Miner, Martin

AbstractIntroductionPrior consensus meetings have addressed the relationship between phosphodiesterase type 5 (PDE5) inhibition and cardiac health. Given significant accumulation of new data in the past decade, a fourth consensus conference on this topic was convened in Pasadena, California, on March 10 and 11, 2023.ObjectivesOur meeting aimed to update existing knowledge, assess current guidelines, and make recommendations for future research and practice in this area.MethodsAn expert panel reviewed existing research and clinical practice guidelines.ResultsKey findings and clinical recommendations are the following: First, erectile dysfunction (ED) is a risk marker and enhancer for cardiovascular (CV) disease. For men with ED and intermediate levels of CV risk, coronary artery calcium (CAC) computed tomography should be considered in addition to previous management algorithms. Second, sexual activity is generally safe for men with ED, although stress testing should still be considered for men with reduced exercise tolerance or ischemia. Third, the safety of PDE5 inhibitor use with concomitant medications was reviewed in depth, particularly concomitant use with nitrates or alpha-blockers. With rare exceptions, PDE5 inhibitors can be safely used in men being treated for hypertension, lower urinary tract symptoms and other common male disorders. Fourth, for men unresponsive to oral therapy or with absolute contraindications for PDE5 inhibitor administration, multiple treatment options can be selected. These were reviewed in depth with clinical recommendations. Fifth, evidence from retrospective studies points strongly toward cardioprotective effects of chronic PDE5-inhibitor use in men. Decreased rates of adverse cardiac outcomes in men taking PDE-5 inhibitors has been consistently reported from multiple studies. Sixth, recommendations were made regarding over-the-counter access and potential risks of dietary supplement adulteration. Seventh, although limited data exist in women, PDE5 inhibitors are generally safe and are being tested for use in multiple new indications.ConclusionStudies support the overall cardiovascular safety of the PDE5 inhibitors. New indications and applications were reviewed in depth.

Abstract Background In 1999, 1 year after the approval of the first oral phosphodiesterase type 5 (PDE5) inhibitor for the treatment of erectile dysfunction (ED), the first Princeton Consensus Conference was held to address the clinical management of men with ED who also had cardiovascular disease. These issues were readdressed in the second and third conferences. In the 13 years since the last Princeton Consensus Conference, the experience with PDE5 inhibitors is more robust, and recent new data have emerged regarding not only safety and drug–drug interactions, but also a potential cardioprotective effect of these drugs. Aim In March 2023, an interdisciplinary group of scientists and practitioners met for the fourth Princeton Consensus Guidelines at the Huntington Medical Research Institutes in Pasadena, California, to readdress the cardiovascular workup of men presenting with ED as well as the approach to treatment of ED in men with known cardiovascular disease. Method A series of lectures from experts in the field followed by Delphi-type discussions were developed to reach consensus. Outcomes Consensus was reached regarding a number of issues related to erectile dysfunction and the interaction with cardiovascular health and phosphodiesterase-5 inhibitors. Results An algorithm based on recent recommendations of the American College of Cardiology and American Heart Association, including the use of computed tomography coronary artery calcium scoring, was integrated into the evaluation of men presenting with ED. Additionally, the issue of nitrate use was further considered in an algorithm regarding the treatment of ED patients with coronary artery disease. Other topics included the psychological effect of ED and the benefits of treating it; the mechanism of action of the PDE5 inhibitors; drug–drug interactions; optimizing use of a PDE5 inhibitors; rare adverse events; potential cardiovascular benefits observed in recent retrospective studies; adulteration of dietary supplements with PDE5 inhibitors; the pros and cons of over-the-counter PDE5 inhibitors; non–PDE5 inhibitor therapy for ED including restorative therapies such as stem cells, platelet-rich plasma, and shock therapy; other non–PDE5 inhibitor therapies, including injection therapy and penile prostheses; the issue of safety and effectiveness of PDE5 inhibitors in women; and recommendations for future studies in the field of sexual dysfunction and PDE5 inhibitor use were discussed. Clinical Implications Algorithms and tables were developed to help guide the clinician in dealing with the interaction of ED and cardiovascular risk and disease. Strengths and Limitations Strengths include the expertise of the participants and consensus recommendations. Limitations included that participants were from the United States only for this particular meeting. Conclusion The issue of the intersection between cardiovascular health and sexual health remains an important topic with new studies suggesting the cardiovascular safety of PDE5 inhibitors.

Motivation: The price of medical treatment continues to rise due to (i) an increasing population; (ii) an aging human growth; (iii) disease prevalence; (iv) a rise in the frequency of patients that utilize health care services; and (v) increase in the price. Objective: Artificial Intelligence (AI) is already well-known for its superiority in various healthcare applications, including the segmentation of lesions in images, speech recognition, smartphone personal assistants, navigation, ride-sharing apps, and many more. Our study is based on two hypotheses: (i) AI offers more economic solutions compared to conventional methods; (ii) AI treatment offers stronger economics compared to AI diagnosis. This novel study aims to evaluate AI technology in the context of healthcare costs, namely in the areas of diagnosis and treatment, and then compare it to the traditional or non-AI-based approaches. Methodology: PRISMA was used to select the best 200 studies for AI in healthcare with a primary focus on cost reduction, especially towards diagnosis and treatment. We defined the diagnosis and treatment architectures, investigated their characteristics, and categorized the roles that AI plays in the diagnostic and therapeutic paradigms. We experimented with various combinations of different assumptions by integrating AI and then comparing it against conventional costs. Lastly, we dwell on three powerful future concepts of AI, namely, pruning, bias, explainability, and regulatory approvals of AI systems. Conclusions: The model shows tremendous cost savings using AI tools in diagnosis and treatment. The economics of AI can be improved by incorporating pruning, reduction in AI bias, explainability, and regulatory approvals.

A diabetic foot infection (DFI) is among the most serious, incurable, and costly to treat conditions. The presence of a DFI renders machine learning (ML) systems extremely nonlinear, posing difficulties in CVD/stroke risk stratification. In addition, there is a limited number of well-explained ML paradigms due to comorbidity, sample size limits, and weak scientific and clinical validation methodologies. Deep neural networks (DNN) are potent machines for learning that generalize nonlinear situations. The objective of this article is to propose a novel investigation of deep learning (DL) solutions for predicting CVD/stroke risk in DFI patients. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) search strategy was used for the selection of 207 studies. We hypothesize that a DFI is responsible for increased morbidity and mortality due to the worsening of atherosclerotic disease and affecting coronary artery disease (CAD). Since surrogate biomarkers for CAD, such as carotid artery disease, can be used for monitoring CVD, we can thus use a DL-based model, namely, Long Short-Term Memory (LSTM) and Recurrent Neural Networks (RNN) for CVD/stroke risk prediction in DFI patients, which combines covariates such as office and laboratory-based biomarkers, carotid ultrasound image phenotype (CUSIP) lesions, along with the DFI severity. We confirmed the viability of CVD/stroke risk stratification in the DFI patients. Strong designs were found in the research of the DL architectures for CVD/stroke risk stratification. Finally, we analyzed the AI bias and proposed strategies for the early diagnosis of CVD/stroke in DFI patients. Since DFI patients have an aggressive atherosclerotic disease, leading to prominent CVD/stroke risk, we, therefore, conclude that the DL paradigm is very effective for predicting the risk of CVD/stroke in DFI patients.

The SARS-CoV-2 virus has caused a pandemic, infecting nearly 80 million people worldwide, with mortality exceeding six million. The average survival span is just 14 days from the time the symptoms become aggressive. The present study delineates the deep-driven vascular damage in the pulmonary, renal, coronary, and carotid vessels due to SARS-CoV-2. This special report addresses an important gap in the literature in understanding (i) the pathophysiology of vascular damage and the role of medical imaging in the visualization of the damage caused by SARS-CoV-2, and (ii) further understanding the severity of COVID-19 using artificial intelligence (AI)-based tissue characterization (TC). PRISMA was used to select 296 studies for AI-based TC. Radiological imaging techniques such as magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound were selected for imaging of the vasculature infected by COVID-19. Four kinds of hypotheses are presented for showing the vascular damage in radiological images due to COVID-19. Three kinds of AI models, namely, machine learning, deep learning, and transfer learning, are used for TC. Further, the study presents recommendations for improving AI-based architectures for vascular studies. We conclude that the process of vascular damage due to COVID-19 has similarities across vessel types, even though it results in multi-organ dysfunction. Although the mortality rate is ~2% of those infected, the long-term effect of COVID-19 needs monitoring to avoid deaths. AI seems to be penetrating the health care industry at warp speed, and we expect to see an emerging role in patient care, reduce the mortality and morbidity rate.

Background and Motivation: Parkinson’s disease (PD) is one of the most serious, non-curable, and expensive to treat. Recently, machine learning (ML) has shown to be able to predict cardiovascular/stroke risk in PD patients. The presence of COVID-19 causes the ML systems to become severely non-linear and poses challenges in cardiovascular/stroke risk stratification. Further, due to comorbidity, sample size constraints, and poor scientific and clinical validation techniques, there have been no well-explained ML paradigms. Deep neural networks are powerful learning machines that generalize non-linear conditions. This study presents a novel investigation of deep learning (DL) solutions for CVD/stroke risk prediction in PD patients affected by the COVID-19 framework. Method: The PRISMA search strategy was used for the selection of 292 studies closely associated with the effect of PD on CVD risk in the COVID-19 framework. We study the hypothesis that PD in the presence of COVID-19 can cause more harm to the heart and brain than in non-COVID-19 conditions. COVID-19 lung damage severity can be used as a covariate during DL training model designs. We, therefore, propose a DL model for the estimation of, (i) COVID-19 lesions in computed tomography (CT) scans and (ii) combining the covariates of PD, COVID-19 lesions, office and laboratory arterial atherosclerotic image-based biomarkers, and medicine usage for the PD patients for the design of DL point-based models for CVD/stroke risk stratification. Results: We validated the feasibility of CVD/stroke risk stratification in PD patients in the presence of a COVID-19 environment and this was also verified. DL architectures like long short-term memory (LSTM), and recurrent neural network (RNN) were studied for CVD/stroke risk stratification showing powerful designs. Lastly, we examined the artificial intelligence bias and provided recommendations for early detection of CVD/stroke in PD patients in the presence of COVID-19. Conclusion: The DL is a very powerful tool for predicting CVD/stroke risk in PD patients affected by COVID-19.

Background: The previous COVID-19 lung diagnosis system lacks both scientific validation and the role of explainable artificial intelligence (AI) for understanding lesion localization. This study presents a cloud-based explainable AI, the “COVLIAS 2.0-cXAI” system using four kinds of class activation maps (CAM) models. Methodology: Our cohort consisted of ~6000 CT slices from two sources (Croatia, 80 COVID-19 patients and Italy, 15 control patients). COVLIAS 2.0-cXAI design consisted of three stages: (i) automated lung segmentation using hybrid deep learning ResNet-UNet model by automatic adjustment of Hounsfield units, hyperparameter optimization, and parallel and distributed training, (ii) classification using three kinds of DenseNet (DN) models (DN-121, DN-169, DN-201), and (iii) validation using four kinds of CAM visualization techniques: gradient-weighted class activation mapping (Grad-CAM), Grad-CAM++, score-weighted CAM (Score-CAM), and FasterScore-CAM. The COVLIAS 2.0-cXAI was validated by three trained senior radiologists for its stability and reliability. The Friedman test was also performed on the scores of the three radiologists. Results: The ResNet-UNet segmentation model resulted in dice similarity of 0.96, Jaccard index of 0.93, a correlation coefficient of 0.99, with a figure-of-merit of 95.99%, while the classifier accuracies for the three DN nets (DN-121, DN-169, and DN-201) were 98%, 98%, and 99% with a loss of ~0.003, ~0.0025, and ~0.002 using 50 epochs, respectively. The mean AUC for all three DN models was 0.99 (p < 0.0001). The COVLIAS 2.0-cXAI showed 80% scans for mean alignment index (MAI) between heatmaps and gold standard, a score of four out of five, establishing the system for clinical settings. Conclusions: The COVLIAS 2.0-cXAI successfully showed a cloud-based explainable AI system for lesion localization in lung CT scans.

Background: COVID-19 is a disease with multiple variants, and is quickly spreading throughout the world. It is crucial to identify patients who are suspected of having COVID-19 early, because the vaccine is not readily available in certain parts of the world. Methodology: Lung computed tomography (CT) imaging can be used to diagnose COVID-19 as an alternative to the RT-PCR test in some cases. The occurrence of ground-glass opacities in the lung region is a characteristic of COVID-19 in chest CT scans, and these are daunting to locate and segment manually. The proposed study consists of a combination of solo deep learning (DL) and hybrid DL (HDL) models to tackle the lesion location and segmentation more quickly. One DL and four HDL models—namely, PSPNet, VGG-SegNet, ResNet-SegNet, VGG-UNet, and ResNet-UNet—were trained by an expert radiologist. The training scheme adopted a fivefold cross-validation strategy on a cohort of 3000 images selected from a set of 40 COVID-19-positive individuals. Results: The proposed variability study uses tracings from two trained radiologists as part of the validation. Five artificial intelligence (AI) models were benchmarked against MedSeg. The best AI model, ResNet-UNet, was superior to MedSeg by 9% and 15% for Dice and Jaccard, respectively, when compared against MD 1, and by 4% and 8%, respectively, when compared against MD 2. Statistical tests—namely, the Mann–Whitney test, paired t-test, and Wilcoxon test—demonstrated its stability and reliability, with p < 0.0001. The online system for each slice was <1 s. Conclusions: The AI models reliably located and segmented COVID-19 lesions in CT scans. The COVLIAS 1.0Lesion lesion locator passed the intervariability test.

Purpose: The role of erectile dysfunction (ED) has recently shown an association with the risk of stroke and coronary heart disease (CHD) via the atherosclerotic pathway. Cardiovascular disease (CVD)/stroke risk has been widely understood with the help of carotid artery disease (CTAD), a surrogate biomarker for CHD. The proposed study emphasizes artificial intelligence-based frameworks such as machine learning (ML) and deep learning (DL) that can accurately predict the severity of CVD/stroke risk using carotid wall arterial imaging in ED patients. Methods: Using the PRISMA model, 231 of the best studies were selected. The proposed study mainly consists of two components: (i) the pathophysiology of ED and its link with coronary artery disease (COAD) and CHD in the ED framework and (ii) the ultrasonic-image morphological changes in the carotid arterial walls by quantifying the wall parameters and the characterization of the wall tissue by adapting the ML/DL-based methods, both for the prediction of the severity of CVD risk. The proposed study analyzes the hypothesis that ML/DL can lead to an accurate and early diagnosis of the CVD/stroke risk in ED patients. Our finding suggests that the routine ED patient practice can be amended for ML/DL-based CVD/stroke risk assessment using carotid wall arterial imaging leading to fast, reliable, and accurate CVD/stroke risk stratification. Summary: We conclude that ML and DL methods are very powerful tools for the characterization of CVD/stroke in patients with varying ED conditions. We anticipate a rapid growth of these tools for early and better CVD/stroke risk management in ED patients.

Diabetes is one of the main causes of the rising cases of blindness in adults. This microvascular complication of diabetes is termed diabetic retinopathy (DR) and is associated with an expanding risk of cardiovascular events in diabetes patients. DR, in its various forms, is seen to be a powerful indicator of atherosclerosis. Further, the macrovascular complication of diabetes leads to coronary artery disease (CAD). Thus, the timely identification of cardiovascular disease (CVD) complications in DR patients is of utmost importance. Since CAD risk assessment is expensive for low-income countries, it is important to look for surrogate biomarkers for risk stratification of CVD in DR patients. Due to the common genetic makeup between the coronary and carotid arteries, low-cost, high-resolution imaging such as carotid B-mode ultrasound (US) can be used for arterial tissue characterization and risk stratification in DR patients. The advent of artificial intelligence (AI) techniques has facilitated the handling of large cohorts in a big data framework to identify atherosclerotic plaque features in arterial ultrasound. This enables timely CVD risk assessment and risk stratification of patients with DR. Thus, this review focuses on understanding the pathophysiology of DR, retinal and CAD imaging, the role of surrogate markers for CVD, and finally, the CVD risk stratification of DR patients. The review shows a step-by-step cyclic activity of how diabetes and atherosclerotic disease cause DR, leading to the worsening of CVD. We propose a solution to how AI can help in the identification of CVD risk. Lastly, we analyze the role of DR/CVD in the COVID-19 framework.