD and diagnosed based on modified criteria. METHODS: A nested case-control study was performed on the participants of the first phase of the Persian Sabzevar Cohort Study (PSCS), a survey that was conducted in northeastern Iran and enrolled 4,242 participants aged 35-70 years. In total, 968 MAFLD cases and 964 controls adjusted for age and sex were recruited. Data including demographic, lifestyle, anthropometric, biochemical, sleep pattern, and dietary intake information was collected. RESULTS: The mean (SD [standard deviation]) age of participants was 49.2 (8.8) years, and 39.9% of the participants were males. The prevalence of MAFLD was 22.8% (95% CI [confidence interval] 19.2 - 26.3%). Increased body mass index (BMI) (OR [odds ratios] 5.51, 95% CI 2.73 - 11.10), waist circumference (WC) (OR 1.85, 95% CI 1.44 - 2.38), blood concentrations of triglycerides (TG) (OR 1.10, 95% CI 1.06 - 1.15), total cholesterol (TC) (OR 1.02, 95% CI 1.003 - 1.04), and alanine aminotransferase (AST) (OR 1.10, 95% CI 1.05 - 1.16) were significantly associated with an increased risk of the MAFLD (p-value <0.05). Furthermore, the odds of MAFLD risk was 43% higher in subjects who slept ≤ 5 hrs/day than those with ≥ 7 hrs per day of sleep (OR 1.43; 95% CI 1.07 - 1.92, p-value = 0.01). CONCLUSION: In this study, it was found that MAFLD was best predicted by BMI, WC, and serum levels of TG, total cholesterol, and AST. Sleeping ≤ 5hrs/day compared to ≥ 7hrs/day was associated with an increased risk of MAFLD.

Signal transduction pathway mutations in gastrointestinal (GI) cancers: a systematic review and meta-analysis.

The present study was conducted to evaluate the prevalence of the signaling pathways mutation rate in the Gastrointestinal (GI) tract cancers in a systematic review and meta-analysis study. The study was performed based on the PRISMA criteria. Random models by confidence interval (CI: 95%) were used to calculate the pooled estimate of prevalence via Metaprop command. The pooled prevalence indices of signal transduction pathway mutations in gastric cancer, liver cancer, colorectal cancer, and pancreatic cancer were 5% (95% CI: 3-8%), 12% (95% CI: 8-18%), 17% (95% CI: 14-20%), and 20% (95% CI: 5-41%), respectively. Also, the mutation rates for Wnt pathway and MAPK pathway were calculated to be 23% (95% CI, 14-33%) and 20% (95% CI, 17-24%), respectively. Moreover, the most popular genes were APC (in Wnt pathway), KRAS (in MAPK pathway) and PIK3CA (in PI3K pathway) in the colorectal cancer, pancreatic cancer, and gastric cancer while they were beta-catenin and CTNNB1 in liver cancer. The most altered pathway was Wnt pathway followed by the MAPK pathway. In addition, pancreatic cancer was found to be higher under the pressure of mutation compared with others based on pooled prevalence analysis. Finally, APC mutations in colorectal cancer, KRAS in gastric cancer, and pancreatic cancer were mostly associated gene alterations.

Frequent incidence of double minute chromosomes in cancers, with special up-to-date reference to leukemia.

Double minute chromosomes (DMs) are small chromatin bodies consisting of gene amplification in an extrachromosomal location. Although found in an variety of human tumor cells, their presence in hematologic malignancies is rare and their role in leukemogenesis is controversial. However, they are thought to be involved in tumorigenesis and in drug resistance, representing a mechanism for upregulated oncogene expression generally associated with a poor prognosis. The presence of DMs has been associated with a rapid disease course, low response rate, and short survival. Little knowledge is, however, available on DMs in leukemias. To elucidate this issue, a web-based search for all types of articles published was initiated using MEDLINE/PubMed, the Mitelman database and other pertinent references on websites. We found that DMs have the highest frequency in adrenal carcinoma (28.6%), and lowest rate noted as 2.6% for large intestine. The large Mitelman database and other web based pertinent reports provide novel knowledge of DMs and their association in the wide field of cancers.

Cancer epidemiology and control in North-Western and Central Asia - past, present and future.

The North-Western and Central region of Asia stretches from Turkey through Armenia, Georgia and Azerbaijan, to Iran and Turkmenistan, Uzbekistan, Kazakhstan, Kyrgyzstan, Tadjikistan and Afghanistan. These countries in the main share Turkic, Iranian or Caucasus ethnicity and culture and can be considered as a regional entity for cooperation in control of cancer. The present review of cancer registry and other epidemiological data was undertaken to provide an evidence base for cancer control programs and pointers to possible research collaboration. The most prevalent cancer site in males is the lung in the Western part of the region and the stomach in most of Iran and Central Asia, followed by the oesophagus in the latter two. Bladder cancer is comparatively frequent throughout. In females breast cancer is number one, generally followed by gastric, oesophageal or cervical lesions. However, there are interesting differences between countries or regions, particularly regarding the stomach. General tendencies for increase in adenocarcinomas but decrease in squamous cell carcinomas and gastric cancer point to change in environmental influence over time. Variation in risk factors depends to some extent on the level of economic development but overall the countries of the region face similar challenges in achieving effective cancer control, underlying the necessity for cooperation.

Antibody response to pneumococcal capsular polysaccharide vaccination in patients with chronic kidney disease.

Patients with chronic kidney disease (CKD) or on dialysis are at greater risk of infection, which might be due to a defective immune function. While there are controversial reports on efficacy of vaccination in this group of patients, the aim of this study was to evaluate the antibody response to pneumococcal capsular polysaccharide vaccine (PPV23) in CKD patients. Sixty-six patients with CKD and 40 healthy individuals were vaccinated with PPV23. Blood samples were taken before and four weeks after vaccination. Specific antibodies against whole pneumococcal antigens were measured using an enzyme-linked immunosorbent assay (ELISA) technique. Among the 66 vaccinated patients, 14 (21%) were hypo-responsive to vaccine (group 1), while 52 had a normal specific-antibody response (group 2). Post-vaccination, anti-pneumococcal IgG titers in group 1 were significantly lower than those in group 2 (p = 0.012 for IgG post-vaccination and p = 0.020 for IgG2 post-vaccination). The fold increase or ratio increase of the anti-pneumococcal IgG titer in patients of group 1 was also significantly lower than that in group 2 or the healthy control group (p = 0.001 versus group 2 and p = 0.005 versus control group). During follow-up of both patient groups, group 1 patients developed more episodes of pneumococcal infections than those patients in group 2 (p = 0.007). In conclusion, although the majority of patients with CKD were responders to the polysaccharide vaccine, a substantial proportion of patients failed to mount an adequate antibody response to PPV23 and remained at significant risk of pneumococcal infection. Nevertheless, this vaccination policy should be administered as it could prevent infection in responder patients.

Early detection for breast cancer in iran.

OBJECTIVES: The present study was carried out to assess knowledge, attitudes and practice (KAP) concerning early detection for breast cancer among Iranian health care providers (HCP). METHODS: Three hundred and eighteen HCPs were selected with stratified simple random sampling and given questionnaires to determine their baseline KAP for breast cancer early detection. Results were compared among categories of age, educational level, marriage status and professional experience with the Chi square test. RESULTS: For six knowledge questions, 71.8% participants had four or more correct responses, 80.5% agreed completely with 'women will accept the screening program if the physicians advise it'. However, 48% of female HCPs did not carry out any method of breast cancer screening for themselves during the last year; 81.5% did not carry out breast examinations for the majority of female outpatients and inpatients during last year; only 5.1% recommended breast self examination (BSE) to more than 70% of their female patients. CONCLUSIONS: Knowledge and attitudes are relatively appropriate, but practical measures are not enough. Considering the HCP's role for implementing the national breast cancer control program, improvement in knowledge and attitudes is still important, but this may not be enough to reach to an appropriate level of desired practice.

Cytokine response following transthoracic and transhiatal esophagectomy in patients with esophageal cancer.

Curative esophageal resection is usually performed using either a transthoracic (TT) or transhiatal (TH) approach. Forty patients with esophageal squamous cell carcinoma who underwent esophagectomies (24 TT and 16 TH), 12 patients who underwent surgery for gastric cancer, and 16 healthy individuals were enrolled in this study. Blood samples were taken from the patients, pre- and post-surgery. The levels of synthesis of T-helper 1 and 2 cytokines were assessed in vitro in the presence of mitogen. Our initial data indicated that at admission, 24 h before surgery, blood cells from both groups of esophageal cancer patients produced significantly lower levels of the Th1 cytokines, IFN-gamma and IL-2 than those from cells of healthy donors. Cells collected from gastric cancer patients prior to surgery produced intermediate levels of IFN-gamma and IL-2: significantly lower than healthy donors, and slightly more (non-significant) than esophageal cancer patients. These results contrast with those for the production of Th2 cytokines prior to surgery, which did not differ significantly between any groups: either the esophageal or gastric cancer patients, or healthy donors. Th1 and Th2 cytokine production was then studied using blood cells collected seven days after surgery. Cells from both groups of esophageal cancer patients, undergoing either TT or TH surgery, produced significantly lower levels of the Th1 cytokines, IFN-gamma and IL-2 than those from cells of gastric cancer patients who had undergone surgery. Postoperative and preoperative production was compared. For patients who had undergone TT esophageal resection, we observed that the post-operative production of IL-2, IL-5 and IL-13 was significantly lower than the pre-operative production of those cytokines. Such reduced post-operative compared to pre-operative production was only significant in patients who had undergone TT esophagectomy. A similar, but non-significant trend was observed in patients who had undergone either TH esophagectomy, or gastrectomy. The results indicate that digestive tract cancer patients, both esophageal and gastric, have (prior to surgery), a significantly reduced, basal, mitogen-induced production of Th1 but not of Th2 cytokine. Post-operatively, a significantly reduced production of Th1 and Th2 cytokines, except for IFN-gamma, was observed only in patients who had undergone surgical esophageal resection using the TT method.

Prevalence of human papillomavirus genotypes in women with normal and abnormal cervical cytology in Iran.

INTRODUCTION: HPV infection has a prime etiologic role in development and progression of cervical cancer, one of the most frequent forms of cancer among women in developing countries. This study was designed to determine the most prevalent HPV genotypes in women with normal and abnormal cervical cytology in Iran. MATERIALS AND METHODS: Samples from134 patients, including 127 who attended gynecology clinics and 7 with solid cervical tumors were used. All 127 patients underwent routine Pap tests for cytological evaluation and at the same visit a sample of cervical epithelial cells was obtained by scraping the cervix osteum. In each case HPV infection was primarily evaluated by PCR using GP 5/6 primers and then subtyping was performed in proved infected samples with specific primers for HPV 16, 18, 31, 33, 11 and 6. After cytological evaluation, 50 patients with abnormal Pap tests were categorized as the abnormal group and the remaining 77 patients as the normal group. RESULTS: In the normal group, HPV infection was established in 10 cases (13% infection rate), while 30 HPV positive cases were discovered in the abnormal group (60% infected). The most prevalent genotypes among the infected samples were HPV 16 (76%), HPV18 (12.7%) and HPV11/6 (8.5%). Moreover, all 7 tumor samples were positive for HPV general primers of which, 5 samples were infected with HPV 16, two were co-infected with HPV16,18 and HPV16,31 genotypes and one was infected with HPV 18. CONCLUSIONS: Infection with HPV 16 was found to be significantly higher in abnormal group in comparison with normal group (42% vs. 11.6%, P value <0.005), likewise HPV18 genotypes were proved to be more prevalent in abnormal group (8% vs. 0%, P value <0.05). No significant relation between other HPV genotypes and pathologic cervical changes was obtained. According to our study high rates of infection with HPV genotypes in sexually active Iranian women makes molecular investigation for HPV16 and 18 very essential in clinical approaches to patients with proven dysplasia in their screening tests and also for those patients with borderline (i.e. ASCUS) or incongruous pathology reports. Larger studies are required to determine the most appropriate vaccine with highest protection in Iranian women.

Cancer occurrence in Iran in 2002, an international perspective.

For almost 30 years no population-based cancer statistics have been available with which to estimate the cancer burden in Iran. In 2002 and 2003 two separate reports of population based cancer registries were published from Iran and the cancer incidence rates from these sources have permitted informed estimates of cancer incidence and mortality to be prepared. They suggest that more than 51,000 cases of cancer are diagnosed and 35,000 deaths due to cancer occur each year. The 5 most common cancers in males (by ASR) are stomach (26.1 per 10(5)), esophagus (17.6 ), colon-rectum (8.3), bladder (8.0) and leukemia (4.8), and in females are breast (17.1), esophagus (14.4), stomach (11.1), colon-rectum (6.5) and cervix uteri (4.5). The incidence rates of esophageal and stomach cancer in Iran are high, well above the world average, while the incidence of lung cancer is very low. Breast cancer, although the most common cancer of females in Iran, has rates that are low by world standards, especially those observed in Europe and USA. Similarly, the incidence of cervix cancer in Iran is very low, even lower than such low risk countries as China, Kuwait and Spain. Comparing these rates with the data of 30 years ago, the incidence of esophageal cancer has decreased dramatically, but gastric cancer has increased about two fold.