Search Results (142)

Background and Objectives: Diabetes mellitus (DM) significantly impacts post-surgical recovery and fracture healing; however, few studies have specifically investigated the impact of DM on outcomes in patients undergoing surgical stabilization of rib fractures (SSRF). This study investigated the potential influence of DM on perioperative outcomes following SSRF, using data from Taiwan’s National Health Insurance Research Database (NHIRD). Materials and Methods: Data of 1603 patients with multiple rib fractures who underwent SSRF between 2001 and 2019 were retrospectively analyzed. Patients were categorized into three groups: no DM, DM without chronic complications, and DM with chronic complications. The associations between DM status and perioperative outcomes, including hospital length of stay (LOS), in-hospital mortality, readmission rates, and complications such as pneumonia, surgical site infection (SSI), acute myocardial infarction (AMI), and total hospital costs were determined using univariate and multivariable regression analyses. Results: The mean age of the 1603 patients was 52.0 years, and 71% were male. Patients with DM and chronic complications had higher risks of 14-day readmission (adjusted odds ratio [aOR] = 2.99; 95% confidence interval [CI]: 1.18–7.62), 15–30 day readmission (aOR = 3.28; 95% CI: 1.25–8.60), SSI (aOR = 2.90; 95% CI: 1.37–6.14), AMI (aOR = 3.44; 95% CI: 1.28–9.24), and acute respiratory distress syndrome (ARDS) (aOR = 1.96; 95% CI: 1.03–3.74). In conclusion, DM, particularly DM with chronic complications, significantly increases the risk of adverse short-term outcomes following SSRF. Conclusions: These findings emphasize the need for enhanced care for patients with DM to optimize the outcomes of SSRF. Full article

Background: Peripheral endovascular intervention (PEVI) is routinely performed using standard-dose radiation (SDR), which is associated with elevated levels of radiation. No study has evaluated the outcomes of minimal-dose radiation (MDR) in PEVI. Methods: We performed a prospective observational study of 184 patients (65 ± 12 years) at an academic medical center from January 2019 to March 2020 (mean follow-up of 3.9 ± 3.6 months) and compared the outcomes of MDR (n = 24, 13.0%) and SDR (n = 160, 87.0%) in PEVI. Primary endpoints included air kerma, dose area product (DAP), fluoroscopy time, and contrast use. Secondary endpoints included all-cause mortality, cardiac mortality, acute myocardial infarction, acute kidney injury, stroke, repeat revascularization, vessel dissection/perforation, major adverse limb event, access site complications, and composite of complications. Results: For MDR (68 ± 10 years, mean follow-up of 4.3 ± 5.2 months), the primary endpoints were significantly less than SDR (65 ± 12 years, mean follow-up of 3.8 ± 3.2 months; p < 0.001). Regarding the secondary endpoints, one vessel dissection occurred using MDR, while 36 total complications occurred with SDR (p = 0.037). Conclusions: PEVI using MDR was safe and efficacious. MDR showed a significant decrement in radiation parameters and fluoroscopy time. Therefore, MDR can serve as an effective alternative for PEVI in acute or critical limb ischemia. Full article

Background/Objectives: Randomized studies of patients with unprotected left main coronary artery (ULMCA) disease involve highly selected populations. Therefore, we sought to investigate the 60-month event-free survival of consecutive patients undergoing ULMCA percutaneous coronary intervention (PCI) and determine the best risk score system and independent predictors of event-free survival. Methods: All patients who underwent ULMCA PCI at our center between 1 January 2007 and 31 December 2014 were included. The primary endpoint was the time to cardiac death, target lesion myocardial infarction, or target lesion revascularization (whichever came first) with a follow-up of 60 months. Results: A total of 513 patients (mean age 68 ± 12 years, 64% male, 157 elective, 356 acute) underwent ULMCA PCI. The 60-month incidence of events was 16.8% and 38.0% in elective and acute patients, respectively. There were significantly more events in the acute group during the first 6.5 months. Of the risk scores, the ACEF (AUC = 0.786) and SYNTAX II (AUC = 0.716) scores had the best predictive power in elective and acute patients, respectively. The SYNTAX score proved to be the least predictive in both groups (AUC = 0.638 and 0.614 in the elective and acute groups, respectively). Left ventricular function (hazard ratio (HR) for +10% 0.53 [95% CI, 0.38–0.75] and 0.81 [95% CI, 0.71–0.92] in elective and acute patients, respectively) and, in acute patients, access site (femoral vs. radial HR 1.76 [95% CI, 1.11–2.80]), hyperlipidemia (HR 0.58 [95% CI, 0.39–0.86]), and renal function (HR for +10 mL/min/1.73 m² higher GFR: 0.87 [95% CI, 0.78–0.97]) were independent predictors of event-free survival. Conclusions: Acute ULMCA PCI patients have worse prognosis than elective patients, having more events during the first 6.5 months. Besides anatomical complexity, clinical and procedural parameters determine the prognosis. Full article

Background: Synchronous computation of coronary angiography-derived fractional flow reserve (CAG-FFR) and coronary angiography-derived index of microcirculatory resistance (CAG-IMR) is a novel coronary angiography-based method for on-site assessment of suspected myocardial ischemia in patients with coronary artery disease (CAD). Methods: This trial is a prospective, multicenter, controlled study designed to assess the diagnostic performance of CAG-FFR and CAG-IMR in patients with suspected myocardial ischemia using wire-based FFR and IMR as reference standards. The functional parameters were calculated using a reduced order computational fluid dynamics solver that incorporates thrombolysis in myocardial infarction (TIMI) frame count and aortic pressure recorded by a disposable invasive pressure sensor. Results: CAG-FFR was computed in 325 patients, demonstrating a patient-level diagnostic accuracy of 95.4%, sensitivity of 95.9%, and specificity of 95.1%. The area under the receiver operating characteristic curve (AUC) of CAG-FFR was 0.977. Patient-specific aortic pressure adoption significantly improved the accuracy of CAG-FFR in the “gray zone” compared to fixed-pressure models. In addition, CAG-IMR was successfully computed in 180 patients, showing a patient-level diagnostic accuracy of 95.5%, sensitivity of 96.4%, and specificity of 95.2%. The AUC of CAG-IMR in diagnosing abnormal coronary microcirculatory dysfunction was 0.973. Conclusions: Synchronous computation of CAG-FFR and CAG-IMR demonstrated higher feasibility and excellent diagnostic accuracy compared to wire-based FFR and IMR, highlighting its clinical potential for CAD evaluation. Full article

Objectives: To compare the perioperative complications between robot-assisted (RARN) and laparoscopic (LRN) radical nephrectomy for the treatment of renal cell carcinoma (RCC). Methods: We conducted a retrospective study using the National Surgical Quality Improvement Program (NSQIP) Nephrectomy-Targeted database from 2019 to 2021. After using propensity score matching, we assessed the association between LRN vs. RARN and the outcomes of interest (primary outcomes of 30-day mortality, return to the operating room, myocardial infarction, and stroke; and secondary outcomes of perioperative complications and nephrectomy-specific outcomes). Results: Among the 1545 patients in the study (mean age: 62.9 ± 11.8 years), 722 underwent RARN and 823 underwent LRN. We did not observe any differences in the major complications between the two approaches. However, LRN was associated with an increased chance of surgical site infections compared with RARN (LRN 2.68% vs. RARN 1.19%, p = 0.047). LRN was also associated with a higher likelihood of a prolonged length of stay (OR 1.54, 95% CI: 1.15, 2.06, p = 0.004) and had a 2.7 times higher chance of conversion rate to open surgery (OR 3.70, 95% CI: 3.25, 4.15, p < 0.001) relative to RARN. However, RARN was associated with a longer operative time than LRN (estimated coefficient 30.67, p < 0.001). Conclusion: We found no significant difference in the major complications between RARN and LRN for patients undergoing radical nephrectomy. At the expense of a somewhat longer operative time, RARN was associated with a lower risk of SSI and a lower conversion rate to open RN. LRN and RARN should both be considered and selected on an individualized basis using tumor, patient, and physician factors. Full article

Non-traumatic intracerebral hemorrhage (ICH) is one of the most devastating and disabling forms of stroke; however, there are no effective pharmacological therapies available following the insult. Angiogenesis appears as a key step to overcoming the damage and promoting functional recovery. In this context, endothelial progenitor cells (EPCs) mobilization improves oxidative stress and promotes neovascularization, which has been linked to beneficial outcomes following both ischemic and hemorrhagic stroke. The TNF-like weak inducer of apoptosis (TWEAK), binding to its receptor Fn14, has been suggested as an inducer of EPCs differentiation, viability and migration to the injury site in a model of myocardial infarction. Here, we have performed a proof-of-concept preclinical study in a rat model of ICH where we report that a 50 μg/kg dose of rat recombinant TWEAK (rTWEAK) promotes blood progenitor cells mobilization, mainly EPCs. As soon as 72 h post-injury, brain neovascularization, and, importantly, long-term hematoma reduction and improved functional recovery is reported. In contrast, a higher dose of 150 μg/kg blocked those beneficial outcomes. Therefore, a low dose of rTWEAK treatment promotes neovascularization and reduces brain damage in a rat model of ICH. Further clinical studies will be needed to demonstrate if rTWEAK could represent a new strategy to promote recovery following ICH. Full article

Regenerative medicine is a challenging field in current research and development, whilst translating the findings of novel tissue regenerative agents into clinical application. Protein-based hydrogels are derived from various sources, with animal-derived products being primarily utilized to deliver cells and promote cell genesis and proliferation, thereby aiding in numerous indications, including bone tissue regeneration, cartilage regeneration, spinal cord injury, and wound healing. As biocompatible and biodegradable systems, they are tolerated by the human body, allowing them to exert their beneficial effects in many indications. In this review article, multiple types of animal-derived proteins (e.g., collagen, gelatin, serum albumin, fibrin) were described, and a selection of the recent literature was collected to support the claims behind these innovative systems. During the literature review, special indications were found when applying these hydrogels, including the therapeutic option to treat post-myocardial infarct sites, glaucoma, and others. Maintaining their structure and mechanical integrity is still challenging. It is usually solved by adding (semi)synthetic polymers or small molecules to strengthen or loosen the mechanical stress in the hydrogel’s structure. All in all, this review points out the potential application of value-added delivery systems in regenerative medicine. Full article

Background: Cocaine abuse represents a serious health issue. The cardiovascular system is one of the main sites on which cocaine elicits its toxicity, as indicated by deadly events mainly related to myocardial infarction. The main aim of this study was to characterize the histological and immunohistochemical alterations related to cocaine abuse in cardiac tissue. Methods: Cardiac tissue samples derived from cocaine-related (n = 30) and not-cocaine-related deaths (n = 30). Histomorphology evaluations and immunohistochemistry for inflammatory biomarkers (CD45 and CD3) have been performed on formalin-fixed, paraffin-embedded (FFPE) cardiac tissue samples. Results: A higher frequency of cardiac alterations, such as wavy fibers, interstitial edema, fibrosis and hemorrhagic extravasation, were found in the group of cocaine users compared to the control group. Moreover, immunohistochemical analysis showed higher levels of inflammatory cells infiltrate within the cocaine-related deaths group. Conclusions: These data could shed new light on the complex relationship between cocaine use and cardiac alterations. Specifically, our data support the evidence that cocaine abuse is related to cardiac inflammation. Therefore, the generation of an inflammatory state could promote functional and structural cardiac alterations and lead ultimately to myocardial infarction. This would explain the high frequency of acute myocardial infarction in cocaine users. Full article

Hypertrophic cardiomyopathy (HCM) is the most common hereditary cardiovascular disease. In general, obstructive hypertrophic cardiomyopathy (HOCM) is more closely related to severe clinical symptoms and adverse clinical outcomes. Therefore, it is necessary to explore the possible causes of HOCM, which may help physicians better understand the disease and effectively control and manage the progression of the disease. In recent years, the discovery of lactylation has provided scholars with a new direction to explore the occurrence of diseases. In cardiovascular diseases, this post-translational modification can exacerbate cardiac dysfunction, and it can also promote the cardiac repair process after myocardial infarction. In this study, we used the myocardial tissue of mice carrying the Myh7 V878A gene mutation site for protein lactylation detection. Through a further analysis of the enriched pathways using KEGG enrichment, GO enrichment, and Wiki Pathways enrichment, we found that the enriched pathways with lactylation modifications in the HOCM mice mainly included the fatty acid oxidation pathway, the tricarboxylic acid cycle pathway, the adrenergic signaling pathway in cardiomyocytes, and the cardiomyocyte hypertrophy pathway. Among the above pathways, significant changes in lactylation occurred in proteins including Acads, Acaa2, Mdh2, Myl2, and Myl3. We used the COIP experiment to verify the omics results and the ELISA assay to verify the function of the enzymes. We found that a decrease in lactylation modifications also led to a decrease in enzyme function. The abnormalities of these proteins not only lead to abnormalities in energy metabolism in the myocardial tissue of HOCM but also may affect myocardial contractility, resulting in the impaired contractile function of HOCM. The results of this study lay a preliminary theoretical foundation for further exploring the pathogenesis of HOCM. Full article

Sympathetic nerves innervate bone marrow and various immune organs, where norepinephrine—the primary sympathetic neurotransmitter—directly interacts with immune cells that express adrenergic receptors. This article reviewed the key molecular pathways triggered by sympathetic activation and explored how sympathetic activity influences immune cell migration. Norepinephrine serves as a chemoattractant for monocytes, macrophages, and stem cells, promoting the migration of myeloid cells while inhibiting the migration of lymphocytes at physiological concentrations. We also examined the role of immune cell infiltration in cardiovascular diseases and cancer. Evidence suggests that sympathetic activation increases myeloid cell infiltration into target tissues across various cardiovascular diseases, including atherosclerosis, hypertension, cardiac fibrosis, cardiac hypertrophy, arrhythmia, myocardial infarction, heart failure, and stroke. Conversely, inhibiting sympathetic activity may serve as a potential therapeutic strategy to treat these conditions by reducing macrophage infiltration. Furthermore, sympathetic activation promotes macrophage accumulation in cancer tissues, mirroring its effects in cardiovascular diseases, while suppressing T lymphocyte infiltration into cancerous sites. These changes contribute to increased cancer growth and metastasis. Thus, inhibiting sympathetic activation could help to protect against cancer by enhancing T cell infiltration and reducing macrophage presence in tumors. Full article

Acute myocardial infarction, a leading cause of death globally, is often associated with cardiometabolic disorders such as atherosclerosis and metabolic syndrome. Metabolic treatment of these disorders can improve cardiac outcomes, as exemplified by the GLP-1 agonist semaglutide. Fibroblast growth factor 21 (FGF21), a novel metabolic regulator, plays pivotal roles in lipid mobilization and energy conversion, reducing lipotoxicity, inflammation, mitochondrial health, and subsequent tissue damage in organs such as the liver, pancreas, and heart. Here, we test the therapeutic efficacy of FGF21 in mice with ischemia–reperfusion (I/R) injury, a model of acute myocardial infarction. We employed the strategic method of coating the FGF21-encapsulating liposomal nanoparticles with a neutrophil membrane designed to camouflage FGF21 from macrophage-mediated efferocytotic clearance and promote its targeted accumulation at I/R foci due to the inherent neutrophilic attraction to the inflammatory site. Our findings revealed that the coated FGF21 nanoparticles markedly accumulated within the lesions with a prolonged half-life, in additional to the liver, leading to substantial improvements in cardiac performance by enhancing mitochondrial energetic function and reducing oxidative stress, inflammation, and cell death. Therefore, our research highlights a viable strategy for the enhanced delivery of therapeutical FGF21 analogs to lesions beyond the liver following myocardial infarction. Full article

Introduction: After myocardial infarction (MI), the heart undergoes necrosis, inflammation, scar formation, and remodeling. While restoring blood flow is crucial, it can cause ischemia-reperfusion (IR) injury, driven by reactive oxygen species (ROSs), which exacerbate cell death and tissue damage. This study introduces a mathematical model capturing key post-MI dynamics, including inflammatory responses, IR injury, cardiac remodeling, and stem cell therapy. The model uses nonlinear ordinary differential equations to simulate these processes under varying conditions, offering a predictive tool to understand MI pathophysiology better and optimize treatments. Methods: After myocardial infarction (MI), left ventricular remodeling progresses through three distinct yet interconnected phases. The first phase captures the immediate dynamics following MI, prior to any medical intervention. This stage is mathematically modeled using the system of ordinary differential equations: The second and third stages of the remodeling process account for the system dynamics of medical treatments, including oxygen restoration and subsequent stem cell injection at the injury site. Results: We simulate heart tissue and immune cell dynamics over 30 days for mild and severe MI using the novel mathematical model under medical treatment. The treatment involves no intervention until 2 h post-MI, followed by oxygen restoration and stem cell injection at day 7, which is shown experimentallyand numerically to be optimal. The simulation incorporates a baseline ROS threshold ($R_c$) where subcritical ROS levels do not cause cell damage. Conclusion: This study presents a novel mathematical model that extends a previously published framework by incorporating three clinically relevant parameters: oxygen restoration rate ($\omega$), patient risk factors ($\gamma$), and neutrophil recruitment profile ($\delta$). The model accounts for post-MI inflammatory dynamics, ROS-mediated ischemia-reperfusion (IR) injury, cardiac remodeling, and stem cell therapy. The model’s sensitivity highlights critical clinical insights: while oxygen restoration is vital, excessive rates may exacerbate ROS-driven IR injury. Additionally, heightened patient risk factors (e.g., smoking, obesity) and immunodeficiency significantly impact tissue damage and recovery. This predictive tool offers valuable insights into MI pathology and aids in optimizing treatment strategies to mitigate IR injury and improve post-MI outcomes. Full article

Today, cardiovascular diseases contribute to approximately 17.9 million deaths annually worldwide. With reference to Europe, coronary artery disease (CAD) causes about 3.9 million deaths annually. Considering the positive physical and psychological outcomes of on-site exercise for CAD patients, this study aimed to expand the literature by examining the effects of a 6-month online exercise training program using wearable devices on CAD patients’ perceived well-being, measured with the PERMA profiler. Individual well-being is considered today as an important prerequisite for healthy societies. Thirty patients with a recent myocardial infarction (i.e., <4 weeks) were randomly assigned to either the online home-based or the community-based exercise group. Both groups followed the same 24-week exercise-based cardiac rehabilitation program three times per week. Each session consisted of a 30-min aerobic, followed by a 15-min strength workout, and then a 15-min balance and flexibility training. The results of the Mann–Whitney U tests and the z scores indicated that the Meaning of Life, Health, Accomplishment, Engagement, and Positive Relationship dimensions of the PERMA were statistically improved, and Negative Emotions were decreased. These findings support the importance of cardiac telerehabilitation for patients’ psychological health, demonstrating that online exercise using wearable devices can be a meaningful alternative to on-site exercise for patients with recent myocardial infarction. These results have policy implications as they provide arguments for providing online exercise for CAD patients as an alternative means for improving their psychological health. Full article

Background/Objectives: Immune thrombotic thrombocytopenic purpura (iTTP) is a rare, chronically relapsing disorder that causes life-threatening thrombotic microangiopathy. Many survivors in clinical remission show evidence of ongoing silent cerebral infarction and neurocognitive deficits. Prospective longitudinal studies of this population are needed to acquire a complete understanding of the mechanism behind this ongoing neurologic injury. We aimed to assess the feasibility of a multicenter prospective study of neuropsychological and cognitive function in iTTP survivors in remission and examine novel biomarkers. Methods: We aimed to enroll 50 iTTP patients across three USTMA consortium sites between 2019 and 2022 in a 24-month longitudinal study. Clinical, cognitive, and biomarker assessments, including ADAMTS13 activity, were performed. Results: Despite the COVID-19 pandemic, we enrolled 38 subjects, and 31 (81.6%) completed closeout evaluations at 24 months. Upon the participants’ enrollment in the study, we confirmed previous findings, including high rates of moderate to severe neurocognitive and psychiatric sequelae (anxiety, 47%; depression, 45%; and headaches, 55%). Changes in cognitive function were measurable and included decreased immediate memory and visuospatial abilities. Over this two-year study, we did not see a significant change in neurocognitive findings. There was no association between cognitive function and ADAMTS13 activity; however, we found that the level of soluble thrombomodulin (CD141) was significantly correlated with cognitive impairment. Conclusions: We conclude that a more extensive study is feasible, and at least 5–10 years may be required to detect trends in neurocognitive function. Soluble thrombomodulin is a promising biomarker for cognitive impairment in survivors of iTTP, and it is worthy of additional study. Full article

Cardiac troponin I (cTnI) is a crucial biomarker for the early detection of acute myocardial infarction (AMI), playing a significant role in cardiac health assessment. Molecularly imprinted polymers (MIPs) are valued for their stability, ease of fabrication, reusability, and selectivity. However, using the analyte as a template can be costly, especially if the analyte is expensive. In such cases, a dummy template (DT) with similar chemico-physical properties can be useful. This study aimed to design a DT-MIP for cTnI detection using cytochrome c (Cyt c) as the template, combining computational and experimental approaches. Molecular docking identified binding sites on Cyt c and cTnI for poly(o-phenylenediamine) (5PoPD) pentamers. Interactions and binding energies were examined using all-atom molecular dynamics (MDs) simulations and structural interaction fingerprint (SIFt) calculations. A DT-MIP-modified electrode for cTnI detection was prepared by electropolymerizing o-PD in the presence of Cyt c as a dummy template. Electrochemical techniques monitored the electropolymerization, template removal, and binding of the target analyte. The experimental results showed that the DT-MIPs exhibited a high binding affinity for cTnI, consistent with the binding energies observed in MD simulations. The satisfactory correlation between experimental and computational results validated our model-based approach for the rational design of dummy template molecularly imprinted polymers. Full article