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Search Results (410)

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38 pages, 471 KiB  
Review
Sleep Disorders and Stroke: Pathophysiological Links, Clinical Implications, and Management Strategies
by Jamir Pitton Rissardo, Ibrahim Khalil, Mohamad Taha, Justin Chen, Reem Sayad and Ana Letícia Fornari Caprara
Med. Sci. 2025, 13(3), 113; https://doi.org/10.3390/medsci13030113 - 5 Aug 2025
Abstract
Sleep disorders and stroke are intricately linked through a complex, bidirectional relationship. Sleep disturbances such as obstructive sleep apnea (OSA), insomnia, and restless legs syndrome (RLS) not only increase the risk of stroke but also frequently emerge as consequences of cerebrovascular events. OSA, [...] Read more.
Sleep disorders and stroke are intricately linked through a complex, bidirectional relationship. Sleep disturbances such as obstructive sleep apnea (OSA), insomnia, and restless legs syndrome (RLS) not only increase the risk of stroke but also frequently emerge as consequences of cerebrovascular events. OSA, in particular, is associated with a two- to three-fold increased risk of incident stroke, primarily through mechanisms involving intermittent hypoxia, systemic inflammation, endothelial dysfunction, and autonomic dysregulation. Conversely, stroke can disrupt sleep architecture and trigger or exacerbate sleep disorders, including insomnia, hypersomnia, circadian rhythm disturbances, and breathing-related sleep disorders. These post-stroke sleep disturbances are common and significantly impair rehabilitation, cognitive recovery, and quality of life, yet they remain underdiagnosed and undertreated. Early identification and management of sleep disorders in stroke patients are essential to optimize recovery and reduce the risk of recurrence. Therapeutic strategies include lifestyle modifications, pharmacological treatments, medical devices such as continuous positive airway pressure (CPAP), and emerging alternatives for CPAP-intolerant individuals. Despite growing awareness, significant knowledge gaps persist, particularly regarding non-OSA sleep disorders and their impact on stroke outcomes. Improved diagnostic tools, broader screening protocols, and greater integration of sleep assessments into stroke care are urgently needed. This narrative review synthesizes current evidence on the interplay between sleep and stroke, emphasizing the importance of personalized, multidisciplinary approaches to diagnosis and treatment. Advancing research in this field holds promise for reducing the global burden of stroke and improving long-term outcomes through targeted sleep interventions. Full article
3 pages, 148 KiB  
Correction
Correction: Zarate-Calderon et al. Risk of Cerebrovascular Events in Deep Brain Stimulation for Parkinson’s Disease Focused on STN and GPi: Systematic Review and Meta-Analysis. Brain Sci. 2025, 15, 413
by Cristofer Zarate-Calderon, Carlos Castillo-Rangel, Iraís Viveros-Martínez, Estefanía Castro-Castro, Luis I. García and Gerardo Marín
Brain Sci. 2025, 15(8), 838; https://doi.org/10.3390/brainsci15080838 (registering DOI) - 5 Aug 2025
Abstract
In the original publication, there was a mistake in the legend for Table 1 [...] Full article
(This article belongs to the Section Neurodegenerative Diseases)
12 pages, 451 KiB  
Article
Impact of Metabolically Healthy Obesity on Cardiovascular Outcomes in Older Adults with HFpEF: Insights from a Nationwide Sample
by Adil Sarvar Mohammed, Hafeezuddin Ahmed, Sachin Singh, Cyrus Mutinda Munguti, Lakshmi Subramanian, Sashwath Srikanth, Lakshmi Sai Meghana Kodali, Maya Asami Takagi, Umera Yasmeen, Hassaan Imtiaz, Akhil Jain, Saad Chaudhry and Rupak Desai
J. Clin. Med. 2025, 14(15), 5495; https://doi.org/10.3390/jcm14155495 - 4 Aug 2025
Abstract
Background: Clinical outcomes among older adults hospitalized with heart failure with preserved ejection fraction (HFpEF) in the setting of metabolically healthy obesity (MHO) remain insufficiently explored. This study aimed to evaluate whether MHO status is associated with different rates of major adverse cardiac [...] Read more.
Background: Clinical outcomes among older adults hospitalized with heart failure with preserved ejection fraction (HFpEF) in the setting of metabolically healthy obesity (MHO) remain insufficiently explored. This study aimed to evaluate whether MHO status is associated with different rates of major adverse cardiac and cerebrovascular events (MACCEs) during HFpEF-related hospitalizations compared to patients without MHO. Methods: Data from the 2019 National Inpatient Sample (NIS) database was analyzed using relevant ICD-10 codes to identify HFpEF admissions in older adults. Propensity score matching (1:1) was applied to generate balanced cohorts of patients with and without MHO. Multivariable adjustments were performed to assess primary outcomes, including MACCEs, all-cause mortality (ACM), acute myocardial infarction (AMI), dysrhythmia, cardiac arrest (CA), and stroke. Statistical significance was set at p < 0.05. Results: Each MHO cohort included 22,405 patients with a median age of 75 years. The MHO+ group demonstrated a significantly higher risk of dysrhythmia (OR 1.32, 95% CI 1.21–1.43, p < 0.001). Interestingly, an “obesity paradox” was observed, as the MHO+ cohort had lower odds of MACCEs (OR 0.70, 95% CI 0.61–0.81, p < 0.001), ACM (OR 0.66, 95% CI 0.54–0.82, p < 0.001), and AMI (OR 0.71, 95% CI 0.59–0.86, p = 0.001) compared to MHO−. No significant differences were found for CA or stroke between the groups. Conclusions: Although the MHO+ group had an elevated risk of dysrhythmia, they exhibited more favorable outcomes in terms of MACCEs, ACM, and AMI—supporting the concept of an “obesity paradox.” Further research is needed to better understand the role of MHO as a comorbid condition in patients with HFpEF. Full article
(This article belongs to the Section Cardiology)
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17 pages, 1247 KiB  
Article
Ischemic Mitral Valve Regurgitation in Patients Undergoing Coronary Artery Bypass Grafting—Early and Late-Term Outcomes of Surgical Treatment
by Paweł Walerowicz, Mirosław Brykczyński, Aleksandra Szylińska and Jerzy Pacholewicz
J. Clin. Med. 2025, 14(14), 4855; https://doi.org/10.3390/jcm14144855 - 9 Jul 2025
Viewed by 695
Abstract
Background: Coronary heart disease (CHD) remains the most prevalent pathology within the circulatory system. Among its chronic complications, ischemic mitral valve regurgitation (IMR) is observed in approximately 15% of patients with sustained myocardial ischemia. The presence of this complex valvular defect significantly increases [...] Read more.
Background: Coronary heart disease (CHD) remains the most prevalent pathology within the circulatory system. Among its chronic complications, ischemic mitral valve regurgitation (IMR) is observed in approximately 15% of patients with sustained myocardial ischemia. The presence of this complex valvular defect significantly increases both overall mortality and the incidence of adverse cardiovascular events. Notably, the presence of moderate to severe mitral regurgitation in patients undergoing surgical revascularization has been shown to double the risk of death. Despite the well-established etiology of IMR, data regarding the efficacy of surgical interventions and the determinants of postoperative outcomes remain inconclusive. Methods: The objective of the present study was to evaluate both early and long-term outcomes of surgical treatment of mitral regurgitation in patients undergoing coronary artery bypass grafting (CABG) due to ischemic heart disease. Particular attention was given to the influence of the severity of regurgitation, left ventricular ejection fraction (LVEF), and the dimensions of the left atrium (LA) and left ventricle (LV) on the postoperative prognosis. An additional aim was to identify preoperative risk factors associated with increased postoperative mortality and morbidity. A retrospective analysis was conducted on 421 patients diagnosed with ischemic mitral regurgitation who underwent concomitant mitral valve surgery and CABG. Exclusion criteria included emergent and urgent procedures as well as non-ischemic etiologies of mitral valve dysfunction. Results: The study cohort comprised 34.9% women and 65.1% men, with the mean age of 65.7 years (±7.57). A substantial proportion (76.7%) of patients were aged over 60 years. More than half (51.5%) presented with severe heart failure symptoms, classified as NYHA class III or IV, while over 70% were categorized as CCS class II or III. Among the surgical procedures performed, 344 patients underwent mitral valve repair, and 77 patients required mitral valve replacement. Additionally, 119 individuals underwent concomitant tricuspid valve repair. Short-term survival was significantly affected by the presence of hypertension, prior cerebrovascular events, and chronic kidney disease. In contrast, hypertension and chronic obstructive pulmonary disease were identified as significant predictors of adverse late-term outcomes. Conclusions: Interestingly, neither the preoperative severity of mitral regurgitation nor the echocardiographic measurements of LA and LV dimensions were found to significantly influence surgical outcomes. The perioperative risk, as assessed by the EuroSCORE II (average score: 10.0%), corresponded closely with observed mortality rates following mitral valve repair (9.9%) and replacement (10.4%). Notably, the need for concomitant tricuspid valve surgery was associated with an elevated mortality rate (12.4%). Furthermore, the preoperative echocardiographic evaluation of LA regurgitation severity, as well as LA and LV dimensions, did not exhibit a statistically significant impact on either early or long-term surgical outcomes. However, a reduced LVEF was correlated with increased long-term mortality. The presence of advanced clinical symptoms and the necessity for tricuspid valve repair were independently associated with a poorer late-term prognosis. Importantly, the annual mortality rate observed in the late-term follow-up of patients who underwent surgical treatment of ischemic mitral regurgitation was lower than rates reported in the literature for patients managed conservatively. The EuroSCORE II scale proved to be a reliable and precise tool in predicting surgical risk and outcomes in this patient population. Full article
(This article belongs to the Section Cardiovascular Medicine)
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11 pages, 478 KiB  
Systematic Review
The Role of Immature Platelet Fraction and Reticulated Platelets in Stroke Monitoring and Outcome Prognosis: A Systematic Review
by Alexandra Tsankof, Dimitrios A. Tsakiris, Lemonia Skoura, Panagiota Tsiatsiou, Eleftheria Ztriva, Georgios Ntaios, Christos Savopoulos and Georgia Kaiafa
J. Clin. Med. 2025, 14(13), 4760; https://doi.org/10.3390/jcm14134760 - 5 Jul 2025
Viewed by 393
Abstract
Background/Objectives: Immature platelet fraction (IPF) and reticulated platelets (RPs) are biomarkers reflecting the youngest and most metabolically active platelets in circulation. RPs, a subset of immature platelets, contain residual RNA and have been associated with increased thrombotic potential. Elevated IPF levels indicate [...] Read more.
Background/Objectives: Immature platelet fraction (IPF) and reticulated platelets (RPs) are biomarkers reflecting the youngest and most metabolically active platelets in circulation. RPs, a subset of immature platelets, contain residual RNA and have been associated with increased thrombotic potential. Elevated IPF levels indicate enhanced platelet production, commonly observed during elevated platelet turnover, such as in autoimmune reactions, consumption, and thrombotic events. This systematic review aims to evaluate the potential role of IPF and RPs in the context of cerebrovascular events, specifically ischemic and hemorrhagic stroke, as well as transient ischemic attacks (TIAs), and to assess their clinical utility in stroke monitoring and management. Methods: A comprehensive literature search was conducted in PubMed, Scopus, Cochrane Library, and Web of Science for studies published between 2000 and 2024, which focused on IPF and RPs in human subjects with cerebrovascular events. Results: Six studies met the inclusion criteria. Findings suggest that elevated levels of IPF and RP are associated with the acute and chronic phases of ischemic stroke and TIA and may reflect increased platelet turnover and thrombotic activity. Some evidence supports their role in predicting stroke severity, recurrence, and underlying etiology, although results are not yet consistent across all studies. Conclusions: IPF and RPs are emerging biomarkers with potential applications in acute ischemic stroke and risk stratification. While current evidence is promising, further research is needed to standardize measurement techniques and validate their routine use in clinical practice. Full article
(This article belongs to the Section Vascular Medicine)
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16 pages, 576 KiB  
Article
The Prognostic Potential of Insulin-like Growth Factor-Binding Protein 1 for Cardiovascular Complications in Peripheral Artery Disease
by Ben Li, Farah Shaikh, Houssam Younes, Batool Abuhalimeh, Abdelrahman Zamzam, Rawand Abdin and Mohammad Qadura
J. Cardiovasc. Dev. Dis. 2025, 12(7), 253; https://doi.org/10.3390/jcdd12070253 - 1 Jul 2025
Viewed by 408
Abstract
Background/Objectives: Patients with peripheral artery disease (PAD) have a heightened risk of major adverse cardiovascular events (MACE), including myocardial infarction, stroke, and death. Despite this, limited progress has been made in identifying reliable biomarkers to prognosticate such outcomes. Circulating growth factors, known to [...] Read more.
Background/Objectives: Patients with peripheral artery disease (PAD) have a heightened risk of major adverse cardiovascular events (MACE), including myocardial infarction, stroke, and death. Despite this, limited progress has been made in identifying reliable biomarkers to prognosticate such outcomes. Circulating growth factors, known to influence endothelial function and the progression of atherosclerosis, may hold prognostic value in this context. The objective of this research was to evaluate a broad range of blood-based growth factors to investigate their potential as predictors of MACE in patients diagnosed with PAD. Methods: A total of 465 patients with PAD were enrolled in a prospective cohort study. Baseline plasma levels of five different growth factors were measured, and participants were monitored over a two-year period. The primary outcome was the occurrence of MACE within those two years. Comparative analysis of protein levels between patients who did and did not experience MACE was performed using the Mann–Whitney U test. To assess the individual prognostic significance of each protein for predicting MACE within two years, Cox proportional hazards regression was performed, adjusting for clinical and demographic factors including a history of coronary and cerebrovascular disease. Subgroup analysis was performed to assess the prognostic value of these proteins in females, who may be at higher risk of PAD-related adverse events. Net reclassification improvement (NRI), integrated discrimination improvement (IDI), and area under the receiver operating characteristic curve (AUROC) were calculated to assess the added value of significant biomarkers to model performance for predicting 2-year MACE when compared to using demographic/clinical features alone. Kaplan–Meier curves stratified by IGFBP-1 tertiles compared using log-rank tests and Cox proportional hazards analysis were used to assess 2-year MACE risk trajectory based on plasma protein levels. Results: The average participant age was 71 years (SD 10); 31.1% were female and 47.2% had diabetes. By the end of the two-year follow-up, 18.1% (n = 84) had experienced MACE. Of all proteins studied, only insulin-like growth factor-binding protein 1 (IGFBP-1) showed a significant elevation among patients who suffered MACE versus those who remained event-free (20.66 [SD 3.91] vs. 13.94 [SD 3.80] pg/mL; p = 0.012). IGFBP-1 remained a significant independent predictor of 2-year MACE occurrence in the multivariable Cox analysis (adjusted hazard ratio [HR] 1.57, 95% CI 1.21–1.97; p = 0.012). Subgroup analyses revealed that IGFBP-1 was significantly associated with 2-year MACE occurrence in both females (adjusted HR 1.52, 95% CI 1.16–1.97; p = 0.015) and males (adjusted HR 1.04, 95% CI 1.02–1.22; p = 0.045). Incorporating IGFBP-1 into the clinical risk prediction model significantly enhanced its predictive performance, with an increase in the AUROC from 0.73 (95% CI 0.71–0.75) to 0.79 (95% CI 0.77–0.81; p = 0.01), an NRI of 0.21 (95% CI 0.07–0.36; p = 0.014), and an IDI of 0.041 (95% CI 0.015–0.066; p = 0.008), highlighting the prognostic value of IGFBP-1. Kaplan–Meier analysis showed an increase in the cumulative incidence of 2-year MACE across IGFBP-1 tertiles. Patients in the highest IGFBP-1 tertile experienced a significantly higher event rate compared to those in the lowest tertile (log-rank p = 0.008). In the Cox proportional hazards analysis, the highest tertile of IGFBP-1 was associated with increased 2-year MACE risk compared to the lowest tertile (adjusted HR 1.81; 95% CI: 1.31–2.65; p = 0.001). Conclusions: Among the growth factors analyzed, IGFBP-1 emerged as the sole biomarker independently linked to the development of MACE over a two-year span in both female and male PAD patients. The addition of IGFBP-1 to clinical features significantly improved model predictive performance for 2-year MACE. Measuring IGFBP-1 levels may enhance risk stratification and guide the intensity of therapeutic interventions and referrals to cardiovascular specialists, ultimately supporting more personalized and effective management strategies for patients with PAD to reduce systemic vascular risk. Full article
(This article belongs to the Section Cardiovascular Clinical Research)
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18 pages, 2596 KiB  
Review
Management and Treatment of Carotid Stenosis: Overview of Therapeutic Possibilities and Comparison Between Interventional Radiology, Surgery and Hybrid Procedure
by Lorenzo Aliotta, Livio Maria Gavazzi, Pierantonio Malfa, Pietro Valerio Foti, Stefano Palmucci, Maria Chiara Lo Greco, Corrado Spatola, Corrado Inì, Francesco Tiralongo, Davide Castiglione, Rita Bella, Gianluca Galvano, Giuseppe Lanza, Silvia Gigli, Antonio Basile, Vito Cantisani and Emanuele David
Diagnostics 2025, 15(13), 1679; https://doi.org/10.3390/diagnostics15131679 - 1 Jul 2025
Viewed by 832
Abstract
Carotid stenosis is a common pathology in clinical practice and unfortunately carries a high risk of serious cerebrovascular events. The early recognition of carotid plaque and, consequently, a careful analysis by means of multimodal imaging are the necessary steps to undertake a correct [...] Read more.
Carotid stenosis is a common pathology in clinical practice and unfortunately carries a high risk of serious cerebrovascular events. The early recognition of carotid plaque and, consequently, a careful analysis by means of multimodal imaging are the necessary steps to undertake a correct management pathway, aimed at preventing or, if not possible, reducing the risk of atherogenic phenomena responsible for cerebral infarction. In particular, the presence or absence of clinical symptoms, understood as the occurrence of events such as TIAs in the last 6 months, non-disabling strokes or repeated episodes of amaurosis fugax, and the degree of carotid stenosis, are certainly the most studied parameters, and as reported by several international guidelines, can lead to the best therapeutic strategy: whether to rely on conservative medical therapy or to resort to mechanical revascularization of the carotid stenosis. According to the recommendations of the European Society of Vascular Surgery, mechanical revascularization is recommended for stenosis > 50% in symptomatic patients and stenosis > 60% in asymptomatic patients. In contrast, the latest findings on plaque vulnerability have focused attention on individual patient characteristics and clinical comorbidities that may be responsible for plaque inflammation and should therefore be taken into consideration to decide if revascularization treatment is needed even in those subjects who present stenosis with less degree than reported as critical value. Moreover, further radiological investigations are fundamental to finding the presence of entities such as plaque ulceration, plaque neo-vascularization, fibrous caps, and intraplaque lipid core that are responsible for increased vulnerability. Medical therapy involves interventions aimed at eliminating cardiovascular risk factors by administering drugs that control the comorbidities responsible for worsening carotid stenosis. Recent studies are also evaluating the effectiveness of new plaque-modifying drugs or targeted anti-inflammatory agents in reducing the risk of plaque development and complications. Revascularization therapies, on the other hand, include surgery (CEA), the endovascular technique (CAS), and a new hybrid technique (TCAR): they are all valid alternatives for the treatment of carotid stenosis, each with specific technical difficulties, but on the whole with comparable safety profiles and risk rates of postoperative complications, although some recent emergencies have focused attention on possible short- and long-term gender-dependent outcome differences. The aim of this manuscript is to present the state of the art in the management of patients with carotid stenosis and to take a closer look at revascularization options. In our opinion, the choice of one strategy over another should therefore depend on gender, anatomical features of the patient, preoperative comorbidities, and last but not least, the experience of the center and the multidisciplinary team involved in the management of the patient. Full article
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15 pages, 234 KiB  
Article
Primary Aldosteronism and Cognitive Dysfunction: A Case-Control Study
by Jakov Herceg, Gorana Vukorepa and Sandra Karanović Štambuk
J. Clin. Med. 2025, 14(13), 4618; https://doi.org/10.3390/jcm14134618 - 30 Jun 2025
Viewed by 386
Abstract
Background: Primary aldosteronism is characterized by elevated aldosterone levels, leading to adverse effects such as hypertension, hypokalaemia and increased risk for cardiovascular and cerebrovascular events. Aldosterone impacts the central nervous system by promoting vascular remodelling and oxidative stress, potentially impairing cognitive function. [...] Read more.
Background: Primary aldosteronism is characterized by elevated aldosterone levels, leading to adverse effects such as hypertension, hypokalaemia and increased risk for cardiovascular and cerebrovascular events. Aldosterone impacts the central nervous system by promoting vascular remodelling and oxidative stress, potentially impairing cognitive function. The presence of mineralocorticoid receptors in the hippocampus, a key region for cognition, further suggest a link between primary aldosteronism and cognitive dysfunction. This study aims to further explore the association between hyperaldosteronism and cognitive impairment. Methods: In this pilot study we examined 15 individuals with primary aldosteronism and arterial hypertension alongside 15 age- and sex-matched controls with essential hypertension, all free of previous cerebrovascular events. Clinical and archival laboratory data were obtained. Cognitive function was assessed using the Mini-Mental State Examination and Montreal Cognitive Assessment. Results: Participants with primary aldosteronism had higher blood pressure values, longer duration of hypertension, lower serum potassium levels and higher 24 h urine albumin excretion rate compared to controls. Comorbidities, other characteristics and laboratory values were comparable across the two groups. No differences were observed in Mini-Mental State Examination scores, but Montreal Cognitive Assessment scores were significantly lower in the primary aldosteronism group (25.1 ± 2.2 vs. 27.1 ± 2.2, p = 0.021). Trends of poorer performance in language and attention/executive function domains were noted in primary aldosteronism individuals, as well as a higher number of pathological Montreal Cognitive Assessment scores (7 vs. 3). No significant correlations were found between cognitive test results and aldosterone concentrations or blood pressure in primary aldosteronism group. However, importantly, multiple regression analysis showed that aldosterone levels have a significant impact on Montreal Cognitive Assessment test, independent of blood pressure or duration of hypertension. Conclusions: This study supports an association between hyperaldosteronism and cognitive dysfunction, underscoring the need for more active detection and targeted treatment of primary aldosteronism. These findings warrant further research in larger cohorts to better elucidate this relationship. Full article
(This article belongs to the Section Cardiovascular Medicine)
13 pages, 426 KiB  
Article
Comparison of Clinical Characteristics and Outcomes Between MRSA and MSSA Infections Among Patients in Intensive Care Units
by Gustavo Andrés Urriago-Osorio, Heiler Lozada-Ramos, Jorge Enrique Daza-Arana, Paola Andrea Ruiz-Jiménez, Giovanna Patricia Rivas-Tafurt and Diana Marcela Bonilla-Bonilla
Microorganisms 2025, 13(7), 1519; https://doi.org/10.3390/microorganisms13071519 - 29 Jun 2025
Viewed by 485
Abstract
Staphylococcus aureus infections are an important cause of morbidity and mortality among patients in intensive care units (ICUs), particularly those with multiple comorbidities and critical conditions. Methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) strains differ in resistance, clinical behavior, and prognoses, [...] Read more.
Staphylococcus aureus infections are an important cause of morbidity and mortality among patients in intensive care units (ICUs), particularly those with multiple comorbidities and critical conditions. Methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) strains differ in resistance, clinical behavior, and prognoses, making it important to understand their effects on clinical outcomes. Comparing clinical outcomes of MRSA and MSSA infections is important. This retrospective cohort study analyzed ICU patients with confirmed S. aureus infections at a quaternary care hospital. Demographic, clinical, and comorbidity data were collected. Poisson regression was used to analyze 7-day mortality and identify adjusted risk factors. Seven-day mortality was higher in patients with MSSA than MRSA infections, with an adjusted relative risk for MRSA of 0.380 (95% confidence interval: 0.15–0.95; p = 0.039). Independent risk factors for mortality included lack of an infectious disease consultation, vascular comorbidities, such as peripheral vascular disease and cerebrovascular events, chronic kidney disease, and inotropic support requirement. Patients with MRSA infections required significantly longer ventilatory support (mean 43.5 days vs. 13 days for MSSA; p = 0.019). Staphylococcus aureus infections in ICU patients were associated with poor outcomes, particularly in patients without infectious disease consultation and those with vascular comorbidities. Mortality differences between MRSA and MSSA highlight the importance of appropriate empiric therapy and standardized protocols incorporating infectious disease consultation to improve outcomes in critically ill patients. Full article
(This article belongs to the Special Issue Emerging Infectious Diseases and Multidrug Resistance)
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16 pages, 388 KiB  
Article
Interferon Gamma and Tumor Necrosis Factor Alpha Are Inflammatory Biomarkers for Major Adverse Cardiovascular Events in Patients with Peripheral Artery Disease
by Ben Li, Eva Lindner, Raghad Abuhalimeh, Farah Shaikh, Houssam Younes, Batool Abuhalimeh, Abdelrahman Zamzam, Rawand Abdin and Mohammad Qadura
Biomedicines 2025, 13(7), 1586; https://doi.org/10.3390/biomedicines13071586 - 29 Jun 2025
Viewed by 528
Abstract
Background/Objectives: Major adverse cardiovascular events (MACE)—including heart attacks and strokes—are the leading cause of death in patients with peripheral artery disease (PAD), yet biomarker research for MACE prediction in PAD patients remains limited. Inflammatory proteins play a key role in the progression of [...] Read more.
Background/Objectives: Major adverse cardiovascular events (MACE)—including heart attacks and strokes—are the leading cause of death in patients with peripheral artery disease (PAD), yet biomarker research for MACE prediction in PAD patients remains limited. Inflammatory proteins play a key role in the progression of atherosclerosis and may serve as useful prognostic indicators for systemic cardiovascular risk in PAD. The objective of this study was to evaluate a broad panel of circulating inflammatory proteins to identify those independently associated with 2-year MACE in patients with PAD. Methods: We conducted a prospective cohort study involving 465 patients with PAD. Plasma concentrations of 15 inflammatory proteins were measured at baseline using validated immunoassays. Patients were followed over a two-year period for the development of MACE, defined as a composite endpoint of myocardial infarction, stroke, or mortality. Protein levels were compared between patients with and without MACE using the Mann–Whitney U test. Cox proportional hazards regression was used to determine the independent association of each protein with MACE after adjusting for baseline demographic and clinical variables, including existing coronary and cerebrovascular disease. To validate the findings, a random forest machine learning model was developed to assess the relative importance of each protein for predicting 2-year MACE. Results: The mean age of the cohort was 71 years (SD 10), and 145 participants (31.1%) were female. Over the two-year follow-up, 84 patients (18.1%) experienced MACE. Six proteins were significantly elevated in PAD patients who developed MACE: interferon gamma (IFN-γ; 42.55 [SD 15.11] vs. 33.85 [SD 12.46] pg/mL, p < 0.001), tumor necrosis factor alpha (TNF-α; 9.00 [SD 5.00] vs. 4.65 [SD 4.29] pg/mL, p < 0.001), chemokine (C-X-C motif) ligand 9 (CXCL9; 75.99 [SD 65.14] vs. 5.38 [SD 64.18] pg/mL, p = 0.002), macrophage inflammatory protein-1 beta (MIP-1β; 20.88 [SD 18.10] vs. 15.67 [SD 16.93] pg/mL, p = 0.009), MIP-1δ (25.29 [SD 4.22] vs. 17.98 [SD 4.01] pg/mL, p = 0.026), and interleukin-6 (IL-6; 12.50 [SD 40.00] vs. 6.72 [SD 38.98] pg/mL, p = 0.035). After adjusting for all baseline covariates, only two proteins—TNF-α (adjusted HR 1.66, 95% CI 1.28–2.33, p = 0.001) and IFN-γ (adjusted HR 1.25, 95% CI 1.12–2.29, p = 0.033)—remained significantly and independently associated with 2-year MACE. These findings were corroborated by the random forest model, where TNF-α and IFN-γ received the highest importance scores for predicting 2-year MACE: (TNF-α: 0.15 [95% CI 0.13–0.18], p = 0.002; IFN-γ: 0.19 [95% CI 0.17–0.21], p = 0.001). Conclusions: From a panel of 15 proteins, TNF-α and IFN-γ emerged as inflammatory biomarkers associated with 2-year MACE in PAD patients. Their measurement may aid in cardiovascular risk stratification, helping to identify high-risk individuals who could benefit from early multidisciplinary referrals to cardiology, neurology, and/or vascular medicine specialists to provide intensified medical therapy. Incorporating these biomarkers into PAD management may improve systemic cardiovascular outcomes through more personalized and targeted treatment approaches. Full article
(This article belongs to the Special Issue Advances in Biomarker Discovery for Cardiovascular Disease)
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38 pages, 2786 KiB  
Systematic Review
Obstructive Sleep Apnea and Outcomes in Cardiac Surgery: A Systematic Review with Meta-Analytic Synthesis (PROSPERO CRD420251049574)
by Andrei Raul Manzur, Alina Gabriela Negru, Andreea-Roxana Florescu, Ana Lascu, Iulia Raluca Munteanu, Ramona Cristina Novaconi, Nicoleta Sorina Bertici, Alina Mirela Popa and Stefan Mihaicuta
Biomedicines 2025, 13(7), 1579; https://doi.org/10.3390/biomedicines13071579 - 27 Jun 2025
Viewed by 646
Abstract
Background: Obstructive sleep apnea (OSA) is a prevalent but frequently underdiagnosed comorbidity in patients undergoing cardiac surgery, including coronary artery bypass grafting (CABG), aortic valve replacement (AVR), and mitral valve repair or replacement (MVR). This systematic review and meta-analytic synthesis investigates the [...] Read more.
Background: Obstructive sleep apnea (OSA) is a prevalent but frequently underdiagnosed comorbidity in patients undergoing cardiac surgery, including coronary artery bypass grafting (CABG), aortic valve replacement (AVR), and mitral valve repair or replacement (MVR). This systematic review and meta-analytic synthesis investigates the relationship between OSA and postoperative morbidity and mortality, with particular attention to the predictive utility of established screening instruments. Methods: A systematic search of the PubMed database was conducted (April 2025), identifying 724 articles published in the last ten years. Seventeen primary studies met the inclusion criteria for qualitative synthesis, and four additional studies were included in the meta-analyses. Outcomes assessed included atrial fibrillation, major adverse cardiac and cerebrovascular events (MACCE), acute kidney injury (AKI), respiratory complications, pneumonia, hospital length of stay (LOS), and mortality. Risk of bias was assessed qualitatively based on study design and reporting limitations. This review was registered in the PROSPERO database under registration number CRD420251049574. Results: Meta-analyses demonstrated significantly elevated odds of atrial fibrillation (OR = 2.44, 95% CI: 1.46–4.07), major adverse cardiac and cerebrovascular events (OR = 2.06, 95% CI: 1.61–2.63), acute kidney injury (OR = 2.24, 95% CI: 1.67–3.01), and respiratory complications (OR = 1.15, 95% CI: 1.05–1.25) among patients with OSA. Additionally, OSA was associated with a significantly prolonged hospital length of stay (standardized mean difference [SMD] = 0.62, 95% CI: 0.46–0.78) and a marginal increase in pneumonia risk (OR = 1.07, 95% CI: 1.00–1.15). Evidence regarding stroke, intensive care unit (ICU) stay, and mortality was inconsistent or underpowered. Conclusions: Across core outcomes, findings were consistent across multiple studies involving a large patient population. Obstructive sleep apnea is a clinically consequential risk factor in cardiac surgery, associated with increased perioperative complications and prolonged hospitalization. These findings support the integration of routine OSA screening into preoperative risk assessment protocols. Further prospective, multicenter trials are warranted to assess the efficacy of perioperative management strategies, including continuous positive airway pressure (CPAP) therapy, in improving surgical outcomes. Full article
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19 pages, 785 KiB  
Article
HE4 as a Prognostic Biomarker of Major Adverse Cardiovascular Events in Patients with Abdominal Aortic Aneurysm: A Canadian Prospective Observational Study
by Hamzah Khan, Abdelrahman Zamzam, Farah Shaikh, Muhammad Mamdani, Gustavo Saposnik and Mohammad Qadura
Biomedicines 2025, 13(7), 1562; https://doi.org/10.3390/biomedicines13071562 - 26 Jun 2025
Viewed by 451
Abstract
Background: Abdominal aortic aneurysm (AAA) is a chronic inflammatory disease characterized by the proteolytic breakdown of the extracellular matrix. A clinical biomarker is needed for risk stratification and prognosis. Methods: In this single-center, 5-year observational study, 452 patients were enrolled: 343 with [...] Read more.
Background: Abdominal aortic aneurysm (AAA) is a chronic inflammatory disease characterized by the proteolytic breakdown of the extracellular matrix. A clinical biomarker is needed for risk stratification and prognosis. Methods: In this single-center, 5-year observational study, 452 patients were enrolled: 343 with AAA (≥3 cm), and 109 controls (<3 cm). Plasma levels of six inflammatory proteins (human epididymis protein 4 (HE4), matrix metalloproteinase (MMP) 1 and 3, cathepsin S, chitinase 3 like-1, cathepsin S, and B-cell activating factor (BAFF)) were quantified at baseline. Patients were followed for a total of 5 years (60 months), and major adverse cardiovascular events (MACEs, defined as the composite of myocardial infarction, cerebrovascular attack, and cardiovascular-related death) were recorded. A Cox proportional hazard model was created using biomarker levels, age, sex, hypertension, hypercholesterolemia, diabetes mellitus, smoking status, and coronary artery disease to determine whether the baseline levels of these proteins were associated with MACEs over 5 years. Results: HE4, MMP-3, BAFF, and cathepsin S levels were significantly elevated in AAA patients compared to controls (all p < 0.05). HE4/WFDC2, MMP-3, and Chitinase 3-like 1 were significantly linearly associated with AAA diameter at baseline. With every normalized unit increase in HE4/WFDC2, MMP-3, and Chitinase 3-like 1, there was an increase in abdominal aortic diameter by 0.154 (95% CI: 0.032–0.276, p = 0.013), 0.186 (95% CI: 0.064–0.309, p = 0.003), and 0.231 (0.110–0.353, p < 0.001) centimeters, respectively. Among patients with AAA, elevated HE4 was associated with higher risk of MACEs (adjusted HR 1.249; 95% CI: 1.057–1.476; p = 0.009). Patients with high baseline HE4 (≥9.338 ng/mL) had significantly lower freedom from MACEs at 5 years (76.7% vs. 84.8%, p = 0.022). Conclusions: HE4 may be a potential prognostic biomarker that can be used to risk stratify patients with AAA to better personalize treatment strategies to reduce adverse events. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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17 pages, 1391 KiB  
Article
The Role of the Inflammatory Prognostic Index in Patients with Non-ST Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention
by Ersan Oflar, Muhsin Kalyoncuoğlu, Atilla Koyuncu, Cennet Yıldız Erbaş, Hasan Ali Sinoplu, Fahrettin Katkat and Gündüz Durmuş
J. Clin. Med. 2025, 14(13), 4491; https://doi.org/10.3390/jcm14134491 - 25 Jun 2025
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Abstract
Background/Objectives: To evaluate the prognostic role of the inflammatory prognostic index (IPI) value at admission in major adverse cardiovascular and cerebrovascular events (MACCEs) in individuals with non-ST elevation myocardial infarction (NSTEMI) undergoing percutaneous coronary intervention (PCI). Methods: A total of 1142 NSTEMI patients [...] Read more.
Background/Objectives: To evaluate the prognostic role of the inflammatory prognostic index (IPI) value at admission in major adverse cardiovascular and cerebrovascular events (MACCEs) in individuals with non-ST elevation myocardial infarction (NSTEMI) undergoing percutaneous coronary intervention (PCI). Methods: A total of 1142 NSTEMI patients with a mean age of 61.9 ± 12.5 years were included. Admission C-reactive protein level, serum albumin level, and complete blood counts of participants were collected from hospital records. The IPI was calculated based on the following formula: C-reactive protein/albumin ratio (CAR) x neutrophil-to-lymphocyte ratio (NLR). An aggregate index of systemic inflammation (AISI) value was calculated using the ‘‘neutrophil count x monocyte count x platelet/lymphocyte count’’ formula. The study cohort was divided into two groups according to the median IPI value. Results: Patients with higher IPI values were statistically more likely to suffer from MACCEs within one year (p < 0.001), thus the admission IPI value was found to be associated with future development of MACCEs. Furthermore, it had sufficient discrimination power (AUC = 0.70) and predictive accuracy in identifying MACCEs compared to other inflammatory parameters such as the CAR (AUC = 0.64), the NLR (AUC = 0.64), and the AISI (AUC = 0.59). Adding the IPI to the baseline multivariable logistic regression model significantly improved the model’s discrimination and net clinical benefit effect for identifying patients who would suffer from MACCEs, with a C-index of 0.84 (95% CI: 0.82–0.86) and explanatory power of 23.2% (R2 = 0.232, DeLong test p = 0.001). High-risk patients with an IPI value greater than 2.43 had significantly more adverse events (p < 0.001). Conclusions: The IPI may be a promising inflammatory index for use in clinical practice to determine the risk prediction of MACCEs in NSTEMI patients undergoing PCI. Full article
(This article belongs to the Section Cardiology)
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18 pages, 1598 KiB  
Article
Trends and Predictors of Venous Thromboembolism and Major Hemorrhagic Events in Hospitalized Leukemia Patients: A Cross-Sectional Analysis of the NIS (2016–2020)
by Daniel Antwi-Amoabeng, Bryce D. Beutler, Vijay Neelam and Mark Ulanja
Clin. Pract. 2025, 15(7), 117; https://doi.org/10.3390/clinpract15070117 - 25 Jun 2025
Viewed by 320
Abstract
Background/Objectives: Venous thromboembolism (VTE) and major hemorrhagic events are significant complications in hospitalized leukemia patients, but contemporary analyses of their epidemiology, predictors, and impact on clinical outcomes remain limited. Methods: We conducted a cross-sectional study using the National Inpatient Sample (NIS) database from [...] Read more.
Background/Objectives: Venous thromboembolism (VTE) and major hemorrhagic events are significant complications in hospitalized leukemia patients, but contemporary analyses of their epidemiology, predictors, and impact on clinical outcomes remain limited. Methods: We conducted a cross-sectional study using the National Inpatient Sample (NIS) database from 2016 to 2020. Hospitalized leukemia patients were identified using ICD-10 codes. Trends in the incidence of venous thromboembolism (VTE) and bleeding were assessed across the years, and multivariable logistic regression models were used to evaluate the predictors of VTE and bleeding. We assessed the influence thromboembolic and hemorrhagic complications on length of stay, cost, and mortality outcomes. Results: Among 430,780 leukemia hospitalizations, the overall incidence of VTE was 5.4% and remained stable throughout the study period (p = 0.09), while hemorrhagic events = 5.6%) showed a significant upward trend (p = 0.01). Cerebrovascular accidents, central venous catheter insertion, and protein calorie malnutrition (PCM) were significant predictors of both VTE and hemorrhage. PCM demonstrated a dose-dependent relationship with both complications. VTE was associated with a 33.5% increase in length of stay (LOS) and a 35% increase in cost of care (COC). Hemorrhage was associated with 23.2% increase in LOS and 32.6% increase in COC. Only hemorrhagic events were independently associated with increased mortality (adjusted OR 2.88, p < 0.001). Conclusions: The incidence of VTE in hospitalized leukemia patients has remained stable while hemorrhagic complications have increased significantly. Nutritional status represents a potentially modifiable risk factor for both VTE and bleeding complications. The competing risk between thrombosis and hemorrhage varies with age and nutritional status, suggesting the need for nuanced thromboprophylaxis strategies in this vulnerable population. Full article
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12 pages, 2226 KiB  
Article
The Effect of Skating Exercises as High-Intensity Interval Training on Elderly Stroke Patients
by Min-Su Kim
Brain Sci. 2025, 15(7), 676; https://doi.org/10.3390/brainsci15070676 - 24 Jun 2025
Viewed by 497
Abstract
Background/Objectives: High-intensity interval training (HIIT) can optimize recovery by complementing the low cardiovascular fitness intensities typically achieved in stroke rehabilitation programs. Skating exercise is an HIIT workout developed based on ice skating movements, and we investigated the effects of this exercise on the [...] Read more.
Background/Objectives: High-intensity interval training (HIIT) can optimize recovery by complementing the low cardiovascular fitness intensities typically achieved in stroke rehabilitation programs. Skating exercise is an HIIT workout developed based on ice skating movements, and we investigated the effects of this exercise on the cardiorespiratory fitness of elderly patients with minor stroke. Methods: Participants aged 65 or older with a National Institutes of Health Stroke Scale score of 3 or lower were recruited. This study was designed as a randomized controlled trial, in which the intervention group engaged in skating exercises following HIIT, while the control group underwent moderate-intensity continuous training (MICT). Both groups of participants performed either HIIT or MICT for 20 min per day, four times a week, over three months. Results: A total of 34 elderly patients with minor stroke were recruited, with an average age of 70.7 years. For three months, no fall-down injuries or adverse cardiovascular or cerebrovascular events were reported among patients undergoing HIIT or MICT. Both the intervention and control groups showed significant increases in the measures of aerobic capacity after the intervention. However, the patients in the intervention group exhibited significantly greater improvements in peak oxygen uptake, ventilatory threshold, and peak MET (p = 0.005, p = 0.002, and p = 0.024, respectively). Additionally, the Berg Balance Scale (BBS) scores and the skeletal muscle mass index showed significantly greater enhancements in the intervention group compared to the control group (p = 0.032 and p = 0.032). Conclusions: In conclusion, skating exercise could be a safe and effective HIIT protocol for elderly people who have experienced a minor stroke. Full article
(This article belongs to the Section Neurorehabilitation)
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