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Almost all cell types naturally secret extracellular vesicles (EVs) in the extracellular space with variable metabolic cargo facilitating intracellular communication, posing immune-modulation capacity. Thus, "bacterial extracellular vesicles" (BEVs), with their great immunoregulatory, immune response stimulation and disease condition-altering potential, have gained importance in the medical and therapeutic industry. Various subtypes of BEVs were observed and reported in the literature, such as exosomes (30-150 nm), microvesicles (100-1000 nm), apoptotic bodies (1000-5000 nm), and oncosomes (1000-10,000 nm). As biological systems are complex entities, inserting BEVs requires extra high purity. Various techniques for BEV isolation have been employed alone or with other strategies, such as ultracentrifugation, precipitation, size-exclusion chromatography, affinity-based separation, ultrafiltration, and field-flow fractionation. But to date, no BEV isolation method is considered perfect as the lack of standard protocols limits their scale-up. Medical research has focused on BEVs to explore their diverse therapeutic potential. This review particularly focused on the recent advancements in the potential medical application of BEVs, current challenges, and prospects associated with their scale-up., (© 2024 Wiley‐VCH GmbH.)

Catalytic nanoparticle@metal-organic framework (MOF) composites have attracted significant interest in point-of-care testing (POCT) owing to their prominent catalytic activity. However, the trade-off between high loading efficiency and high catalytic activity remains challenging because high concentrations of nanoparticles tend to cause the misjoining and collapse of the MOFs. Herein, a facile strategy is reported to encapsulate high concentrations of platinum (Pt) nanoparticles into zeolitic imidazolate framework-8 (ZIF-8) using polydopamine (PDA) as a support for Pt@ZIF-8 and as a flexible scaffold for further immobilization of Pt nanoparticles. The resulting composite (Pt@ZIF-8@PDA@Pt) exhibits ultrahigh Pt nanoparticle loading efficiency, exceptional catalytic activity, stability, and a bright colorimetric signal. Following integration with lateral flow immunoassay (LFIA), the detection limits for pre- and post-catalysis detection of B-type natriuretic peptide (NT-proBNP) are 0.18 and 0.015 ng mL -1 , respectively, representing a 6-fold and 70-fold improvement compared to gold nanoparticle-based LFIA. Moreover, Pt@ZIF-8@PDA@Pt-based LFIA achieves 100% diagnostic sensitivity for NT-proBNP in a cohort of 184 clinical samples., (© 2024 Wiley‐VCH GmbH.)

Soluble ST2 (sST2) is the expression of a pathogenic process related to adverse remodeling that ultimately leads to increased mortality in heart failure (HF). Risk score models provide a comprehensive approach for mortality prediction, beyond the use of biomarkers alone. The objective was to determine the additional value of sST2 and two well-validated contemporary risk scores, BCN-Bio-HF and MAGGIC-HF, in predicting mortality and readmission in the acute setting. This prospective study included 129 patients (mean age 75 ± 9 years; 52% males) after an urgent HF visit. Baseline sST2 levels were measured and the two risk scores were calculated. The primary endpoint was all-cause mortality, and the secondary endpoint was HF readmissions. The follow-up period was 3.6 ± 1.9 years. Patients who died (46%) had higher sST2 concentrations (80.5 vs. 42.7 ng/ml; p < 0.001). The BCN-Bio-HF calculator with sST2 demonstrated the best discriminative ability for mortality prediction (area under the ROC curve: 0.792; p < 0.001). In multivariate analysis for each risk score, the MAGGIC-HF score retained its predictive value only in the model without sST2 (3-year risk: HR = 1.036; 95% CI 1.019-1.054; p < 0.001). However, the BCN-Bio-HF score maintained its prognostic value with sST2 (HR = 1.032; 95%CI 1.020-1.044; p < 0.001), as well as without sST2 (HR = 1.035; 95% CI 1.021-1.049; p < 0.001). sST2 was not associated with readmission, and only the BCN-Bio-HF risk of HF hospitalization showed independent predictive value (OR = 1.040; 95% CI 1.005-1.076; p = 0.023). For predicting long-term mortality in HF in the emergency department, the BCN-Bio-HF calculator with sST2 demonstrated superior discrimination and allows estimation of the risk of HF hospitalizations., (© 2023. Springer Nature Japan KK, part of Springer Nature.)

Extracellular vesicles (EVs), acting as an important ingredient of intercellular communication through paracrine actions, have gained tremendous attention in the field of tissue engineering (TE). Moreover, these nanosized extracellular particles (30-140 nm) can be incorporated into biomaterials according to different principles to facilitate signal delivery in various regenerative processes directly or indirectly. Bioactive biomaterials as the carrier will extend the retention time and realize the controlled release of EVs, which further enhance their therapeutic efficiency in tissue regeneration. Herein, the basic biological characteristics of EVs are first introduced, and then their outstanding performance in exerting direct impacts on target cells in tissue regeneration as well as indirect effects on promoting angiogenesis and regulating the immune environment, due to specific functional components of EVs (nucleic acid, protein, lipid, etc.), is emphasized. Furthermore, different design ideas for suitable EV-loaded biomaterials are also demonstrated. In the end, this review also highlights the engineered strategies, which aim at solving the problems related to natural EVs such as highly heterogeneous functions, inadequate tissue targeting capabilities, insufficient yield and scalability, etc., thus promoting the therapeutic pertinence and clinical potential of EV-based approaches in TE., (© 2022 Wiley-VCH GmbH.)

Background: Heart failure (HF) is a common condition that imposes a significant burden on healthcare systems. We aimed to identify subgroups of patients with heart failure admitted to the ICU using routinely measured laboratory biomarkers., Methods: A large dataset (N = 1176) of patients with heart failure admitted to the ICU at the Beth Israel Deaconess Medical Center in Boston, USA, between June 1, 2001, and October 31, 2012, was analyzed. We clustered patients to identify laboratory phenotypes. Cluster profiling was then performed to characterize each cluster, using a binary logistic model., Results: Two distinct clusters of patients were identified (N = 679 and 497). There was a significant difference in the mortality rate between Clusters 1 and 2 (50 [7.4%] vs. 109 [21.9%], respectively, p < 0.001). Patients in the Cluster 2 were significantly older (mean [SD] age = 72.35 [14.40] and 76.37 [11.61] years, p < 0.001) with a higher percentage of chronic kidney disease (167 [24.6%] vs. 262 [52.7%], respectively, p < 0.001). The logistic model was significant (Log-likelihood ratio p < 0.001, pseudo R 2  = 0.746) with an area under the curve of 0.905. The odds ratio for leucocyte count, mean corpuscular volume (MCV), red blood cell (RBC) distribution width, hematocrit (HcT), lactic acid, blood urea nitrogen (BUN), serum potassium, magnesium, and sodium were significant (all p < 0.05)., Conclusion: Laboratory data revealed two phenotypes of ICU-admitted patients with heart failure. The two phenotypes are of prognostic importance in terms of mortality rate. They can be differentiated using blood cell count, kidney function status, and serum electrolyte concentrations., (© 2024 The Author(s). Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Cardio-oncology is an emerging field that aims to ensure optimal cancer treatment while minimising cardiovascular toxicity. The management of cardiovascular toxicity is critical because it can lead to premature discontinuation of treatment, increasing the risk of cancer recurrence and mortality. The 2022 European Society of Cardiology guidelines were a milestone in advocating a patient-centred, multidisciplinary approach. Key components include risk stratification and a standardised criterion for adverse events, incorporating definitions from the International Cardio-Oncology Society. Effective risk stratification, supported by imaging and biomarkers, helps to anticipate cardiovascular problems and implement preventive measures. Future research should focus on understanding mechanisms, developing preventive strategies and implementing personalised medicine. Education and reducing disparities in care are essential to advance cardio-oncology and improve patient outcomes., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

The association of serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) with insulin resistance (IR), as measured by homeostasis model assessment of insulin resistance (HOMA-IR), in the general population is unclear. Our study aimed to characterize its relationship in a large community-based population. Subjects were recruited from the Danyang city between 2017 and 2019. Serum NT-proBNP was measured using an enhanced chemiluminescence immunoassay. IR was defined by a HOMA-IR in the highest sex-specific quartile. Categorical and continuous analyses were performed with sex-specific NT-proBNP tertiles and naturally logarithmically transformed NT-proBNP (lnNTproBNP), respectively. The 2945 participants (mean age 52.8 years) included 1728 (58.7%) women, 1167 (39.6%) hypertensive patients, 269 (9.1%) diabetic patients, and 736 (25.0%) patients with IR. In simple and multivariate-adjusted regression analyses, serum lnNTproBNP were both negatively associated with HOMA-IR (β = -0.19 to -0.25; p < 0.0001). Similar results were also obtained in multiple subgroup analyses. In multiple logistic regression analyses, elevated serum NT-proBNP was associated with lower risks of IR (odds ratios: 0.68 and 0.39; 95% confidence intervals: 0.61-0.74 and 0.30-0.50 for lnNTproBNP and top vs. bottom tertiles, respectively; p < 0.0001). In conclusion, increased serum NT-proBNP level was strongly associated with a lower risk of IR in Chinese., (© 2024 The Author(s). The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Background and Aims: Acute heart failure (AHF) promotes inflammatory activation, which is associated with worse outcomes. Colchicine has proven effective in other cardiovascular conditions characterized by inflammatory activation, but has never been evaluated in the setting of AHF., Methods: This multicenter, randomized, double-blind and placebo-controlled trial included patients with AHF, requiring ≥40 mg of intravenous furosemide, regardless of their left ventricular ejection fraction (LVEF) and inpatient or outpatient setting. Patients were randomized within the first 24 hours of presentation to receive either colchicine or placebo, with loading dose of 2 mg followed by 0.5 mg every 12 hours for 8 weeks., Results: A total of 278 patients (median age 75 years, LVEF 40%, baseline N-terminal pro-B-type natriuretic peptide [NT-proBNP] 4390 pg/mL) were randomized to colchicine (n=141) or placebo (n=137). The primary endpoint, the time-averaged reduction in NT-proBNP levels at 8 weeks, did not differ between the colchicine group (-62.2%, 95% confidence interval [CI] -68.9% to -54.2%) and the placebo group (-62.1%, 95% CI -68.6% to -54.3%) (ratio of change 1.0). The reduction in inflammatory markers was significantly greater with colchicine: ratio of change 0.60 (p<0.001) for C-reactive protein and 0.72 (p=0.019) for interleukin-6. No differences were found in new worsening heart failure episodes (14.9% with colchicine vs. 16.8% with placebo, p=0.698); however, the need for intravenous furosemide during follow-up was lower with colchicine (p=0.043). Diarrhea was slightly more common with colchicine, but it did not result in differences in medication withdrawal (8.5% vs. 8.8%)., Conclusions: Colchicine was safe and effective in reducing inflammation in patients with AHF, however colchicine and placebo exhibited comparable effects on reducing NT-proBNP and preventing new worsening heart failure events., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Osteoarthritis (OA) is marked by cartilage deterioration, subchondral bone changes, and an inflammatory microenvironment. The study introduces the Microneedle-Delivered Polydopamine-Exosome (PDA@Exo MN), a therapeutic that not only preserves cartilage and promotes bone regeneration but also improves localized drug delivery through enhanced penetration capabilities. PDA@Exo MN shows strong reactive oxygen species (ROS) scavenging abilities and high biocompatibility, fostering osteogenesis and balancing anabolic and catabolic processes in cartilage. It directs macrophage polarization from M0 to the anti-inflammatory M2 phenotype. RNA sequencing of treated chondrocytes demonstrates restored cellular function and activated antioxidant responses, with modulated inflammatory pathways. The PI3K-AKT-mTOR pathway's activation, essential for PDA@Exo's effects, is confirmed via bioinformatics and Western blot. In vivo assessments robustly validate that PDA@Exo MN prevents cartilage degradation and OA progression, supported by histological assessments and micro-CT analysis, highlighting its disease-modifying impact. The excellent biocompatibility of PDA@Exo MN, verified through histological (H&E) and blood tests showing no organ damage, underscores its safety and efficacy for OA therapy, making it a novel and multifunctional nanomedical approach in orthopedics, characterized by organ-friendliness and biosecurity., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Heart failure (HF) is a prevalent cardiovascular disease with significant morbidity and mortality rates worldwide. Due to the intricate structure of the heart, diverse cell types, and the complex pathogenesis of HF, further in-depth investigation into the underlying mechanisms  is required. The elucidation of the heterogeneity of cardiomyocytes and the intercellular communication network is particularly important. Traditional high-throughput sequencing methods provide an average measure of gene expression, failing to capture the "heterogeneity" between cells and impacting the accuracy of gene function knowledge. In contrast, single-cell sequencing techniques allow for the amplification of the entire genome or transcriptome at the individual cell level, facilitating the examination of gene structure and expression with unparalleled precision. This approach offers valuable insights into disease mechanisms, enabling the identification of changes in cellular components and gene expressions during hypertrophy associated with HF. Moreover, it reveals distinct cell populations and their unique roles in the HF microenvironment, providing a comprehensive understanding of the cellular landscape that underpins HF pathogenesis. This review focuses on the insights provided by single-cell sequencing techniques into the mechanisms underlying HF and discusses the challenges encountered in current cardiovascular research., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Acute heart failure (AHF) classification and management are primarily based on lung congestion and/or hypoperfusion. The quantification of the vascular and tissue lung damage is not standard practice though biomarkers of lung injury may play a relevant role in this context. Haemodynamic stress promotes alveolar and vascular derangement with loss of functional units, impaired lung capillary permeability and fluid swelling. This culminates in a remodelling process with activation of inflammatory and cytokines pathways. Four families of lung surfactant proteins (i.e., SP-A, SP-B, SP-C, and SP-D), essential for the membrane biology and integrity are released by alveolar type II pneumocites. With deregulation of fluid handling and gas exchange pathways, SPs become sensitive markers of lung injury. We report the pathobiology of lung damage; the pathophysiological and clinical implications of alveolar SPs along with the newest evidence for some classical HF biomarkers that have also shown to reflect a vascular and/or a tissue lung-related activity., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

In recent years, there has been widespread adoption of machine learning (ML) technologies to unravel intricate relationships among diverse parameters in various additive manufacturing (AM) techniques. These ML models excel at recognizing complex patterns from extensive, well-curated datasets, thereby unveiling latent knowledge crucial for informed decision-making during the AM process. The collaborative synergy between ML and AM holds the potential to revolutionize the design and production of AM-printed parts. This review delves into the challenges and opportunities emerging at the intersection of these two dynamic fields. It provides a comprehensive analysis of the publication landscape for ML-related research in the field of AM, explores common ML applications in AM research (such as quality control, process optimization, design optimization, microstructure analysis, and material formulation), and concludes by presenting an outlook that underscores the utilization of advanced ML models, the development of emerging sensors, and ML applications in emerging AM-related fields. Notably, ML has garnered increased attention in AM due to its superior performance across various AM-related applications. It is envisioned that the integration of ML into AM processes will significantly enhance 3D printing capabilities across diverse AM-related research areas., (© 2024 The Authors. Advanced Materials published by Wiley‐VCH GmbH.)

Pediatric pericarditis presents challenges in its management, necessitating effective therapeutic interventions. Colchicine, known for its efficacy in adults, requires further investigation for its application and safety in pediatric cohorts. A systematic search across renowned databases identified relevant literature on colchicine use in pediatric pericarditis. Twenty-nine articles underwent rigorous screening, with 18 studies meeting inclusion criteria. Data extraction, quality assessment, and synthesis were conducted meticulously. Included studies comprised case reports, case series, and retrospective cohort studies. Colchicine demonstrated efficacy in reducing recurrence rates and symptom burden, with doses ranging from 0.25 mg/day to 2 mg/day. Adverse events were minimal, predominantly gastrointestinal. Notably, nausea was the most common side effect reported. The safety profile of colchicine was favorable, with rare instances of hepatic and hematologic toxicity. Colchicine emerges as a promising therapeutic option for pediatric pericarditis, demonstrating efficacy in reducing recurrence rates and alleviating symptoms. Its favorable safety profile suggests potential as a preferred long-term therapy. However, further research, including randomized controlled trials, is warranted to confirm its efficacy and safety and explore potential combination therapies., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Drug repurposing is defined as the use of approved therapeutic drugs for indications different from those for which they were originally designed. Repositioning diminishes both the time and cost for drug development by omitting the discovery stage, the analysis of absorption, distribution, metabolism, and excretion routes, as well as the studies of the biochemical and physiological effects of a new compound. Besides, drug repurposing takes advantage of the increased bioinformatics knowledge and availability of big data biology. There are many examples of drugs with repurposed indications evaluated in in vitro studies, and in pharmacological, preclinical, or retrospective clinical analyses. Here, we briefly review some of the experimental strategies and technical advances that may improve translational research in cardiovascular diseases. We also describe exhaustive research from basic science to clinical studies that culminated in the final approval of new drugs and provide examples of successful drug repurposing in the field of cardiology., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

Coronary artery disease (CAD), acute coronary syndrome (ACS), and heart failure (HF) are major global health issues with high morbidity and mortality rates. Biomarkers like cardiac troponins (cTn) and natriuretic peptides (NPs) are crucial tools in cardiology, but numerous new biomarkers have emerged, proving increasingly valuable in CAD/ACS. These biomarkers are classified based on their mechanisms, such as fibrosis, metabolism, inflammation, and congestion. The integration of established and emerging biomarkers into clinical practice is an ongoing process, and recognizing their strengths and limitations is crucial for their accurate interpretation, incorporation into clinical settings, and improved management of CVD patients. We explored established biomarkers like cTn, NPs, and CRP, alongside newer biomarkers such as Apo-A1, IL-17E, IgA, Gal-3, sST2, GDF-15, MPO, H-FABP, Lp-PLA2, and ncRNAs; provided evidence of their utility in CAD/ACS diagnosis and prognosis; and empowered clinicians to confidently integrate these biomarkers into clinical practice based on solid evidence., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: Heart failure (HF) elicits a pro-inflammatory state, which is associated with impaired clinical outcomes, but no anti-inflammatory therapies have demonstrated a clinical benefit yet. Inflammatory pathways related with the interleukin-1 axis are overactivated during episodes of acute HF. Colchicine, an anti-inflammatory drug with proven benefits in acute pericarditis and ischaemic heart disease, may target this inflammatory response. This study aims to assess the efficacy of colchicine in acute HF patients., Methods: COLICA is a multicentre, randomized, double-blind, placebo-controlled trial enrolling 278 patients across 12 sites. Patients presenting with acute HF, clinical evidence of congestion requiring ≥40 mg of intravenous furosemide and N-terminal pro-B-type natriuretic peptide (NT-proBNP) >900 pg/ml, are eligible for participation. Patients are enrolled irrespective of left ventricular ejection fraction, HF type (new-onset or not) and setting (hospital or outpatient clinic). Patients are randomized 1:1 within the first 24 h of presentation to either placebo or colchicine, with an initial loading dose of 2 mg followed by 0.5 mg every 12 h for 8 weeks (reduced dose if <70 kg, >75 years old, or glomerular filtration rate <50 ml/min/1.73 m 2 ). The primary efficacy endpoint is the time-averaged proportional change in NT-proBNP concentrations from baseline to week 8. Key secondary and exploratory outcomes include symptoms, diuretic use, worsening HF episodes, related biomarkers of cardiac stress and inflammation, total and cardiovascular readmissions, mortality and safety events., Conclusion: COLICA will be the first randomized trial testing the efficacy and safety of colchicine for acute HF., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Patients with advanced heart failure are implanted with a left ventricular assist device (LVAD) as a bridge-to-transplantation or destination therapy. Despite advances in pump design, the risk of stroke remains high. LVAD implantation significantly alters intraventricular hemodynamics, where regions of stagnation or elevated shear stresses promote thrombus formation. Third generation pumps incorporate a pulsatility mode that modulates rotational speed of the pump to enhance in-pump washout. We investigated how the timing of the pulsatility mode with the cardiac cycle affects intraventricular hemodynamic factors linked to thrombus formation. Computational fluid dynamics simulations with Lagrangian particle tracking to model platelet behavior in a patient-specific left ventricle captured altered intraventricular hemodynamics due to LVAD implantation. HeartMate 3 incorporates a pulsatility mode that modulates the speed of the pump every two seconds. Four different timings of this pulsatility mode with respect to the cardiac cycle were investigated. A strong jet formed between the mitral valve and inflow cannula. Blood stagnated in the left ventricular outflow tract beneath a closed aortic valve, in the near-wall regions off-axis of the jet, and in a large counterrotating vortex near the anterior wall. Computational results showed good agreement with particle image velocimetry results. Synchronization of the pulsatility mode with peak systole decreased stasis, reflected in the intraventricular washout of virtual contrast and Lagrangian particles over time. Temporal synchronization of HeartMate 3 pulsatility with the cardiac cycle reduces intraventricular stasis and could be beneficial for decreasing thrombogenicity., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Guideline-directed medical therapy (GDMT) in patients with heart failure and reduced ejection fraction (HFrEF) reduces morbidity and mortality, but its implementation is often poor in daily clinical practice. Barriers to implementation include clinical and organizational factors that might contribute to clinical inertia, i.e. avoidance/delay of recommended treatment initiation/optimization. The spectrum of strategies that might be applied to foster GDMT implementation is wide, and involves the organizational set-up of heart failure care pathways, tailored drug initiation/optimization strategies increasing the chance of successful implementation, digital tools/telehealth interventions, educational activities and strategies targeting patient/physician awareness, and use of quality registries. This scientific statement by the Heart Failure Association of the ESC provides an overview of the current state of GDMT implementation in HFrEF, clinical and organizational barriers to implementation, and aims at suggesting a comprehensive framework on how to overcome clinical inertia and ultimately improve implementation of GDMT in HFrEF based on up-to-date evidence., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

In the last years, major progress has occurred in heart failure (HF) management. The 2023 ESC focused update of the 2021 HF guidelines introduced new key recommendations based on the results of the last years of science. First, two drugs, sodium-glucose co-transporter-2 (SGLT2) inhibitors and finerenone, a novel nonsteroidal, selective mineralocorticoid receptor antagonist (MRA), are recommended for the prevention of HF in patients with diabetic chronic kidney disease (CKD). Second, SGLT2 inhibitors are now recommended for the treatment of HF across the entire left ventricular ejection fraction spectrum. The benefits of quadruple therapy in patients with HF with reduced ejection fraction (HFrEF) are well established. Its rapid and early up-titration along with a close follow-up with frequent clinical and laboratory re-assessment after an episode of acute HF (the so-called 'high-intensity care' strategy) was associated with better outcomes in the STRONG-HF trial. Patients experiencing an episode of worsening HF might require a fifth drug, vericiguat. In the STEP-HFpEF-DM and STEP-HFpEF trials, semaglutide 2.4 mg once weekly administered for 1 year decreased body weight and significantly improved quality of life and the 6 min walk distance in obese patients with HF with preserved ejection fraction (HFpEF) with or without a history of diabetes. Further data on safety and efficacy, including also hard endpoints, are needed to support the addition of acetazolamide or hydrochlorothiazide to a standard diuretic regimen in patients hospitalized due to acute HF. In the meantime, PUSH-AHF supported the use of natriuresis-guided diuretic therapy. Further options and most recent evidence for the treatment of HF, including specific drugs for cardiomyopathies (i.e., mavacamten in hypertrophic cardiomyopathy and tafamidis in transthyretin cardiac amyloidosis), device therapies, cardiac contractility modulation and percutaneous treatment of valvulopathies, with the recent finding from the TRILUMINATE Pivotal trial, are also reviewed in this article., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

CRISPR-Cas13 holds substantial promise for tissue repair through its RNA editing capabilities and swift catabolism. However, conventional delivery methods fall short in addressing the heightened inflammatory response orchestrated by macrophages during the acute stages of tendon injury. In this investigation, macrophage-targeting cationic polymers are systematically screened to facilitate the entry of Cas13 ribonucleic-protein complex (Cas13 RNP) into macrophages. Notably, SPP1 (OPN encoding)-producing macrophages are recognized as a profibrotic subtype that emerges during the inflammatory stage. By employing ROS-responsive release mechanisms tailored for macrophage-targeted Cas13 RNP editing systems, the overactivation of SPP1 is curbed in the face of an acute immune microenvironment. Upon encapsulating this composite membrane around the tendon injury site, the macrophage-targeted Cas13 RNP effectively curtails the emergence of injury-induced SPP1-producing macrophages in the acute phase, leading to diminished fibroblast activation and mitigated peritendinous adhesion. Consequently, this study furnishes a swift RNA editing strategy for macrophages in the inflammatory phase triggered by ROS in tendon injury, along with a pioneering macrophage-targeted carrier proficient in delivering Cas13 into macrophages efficiently., (© 2024 Wiley‐VCH GmbH.)

Preclinical animal studies are essential to the development of safe and effective stem cell therapies. Bioluminescence imaging (BLI) is a powerful tool in animal studies that enables the real-time longitudinal monitoring of stem cells in vivo to elucidate their regenerative properties. This review describes the application of BLI in preclinical stem cell research to address critical challenges in producing successful stem cell therapeutics. These challenges include stem cell survival, proliferation, homing, stress response, and differentiation. The applications presented here utilize bioluminescence to investigate a variety of stem and progenitor cells in several different in vivo models of disease and implantation. An overview of luciferase reporters is provided, along with the advantages and disadvantages of BLI. Additionally, BLI is compared to other preclinical imaging modalities and potential future applications of this technology are discussed in emerging areas of stem cell research., (© 2020 The Authors. Biotechnology Journal published by Wiley-VCH GmbH.)

Tissue engineering (TE) is a strongly expanding research area. TE approaches require biocompatible scaffolds, cells, and different applied stimuli, which altogether mimic the natural tissue microenvironment. Also, the extracellular matrix serves as a structural base for cells and as a source of growth factors and biophysical cues. The 3D characteristics of the microenvironment is one of the most recognized key factors for obtaining specific cell responses in vivo, being the physical cues increasingly investigated. Supporting those advances is the progress of smart and multifunctional materials design, whose properties improve the cell behavior control through the possibility of providing specific chemical and physical stimuli to the cellular environment. In this sense, a varying set of bioreactors that properly stimulate those materials and cells in vitro, creating an appropriate biomimetic microenvironment, is developed to obtain active bioreactors. This review provides a comprehensive overview on the important microenvironments of different cells and tissues, the smart materials type used for providing such microenvironments and the specific bioreactor technologies that allow subjecting the cells/tissues to the required biomimetic biochemical and biophysical cues. Further, it is shown that microfluidic bioreactors represent a growing and interesting field that hold great promise for achieving suitable TE strategies., (© 2020 Wiley-VCH GmbH.)

Biodegradable polymers play a pivotal role in in situ tissue engineering. Utilizing various technologies, researchers have been able to fabricate 3D tissue engineering scaffolds using biodegradable polymers. They serve as temporary templates, providing physical and biochemical signals to the cells and determining the successful outcome of tissue remodeling. Furthermore, a biodegradable scaffold also presents the fourth dimension for tissue engineering, namely time. The properties of the biodegradable polymer change over time, presenting continuously changing features during the degradation process. These changes become more complicated when different materials are combined together to fabricate a composite or heterogeneous scaffold. This review undertakes a systematic analysis of the basic characteristics of biodegradable polymers and describe recent advances in making composite biodegradable scaffolds for in situ tissue engineering and regenerative medicine. The interaction between implanted biodegradable biomaterials and the in vivo environment are also discussed, including the properties and functional changes of the degradable scaffold, the local effect of degradation on the contiguous tissue and their evaluation using both in vitro and in vivo models., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Early risk stratification is necessary to prevent chronic kidney disease progression and complications. This systematic review aims to evaluate the association of soluble suppression of tumorigenicity 2 (sST2), a member of the interleukin-1 receptor family, with all-cause mortality, cardiovascular disease and renal function deterioration among chronic kidney disease patients., Methods: PubMed, Scopus, Web of Science, CENTRAL and Google Scholar were systematically searched from inception to December 20, 2023. Cohort studies examining the prognostic role of sST2 levels in pre-dialysis and dialysis patients were included. In case of 3 or more studies per outcome, conventional and dose-response meta-analyses were conducted., Results: Overall, 21 studies were included comprising 15,100 patients. In pre-dialysis patients, the qualitative synthesis of studies suggested that high sST2 is associated with significantly increased all-cause mortality, while evidence regarding cardiovascular events or kidney disease progression was conflicting. In the dialysis population, high sST2 was linked to an elevated risk of all-cause (Hazard ratio-HR: 3.00, 95% confidence intervals-CI: 1.95-4.61) and cardiovascular (HR: 2.38, 95% CI: 1.69-3.34) mortality. Dose-response meta-analysis suggested a log-linear association of sST2 with both all-cause (χ 2 : 34.65, p value < 0.001) and cardiovascular (χ 2 : 29.14, p value < 0.001) mortality, whereas findings regarding cardiovascular events were limited with mixed results., Conclusions: High sST2 values are associated with an increased risk of all-cause mortality in pre-dialysis and dialysis patients, as well as with an elevated risk of cardiovascular mortality in the dialysis population. Further studies are needed to elucidate its potential association with cardiovascular events and kidney disease progression., (© 2024. The Author(s).)

Aims: The aim of this analysis was to provide data on the overall comorbidity burden, both cardiovascular (CV) and non-CV, in a large real-world heart failure (HF) population across the ejection fraction (EF)., Methods and Results: Patients with HF from the Swedish HF Registry between 2000 and 2021 were included. Of 91 463 patients (median age 76 years [interquartile range 67-82]), 98% had at least one among the 17 explored comorbidities (94% at least one CV and 85% at least one non-CV comorbidity). All comorbidities, except for coronary artery disease (CAD), were more frequent in HF with preserved EF (HFpEF). Patients with multiple comorbidities were older, more likely female, inpatients, with HFpEF, worse New York Heart Association class and higher N-terminal pro-B-type natriuretic peptide levels. In a multivariable Cox model, 12 comorbidities were independently associated with a higher risk of death from any cause. The highest risk was associated with dementia (hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.45-1.65), chronic kidney disease (HR 1.37, 95% CI 1.34-1.41), chronic obstructive pulmonary disease (HR 1.32, 95% CI 1.28-1.35). Obesity was associated with a lower risk of all-cause death (HR 0.81, 95% CI 0.79-0.84). CAD and valvular heart disease were associated with a higher risk of all-cause and CV mortality, but not non-CV mortality, whereas cancer and musculo-skeletal disease increased the risk of non-CV mortality. A significant interaction with EF was observed for several comorbidities. Occurrence of CV and non-CV outcomes was related to the number of CV and non-CV comorbidities, respectively., Conclusion: The burden of both CV and non-CV comorbidities was high in HF regardless of EF, but overall higher in HFpEF. Multimorbidity was associated with a high risk of death with a different burden on CV or non-CV outcomes., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: A high-intensity care (HIC) strategy with rapid guideline-directed medical therapy (GDMT) up-titration and close follow-up visits improved outcomes, compared to usual care (UC), in patients recently hospitalized for acute heart failure (AHF). Hypotension is a major limitation to GDMT implementation. We aimed to assess the impact of baseline systolic blood pressure (SBP) on the effects of HIC versus UC and the role of early SBP changes in STRONG-HF., Methods and Results: A total of 1075 patients hospitalized for AHF with SBP ≥100 mmHg were included in STRONG-HF. For the purpose of this post-hoc analysis, patients were stratified by tertiles of baseline SBP (<118, 118-128, and ≥129 mmHg) and, in the HIC arm, by tertiles of changes in SBP from the values measured before discharge to those measured at 1 week after discharge (≥2 mmHg increase, ≤7 mmHg decrease to <2 mmHg increase, and ≥8 mmHg decrease). The primary endpoint was 180-day heart failure rehospitalization or death. The effect of HIC versus UC on the primary endpoint was independent of baseline SBP evaluated as tertiles (p interaction  = 0.77) or as a continuous variable (p interaction  = 0.91). In the HIC arm, patients with increased, stable and decreased SBP at 1 week reached 83.5%, 76.2% and 75.3% of target doses of GDMT at day 90. The risk of the primary endpoint was not significantly different between patients with different SBP changes at 1 week (adjusted p = 0.46)., Conclusions: In STRONG-HF, the benefits of HIC versus UC were independent of baseline SBP. Rapid GDMT up-titration was performed also in patients with an early SBP drop, resulting in similar 180-day outcome as compared to patients with stable or increased SBP., (© 2024 European Society of Cardiology.)

Aim: Persistent symptoms despite guideline-directed medical therapy (GDMT) and poor tolerance of GDMT are hallmarks of patients with advanced heart failure (HF) with reduced ejection fraction (HFrEF). However, real-world data on GDMT use, dose, and prognostic implications are lacking., Methods and Results: We included 699 consecutive patients with HFrEF and at least one 'I NEED HELP' marker for advanced HF enrolled in a multicentre registry. Beta-blockers (BB) were administered to 574 (82%) patients, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers or angiotensin receptor-neprilysin inhibitors (ACEi/ARB/ARNI) were administered to 381 (55%) patients and 416 (60%) received mineralocorticoid receptor antagonists (MRA). Overall, ≥50% of target doses were reached in 41%, 22%, and 56% of the patients on BB, ACEi/ARB/ARNI and MRA, respectively. Hypotension, bradycardia, kidney dysfunction and hyperkalaemia were the main causes of underprescription and/or underdosing, but up to a half of the patients did not receive target doses for unknown causes (51%, 41%, and 55% for BB, ACEi/ARB/ARNI and MRA, respectively). The proportions of patients receiving BB and ACEi/ARB/ARNI were lower among those fulfilling the 2018 HFA-ESC criteria for advanced HF. Treatment with BB and ACEi/ARB/ARNI were associated with a lower risk of death or HF hospitalizations (adjusted hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.48-0.84, and HR 0.74, 95% CI 0.58-0.95, respectively)., Conclusions: In a large, real-world, contemporary cohort of patients with severe HFrEF, with at least one marker for advanced HF, prescription and uptitration of GDMT remained limited. A significant proportion of patients were undertreated due to unknown reasons suggesting a potential role of clinical inertia either by the prescribing healthcare professional or by the patient. Treatment with BB and ACEi/ARB/ARNI was associated with lower mortality/morbidity., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aim: Left atrial (LA) myopathy is increasingly recognized as an important phenotypic trait in heart failure (HF) with preserved ejection fraction (HFpEF). Right atrial (RA) remodelling and dysfunction also develop in HFpEF, but little data are available regarding the clinical characteristics and pathophysiology among patients with isolated LA, RA, or biatrial myopathy., Methods and Results: Patients with HFpEF underwent invasive haemodynamic exercise testing, comprehensive imaging including speckle tracking strain echocardiography, and clinical follow-up at Mayo Clinic between 2006 and 2018. LA myopathy was defined as LA volume index >34 ml/m 2 and/or LA reservoir strain ≤24% and RA myopathy by RA volume index >39 ml/m 2 in men and >33 ml/m 2 in women and/or RA reservoir strain ≤19.8%. Of 476 consecutively evaluated patients with HFpEF defined by invasive exercise testing with evaluable atrial structure/function, 125 (26%) had no atrial myopathy, 147 (31%) had isolated LA myopathy, 184 (39%) had biatrial myopathy, and 20 (4%) had isolated RA myopathy. Patients with HFpEF and biatrial myopathy had more atrial fibrillation, poorer left ventricular systolic and diastolic function, more severe pulmonary vascular disease, tricuspid regurgitation, ventricular interdependence and right ventricular dysfunction, and poorer cardiac output reserve with exercise. There were 94 patients with events over a median follow-up of 2.9 (interquartile range 1.4-4.6) years. Individuals with biatrial myopathy had an 84% higher risk of HF hospitalization or death as compared to those with isolated LA myopathy (hazard ratio 1.84; 95% confidence interval 1.16-2.92, p = 0.01)., Conclusions: Biatrial myopathy identifies patients with more advanced HFpEF characterized by more severe pulmonary vascular disease, right HF, poorer cardiac reserve, and a greater risk for adverse outcomes. Further study is required to define optimal strategies to treat and prevent biatrial myopathy in HFpEF., (© 2023 European Society of Cardiology.)

Background: Transthyretin amyloid cardiomyopathy is characterized by the deposition of misfolded monomeric transthyretin (TTR) in the heart. Acoramidis is a high-affinity TTR stabilizer that acts to inhibit dissociation of tetrameric TTR and leads to more than 90% stabilization across the dosing interval as measured ex vivo., Methods: In this phase 3, double-blind trial, we randomly assigned patients with transthyretin amyloid cardiomyopathy in a 2:1 ratio to receive acoramidis hydrochloride at a dose of 800 mg twice daily or matching placebo for 30 months. Efficacy was assessed in the patients who had an estimated glomerular filtration rate of at least 30 ml per minute per 1.73 m 2 of body-surface area. The four-step primary hierarchical analysis included death from any cause, cardiovascular-related hospitalization, the change from baseline in the N-terminal pro-B-type natriuretic peptide (NT-proBNP) level, and the change from baseline in the 6-minute walk distance. We used the Finkelstein-Schoenfeld method to compare all potential pairs of patients within strata to generate a P value. Key secondary outcomes were death from any cause, the 6-minute walk distance, the score on the Kansas City Cardiomyopathy Questionnaire-Overall Summary, and the serum TTR level., Results: A total of 632 patients underwent randomization. The primary analysis favored acoramidis over placebo (P<0.001); the corresponding win ratio was 1.8 (95% confidence interval [CI], 1.4 to 2.2), with 63.7% of pairwise comparisons favoring acoramidis and 35.9% favoring placebo. Together, death from any cause and cardiovascular-related hospitalization contributed more than half the wins and losses to the win ratio (58% of all pairwise comparisons); NT-proBNP pairwise comparisons yielded the highest ratio of wins to losses (23.3% vs. 7.0%). The overall incidence of adverse events was similar in the acoramidis group and the placebo group (98.1% and 97.6%, respectively); serious adverse events were reported in 54.6% and 64.9% of the patients., Conclusions: In patients with transthyretin amyloid cardiomyopathy, the receipt of acoramidis resulted in a significantly better four-step primary hierarchical outcome containing components of mortality, morbidity, and function than placebo. Adverse events were similar in the two groups. (Funded by BridgeBio Pharma; ATTRibute-CM ClinicalTrials.gov number, NCT03860935.)., (Copyright © 2024 Massachusetts Medical Society.)

Heart failure, a pervasive global health burden, necessitates innovative therapeutic strategies. Extracellular vesicles (EVs) have emerged as promising contenders for cardiac repair, owing to their profound influence on fibrosis and inflammation. Merging EVs with biomaterials holds the potential for a synergistic leap in therapeutic efficacy. In this review, the impact of combining EVs with biomaterials in preclinical heart failure models is scrutinized. Fifteen studies, predominantly employing mesenchymal stromal cell-derived EVs along with hyaluronic acid or peptides in coronary ligation models, meet these stringent criteria. The amalgamation of EVs and biomaterials consistently enhances cardiac ejection fraction (1.39; 95% CI: 0.68, 2.11; p = 0.0001) and fractional shortening (1.46, 95% CI: 0.70, 2.22; p = 0.0002) compared to EV monotherapy. Secondary outcomes similarly showcased improvement in the combined treatment group. Although the number of studies analyzed is modest, no indications of publication bias surface. In summary, combination therapy with EVs and biomaterials enhances therapeutic benefit in preclinical heart failure models. The consistent improvement observed across diverse EV sources, biomaterials, and animal models underscores the exciting potential of this synergistic approach., (© 2023 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)

Background and Aims: Even though vegetation size in infective endocarditis (IE) has been associated with embolic events (EEs) and mortality risk, it is unclear whether vegetation size associated with these potential outcomes is different in left-sided IE (LSIE). This study aimed to seek assessing the vegetation cut-off size as predictor of EE or 30-day mortality for LSIE and to determine risk predictors of these outcomes., Methods: The European Society of Cardiology EURObservational Research Programme European Infective Endocarditis is a prospective, multicentre registry including patients with definite or possible IE throughout 2016-18. Cox multivariable logistic regression analysis was performed to assess variables associated with EE or 30-day mortality., Results: There were 2171 patients with LSIE (women 31.5%). Among these affected patients, 459 (21.1%) had a new EE or died in 30 days. The cut-off value of vegetation size for predicting EEs or 30-day mortality was >10 mm [hazard ratio (HR) 1.38, 95% confidence interval (CI) 1.13-1.69, P = .0015]. Other adjusted predictors of risk of EE or death were as follows: EE on admission (HR 1.89, 95% CI 1.54-2.33, P < .0001), history of heart failure (HR 1.53, 95% CI 1.21-1.93, P = .0004), creatinine >2 mg/dL (HR 1.59, 95% CI 1.25-2.03, P = .0002), Staphylococcus aureus (HR 1.36, 95% CI 1.08-1.70, P = .008), congestive heart failure (HR 1.40, 95% CI 1.12-1.75, P = .003), presence of haemorrhagic stroke (HR 4.57, 95% CI 3.08-6.79, P < .0001), alcohol abuse (HR 1.45, 95% CI 1.04-2.03, P = .03), presence of cardiogenic shock (HR 2.07, 95% CI 1.29-3.34, P = .003), and not performing left surgery (HR 1.30 95% CI 1.05-1.61, P = .016) (C-statistic = .68)., Conclusions: Prognosis after LSIE is determined by multiple factors, including vegetation size., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Extracellular vesicles (EVs) are secreted by all living cells and are found in body fluids. They exert numerous physiological and pathological functions and serve as cargo shuttles. Due to their safety and inherent bioactivity, they have emerged as versatile therapeutic agents, biomarkers, and potential drug carriers. Despite the growing interest in EVs, current progress in this field is, in part, limited by relatively inefficient isolation techniques. Conventional methods are indeed slow, laborious, require specialized laboratory equipment, and may result in low yield and purity. This work describes an electrochemically controlled "all-in-one" device enabling capturing, loading, and releasing of EVs. The device is composed of a fluidic channel confined within antibody-coated microstructured electrodes. It rapidly isolates EVs with a high level of purity from various biofluids. As a proof of principle, the device is applied to isolate EVs from skin wounds of healthy and diabetic mice. Strikingly, it is found that EVs from healing wounds of diabetic mice are enriched in mitochondrial proteins compared to those of healthy mice. Additionally, the device improves the loading protocol of EVs with polyplexes, and may therefore find applications in nucleic acid delivery. Overall, the electrochemical device can greatly facilitate the development of EVs-based technologies., (© 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

This review briefly emphasizes the different detection approaches (electrochemical sensors, chemiluminescence, surface-enhanced Raman scattering), functional nanostructure materials (quantum dots, metal nanoparticles, metal nanoclusters, magnetic nanomaterials, metal oxide nanoparticles, polymer-based nanomaterials, and carbonaceous nanomaterials) and detection mechanisms. Furthermore, the emphasis of this review is on the integration of functional nanomaterials with optical spectroscopic techniques for the identification of various biomarkers (nucleic acids, glucose, uric acid, oxytocin, dopamine, ascorbic acid, bilirubin, spermine, serotonin, thiocyanate, Pb 2+ , Cu 2+ , Hg 2+ , F - , peptides), and cancer biomarkers (mucin 1, prostate specific antigen, carcinoembryonic antigen, CA15-3, human epidermal growth factor receptor 2, C-reactive protein, and interleukin-6). Analytical characteristics of nanomaterials-based optical sensors are summarized in the tables, providing the insights of nanomaterials-based optical sensors for biomarkers detection. Finally, the opportunities and challenges of nanomaterials-based optical analytical approaches for the detection of various biomarkers (inorganic, organic, biomolecules, peptides and proteins) are discussed., (© 2022 John Wiley & Sons Ltd.)

Background: FGF23 mediates cardiac fibrosis through the activation of pro-fibrotic factors in in vitro models and is markedly elevated in kidney disease. Left atrial global longitudinal strain (LA GLS) derived by echocardiographic speckle-tracking measures longitudinal shortening of the LA walls, quantifies atrial performance and may enable detection of early LA remodeling in the setting of normal ventricular function. We hypothesized that LA GLS is abnormal in children on hemodialysis (HD) compared to healthy controls of comparable age/sex distribution and that, among HD patients, greater FGF23 levels are associated with abnormal LA GLS., Methods: Clinical and echocardiographic data from 29 children receiving HD and 13 healthy controls were collected in a cross-sectional single-center study. Plasma FGF23 concentrations were measured using ELISA. The primary outcome was LA GLS measured using 2D speckle-tracking strain analysis. Linear regression analysis was used to investigate predictors of LA GLS in HD., Results: Median dialysis vintage was 1.5 (IQR 0.5-4.3) years. Median intact FGF23 levels were substantially higher in the HD vs. control group (1206 [215, 4707] vs. 51 [43, 66.5] pg/ml; P = 0.0001), and LA GLS was 39.9% SD 11.6 vs. 32.8% SD 5.7 (P = 0.04). Among HD patients, higher FGF23 was associated with lower LA GLS (β per unit Ln-FGF23: - 2.7; 95% CI slope - 5.4, - 0.1; P = 0.04 after adjustment for age, body size, and HD vintage. FGF23 was not associated with LA phasic reservoir, conduit, or contractile strain., Conclusions: In children on HD and preserved left ventricular ejection fraction, greater FGF23 is associated with lower LA GLS (indicative of impaired atrial performance). A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Sarcopenia is a geriatric disease characterized by reduced muscle function and mass. The capacity to self-renew and myogenesis of satellite cells (SCs) declines with age, resulting in age-related sarcopenia. MicroRNAs (miRNAs) can regulate the proliferation and myogenesis of SCs. In this study, it is identified that miR-467a-3p and miR-874-5p could respectively mediate the stemness and myogenesis of SCs by performing bioinformatics analysis. AntagomiR-467a-3p (ant-467a) and antagomiR-874-5p (ant-874) improve the stemness and myogenesis of SCs, respectively. SC-targeting extracellular vesicles (EVs) are constructed by overexpressing TSG101 on the surface of EVs isolated from bone marrow mesenchymal stem cells. Ant-467a loaded EVs (EVs-467a) and ant-874 loaded EVs (EVs-874) are prepared by transferring ant-467a and ant-874 into SC-targeting EVs. EVs-467a and EVs-874 are more effective than ant-467a and ant-874 in promoting the stemness and myogenesis of SCs. Sequentially intermuscular injection of EVs-467a and EVs-874 significantly improve sarcopenia in ovariectomy mice. The effects of multiple injections of EVs-467a and EVs-874 in the treatment of sarcopenia could be achieved by using a hierarchically injectable hydrogel to sustainedly release EVs-467a and EVs-874 in vivo. The findings provide an EV-based SC-targeting antagomiRNAs controlled release strategy as a novel therapy against sarcopenia., (© 2023 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)

Coronavirus disease 2019 (COVID-19) continues to threaten human health, economic development, and national security. Although many vaccines and drugs have been explored to fight against the major pandemic, their efficacy and safety still need to be improved. Cell-based biomaterials, especially living cells, extracellular vesicles, and cell membranes, offer great potential in preventing and treating COVID-19 owing to their versatility and unique biological functions. In this review, the characteristics and functions of cell-based biomaterials and their biological applications in COVID-19 prevention and therapy are described. First the pathological features of COVID-19 are summarized, providing enlightenment on how to fight against COVID-19. Next, the classification, organization structure, characteristics, and functions of cell-based biomaterials are focused on. Finally, the progress of cell-based biomaterials in overcoming COVID-19 in different aspects, including the prevention of viral infection, inhibition of viral proliferation, anti-inflammation, tissue repair, and alleviation of lymphopenia are comprehensively described. At the end of this review, a look forward to the challenges of this aspect is presented., (© 2023 Wiley-VCH GmbH.)

This work presents a novel nanoparticle-based thermosensor implant able to reveal the precise temperature variations along the polymer filaments, as it contracts and expands due to changes in the macroscale local temperature. The multimodal device is able to trace the position and the temperature of a polypropylene mesh, employed in abdominal hernia repair, by combining plasmon resonance and Raman spectroscopy with hydrogel responsive system. The novelty relies on the attachment of the biocompatible nanoparticles, based on gold stabilized by a chitosan-shell, already charged with the Raman reporter (RaR) molecules, to the robust prosthesis, without the need of chemical linkers. The SERS enhanced effect observed is potentiated by the presence of a quite thick layer of the copolymer (poly(N-isopropylacrylamide)-co-poly(acrylamide)) hydrogel. At temperatures above the LCST of PNIPAAm-co-PAAm, the water molecules are expulsed and the hydrogel layer contracts, leaving the RaR molecules more accessible to the Raman source. In vitro studies with fibroblast cells reveal that the functionalized surgical mesh is biocompatible and no toxic substances are leached in the medium. The mesh sensor opens new frontiers to semi-invasive diagnosis and infection prevention in hernia repair by using SERS spectroscopy. It also offers new possibilities to the functionalization of other healthcare products., (© 2023 Wiley-VCH GmbH.)

Peripheral nerve injury (PNI) is the most common neurological injury in civilian and military injuries, with over 360,000 PNI procedures performed in the US yearly. Segmental loss of nerve tissue results in a nerve gap precluding a tension-free primary repair, and in these cases, interpositional autologous or acellular nerve allografts are used to bridge the gap. Graft ischemia time is a critical factor in achieving satisfactory nerve regeneration. Rapid nerve graft revascularization is essential in order to sustain Schwann cell growth which in turn is crucial for axonal regeneration. Currently, nerve autografts are considered the gold standard for segmental nerve gaps but are associated with several disadvantages such as limited supply of expendable donor tissue, increased operative time, and donor site morbidity. Hence, readily available, off-the-shelf nerve allografts or scaffolds are being investigated since they provide advantages such as a virtually limitless sourcing, a wide variety of sizes to match recipient nerves, and no donor site morbidity. New, exciting advances in tissue engineering to augment revascularization of nerve allografts or conduits have been investigated. Strategies include pro-angiogenic mesenchymal stem cells, extracellular vesicles, functionalized scaffolds, bioactive peptides, and three-dimensional bioprinting. This article discusses these bioengineering advances and future strategies aimed at enhancing nerve graft and scaffold revascularization. This article is categorized under: Neurological Diseases > Biomedical Engineering Neurological Diseases > Molecular and Cellular Physiology., (© 2023 Wiley Periodicals LLC.)

Cell-based nanotherapy holds great potential to transform diagnosis and treatment patterns for human diseases, especially for cardiovascular diseases (CVDs). Surface coating with cell membrane has become a powerful strategy for functionalization of therapeutic nanoparticles to achieve biological performances of superior biocompatibility, immune evasion, and specificity. Additionally, extracellular vesicles (EVs) play key roles in the progression of CVDs with their ability of transferring cargos to distant tissues, thus emerging as an appealing option for the diagnosis and therapy of CVDs. In this review, recent progress in cell-based nanotherapy for CVDs is summarized, and different sources of EVs and biomimetic nanoplatforms derived from natural cells are highlighted. Meanwhile, their promising biomedical applications in the diagnosis and targeted treatment of different CVDs are also provided, followed by a discussion of their potential challenges and future prospects., (© 2023 Wiley-VCH GmbH.)

Episodes of worsening symptoms and signs characterize the clinical course of patients with chronic heart failure (HF). These events are associated with poorer quality of life, increased risks of hospitalization and death and are a major burden on healthcare resources. They usually require diuretic therapy, either administered intravenously or by escalation of oral doses or with combinations of different diuretic classes. Additional treatments may also have a major role, including initiation of guideline-recommended medical therapy (GRMT). Hospital admission is often necessary but treatment in the emergency service or in outpatient clinics or by primary care physicians has become increasingly used. Prevention of first and recurring episodes of worsening HF is an essential component of HF treatment and this may be achieved through early and rapid administration of GRMT. The aim of the present clinical consensus statement by the Heart Failure Association of the European Society of Cardiology is to provide an update on the definition, clinical characteristics, management and prevention of worsening HF in clinical practice., (© 2023 European Society of Cardiology.)

Aim: To investigate the relationship between heart rate and survival in patients with heart failure (HF) and coexisting atrial fibrillation (AF)., Methods and Results: Patients with AF included in the Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) meta-analysis were the main focus of this analysis (3259 patients from 17 studies). The outcome was all-cause mortality at 3 years. Heart rate was analysed as a categorical (tertiles; T1 ≤77 b.p.m., T2 78-98 b.p.m., T3 ≥98 b.p.m.) and continuous variable. Cox proportional hazard models were used to compare the risk of all-cause death between tertiles of baseline heart rate. Patients in the highest tertile were more often female, less likely to have an ischaemic aetiology or diabetes, had a lower ejection fraction but higher blood pressure and New York Heart Association (NYHA) class. Higher heart rate was associated with higher mortality in patients with sinus rhythm (SR) but not in those in AF. In patients with heart failure and reduced ejection fraction (HF-REF) and AF, death rates per 100 patient years were lowest in the highest heart rate tertile (T1 18.9 vs. T3 15.9) but this difference was not statistically significant (P = 0.10). In patients with heart failure and preserved ejection fraction (HF-PEF), death rates per 100 patient years were highest in the highest heart rate tertile (T1 14.6 vs. T3 16.0, P = 0.014). However, after adjustment for other important prognostic variables, higher heart rate was no longer associated with higher mortality in HF-PEF (or HF-REF)., Conclusions: In this meta-analysis of patients with HF, heart rate does not have the same prognostic significance in patients in AF as it does in those in SR, irrespective of ejection fraction or treatment with beta-blocker., (© 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.)

Cardiovascular diseases (CVDs) have been the leading cause of death worldwide during the past several decades. Cell loss is the main problem that results in cardiac dysfunction and further mortality. Cell therapy aiming to replenish the lost cells is proposed to treat CVDs especially ischemic heart diseases which lead to a big portion of cell loss. Due to the direct injection's low cell retention and survival ratio, cell therapy using biomaterials as cell carriers has attracted more and more attention because of their promotion of cell delivery and maintenance at the aiming sites. In this review, the three main factors involved in cell therapy for myocardial tissue regeneration: cell sources (somatic cells, stem cells, and engineered cells), chemical components of cell carriers (natural materials, synthetic materials, and electroactive materials), and categories of cell delivery materials (patches, microspheres, injectable hydrogels, nanofiber and microneedles, etc.) are systematically summarized. An introduction of the methods including magnetic resonance/radionuclide/photoacoustic and fluorescence imaging for tracking the behavior of transplanted cells in vivo is also included. Current challenges of biomaterials-based cell therapy and their future directions are provided to give both beginners and professionals a clear view of the development and future trends in this area., (© 2023 Wiley-VCH GmbH.)