Forme Fruste Keratoconus Detection with OCT Corneal Topography Using Artificial Intelligence Algorithms.

PURPOSE: Distinguishing early Keratoconus (KC) from normal corneas is challenging owing to their striking similarities. The aim of our study was to identify discriminating parameters to differentiate a normal cornea from a Form Fruste Keratoconus (FFKC) with the Swept-Source (SS) OCT-topography CASIA 2 (Tomey,Japan) using machine learning artificial intelligence algorithms. SETTING: The study was monocentric, carried out in Bordeaux. DESIGN: This was a retrospective study, case control. METHODS: Three groups were included: KC group (108 eyes), FFKC (88 eyes) and normal corneas (162 eyes).The data were analyzed and processed using the Dataiku data science platform. Machine learning models (Random Forest, Logistic Regression) were used to develop a multiclass classifier for automated early KC detection. The models were trained using a training database and tested using a test database. Then algorithms were compared to the Ectasia Screening Index (ESI), which is an OCT-topography inherent screening score for ectasia. RESULTS: The Logistic Regression (LR), and Random Forest (RF) detected FFKC with an AUC of 0,99, and 0,98 respectively. The sensitivities of LR (100%), RF (84%) were better than the ESI (28%) for the diagnosis of FFKC. However, ESI has a maximum specificity (100%) compared to the RL (100%) and 90% for RF. CONCLUSION: This study identified discriminating topographic parameters to be considered in refractive surgery screening on SS-OCT CASIA 2. We developed an algorithm capable of classifying normal eyes versus FFKC cases, with improved performance compared to the ESI score.

[Implementation of edoxaban anti-Xa activity assay in a hospital laboratory and evaluation of its analytical performance]. / Mise en place du dosage de l'activité anti-Xa de l'edoxaban dans un laboratoire hospitalier et évaluation de ses performances analytiques.

Edoxaban is a direct oral anticoagulant available in Europe but not in France. Given the high tourist traffic in France, understanding the pharmacology of edoxaban and the availability of its laboratory testing seemed crucial in emergency situations. The aim of this work was to describe the methodology for measuring the anti-Xa activity of edoxaban, highlighting pre-analytical and analytical aspects, along with essential clinico-biological data for therapeutic guidance. The analysis was performed using the chromogenic method on the STAR-Max analyzer, with the STA®-Liquid ANTI-Xa kit (Diagnostica Stago®). Anti-Xa Edoxaban level measurement has a detection limit of 15 ng/mL, a quantification limit of 20 ng/mL and a linearity limit of 400 ng/mL. Repeatability, intermediate precision, accuracy, and measurement uncertainty studies were conducted to assess method performance, meeting quality requirements. The comparison between two STAR-Max® analyzers showed excellent results with linear regression and a low bias with good precision and no loss of dispersion regardless of edoxaban levels. In conclusion, although the measurement of edoxaban level may be rarely necessary in clinical practice, its implementation is straightforward. The availability of edoxaban in neighboring countries, underscores the importance of having its measurement available in hospital laboratories.

[Evaluation of a semi-automated test for quantification of von Willebrand multimers]. / Évaluation d'un test semi-automatisé de quantification des multimères du facteur von Willebrand.

The assessment of von Willebrand factor (VWF) multimer distribution, particularly following the implantation of circulatory support devices, is a crucial parameter in hemostasis. Our study aimed to evaluate the semi-automated quantification of VWF multimers using the Sebia Hydrasys analyzer. Our analysis focused on quantifying high molecular weight, intermediate weight, and low molecular weight VWF multimers. Electrophoretic migration was performed using the Hydrasys 2 scan, and interpretation was carried out using densitometric analysis with the Phoresis software. The Hydrasys scan 2 successfully separated all the expected VWF multimer profiles based on the type of von Willebrand disease. The analysis revealed that in patients with circulatory support devices, elevated levels of plasma VWF rendered multimer migration unanalyzable using the methodology recommended by the manufacturer. Therefore, adjustment to a 100 % VWF antigenic level improved gel precision. We also suggest using as a standardized control the Cryocheck™ plasma, and have established reference values. Overall, this semi-automated, standardized, and optimized VWF multimer analysis system allows for an effective assessment of the VWF multimeric profile.

Targeting TXNIP in endothelial progenitors mitigates IL-8-induced neutrophil recruitment under metabolic stress.

BACKGROUND: This study explores the potential role of Thioredoxin-interacting protein (TXNIP) silencing in endothelial colony-forming cells (ECFCs) within the scope of age-related comorbidities and impaired vascular repair. We aim to elucidate the effects of TXNIP silencing on vasculogenic properties, paracrine secretion, and neutrophil recruitment under conditions of metabolic stress. METHODS: ECFCs, isolated from human blood cord, were transfected with TXNIP siRNA and exposed to a high glucose and ß-hydroxybutyrate (BHB) medium to simulate metabolic stress. We evaluated the effects of TXNIP silencing on ECFCs' functional and secretory responses under these conditions. Assessments included analyses of gene and protein expression profiles, vasculogenic properties, cytokine secretion and neutrophil recruitment both in vitro and in vivo. The in vivo effects were examined using a murine model of hindlimb ischemia to observe the physiological relevance of TXNIP modulation under metabolic disorders. RESULTS: TXNIP silencing did not mitigate the adverse effects on cell recruitment, vasculogenic properties, or senescence induced by metabolic stress in ECFCs. However, it significantly reduced IL-8 secretion and consequent neutrophil recruitment under these conditions. In a mouse model of hindlimb ischemia, endothelial deletion of TXNIP reduced MIP-2 secretion and prevented increased neutrophil recruitment induced by age-related comorbidities. CONCLUSIONS: Our findings suggest that targeting TXNIP in ECFCs may alleviate ischemic complications exacerbated by metabolic stress, offering potential clinical benefits for patients suffering from age-related comorbidities.

Extracellular Microvesicles vs. Mitochondria: Competing for the Top Spot in Cardiovascular Regenerative Medicine.

Regenerative medicine aims to restore, replace, and regenerate human cells, tissues, and organs. Despite significant advancements, many cell therapy trials for cardiovascular diseases face challenges like cell survival and immune compatibility, with benefits largely stemming from paracrine effects. Two promising therapeutic tools have been recently emerged in cardiovascular diseases: extracellular vesicles (EVs) and mitochondrial transfer. Concerning EVs, the first pivotal study with EV-enriched secretome derived from cardiovascular progenitor cells has been done treating heart failure. This first in man demonstrated the safety and feasibility of repeated intravenous infusions and highlighted significant clinical improvements, including enhanced cardiac function and reduced symptoms in heart failure patients. The second study uncovered a novel mechanism of endothelial regeneration through mitochondrial transfer via tunneling nanotubes (TNTs). This research showed that mesenchymal stromal cells (MSCs) transfer mitochondria to endothelial cells, significantly enhancing their bioenergetics and vessel-forming capabilities. This mitochondrial transfer was crucial for endothelial cell engraftment and function, offering a new strategy for vascular regeneration without the need for additional cell types. Combining EV and mitochondrial strategies presents new clinical opportunities. These approaches could revolutionize regenerative medicine, offering new hope for treating cardiovascular and other degenerative diseases. Continued research and clinical trials will be crucial in optimizing these therapies, potentially leading to personalized medicine approaches that enhance patient outcomes.

Multi-ancestry polygenic risk scores for venous thromboembolism.

Venous thromboembolism (VTE) is a significant contributor to morbidity and mortality, with large disparities in incidence rates between Black and White Americans. Polygenic risk scores (PRSs) limited to variants discovered in genome-wide association studies in European-ancestry samples can identify European-ancestry individuals at high risk of VTE. However, there is limited evidence on whether high-dimensional PRS constructed using more sophisticated methods and more diverse training data can enhance the predictive ability and their utility across diverse populations. We developed PRSs for VTE using summary statistics from the International Network against Venous Thrombosis (INVENT) consortium genome-wide association studies meta-analyses of European- (71 771 cases and 1 059 740 controls) and African-ancestry samples (7482 cases and 129 975 controls). We used LDpred2 and PRS-CSx to construct ancestry-specific and multi-ancestry PRSs and evaluated their performance in an independent European- (6781 cases and 103 016 controls) and African-ancestry sample (1385 cases and 12 569 controls). Multi-ancestry PRSs with weights tuned in European-ancestry samples slightly outperformed ancestry-specific PRSs in European-ancestry test samples (e.g. the area under the receiver operating curve [AUC] was 0.609 for PRS-CSx_combinedEUR and 0.608 for PRS-CSxEUR [P = 0.00029]). Multi-ancestry PRSs with weights tuned in African-ancestry samples also outperformed ancestry-specific PRSs in African-ancestry test samples (PRS-CSxAFR: AUC = 0.58, PRS-CSx_combined AFR: AUC = 0.59), although this difference was not statistically significant (P = 0.34). The highest fifth percentile of the best-performing PRS was associated with 1.9-fold and 1.68-fold increased risk for VTE among European- and African-ancestry subjects, respectively, relative to those in the middle stratum. These findings suggest that the multi-ancestry PRS might be used to improve performance across diverse populations to identify individuals at highest risk for VTE.

Hyperthermia for Targeting Cancer and Cancer Stem Cells: Insights from Novel Cellular and Clinical Approaches.

The Cellular Heat Shock Response and in particular heat shock protein activation are vital stress reactions observed in both healthy and cancer cells. Hyperthermia (HT) has been proposed for several years as an advancing non-invasive cancer therapy. It selectively targets cancer cells through mechanisms influenced by temperature and temperature variations. This article delves into the impact of HT on cancer cells, especially cancer stem cells (CSCs), essential contributors to cancer recurrence and metastasis. HT has shown promise in eliminating CSCs, sensitizing them to conventional treatments and modulating the tumor microenvironment. The exploration extends to mesenchymal stem cells (MSCs), which exhibit both pro-tumorigenic and anti-tumorigenic effects. HT's potential in recruiting therapeutic MSCs for targeted delivery of antitumoral agents is also discussed. Furthermore, the article introduces Brain Thermodynamics-guided Hyperthermia (BTGH) technology, a breakthrough in temperature control and modulation of heat transfer under different conditions. This non-invasive method leverages the brain-eyelid thermal tunnel (BTT) to monitor and regulate internal brain temperature. BTGH technology, with its precision and noninvasive continuous monitoring capabilities, is under clinical investigation for applications in neurological disorders and cancer. The innovative three-phase approach involves whole-body HT, targeted brain HT, and organ-specific HT. In conclusion, the exploration of localized or whole-body HT offers promising avenues for cancer, psychiatric and neurological diseases. The ongoing clinical investigations and potential applications underscore the significance of understanding and harnessing heat's responses to enhance human health.

The Onset of Intussusceptive Angiogenesis in COVID-19 Patients Might Come from the Mobilization of Stem Cell Sub-Populations Expressing the Hemangioblast Marker CD143.

COVID-19 and infectious diseases have been included in strategic development goals (SDG) of United Nations (UN). The SARS-CoV-2 pandemic has unveiled complex pathophysiological mechanisms underpinning COVID-19, notably inducing a systemic acquired vascular hemopathy characterized by endothelial dysfunction and intussusceptive angiogenesis, a rapid vascular remodeling process identified as a hallmark in severe COVID-19 cases affecting pulmonary and cardiac tissues. Stem cell migration have been proposed as significant regulators of this neoangiogenic process. In a monocentric cross-sectional study, through spectral flow cytometry analysis of peripheral blood mononuclear cells, we identified a distinct stem cell subpopulation mobilized in critical COVID-19. Indeed, by an unsupervised analysis generating a UMAP representation we highlighted eleven different clusters in critical and non-critical COVID-19 patients. Only one cluster was significantly associated to critical COVID-19 compared to non-critical patients. This cluster expressed the markers: CD45dim, CD34+, CD117+, CD147+, and CD143+, and were negative for CD133. Higher level of expression of hemangioblast markers CD143 were found in critical COVID-19 patients. This population, indicative of hemangioblast-like cells, suggests a key role in COVID-19-related neoangiogenesis, potentially driving the severe vascular complications observed. Our findings underscore the need for further investigation into the contributions of adult stem cells in COVID-19 pathology, offering new insights into therapeutic targets and interventions.

DOAC-Remove to counteract the interference of anti-Xa oral anticoagulants on the monitoring of heparin.

INTRODUCTION: The monitoring of unfractionated heparin (UFH) by anti-factor Xa activity (AXA) is commonly used to ensure effective anticoagulation and prevent bleeding risk. However, in patients previously treated with an anti-Xa direct oral anticoagulant (DOAC) switching to UFH therapy, there is a risk of interference that may lead to inappropriate anticoagulation. The first objective of this study was to validate DOAC-Remove to remove DOAC for measuring UFH specific AXA. The second objective was to assess the length of DOAC interference on UFH monitoring and to identify potential predictive factors. MATERIALS AND METHODS: This monocentric retrospective study included all patients admitted from April 2019 to April 2021 previously treated with anti-Xa DOAC, and for whom an interference on UFH monitoring was suspected. Interference was defined as a difference in the AXA measured before and after using DOAC-Remove >2.8-fold standard deviation of the method. RESULTS: Removal with DOAC-Remove was specific of DOAC (apixaban n = 42, rivaroxaban n = 41, UFH n = 20) and sufficient to avoid interference on UFH AXA measurement. The exact interference length was 6.0 days [IQR 3.0-11.0] for apixaban (n = 26) and 4.5 days [IQR 2.0-5.8] for rivaroxaban (n = 20). Among the 89 patients sorted based on an interference length ≤ or >3 days, 74 (83.1%) presented an interference greater than 3 days. Correlations were observed with age for apixaban and creatinine for rivaroxaban. CONCLUSIONS: Our results suggest that DOAC-Remove could be of high interest in patients receiving UFH previously treated with an anti-Xa DOAC even if DOAC was stopped for more than 3 days.

Evaluating the efficacy of Rho kinase inhibitor eye drops in the management of corneal edema: A single-center retrospective cohort study.

PURPOSE: This study aimed to evaluate the efficacy of ripasudil in managing various corneal edema conditions. MATERIALS AND METHODS: This single-center retrospective analysis was conducted at Hadassah Medical Center and involved 16 patients with 17 eyes. Patients were selected based on diagnostic criteria, primarily corneal edema. The conditions were as follows, listed by frequency: postcataract surgery (31.25%), postpenetrating keratoplasty (25%), post-Descemet's membrane endothelial keratoplasty (18.75%), Fuchs' endothelial corneal dystrophy (12.5%), status post-Ahmed glaucoma valve (6.25%), and status posttrabeculectomy (6.25%). The treatment regimen involved topical administration of ripasudil hydrochloride hydrate (Glanatec® 0.4%), administered three times a day or tailored to condition severity. Efficacy was assessed using pre- and posttreatment measurements of best-corrected visual acuity (BCVA), central corneal thickness (CCT), and endothelial cell count (ECC), along with slit-lamp and optical coherence tomography examinations. RESULTS: The average duration of ripasudil treatment was approximately 4.9 ± 2.2 months. Significant improvements were observed in BCVA, changing from a pretreatment value of 1.106 ± 0.817 logMAR to a posttreatment value of 0.56 ± 0.57 logMAR (P = 0.0308). CCT also showed a significant reduction, from 619.50 ± 56.36 µm pretreatment to 572.5 ± 75.48 µm posttreatment (P = 0.0479). ECC showed a marginal but not statistically significant increase, from 849.00 ± 570.72 cells/mm² pretreatment to 874.75 ± 625.59 cells/mm² posttreatment (P = 0.9010). CONCLUSION: The study provides robust evidence supporting the use of ripasudil in managing corneal edema. Significant improvements in key ocular metrics such as BCVA and CCT were observed, enhancing the overall quality of life for patients suffering from various forms of corneal edema.

[New anticoagulants in 2024: Development of factor XI and XIa inhibitors]. / Les nouveaux anticoagulants en 2024 : développement des inhibiteurs du facteur XI et du XIa.

Thrombosis remains one of the leading causes of death in the world. The history of anticoagulation has evolved considerably from non-specific drugs (i.e., heparins and vitamin K antagonists, VKA) to agents that directly target specific coagulation factors (i.e., argatroban, fondaparinux and direct oral anticoagulants, DOAC). Since the last decade, DOAC are widely used in clinical practice because of their ease to use, their favorable pharmacological profile and the fact that they do not require monitoring. However, despite having a better safety profile than vitamin K antagonist, their bleeding risk is not negligible. New anticoagulants targeting the contact phase of coagulation are currently being developed and could make it possible to prevent the risk of thrombosis without impairing hemostasis. Epidemiological and preclinical data on FXI deficiency make FXI a promising therapeutic target. The aim of this review is to summarize the results of the various clinical trials available that focus on FXI/FXIa inhibition, and to highlight the challenges that this new therapeutic class of anticoagulants will face.

Acute phase determinant of post-thrombotic syndrome: A review of the literature.

BACKGROUND: Post-thrombotic syndrome (PTS) is the main long-term complication of deep vein thrombosis (DVT). Several therapies are being evaluated to prevent or to treat PTS. Identifying the patients most likely to benefit from these therapies presents a significant challenge. OBJECTIVES: The objective of this review was to identify risk factors for PTS during the acute phase of DVT. ELIGIBILITY CRITERIA: We searched the PubMed and Cochrane databases for studies published between January 2000 and January 2021, including randomized clinical trials, meta-analyses, systematic reviews and observational studies. RESULTS: Risk factors for PTS such as proximal location of DVT, obesity, chronic venous disease, history of DVT are associated with higher risk of PTS. On the initial ultrasound-Doppler, a high thrombotic burden appears to be a predictor of PTS. Among the evaluated biomarkers, some inflammatory markers such as ICAM-1, MMP-1 and MMP-8 appear to be associated with a higher risk of developing PTS. Coagulation disorders are not associated with risk of developing PTS. Role of endothelial biomarkers in predicting PTS has been poorly explored. Lastly, vitamin K antagonist was associated with a higher risk of developing PTS when compared to direct oral anticoagulants and low molecular weight heparin. CONCLUSIONS: Several risk factors during the acute phase of VTE are associated with an increased risk of developing PTS. There is a high-unmet medical need to identify potential biomarkers for early detection of patients at risk of developing PTS after VTE. Inflammatory and endothelial biomarkers should be explored in larger prospective studies to identify populations that could benefit from new therapies.

Understanding the Angiogenic Characteristics of Clinical-Grade Mesenchymal Stromal Cells Isolated from Human Umbilical Cord.

Addressing the challenges in managing ischemic tissue repair and remodelling remains a prominent clinical concern. Current research is heavily concentrated on identifying innovative cell-based therapies with the potential to enhance revascularization in patients affected by these diseases. We have previously developed and validated a manufacturing process for human umbilical cord mesenchymal stromal cells (UC-MSCs)-based cell therapy medicinal product, according to Good Manufacturing Practices. In this study, we demonstrate that these UC-MSCs enhance the proliferation and migration of endothelial cells and the formation of capillary structures. Moreover, UC-MSCs and endothelial cells interact, allowing UC-MSCs to acquire a perivascular cell phenotype and consequently provide direct support to the newly formed vascular network. This characterization of the proangiogenic properties of this UC-MSCs based-cell therapy medicinal product is an essential step for its therapeutic assessment in the clinical context of vascular regeneration.

Treatment of Rapid Progression of Myopia: Topical Atropine 0.05% and MF60 Contact Lenses.

This retrospective study evaluates the effectiveness of combining 0.05% atropine with MF60 contact lenses in managing rapid myopia progression in children over one year. The study involved three groups: the treatment group (TG) with 15 children (53% male, average age 12.9 ± 1.04), the MF group (MF) with 12 children (50% male, average age 12.8 ± 0.8) using only MF60 lenses, and the control group (CG) with 14 children (43% male, average age 12.1 ± 0.76). Baseline myopia and axial length (AL) were similar across groups, with the TG, MF, and CG showing -4.02 ± 0.70 D, -4.18 ± 0.89 D, -3.86 ± 0.99 D, and 24.72 ± 0.73 mm, 24.98 ± 0.70 mm, 24.59 ± 1.02 mm, respectively. Prior to the study, all groups exhibited significant myopia and AL progression, with no previous myopia control management. The treatment involved daily 0.05% atropine instillation, the use of MF60 lenses and increased outdoor activity. Biannual cycloplegic refraction and slit lamp evaluations confirmed no adverse reactions. After one year, the TG showed a significant reduction in myopia and AL progression (-0.43 ± 0.46 D, p < 0.01; 0.22 ± 0.23 mm, p < 0.01), whereas the CG showed minimal change (-1.30 ± 0.43 D, p = 0.36; 0.65 ± 0.35 mm, p = 0.533). The MF group also exhibited a notable decrease (-0.74 ± 0.45 D, p < 0.01; 0.36 ± 0.23 mm). Increased outdoor activity during the treatment year did not significantly impact myopia control, suggesting its limited additional effect in this cohort. The study concludes that the combination of 0.05% atropine and peripheral defocus soft contact lenses effectively controls myopia progression in children.

Tissue engineering strategies for breast reconstruction: a literature review of current advances and future directions.

Background and Objective: Mastectomy is a primary treatment for breast cancer patients, and both autologous and implant-based reconstructive techniques have shown excellent results. In recent years, advancements in bioengineering have led to a proliferation of innovative approaches to breast reconstruction. This article comprehensively explores the promising perspectives offered by bioengineering and tissue engineering in the field of breast reconstruction. Methods: A literature review was conducted between April and June 2023 on PubMed and Google Scholar Databases. All English and French articles related to bioengineering applied to the field of breast reconstruction were included. We used the Evidence-Based Veterinary Medicine Association (EBVM) Toolkit 14 checklist for narrative reviews as a quality assurance measure and the Scale for the Assessment of Narrative Review Articles (SANRA) tool to self-assess our methodology. Key Content and Findings: Over 130 references related to breast bioengineering were included. The analysis revealed four key applications: enhancing the quality of the skin envelope, improving the viability of fat grafting, creating breast shape and volume via bio-printing, and optimizing nipple reconstruction through engineering techniques. The primary identified approaches revolved around establishing structural support and enhancing cellular viability. Structural techniques predominantly involved the implementation of 3D printed, decellularized, or biocompatible material scaffolds. Meanwhile, promoting cellular content trophicity primarily focused on harnessing the regenerative potential of adipose-derived stem cells (ADSCs) and increasing the tissue's survivability and cell trophicity. Conclusions: Tissue and bioengineering hold immense promise in the field of breast reconstruction, offering a diverse array of approaches. By combining existing techniques with novel advancements, they have the potential to significantly enhance the therapeutic options available to plastic and reconstructive surgeons.

Multi-ancestry polygenic risk scores for venous thromboembolism.

Venous thromboembolism (VTE) is a significant contributor to morbidity and mortality, with large disparities in incidence rates between Black and White Americans. Polygenic risk scores (PRSs) limited to variants discovered in genome-wide association studies in European-ancestry samples can identify European-ancestry individuals at high risk of VTE. However, there is limited evidence on whether high-dimensional PRS constructed using more sophisticated methods and more diverse training data can enhance the predictive ability and their utility across diverse populations. We developed PRSs for VTE using summary statistics from the International Network against Venous Thrombosis (INVENT) consortium GWAS meta-analyses of European- (71,771 cases and 1,059,740 controls) and African-ancestry samples (7,482 cases and 129,975 controls). We used LDpred2 and PRSCSx to construct ancestry-specific and multi-ancestry PRSs and evaluated their performance in an independent European- (6,261 cases and 88,238 controls) and African-ancestry sample (1,385 cases and 12,569 controls). Multi-ancestry PRSs with weights tuned in European- and African-ancestry samples, respectively, outperformed ancestry-specific PRSs in European- (PRSCSXEUR: AUC=0.61 (0.60, 0.61), PRSCSX_combinedEUR: AUC=0.61 (0.60, 0.62)) and African-ancestry test samples (PRSCSXAFR: AUC=0.58 (0.57, 0.6), PRSCSX_combined AFR: AUC=0.59 (0.57, 0.60)). The highest fifth percentile of the best-performing PRS was associated with 1.9-fold and 1.68-fold increased risk for VTE among European- and African-ancestry subjects, respectively, relative to those in the middle stratum. These findings suggest that the multi-ancestry PRS may be used to identify individuals at highest risk for VTE and provide guidance for the most effective treatment strategy across diverse populations.

Hemocompatibility and biophysical interface of left ventricular assist devices and total artificial hearts.

ABSTRACT: Over the past 2 decades, there has been a significant increase in the utilization of long-term mechanical circulatory support (MCS) for the treatment of cardiac failure. Left ventricular assist devices (LVADs) and total artificial hearts (TAHs) have been developed in parallel to serve as bridge-to-transplant and destination therapy solutions. Despite the distinct hemodynamic characteristics introduced by LVADs and TAHs, a comparative evaluation of these devices regarding potential complications in supported patients, has not been undertaken. Such a study could provide valuable insights into the complications associated with these devices. Although MCS has shown substantial clinical benefits, significant complications related to hemocompatibility persist, including thrombosis, recurrent bleeding, and cerebrovascular accidents. This review focuses on the current understanding of hemostasis, specifically thrombotic and bleeding complications, and explores the influence of different shear stress regimens in long-term MCS. Furthermore, the role of endothelial cells in protecting against hemocompatibility-related complications of MCS is discussed. We also compared the diverse mechanisms contributing to the occurrence of hemocompatibility-related complications in currently used LVADs and TAHs. By applying the existing knowledge, we present, for the first time, a comprehensive comparison between long-term MCS options.