Atefeh Talebi

BACKGROUND: There are concerns that renin-angiotensin system inhibitors are less effective in Black patients than non-Black patients with heart failure (HF). We examined the efficacy and safety of mineralocorticoid-receptor antagonists (MRAs), compared with placebo, in patients with HF with reduced ejection fraction or HF with mildly reduced/preserved ejection fraction, according to self-reported race (Black or non-Black). METHODS: This was a post hoc individual participant data meta-analysis of the 4 large placebo-controlled trials comparing MRAs to placebo in patients with HF with reduced ejection fraction (RALES [Randomized Aldactone Evaluation Study], EMPHASIS-HF [Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure]) and HF with mildly reduced/preserved ejection fraction (TOPCAT [Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist], FINEARTS-HF [Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure]). The primary outcome was a composite of cardiovascular death or first HF hospitalization. RESULTS: Of the 13 846 patients randomized in the 4 trials, 577 (4.2%) identified as Black. Despite being younger (64 versus 70 years), rates of HF hospitalizations and death were higher in Black than non-Black patients. The hazard ratio for MRA versus placebo for the primary composite outcome was 0.87 (95% CI, 0.66–1.15) in Black patients and 0.77 (95% CI, 0.72–0.82) in non-Black patients ( P _interaction =0.34), with 3.9 and 2.7 fewer events per 100 person-years of treatment, respectively. For first HF hospitalization, the hazard ratios were 0.86 (95% CI, 0.63–1.17) and 0.73 (95% CI, 0.68–0.80) for Black and non-Black patients, respectively ( P _interaction =0.36). The corresponding hazard ratios for cardiovascular death were 0.75 (95% CI, 0.48–1.17) and 0.81 (95% CI, 0.74–0.90), respectively ( P _interaction =0.80). Adverse events with MRAs, compared with placebo, were not modified by race. The effects of MRAs in patients with HF with reduced ejection fraction and HF with preserved ejection fraction, individually, were not modified by race. CONCLUSIONS: There was no statistically significant evidence of heterogeneity in the absolute or relative effects of MRAs on clinical outcomes between Black and non-Black patients with HF, regardless of HF phenotype.

Background: Increased public access to data from disparate sources provides opportunities to study and validate predictive and subphenotype models in heterogeneous disease conditions using aggregated individual patient data. Robust, explicit, and transparent harmonization of data elements is critical to ensure interpretability, reproducibility, and generalizability of secondary and retrospective analyses. Methods & Results: We designed and implemented ADAPT (Aggregating Data to Accelerate Personalized Therapy), a scalable framework using multiple software packages (R, SQL, BigQuery) that enables rapid, explicit harmonization of structured data elements from randomized trials and observational studies using a standard spreadsheet interface. User-specified criteria are applied to primary study data to produce harmonized longitudinal datasets comprised of demographics, medical history, quantitative observations, repeated measures, and clinical outcomes. We demonstrate this functionality using 26 clinical studies found in the National Heart, Lung, and Blood Institute’s BioLINCC resource. We illustrate the scalability of ADAPT to the order of billions of datapoints using administrative clinical data in a cloud-computing platform. We also present examples of collaborators using ADAPT for independent harmonization tasks for secondary analyses and democratization of publicly available data. Conclusion: ADAPT is a disease-agnostic, extensible, and scalable platform to support robust, transparent harmonization of structured research data using interfaces accessible to a variety of researchers regardless of programming ability. It extends FAIR principles beyond research data to also represent harmonization analyses by improving F indability of harmonization decisions, A ccessibility of methods to other stakeholders, I nteroperability with independent analyses and datasets, and R eusability through efficient implementation in a variety of analysis environments.

Background: Women with heart failure (HF) ejection fraction appeared to respond more favorably to sacubitril/valsartan, compared with valsartan, than men in PARAGON‐HF (Prospective Comparison of ARNI With ARB Global Outcomes in Heart Failure With Preserved Ejection Fraction), driven by a greater reduction in total (first and recurrent) HF hospitalizations. Sex‐specific efficacy and safety of sacubitril/valsartan in PARADIGM‐HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) remain unreported. Methods and Results: This post hoc analysis of PARADIGM‐HF examined sex‐based outcomes in patients with HF and reduced ejection fraction randomized to sacubitril/valsartan or enalapril. The primary end point was a composite of cardiovascular death or HF hospitalization. Secondary and exploratory efficacy outcomes, biomarker changes, and safety outcomes were also assessed. Among 8399 participants, 1832 (21.8%) were women. Women were older, had worse New York Heart Association functional class and Kansas City Cardiomyopathy Questionnaire scores, more symptoms of HF, and lower estimated glomerular filtration rate, yet had lower rates of HF hospitalization (and other worsening of HF) and cardiovascular death than men. Compared with enalapril, sacubitril/valsartan reduced the risk of the primary end point to a similar extent in both sexes: hazard ratios, 0.76 (95% CI, 0.62–0.94) in women and 0.80 (95% CI, 0.73–0.89) in men ( P ‐interaction=0.62). Results were consistent for the individual components of the primary outcome. The rate ratio for total HF hospitalizations was 0.66 (95% CI, 0.48–0.89) in women and 0.80 (95% CI, 0.69–0.94) in men ( P ‐interaction=0.25). Randomized treatment discontinuation and adverse effects of interest were similar in women and men. Conclusions: In PARADIGM‐HF, sacubitril/valsartan, compared with enalapril, reduced the risk of HF hospitalizations, death from cardiovascular causes, and death from any cause similarly in women and men with HF with reduced ejection fraction. In addition, sacubitril/valsartan was safe and well tolerated, irrespective of sex. Registration: URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT01035255.

Background: Alopecia areata (AA) is an immune‐mediated nonscarring hair loss disorder with multiple subtypes, including alopecia universalis (AU). Previous studies have shown a link between serum lipid profile and alopecia. We aimed to investigate the frequency of fatty liver in patients with AU and patchy alopecia areata (PAA) compared to a control group.Methods: This case–control study included patients with AU and PAA referred to a dermatology clinic from September 23, 2019 to September 23, 2020. A group of individuals without hair loss disorders attending the same clinic were selected as controls. Participants' general information, including age, sex, weight, height, and waist circumference (WC), was recorded. Body mass index (BMI) was calculated for all participants. Also, hyperlipidemia and statin use were noted and liver enzymes were evaluated. For AU and PAA patients, disease duration and the Severity of Alopecia Tool (SALT) score were also recorded. Then, all subjects underwent ultrasound to assess fatty liver and its grade.Results: Overall, 32 patients were included in each group. All three groups were comparable in age, sex, weight, height, BMI, WC, hyperlipidemia, abnormal liver enzymes, and statin use. Disease duration and SALT score were significantly higher in the AU than in the PAA group (p = 0.009 and p < 0.001, respectively). The frequency of fatty liver was the highest in AU patients (40.6%), followed by 34.4% in PAA patients, and 21.9% in controls (p = 0.263). This was also the case for grade‐1 fatty liver, while grade‐2 was more common in PAA patients, and grade‐3 was only observed in one patient from the AU group (p = 0.496).Conclusions: Fatty liver was more frequent in AU and PAA patients than controls, without statistically significant differences. There might be an association between fatty liver and AA, particularly the AU subtype.

Long noncoding RNAs (lncRNAs), as well-known modulator of the epigenetic processes, have been shown to contribute to normal cellular physiological and pathological conditions such as cancer. Through the interaction with epigenetic regulators, an aberrant regulation of gene expression can be resulted due to their dysregulation, which in turn, can be involved in tumorigenesis. In the present study, we reviewed the lncRNAs’ function and mechanisms that contributed to aberrant epigenetic regulation, which is directly related to gastrointestinal cancer (GI) development and progression. Findings indicated that epigenetic alterations may involve in tumorigenesis and are valuable biomarkers in case of diagnosing, assessing of risk factors, and predicting of GI cancers. This review summarized the accumulated evidence for biological and clinical application to use lncRNAs in GI cancers, including colorectal, gastric, oral, liver, pancreatic and oesophageal cancer.

Background: Tumor-specific neoantigens are ideal targets for cancer immunotherapy. As research findings have proved, neoantigen-specific T cell activity is immunotherapy’s most important determinant. Main text: There is sufficient evidence showing the role of neoantigens in clinically successful immunotherapy, providing a justification for targeting. Because of the significance of the pre-existing anti-tumor immune response for the immune checkpoint inhibitor, it is believed that personalized neoantigen-based therapy may be an imperative approach for cancer therapy. Thus, intensive attention is given to strategies targeting neoantigens for the significant impact with other immunotherapies, such as the immune checkpoint inhibitor. Today, several algorithms are designed and optimized based on Next-Generation Sequencing and public databases, including dbPepNeo, TANTIGEN 2.0, Cancer Antigenic Peptide Database, NEPdb, and CEDAR databases for predicting neoantigens in silico that stimulates the development of T cell therapies, cancer vaccine, and other ongoing immunotherapy approaches. Conclusions: In this review, we deliberated the current developments in understanding and recognition of the immunogenicity of newly found gastrointestinal neoantigens as well as their functions in immunotherapies and cancer detection. We also described how neoantigens are being developed and how they might be used in the treatment of GI malignancies.

Over time, a focus on blood pressure has transferred from diastolic pressure to systolic pressure. Formal analyses of differences in predictive value are scarce. Our goal of the study was whether office SBP adds prognostic information to office DBP and whether both 24-h ambulatory SBP and 24-h ambulatory DBP is specifically important. The authors examined 2097 participants from a population cohort recruited in Copenhagen, Denmark. Cause-specific Cox regression was performed to predict 10-year person-specific absolute risks of fatal and non-fatal cardiovascular (CV) events. Also, the time-dependent area under the receiver operator curve (AUC) was utilized to evaluate discriminative ability. The calibration plots of the models (Hosmer-May test) were calculated as well as the Brier score which combines (discrimination and calibration). Adding both 24-h ambulatory SBP and 24-h ambulatory diastolic blood pressure did not significantly increase AUC for CV mortality and CV events. Moreover, adding both office SBP and office DBP did not significantly improve AUC for both CV mortality and CV events. The difference in AUC (95% confidence interval; p-value) was .26% (-.2% to .73%; .27) for 10-year CV mortality and .69% (-.09% to 1.46%; .082) for 10-year risk of CV events. The difference in AUC was .12% (-.2% to .44%; .46) for 10-year CV mortality and .04% (-.35 to .42%; .85) for 10-year risk of CV events. Moreover, for both CV mortality and CV events, office SBP did not improve prognostic information to office DBP. In addition, the Brier scores of office BP in both CV mortality and CV events were .078 and .077, respectively. Furthermore, the Brier scores were .077 and .078 in CV mortality and CV events of 24-h ambulatory. For the average population as those participating in a population survey, the 10-year discriminative ability for long-term predictions of CV death and CV events is not improved by adding systolic to diastolic blood pressure. This finding is found for ambulatory as well as office blood pressure.

Gastric cancer (GC) is the fifth most frequent malignancy worldwide and the third leading cause of cancer-associated mortality. The study’s goal was to construct a predictive model and nomograms to predict the survival of GC patients. This historical cohort study assessed 733 patients who underwent treatments for GC. The univariate and multivariable Cox proportional hazard (CPH) survival analyses were applied to identify the factors related to overall survival (OS). A dynamic nomogram was developed as a graphical representation of the CPH regression model. The internal validation of the nomogram was evaluated by Harrell’s concordance index (C-index) and time-dependent AUC. The results of the multivariable Cox model revealed that the age of patients, body mass index (BMI), grade of tumor, and depth of tumor elevate the mortality hazard of gastric cancer patients (P < 0.05). The built nomogram had a discriminatory performance, with a C-index of 0.64 (CI 0.61, 0.67). We constructed and validated an original predictive nomogram for OS in patients with GC. Furthermore, nomograms may help predict the individual risk of OS in patients treated for GC.

Background: The increasing prevalence of colorectal cancer (CRC) in the past three decades in Iran has made it as a key public health burden. The goal of the study was to predict the metastasis in CRC patients using machine learning approach. Methods: This study is focused on 1127 CRC patients, who underwent proper treatments in tertiary Taleghani Hospital. The machine learning approach including Naive Bayes (NB), Random Forest (RF), Support Vector Machine (SVM), Neural Network (NN), Regression Tree (RT) and Logistic Regression (LR) were used for the prediction of metastasis in CRC. Receiver operating characteristic (ROC) curve, sensitivity, specificity and AUC were carried out to evaluate the performance of the approaches Results: Out of 1127 patients, 183(16%) experienced metastasis. In prediction of metastasis, the NN and RF had the most sensitivity. Also the specificity of NN and DT were greater in comparison to other methods. The NN had the highest AUC (0.99%), topmost sensitivity (98.5%) and accuracy (99.6%).Conclusion: Both tumor stage and size of tumor were regarded as indispensable variables in RF model, whereas the NN generally outperformed other ML-based approaches.