Novel regimens and treatment strategies in neoadjuvant therapy for colorectal cancer: A systematic review.

Objective: The objective of this systematic review was to describe novel regimens and treatment strategies in neoadjuvant therapy for colorectal cancer (CRC). The aim was to summarize the current advancements in neoadjuvant chemotherapy (NACT) for CRC, including the use of cytotoxic drugs, targeted treatments, and immunotherapy. The analysis aimed to provide insights into the potential benefits and drawbacks of these novel approaches and highlight the need for further research to optimize NACT use in CRC and improve patient outcomes. Methods: From October 20, 2023, to December 10, 2023, a comprehensive literature search was conducted across multiple databases, including PubMed, Ovid, Web of Science, the Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Embase, and Scopus. Studies addressing the use of and treatment strategies for CRC and neoadjuvant therapies were included. Screening was conducted in two steps, initially by title and abstract and then by full-text articles. English-language articles were considered, while preprints, non-English publications, and articles published as grey literature were excluded from the study. A total of 85 studies were selected for further analysis after screening and filtering. Results: After filtering out duplicates and items that were irrelevant to our research query from the initial database search's 510 results, 397 unique articles were found. Eighty-five studies were chosen for additional analysis after the articles underwent two rounds of screening. Conclusion: The review concluded that neoadjuvant therapy for CRC has evolved beyond conventional approaches and holds promise for improving patient outcomes. Future prospects for advancing neoadjuvant approaches are promising, with ongoing clinical trials investigating the refinement of strategies, identification of predictive biomarkers, and optimization of patient selection. The adoption of novel regimens, precision medicine, and immunotherapy offers opportunities to redefine treatment paradigms and enhance patient care in CRC.

Artificial intelligence-enhanced electrocardiography for accurate diagnosis and management of cardiovascular diseases.

Electrocardiography (ECG), improved by artificial intelligence (AI), has become a potential technique for the precise diagnosis and treatment of cardiovascular disorders. The conventional ECG is a frequently used, inexpensive, and easily accessible test that offers important information about the physiological and anatomical state of the heart. However, the ECG can be interpreted differently by humans depending on the interpreter's level of training and experience, which could make diagnosis more difficult. Using AI, especially deep learning convolutional neural networks (CNNs), to look at single, continuous, and intermittent ECG leads that has led to fully automated AI models that can interpret the ECG like a human, possibly more accurately and consistently. These AI algorithms are effective non-invasive biomarkers for cardiovascular illnesses because they can identify subtle patterns and signals in the ECG that may not be readily apparent to human interpreters. The use of AI in ECG analysis has several benefits, including the quick and precise detection of problems like arrhythmias, silent cardiac illnesses, and left ventricular failure. It has the potential to help doctors with interpretation, diagnosis, risk assessment, and illness management. Aside from that, AI-enhanced ECGs have been demonstrated to boost the identification of heart failure and other cardiovascular disorders, particularly in emergency department settings, allowing for quicker and more precise treatment options. The use of AI in cardiology, however, has several limitations and obstacles, despite its potential. The effective implementation of AI-powered ECG analysis is limited by issues such as systematic bias. Biases based on age, gender, and race result from unbalanced datasets. A model's performance is impacted when diverse demographics are inadequately represented. Potentially disregarded age-related ECG variations may result from skewed age data in training sets. ECG patterns are affected by physiological differences between the sexes; a dataset that is inclined toward one sex may compromise the accuracy of the others. Genetic variations influence ECG readings, so racial diversity in datasets is significant. Furthermore, issues such as inadequate generalization, regulatory barriers, and interpretability concerns contribute to deployment difficulties. The lack of robustness in models when applied to disparate populations frequently hinders their practical applicability. The exhaustive validation required by regulatory requirements causes a delay in deployment. Difficult models that are not interpretable erode the confidence of clinicians. Diverse dataset curation, bias mitigation strategies, continuous validation across populations, and collaborative efforts for regulatory approval are essential for the successful deployment of AI ECG in clinical settings and must be undertaken to address these issues. To guarantee a safe and successful deployment in clinical practice, the use of AI in cardiology must be done with a thorough understanding of the algorithms and their limits. In summary, AI-enhanced electrocardiography has enormous potential to improve the management of cardiovascular illness by delivering precise and timely diagnostic insights, aiding clinicians, and enhancing patient outcomes. Further study and development are required to fully realize AI's promise for improving cardiology practices and patient care as technology continues to advance.

Association of serum digoxin concentration with morbidity and mortality in patients with atrial fibrillation, heart failure and reduced ejection fraction of 45 % or below.

BACKGROUND: Atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF) are common cardiovascular conditions linked to significant health burdens. This review aims to study the relationship of serum digoxin concentration and mortality and morbidity outcomes in defined population. METHODS: We conducted a thorough search of databases such as PubMed, Google Scholar, and Cochrane Library, from inception until 20th Aug 2023. Studies that explored the relationship between serum digoxin concentration and mortality, morbidity, or other clinical endpoints in AF and HFrEF patients (ejection fraction ≤45 %) were eligible for inclusion. RESULTS: The selected studies exhibited a wide range of designs, patient cohorts, and measured outcomes. The association between serum digoxin concentration, mortality and morbidity endpoints like hospitalization rates and cardiovascular events were assessed in these studies. Despite the methodological diversity, our systematic review uncovered consistent trends across the studies, suggesting that elevated serum digoxin concentrations may correlate with higher mortality and morbidity in AF and HFrEF patients. CONCLUSION: This systematic review emphasizes the need for cautious management of serum digoxin levels in patients with concurrent AF and HFrEF. While digoxin remains a valuable treatment for heart failure, its potential adverse effects on outcomes in this specific patient subgroup call for vigilant monitoring and individualized treatment approaches. Further research is required to elucidate the dose-response relationship and potential confounding factors influencing outcomes associated with serum digoxin concentration in AF and HFrEF patients. Clinicians should consider these findings when making therapeutic decisions to enhance patient care and outcomes.

Study of telomerase reverse transcriptase and uterine-ovarian-specific genes expression in the endometrial tissue of ovariectomized female Sprague-Dawley rats.

BACKGROUND: An in vivo study was carried out to study of telomerase reverse transcriptase and Uterine-Ovarian-specific genes expression in the endometrial tissue of ovariectomized female Sprague-Dawley rats. MATERIAL AND METHODS: Twenty-four female Sprague-Dawley rats divided into 4 groups of six rats. The first and second groups were ovariectomized and given tamoxifen and tamoxifen-loaded SLN respectively for six days continuously. Group 3 served as the untreated ovariectomized control group and group 4 was made up of untreated normal healthy rats. At the end of the study, the rats were sacrificed and study of the genes expression and serum zinc and copper were carried out. RESULTS: The results showed that the expression of TERT in the group treated with tamoxifen, and tamoxifen-loaded solid lipid nanoparticles, significantly decreased (p<0.001) compared with ovariectomized control group. The results also revealed that the treatment with tamoxifen-loaded solid lipid nanoparticles increased expression of UO-44 gene compared to ovariectomized control group, while there was no difference between tamoxifen treated and control group. CONCLUSIONS: Encapsulation of tamoxifen in solid lipid nanoparticles increased its targeting efficiency and improved the impact of the drug on the serum levels of some trace elements.

Effects of tamoxifen-loaded solid lipid nanoparticles on the estrogen receptor-α (ER-α) and vascular endothelial growth factor-A (VEGF-A) genes expression in the endometrial tissue of ovariectomized female Sprague-Dawley rats.

BACKGROUND: The effect of tamoxifen on endometrial carcinogenesis stems from its estrogen agonist effect. An in vivo study was carried out to compare the effect of tamoxifen-loaded solid lipid nanoparticles and free drug on the ER-α and VEGF-A genes expression. MATERIAL AND METHODS: Twenty-four female Sprague-Dawley rats divided into 4 groups of six rats were used for this study. The first and second groups were ovariectomized and given tamoxifen and tamoxifen-loaded SLN respectively for six days continuously. Group 3 served as the untreated ovariectomized control group and group 4 was made up of untreated normal healthy rats. At the end of the study, the rats were sacrificed and study of the genes expression and serum oxidative stress were carried out. RESULTS: The results of this study showed that treatment with tamoxifen-loaded SLN significantly reduced the mRNA levels of ERα and VEGF-A gene and the total oxidant status compared to the ovariectomized control group. CONCLUSIONS: The results of this study revealed that encapsulation of tamoxifen in solid lipid nanoparticles may have less adverse effects on the oxidative stress status and incidence of endometrial cancer.

Evaluation of adenosine deaminase (ADA) isoenzymes activity and tumor necrosis factor-α (TNFα) concentration in chronic heart failure.

INTRODUCTION: Chronic heart failure (CHF) has recently been considered as an inflammatory disease. Enhanced production of tumor necrosis factor-α (TNFα) in CHF patients has been proved. To compensate deleterious effects of TNα, the concentration of adenosine is increased in CHF. However, concurrent determination of serum TNFα and enzymatic activities of ADA and its ADA1 and ADA2 isoenzymes, as the main regulators of adenosine concentration, has not yet been carried out. MATERIALS AND METHODS: Blood samples were collected from 52 CHF patients and 55 healthy controls. Laboratory routine tests were performed, and after determining the concentration of TNFα, total ADA (tADA) as well as ADA1 and ADA2 isoenzyme activities were measured. RESULTS: Mean concentration of TNFα increased over 2 fold in CHF patients (12.54 ± 11.69 pg/ml compared with 6.0 ± 6.58 pg/ml in controls). The highest level of TNFα was observed in patients with the final stage of the disease (NHYA IV subgroup), according to the New York Heart Association classification. tADA activity was significantly lower in CHF patients compared with controls (19.29 ± 9.73 and 24.3 ± 6.01 U/L, respectively). ADA2 activity markedly decreased in CHF patients and showed a direct correlation with tADA (r = 0.641, P = 0001). In addition, the lowest levels of tADA and ADA2 activities were observed in patients from the 4(th) quartile of NYHA classification. CONCLUSION: Adenosine deaminase activity is reduced in CHF patients to give rise to the concentration of adenosine, thereby attenuating pathologic consequences of CHF. Therefore, it is concluded that ADA activity is of paramount importance in pathophysiology of heart failure and might be used for diagnostic purposes or treatment targets.

Diagnostic value of serum adenosine deaminase activity in HIV infected patients of Kurdish population.

BACKGROUND: Adenosine deaminase (ADA) is a hydrolytic enzyme involved in the deamination of adenosine to inosine. ADA is involved in T-lymphocyte differentiation and development. This study was aimed to determine the diagnostic value of the adenosine deaminase (ADA) activity test for the diagnosis of HIV positive patients in the Kurdish population. METHODS: This descriptive analytical case-control study was performed on 30 healthy and 60 HIV positive subjects. Blood CD4+ cell count was recorded and serum total ADA, and ADA1 and ADA2 isoenzyme activities were determined. RESULTS: Serum total ADA and ADA2 isoenzyme activity was significantly higher in HIV positive patients than in healthy subjects. CD4+ cell counts markedly decreased in all patients and showed a significant inverse correlation with ADA activities. Using a cut-off level of 36.52 U/L and 30.98 U/L for serum total ADA and ADA2, respectively, sensitivity and specificity were 90.9% and 90.27% for total ADA and 93% and 90% for ADA2, respectively. CONCLUSIONS: Serum ADA was significantly increased in HIV infected patients. Therefore, because of its low cost and simplicity to perform, ADA activity might be considered a useful diagnostic tool among the other markers in this disease.