The sympathetic nervous system in heart failure revisited.

Several attempts have been made, by the scientific community, to develop a unifying hypothesis that explains the clinical syndrome of heart failure (HF). The currently widely accepted neurohormonal model has substituted the cardiorenal and the cardiocirculatory models, which focused on salt-water retention and low cardiac output/peripheral vasoconstriction, respectively. According to the neurohormonal model, HF with eccentric left ventricular (LV) hypertrophy (LVH) (systolic HF or HF with reduced LV ejection fraction [LVEF] or HFrEF) develops and progresses because endogenous neurohormonal systems, predominantly the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS), exhibit prolonged activation following the initial heart injury exerting deleterious hemodynamic and direct nonhemodynamic cardiovascular effects. However, there is evidence to suggest that SNS overactivity often preexists HF development due to its association with HF risk factors, is also present in HF with preserved LVEF (diastolic HF or HFpEF), and that it is linked to immune/inflammatory factors. Furthermore, SNS activity in HF may be augmented by coexisting noncardiac morbidities and modified by genetic factors and demographics. The purpose of this paper is to provide a contemporary overview of the complex associations between SNS overactivity and the development and progression of HF, summarize the underlying mechanisms, and discuss the clinical implications as they relate to therapeutic interventions mitigating SNS overactivity.

Machine learning and artificial intelligence in cardiac transplantation: A systematic review.

BACKGROUND: This review aims to systematically evaluate the currently available evidence investigating the use of artificial intelligence (AI) and machine learning (ML) in the field of cardiac transplantation. Furthermore, based on the challenges identified we aim to provide a series of recommendations and a knowledge base for future research in the field of ML and heart transplantation. METHODS: A systematic database search was conducted of original articles that explored the use of ML and/or AI in heart transplantation in EMBASE, MEDLINE, Cochrane database, and Google Scholar, from inception to November 2021. RESULTS: Our search yielded 237 articles, of which 13 studies were included in this review, featuring 463 850 patients. Three main areas of application were identified: (1) ML for predictive modeling of heart transplantation mortality outcomes; (2) ML in graft failure outcomes; (3) ML to aid imaging in heart transplantation. The results of the included studies suggest that AI and ML are more accurate in predicting graft failure and mortality than traditional scoring systems and conventional regression analysis. Major predictors of graft failure and mortality identified in ML models were: length of hospital stay, immunosuppressive regimen, recipient's age, congenital heart disease, and organ ischemia time. Other potential benefits include analyzing initial lab investigations and imaging, assisting a patient with medication adherence, and creating positive behavioral changes to minimize further cardiovascular risk. CONCLUSION: ML demonstrated promising applications for improving heart transplantation outcomes and patient-centered care, nevertheless, there remain important limitations relating to implementing AI into everyday surgical practices.

Bioinformatic Analysis of the BCL-xL/BCL2L1 Interactome in Patients with Pancreatic Cancer.

Objectives: The aim of the present study was to analyze the differential gene expression of BCL-xL/BCL2L and the associated genetic, molecular, and biologic functions in pancreatic ductal adenocarcinoma (PDAC) by employing advanced bioinformatics to investigate potential candidate genes implicated in the pathogenesis of PDAC. Materials and Methods: Bioinformatic techniques were employed to build the gene network of BCL-xL, to assess the translational profile of BCL-xL in PDAC, assess its role in predicting PDAC, and investigate the associated biologic functions and the regulating miRNA families. Results: Microarray data extracted from one dataset was incorporated, including 130 samples (PDAC: 69; Control: 61). In addition, the expression level of BCL-xL was higher in PDAC compared to control samples (p < 0.001). Furthermore, BCL-xL demonstrated excellent discrimination (AUC: 0.83 [95% Confidence Intervals: 0.76, 0.90]; p < 0.001) and calibration (R squared: 0.31) traits for PDAC. A gene set enrichment analysis (GSEA) demonstrated the molecular functions and miRNA families (hsa-miR-4804-5p, hsa-miR-4776-5p, hsa-miR-6770-3p, hsa-miR-3619-3p, and hsa-miR-7152-3p) related to BCL-xL. Conclusions: The current findings unveil the biological implications of BCL-xL in PDAC and the related molecular functions and miRNA families.

Validation of the Surgical Outcome Risk Tool (SORT) for Predicting Postoperative Mortality in Colorectal Cancer Patients Undergoing Surgery and Subgroup Analysis.

BACKGROUND: The accurate evaluation of perioperative risk is crucial to facilitate the shared decision-making process. Surgical outcome risk tool (SORT) has been developed to provide enhanced and more feasible identification of high-risk surgical patients. Nonetheless, SORT has not been validated for patients with colorectal cancer undergoing surgery. Our aim was to determine whether SORT can accurately predict mortality after surgery for colorectal cancer and to compare it with traditional risk models. METHOD: 526 patients undergoing surgery performed by a colorectal surgical team in a single Greek tertiary hospital (2011-2019) were included. Five risk models were evaluated: (1) SORT, (2) Physiology and Operative Severity Score for the enumeration of Mortality and Morbidity (POSSUM), (3) Portsmouth POSSUM (P-POSSUM), (4) Colorectal POSSUM (CR-POSSUM), and (5) the Association of Great Britain and Ireland (ACPGBI) score. Model accuracy was assessed by observed to expected (O:E) ratios, and area under Receiver Operating Characteristic curve (AUC). RESULTS: Ten patients (1.9%) died within 30 days of surgery. SORT was associated with an excellent level of discrimination [AUC:0.81 (95% CI:0.68-0.94); p = 0.001] and provided the best performing calibration of all models in the entire dataset analysis (H-L:2.82; p = 0.83). Nonetheless, SORT underestimated mortality. SORT model demonstrated excellent discrimination and calibration predicting perioperative mortality in patients undergoing (1) open surgery, (2) emergency/acute surgery, and (3) in cases with colon-located cancer. CONCLUSION: SORT is an easily adopted risk-assessment tool, associated with enhanced accuracy, that could be implemented in the perioperative pathway of patients undergoing surgery for colorectal cancer.

Uniportal Versus Multiportal Video-Assisted Thoracoscopic Lobectomy for Lung Cancer: An Updated Meta-analysis.

OBJECTIVE: We reviewed the available literature on patients with lung cancer undergoing either uniportal (UVATS) or multiport video-assisted thoracoscopic surgery (MVATS). METHODS: Original research studies that evaluated perioperative and long-term outcomes of UVATS versus MVATS were identified, from January 1990 to April 2020. The perioperative, along with the oncologic and long-term survival outcomes, were calculated according to either a fixed or a random effect model, appropriately. The Q statistics and I2 statistic were used to test for heterogeneity among the studies. RESULTS: Twenty studies were included, incorporating a total of 1,469 patients treated with UVATS and 3,231 treated with MVATS. The incidence of complications was lower in patients treated with UVATS [OR: 0.76 (95% CI 0.62, 0.93); p = 0.008]. The chest tube duration was significantly lower in the UVATS group (WMD: - 0.63 [95% CI - 1.03, - 0.23]; p = 0.002). Length of hospital stay (L.O.S.) was also lower in the UVATS patient group (WMD: - 0.54 [- 0.94, - 0.13]; p = 0.009), along with postoperative pain [WMD: - 0.57 (95% CI - 0.97, - 0.18); p = 0.004]. No significant differences were found regarding the mean operative time (M.O.T.), mean blood loss, the number of resected lymph nodes, the 30-day mortality, along with the survival at 1 and 3 years postoperatively. CONCLUSIONS: The present meta-analysis indicates that UVATS is associated with enhanced outcomes in patients undergoing surgery for lung cancer. Well-designed, randomized studies, comparing UVATS to MVATS, are necessary to further assess their long-term clinical outcomes.

Iatrogenic Bile Duct Injuries: A Critical Appraisal of Classification Systems.

Bile duct injuries represent the most dramatic complications after an open or laparoscopic cholecystectomy. The detrimental effects on patient quality of life and overall survival are the most obvious consequences of such injuries. An effective treatment strategy after accurate mapping of the injury type is the only method of averting these morbid consequences. Several classification systems have been proposed in an attempt to accurately describe and categorize bile duct injuries. The critical question is whether we truly need all these systems and whether each of these systems adds value to the existing knowledge base, or further obscures the field. Each classification system has several advantages to base its clinical utility on, but entails a reasonable number of limitations as well. Currently, a tailored approach adopting the classification system which provides the most appropriate guidance - either in terms of diagnosis or treatment decision making - appears to be the most justified option.

A meta-analysis of liver-first versus classical strategy for synchronous colorectal liver metastases.

BACKGROUND: This study aimed to compare the perioperative outcomes of liver-first (LFS) and classical (CS) strategy for the management of synchronous colorectal liver metastases (sCRLM). METHOD: A literature search was performed in PubMed, Scopus, and Cochrane databases, in accordance with the PRISMA guidelines. The odds ratio, weighted mean difference, and 95% confidence interval were evaluated by means of the random-effects model. RESULTS: Ten articles met the inclusion criteria, incorporating 3656 patients. Patients in the LFS group reported increased size of sCRLM and a higher rate of major hepatectomies. This study reveals comparable overall survival and disease-free survival at 1, 3, and 5 years postoperatively between the two strategies. Moreover, the mean operative time, length of hospital stay, the incidence of severe complications, and the 30-day and 90-day mortality were similar between the two groups. The mean intraoperative blood loss was significantly increased in the LFS group. CONCLUSION: These outcomes suggest that both approaches are feasible and safe. Given the lack of randomized clinical trials, this meta-analysis represents the best currently available evidence. However, the results should be treated with caution given the small number of the included studies. Randomized trials comparing LFS to CS are necessary to further evaluate their outcomes.

In Silico Transcriptomic Analysis of the Chloride Intracellular Channels (CLIC) Interactome Identifies a Molecular Panel of Seven Prognostic Markers in Patients with Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis. In this context, the identification of biomarkers regarding the PDAC diagnosis, monitoring, and prognosis is crucial. OBJECTIVES: The purpose of the current study was to investigate the differential gene expression profile of the chloride intracellular channel (CLIC) gene family network in patients with PDAC, in order to suggest novel biomarkers. METHODS: In silico techniques were used to construct the interactome of the CLIC gene family, identify the differentially expressed genes (DEGs) in PDAC as compared to healthy controls, and evaluate their potential prognostic role. RESULTS: Transcriptomic data of three microarray datasets were included, incorporating 114 tumor and 59 normal pancreatic samples. Twenty DEGs were identified; eight were up-regulated and twelve were downregulated. A molecular signature of seven genes (Chloride Intracellular Channel 1 - CLIC1; Chloride Intracellular Channel 3 - CLIC3; Chloride Intracellular Channel 4 - CLIC4; Ganglioside Induced Differentiation Associated Protein 1 - GDAP1; Ganglioside Induced Differentiation Associated Protein 1 Like 1 - GDAP1L1; Glutathione S-Transferase Pi 1 - GSTP1; Prostaglandin E Synthase 2 - PTGES2) were identified as prognostic markers associated with overall survival. Positive correlations were reported regarding the expression of CLIC1-CLIC3, CLIC4-CLIC5, and CLIC5-CLIC6. Finally, gene set enrichment analysis demonstrated the molecular functions and miRNA families (hsa-miR-122, hsa-miR-618, hsa-miR-425, and hsa-miR-518) relevant to the seven prognostic markers. CONCLUSION: These outcomes demonstrate a seven-gene molecular panel that predicts the patients' prospective survival following pancreatic resection for PDAC.

Transcriptomic analysis of the Aquaporin (AQP) gene family interactome identifies a molecular panel of four prognostic markers in patients with pancreatic ductal adenocarcinoma.

BACKGROUND: This study aimed to assess the differential gene expression of aquaporin (AQP) gene family interactome in pancreatic ductal adenocarcinoma (PDAC) using data mining techniques to identify novel candidate genes intervening in the pathogenicity of PDAC. METHOD: Transcriptome data mining techniques were used in order to construct the interactome of the AQP gene family and to determine which genes members are differentially expressed in PDAC as compared to controls. The same techniques were used in order to evaluate the potential prognostic role of the differentially expressed genes. RESULTS: Transcriptome microarray data of four GEO datasets were incorporated, including 142 primary tumor samples and 104 normal pancreatic tissue samples. Twenty differentially expressed genes were identified, of which nineteen were downregulated and one up-regulated. A molecular panel of four genes (Aquaporin 7 - AQP7; Archain 1 - ARCN1; Exocyst Complex Component 3 - EXOC3; Coatomer Protein Complex Subunit Epsilon - COPE) were identified as potential prognostic markers associated with overall survival. CONCLUSION: These outcomes should be further assessed in vitro in order to fully understand the role of these genes in the pathophysiological mechanism of PDAC.

Tumor-treating fields as a fourth treating modality for glioblastoma: a meta-analysis.

BACKGROUND: We aim to review the available literature on patients suffering from glioblastoma treated with tumor-treating fields (TTFields) plus radio chemotherapy or conventional radio chemotherapy alone, to compare the efficacy and safety of the two methods. METHODS: A systematic literature search was performed in PubMed, Cochrane library, and Scopus databases, in accordance with the PRISMA guidelines. Six studies met the inclusion criteria incorporating 1806 patients for the qualitative analysis and 1769 for the quantitative analysis. RESULTS: This study reveals increased median overall survival (weighted mean difference (WMD) 3.29 [95% confidence interval (CI) 2.37, 4.21]; p < 0.00001), survival at 1 year (odds ratio (OR) 1.81 [95% CI 1.41, 2.32]; p < 0.00001) and 2 years (OR 2.33 [95% CI 1.73, 3.14]; p < 0.00001), and median progression-free survival (WMD 2.35 [95% CI 1.76, 2.93]; p < 0.00001) along with progression-free survival at 6 months (WMD 6.86 [95% CI 5.91, 7.81]; p < 0.00001) for the patients treated with TTFields. Survival at 3 years was comparable between the two groups. TTFields were associated with fewer adverse events compared to chemotherapy along with similar incidence of skin irritation. CONCLUSIONS: TTFields are a safe and efficient novel treatment modality. More randomized controlled studies, with longer follow-up, are necessary to further assess the clinical outcomes of TTFields.

A meta-analysis of laparoscopic versus open left lateral hepatic sectionectomy.

BACKGROUND: This study aimed to assess the perioperative outcomes of laparoscopic left lateral sectionectomy (LLLS) compared with an open (OLLS) approach. METHOD: A systematic literature search was performed in PubMed, Scopus and Cochrane library, in accordance with the PRISMA guidelines. The Odds Ratio (ORs), the weighted mean difference (WMD) and 95% confidence interval (95% CI) were evaluated, by means of Random-Effects model. RESULTS: Ten articles met the inclusion criteria and incorporated 2640 patients. This study reveals comparable mean operative time, mean operative margin size and rate of R1 resection between LLLS and OLLS. The intraoperative mean blood loss, mean length of ICU stay, mean hospital stay were significantly increased in the OLLS group (p < 0.05). Complications were assessed according to the Clavien-Dindo classification. The incidence of grade I-II complications was similar between the two groups. The incidence of grade III-V complications was increased in the OLLS group (p = 0.008). The mean perioperative cost was similar between the two techniques. CONCLUSION: These outcomes for left lateral sectionectomy suggest that both approaches are feasible and safe. However, the results should be treated with caution given the small number of the included randomized controlled studies and potential for selection bias between the two techniques.

Latest updates on structure and recommendations of cardiac rehabilitation programs in chronic heart failure.

Chronic heart failure (HF) is a clinical syndrome with high morbidity and mortality worldwide. Cardiac rehabilitation (CR) is a medically supervised program designed to maintain or improve cardiovascular health of people living with HF, recommended by both American and European guidelines. A CR program consists of a multispecialty group including physicians, nurses, physiotherapists, trainers, nutritionists, and psychologists with the common purpose of improving functional capacity and quality of life of chronic HF patients. Physical activity, lifestyle, and psychological support are core components of a successful CR program. CR has been shown to be beneficial in all ejection fraction categories in HF and most patients, who are stable under medication, are capable of participating. An individualized exercise prescription should be developed on the basis of a baseline evaluation in all patients. The main modalities of exercise training are aerobic exercise and muscle strength training of different intensity and frequency. It is important to set the appropriate clinical outcomes from the beginning, in order to assess the effectiveness of a CR program. There are still significant limitations that prevent patients from participating in these programs and need to be solved. A significant limitation is the generally low quality of research in CR and the presence of negative trials, such as the rehabilitation after myocardial infarction trial, where comprehensive rehabilitation following myocardial infraction had no important effect on mortality, morbidity, risk factors, or health-related quality of life or activity. In the present editorial, we present all the updated knowledge and recommendations in CR programs.

Heart Transplantation.

Heart transplantation (HTx) remains the last therapeutic resort for patients with advanced heart failure. The present work is a clinically focused review discussing current issues in heart transplantation. Several factors have been associated with the outcome of HTx, such as ABO and HLA compatibility, graft size, ischemic time, age, infections, and the cause of death, as well as imaging and laboratory tests. In 2018, UNOS changed the organ allocation policy for HTx. The aim of this change was to prioritize patients with a more severe clinical condition resulting in a reduction in mortality of people on the waiting list. Advanced heart failure and resistant angina are among the main indications of HTx, whereas active infection, peripheral vascular disease, malignancies, and increased body mass index (BMI) are important contraindications. The main complications of HTx include graft rejection, graft angiopathy, primary graft failure, infection, neoplasms, and retransplantation. Recent advances in the field of HTx include the first two porcine-to-human xenotransplantations, the inclusion of hepatitis C donors, donation after circulatory death, novel monitoring for acute cellular rejection and antibody-mediated rejection, and advances in donor heart preservation and transportation. Lastly, novel immunosuppression therapies such as daratumumab, belatacept, IL 6 directed therapy, and IgG endopeptidase have shown promising results.

Artificial Intelligence in Heart Failure: Friend or Foe?

In recent times, there have been notable changes in cardiovascular medicine, propelled by the swift advancements in artificial intelligence (AI). The present work provides an overview of the current applications and challenges of AI in the field of heart failure. It emphasizes the "garbage in, garbage out" issue, where AI systems can produce inaccurate results with skewed data. The discussion covers issues in heart failure diagnostic algorithms, particularly discrepancies between existing models. Concerns about the reliance on the left ventricular ejection fraction (LVEF) for classification and treatment are highlighted, showcasing differences in current scientific perceptions. This review also delves into challenges in implementing AI, including variable considerations and biases in training data. It underscores the limitations of current AI models in real-world scenarios and the difficulty in interpreting their predictions, contributing to limited physician trust in AI-based models. The overarching suggestion is that AI can be a valuable tool in clinicians' hands for treating heart failure patients, as far as existing medical inaccuracies have been addressed before integrating AI into these frameworks.

Assessment of Myocardial Viability in Ischemic Cardiomyopathy With Reduced Left Ventricular Function Undergoing Coronary Artery Bypass Grafting.

BACKGROUND: We aim to provide a comprehensive review of the current state of knowledge of myocardial viability assessment in patients undergoing coronary artery bypass grafting (CABG), with a focus on the clinical markers of viability for each imaging modality. We also compare mortality between patients with viable myocardium and those without viability who undergo CABG. METHODS: A systematic database search with meta-analysis was conducted of comparative original articles (both observations and randomized controlled studies) of patients undergoing CABG with either viable or nonviable myocardium, in EMBASE, MEDLINE, Cochrane database, and Google Scholar, from inception to 2022. Imaging modalities included were dobutamine stress echocardiography (DSE), cardiac magnetic resonance (CMR), single-photon emission computed tomography (SPECT), and positron emission tomography (PET). RESULTS: A total of 17 studies incorporating a total of 2317 patients were included. Across all imaging modalities, the relative risk of death post-CABG was reduced in patients with versus without viability (random-effects model: odds ratio: 0.42; 95% confidence interval: 0.29-0.61; p < 0.001). Imaging for myocardial viability has significant clinical implications as it can affect the accuracy of the diagnosis, guide treatment decisions, and predict patient outcomes. Generally, based on local availability and expertise, either SPECT or DSE should be considered as the first step in evaluating viability, while PET or CMR would provide further evaluation of transmurality, perfusion metabolism, and extent of scar tissue. CONCLUSION: The assessment of myocardial viability is an essential component of preoperative evaluation in patients with ischemic heart disease undergoing surgical revascularization. Careful patient selection and individualized assessment of viability remain paramount.

Prevention of Anthracyclines and HER2 Inhibitor-Induced Cardiotoxicity: A Systematic Review and Meta-Analysis.

BACKGROUND: This meta-analysis and systematic review aim to consolidate evidence on cardiotoxicity prevention and treatment strategies in patients receiving anthracyclines or HER2 receptor inhibitors, vital treatments for breast cancer and hematologic malignancies. By synthesizing existing research, the goal is to provide impactful insights that enhance patient care and outcomes. METHODS: Comprehensive research across PubMed, Scopus, EMBASE, and the Cochrane Central Register for Controlled Trials was conducted, selecting clinical trials focusing on cardioprotection in anthracyclines or HER2 inhibitor-treated individuals. Effect sizes were computed using OpenMeta (Analyst), with leave-out meta-analysis to assess potential small study effects. Meta-regression explored treatment duration and sample size effects. Evidence quality for primary outcomes was evaluated using ROB, Robins 2, and Newcastle-Ottawa tools. RESULTS: Twenty -three studies involving a total of 14,652 patients (13,221 adults and 1431 kids) were included in the current systematic review and meta-analysis. The risk of bias and methodological quality of the included studies suggested good and moderate quality. Patients prescribed ß-blockers demonstrated a 74% lower likelihood of exhibiting cardiotoxicity symptoms (OR 1.736). Similarly, the use of dexrazoxane was linked to a threefold decrease in cardiac abnormalities risk (OR 2.989), and ACE inhibitor administration showed half the risk compared with the control group (OR 1.956). CONCLUSIONS: Through this systematic review and meta-analysis, it was shown that there is a reduction in cardiotoxicity from either anthracyclines or HER2 inhibitors in patients receiving pharmacoprophylaxis.

Validation of Perioperative Troponin Levels for Predicting Postoperative Mortality and Long-Term Survival in Patients Undergoing Surgery for Hepatobiliary and Pancreatic Cancer.

Background: Hepatopancreato and biliary (HPB) tumors represent some of the leading cancer-related causes of death worldwide, with the majority of patients undergoing surgery in the context of a multimodal treatment strategy. Consequently, the implementation of an accurate risk stratification tool is crucial to facilitate informed consent, along with clinical decision making, and to compare surgical outcomes among different healthcare providers for either service evaluation or clinical audit. Perioperative troponin levels have been proposed as a feasible and easy-to-use tool in order to evaluate the risk of postoperative myocardial injury and 30-day mortality. The purpose of the present study is to validate the perioperative troponin levels as a prognostic factor regarding postoperative myocardial injury and 30-day mortality in Greek adult patients undergoing HPB surgery. Method: In total, 195 patients undergoing surgery performed by a single surgical team in a single tertiary hospital (2020-2022) were included. Perioperative levels of troponin before surgery and at 24 and 48 h postoperatively were assessed. Model accuracy was assessed by observed-to-expected (O:E) ratios, and area under the receiver operating characteristic curve (AUC). Survival at one year postoperatively was compared between patients with high and normal TnT levels at 24 h postoperatively. Results: Thirteen patients (6.6%) died within 30 days of surgery. TnT levels at 24 h postoperatively were associated with excellent discrimination and provided the best-performing calibration. Patients with normal TnT levels at 24 h postoperatively were associated with higher long-term survival compared to those with high TnT levels. Conclusions: TnT at 24 h postoperatively is an efficient risk assessment tool that should be implemented in the perioperative pathway of patients undergoing surgery for HPB cancer.