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Search Results (823)

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19 pages, 487 KiB  
Review
Recent Trends in the Management of Varicocele
by Tamás Takács, Anett Szabó and Zsolt Kopa
J. Clin. Med. 2025, 14(15), 5445; https://doi.org/10.3390/jcm14155445 - 2 Aug 2025
Viewed by 477
Abstract
Varicocele is a common, potentially correctable condition associated with impaired male fertility. Despite being frequently encountered in clinical andrology, its pathophysiological mechanisms, diagnostic criteria, and therapeutic approaches remain areas of active investigation and debate. The authors conducted a comprehensive literature search, using the [...] Read more.
Varicocele is a common, potentially correctable condition associated with impaired male fertility. Despite being frequently encountered in clinical andrology, its pathophysiological mechanisms, diagnostic criteria, and therapeutic approaches remain areas of active investigation and debate. The authors conducted a comprehensive literature search, using the PubMed database, covering clinical studies, systematic reviews, meta-analyses, and current international guidelines from the past ten years. Emphasis was placed on studies investigating novel diagnostic modalities, therapeutic innovations, and prognostic markers. Emerging evidence supports the multifactorial pathophysiology of varicocele, involving oxidative stress, hypoxia, inflammatory pathways, and potential genetic predisposition. Biomarkers, including microRNAs, antisperm antibodies, and sperm DNA fragmentation, offer diagnostic and prognostic utility, though their routine clinical implementation requires further validation. Advances in imaging, such as shear wave elastography, may improve diagnostic accuracy. While microsurgical subinguinal varicocelectomy remains the gold standard, technological refinements and non-surgical alternatives are being explored. Indications for treatment have expanded to include selected cases of non-obstructive azoospermia, hypogonadism, and optimization for assisted reproduction, though high-level evidence is limited. Full article
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19 pages, 2656 KiB  
Article
Circulating Lipid Profiles Indicate Incomplete Metabolic Recovery After Weight Loss, Suggesting the Need for Additional Interventions in Severe Obesity
by Alina-Iuliana Onoiu, Vicente Cambra-Cortés, Andrea Jiménez-Franco, Anna Hernández-Aguilera, David Parada, Francesc Riu, Antonio Zorzano, Jordi Camps and Jorge Joven
Biomolecules 2025, 15(8), 1112; https://doi.org/10.3390/biom15081112 - 1 Aug 2025
Viewed by 117
Abstract
The effects of long-term adjustments in body weight on the lipid balance in patients with severe obesity are not well understood. This study aimed to evaluate a non-invasive lipidomic approach to identifying biomarkers that could help predict which patients may require additional therapies [...] Read more.
The effects of long-term adjustments in body weight on the lipid balance in patients with severe obesity are not well understood. This study aimed to evaluate a non-invasive lipidomic approach to identifying biomarkers that could help predict which patients may require additional therapies before and after weight loss. Using mass spectrometry, 275 lipid species were analysed in non-obese controls, patients with severe obesity, and patients one year after bariatric surgery. The results showed that severe obesity disrupts lipid pathways, contributing to lipotoxicity, inflammation, mitochondrial stress, and abnormal lipid metabolism. Although weight loss improved these disturbances, surgery did not fully normalise the lipid profiles of all patients. Outcomes varied depending on their baseline liver health and genetic differences. Persistent alterations in cholesterol handling, membrane composition, and mitochondrial function were observed in partial responders. Elevated levels of sterol lipids, glycerophospholipids, and sphingolipids emerged as markers of complete metabolic recovery, identifying candidates for targeted post-surgical interventions. These findings support the use of lipidomics to personalise obesity treatment and follow-up. Full article
(This article belongs to the Section Molecular Biomarkers)
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14 pages, 454 KiB  
Article
The Evaluation of Blood Prooxidant–Antioxidant Balance Indicators and Cortisol Pre- and Post-Surgery in Patients with Benign Parotid Gland Tumors: A Preliminary Study
by Sebastian Bańkowski, Jan Pilch, Bartosz Witek, Jarosław Markowski, Wirginia Likus, Michał Rozpara and Ewa Sadowska-Krępa
J. Clin. Med. 2025, 14(15), 5425; https://doi.org/10.3390/jcm14155425 - 1 Aug 2025
Viewed by 223
Abstract
Background: The majority of parotid gland tumors are benign, e.g., pleomorphic adenoma (PA) and Warthin’s tumor (WT). From a biomedical point of view, oxidative stress is of significant importance due to its established association with the initiation and progression of various types of [...] Read more.
Background: The majority of parotid gland tumors are benign, e.g., pleomorphic adenoma (PA) and Warthin’s tumor (WT). From a biomedical point of view, oxidative stress is of significant importance due to its established association with the initiation and progression of various types of cancer, including parotid gland cancers. This study aimed to assess whether blood prooxidant–antioxidant markers could aid in diagnosing and guiding surgery for recurrent malignancies after parotid tumor treatment. Methods: We examined patients (n = 20) diagnosed with WT (n = 14) and PA (n = 6) using histopathological verification and computed tomography (CT) who qualified for surgical treatment. Blood samples were taken before the surgery and again 10 days later for biochemical analysis. The activities of the antioxidant enzymes (SOD, CAT and GPx), the non-enzymatic antioxidants (GSH and UA) and oxidative stress markers (MDA and TOS) were determined in the blood. The activities of CK and LDH and the concentrations of Cor and TAS were measured in the serum. Hb and Ht were determined in whole blood. Results: The patients’ SOD, CAT, and GPx activities after surgery did not differ significantly from their preoperative levels. However, following surgery, their serum TOS levels were significantly elevated in all the patients compared to baseline. In contrast, the plasma MDA concentrations were markedly reduced after surgery. Similarly, the GSH concentrations showed a significant decrease postoperatively. No significant changes were observed in the CK and LDH activities, TAS concentrations, or levels of Hb, Ht and Cor following surgery. Conclusions: The surgical removal of salivary gland tumors did not result in a reduction in oxidative stress at 10 days after surgery. Therefore, further studies are needed to determine the effectiveness of endogenous defense mechanisms in counteracting the oxidative stress induced by salivary gland tumors. Full article
(This article belongs to the Section Oncology)
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16 pages, 738 KiB  
Review
A Rationale for the Use of Ivabradine in the Perioperative Phase of Cardiac Surgery: A Review
by Christos E. Ballas, Christos S. Katsouras, Konstantinos C. Siaravas, Ioannis Tzourtzos, Amalia I. Moula and Christos Alexiou
J. Cardiovasc. Dev. Dis. 2025, 12(8), 294; https://doi.org/10.3390/jcdd12080294 - 31 Jul 2025
Viewed by 468
Abstract
This review explores the advantages of ivabradine in the management of cardiac surgery patients, particularly highlighting its heart rate (HR)-reducing properties, its role in minimizing the impact of atrial fibrillation, and its contributions to improving left ventricular diastolic function, as well as reducing [...] Read more.
This review explores the advantages of ivabradine in the management of cardiac surgery patients, particularly highlighting its heart rate (HR)-reducing properties, its role in minimizing the impact of atrial fibrillation, and its contributions to improving left ventricular diastolic function, as well as reducing pain, stress, and anxiety. In parallel, studies provide evidence that ivabradine influences endothelial inflammatory responses through mechanisms such as biomechanical modulation. Unlike traditional beta-blockers that may induce hypotension, ivabradine selectively inhibits hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, allowing for effective HR reduction without compromising blood pressure stability. This characteristic is particularly beneficial for patients at risk of atrial fibrillation post-surgery, where HR control is crucial for cardiovascular stability. This is an area in which ivabradine appears to play a role prophylactically, possibly in combination with beta-blockers. Furthermore, ivabradine has been associated with enhanced diastolic parameters in left ventricular function, reflecting its potential to improve surgical outcomes in patients with compromised heart function. In addition to its cardiovascular benefits, it appears to alleviate psychological stress and anxiety, common in postoperative settings, by moderating the neuroendocrine response to stress, thereby reducing stress-induced hormone levels. Furthermore, it has notable analgesic properties, contributing to pain management through its action on HCN channels in both the peripheral and central nervous systems. Collectively, these findings indicate that ivabradine may serve as a valuable therapeutic agent in the perioperative care of cardiac surgery patients, addressing both physiological and psychological challenges during recovery. Full article
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14 pages, 875 KiB  
Article
A Comparative Study of Brain Injury Biomarker S100β During General and Spinal Anesthesia for Caesarean Delivery: A Prospective Study
by Mungun Banzar, Nasantogtokh Erdenebileg, Tulgaa Surjavkhlan, Enkhtsetseg Jamsranjav, Munkhtsetseg Janlav and Ganbold Lundeg
Medicina 2025, 61(8), 1382; https://doi.org/10.3390/medicina61081382 - 30 Jul 2025
Viewed by 799
Abstract
Background and Objectives: Anesthetic agents may influence brain function, and emerging evidence suggests possible neurotoxicity under certain conditions. S100β is a well-established biomarker of brain injury and blood–brain barrier disruption, and its prolonged elevation beyond 6–12 h, despite a short half-life, may [...] Read more.
Background and Objectives: Anesthetic agents may influence brain function, and emerging evidence suggests possible neurotoxicity under certain conditions. S100β is a well-established biomarker of brain injury and blood–brain barrier disruption, and its prolonged elevation beyond 6–12 h, despite a short half-life, may indicate ongoing neuronal injury. Its use in cesarean section (C-section) remains limited, despite the potential neurological implications of both surgical stress and anesthetic technique. This study evaluates potential brain injury during caesarean section by comparing maternal and neonatal S100β levels under general and spinal anesthesia. Materials and Methods: This observational prospective study compared changes in the S100β brain damage biomarker in maternal (pre- and post-surgery) and umbilical artery blood during elective c-sections under general or spinal anesthesia. The 60 parturient women who underwent a C-section from 1 July 2021 to 30 December 2023 were evenly distributed into 2 groups: General anesthesia (GA) (n = 30) and Spinal anesthesia (SA) group (n = 30). It included healthy term pregnant women aged 18–40, ASA I–II and excluded those with major comorbidities or emergency conditions. Results: S100β concentrations slightly increased once the C-section was over in both the SA and GA groups, but without notable differences. In the SA and GA groups, preoperative S100β concentration in maternal blood was 195.1 ± 36.2 ng/L, 193.0 ± 54.3 ng/L, then increased to 200.9 ± 42.9 ng/L, 197.0 ± 42.7 at the end of operation. There was no statistically significant difference in S100β concentrations between the spinal and general anesthesia groups (p = 0.86). Conclusions: S100β concentrations slightly increased after C-section in both groups. The form of anesthesia seems to be irrelevant for the S100β level. However, further research is needed to confirm these findings and fully evaluate any potential long-term effects. Full article
(This article belongs to the Special Issue Advanced Research on Anesthesiology and Pain Management)
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16 pages, 1308 KiB  
Review
Multimodality Imaging in Aldosterone-Induced Cardiomyopathy: Early Detection and Prognostic Implications
by Francesca Zoccatelli, Gabriele Costa, Matteo Merlo, Francesca Pizzolo, Simonetta Friso and Luigi Marzano
Diagnostics 2025, 15(15), 1896; https://doi.org/10.3390/diagnostics15151896 - 29 Jul 2025
Viewed by 407
Abstract
Primary aldosteronism (PA), the most common cause of secondary hypertension, is increasingly recognized as an independent driver of adverse cardiac remodeling, mediated through mechanisms beyond elevated blood pressure alone. Chronic aldosterone excess leads to myocardial fibrosis, left ventricular hypertrophy, and diastolic dysfunction via [...] Read more.
Primary aldosteronism (PA), the most common cause of secondary hypertension, is increasingly recognized as an independent driver of adverse cardiac remodeling, mediated through mechanisms beyond elevated blood pressure alone. Chronic aldosterone excess leads to myocardial fibrosis, left ventricular hypertrophy, and diastolic dysfunction via mineralocorticoid receptor activation, oxidative stress, inflammation, and extracellular matrix dysregulation. These changes culminate in a distinct cardiomyopathy phenotype, often underrecognized in early stages. Multimodality cardiac imaging, led primarily by conventional and speckle-tracking echocardiography, and complemented by exploratory cardiac magnetic resonance (CMR) techniques such as T1 mapping and late gadolinium enhancement, enables non-invasive assessment of structural, functional, and tissue-level changes in aldosterone-mediated myocardial damage. While numerous studies have established the diagnostic and prognostic relevance of imaging in PA, several gaps remain. Specifically, the relative sensitivity of different modalities in detecting subclinical myocardial changes, the long-term prognostic significance of imaging biomarkers, and the differential impact of adrenalectomy versus medical therapy on cardiac reverse remodeling require further clarification. Moreover, the lack of standardized imaging-based criteria for defining and monitoring PA-related cardiomyopathy hinders widespread clinical implementation. This narrative review aims to synthesize current knowledge on the pathophysiological mechanisms of aldosterone-induced cardiac remodeling, delineate the strengths and limitations of existing imaging modalities, and critically evaluate the comparative effects of surgical and pharmacologic interventions. Emphasis is placed on early detection strategies, identification of imaging biomarkers with prognostic utility, and integration of multimodal imaging into clinical decision-making pathways. By outlining current evidence and highlighting key unmet needs, this review provides a framework for future research aimed at advancing personalized care and improving cardiovascular outcomes in patients with PA. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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28 pages, 4633 KiB  
Review
Innovative Strategies in Hernia Mesh Design: Materials, Mechanics, and Modeling
by Evangelia Antoniadi, Nuno Miguel Ferreira, Maria Francisca Vaz, Marco Parente, Maria Pia Ferraz and Elisabete Silva
Materials 2025, 18(15), 3509; https://doi.org/10.3390/ma18153509 - 26 Jul 2025
Viewed by 431
Abstract
Hernia is a physiological condition that significantly impacts patients’ quality of life. Surgical treatment for hernias often involves the use of specialized meshes to support the abdominal wall. While this method is highly effective, it frequently leads to complications such as pain, infections, [...] Read more.
Hernia is a physiological condition that significantly impacts patients’ quality of life. Surgical treatment for hernias often involves the use of specialized meshes to support the abdominal wall. While this method is highly effective, it frequently leads to complications such as pain, infections, inflammation, adhesions, and even the need for revision surgeries. According to the Food and Drug Administration (FDA), hernia recurrence rates can reach up to 11%, surgical site infections occur in up to 21% of cases, and chronic pain incidence ranges from 0.3% to 68%. These statistics highlight the urgent need to improve mesh technologies to minimize such complications. The design and material composition of meshes are critical in reducing postoperative complications. Moreover, integrating drug-eluting properties into the meshes could address issues like infections and inflammation by enabling localized delivery of antibiotics and anti-inflammatory agents. Mesh design is equally important, with innovative structures like auxetic designs offering enhanced mechanical properties, flexibility, and tissue integration. These advanced designs can distribute stress more evenly, reduce fatigue, and improve performance in areas subjected to high pressures, such as during intense coughing, sneezing, or heavy lifting. Technological advancements, such as 3D printing, enable the precise fabrication of meshes with tailored designs and properties, providing new opportunities for innovation. By addressing these challenges, the development of next-generation mesh implants has the potential to reduce complications, improve patient outcomes, and significantly enhance quality of life for individuals undergoing hernia repair. Full article
(This article belongs to the Section Biomaterials)
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18 pages, 1621 KiB  
Article
Inflammatory Metabolic Index and Metabolic-Inflammatory Stress Index as New Biomarkers for Complicated and Perforated Acute Appendicitis
by Sidere M. Zorrilla-Alfaro, Nestor A. Lechuga-Garcia, Arturo Araujo-Conejo, Leticia A. Ramirez-Hernandez, Idalia Garza-Veloz, Alejandro Mauricio-Gonzalez, Ivan Delgado-Enciso, Iram P. Rodriguez-Sanchez and Margarita L. Martinez-Fierro
J. Clin. Med. 2025, 14(15), 5281; https://doi.org/10.3390/jcm14155281 - 25 Jul 2025
Viewed by 461
Abstract
Background: Acute appendicitis is a common emergency requiring abdominal surgery. Despite its prevalence, there are no specific biomarkers for its diagnosis and prognosis. The aim of this study was to assess the basic laboratory tests of patients with acute appendicitis and to [...] Read more.
Background: Acute appendicitis is a common emergency requiring abdominal surgery. Despite its prevalence, there are no specific biomarkers for its diagnosis and prognosis. The aim of this study was to assess the basic laboratory tests of patients with acute appendicitis and to evaluate and integrate biochemical variables into the diagnosis of appendicitis. Methods: This was a retrospective, cross-sectional cohort study that included data from patients who underwent an appendectomy. Two groups of patients were considered based on their surgical (non-complicated/complicated appendicitis) or pathological diagnosis (non-perforated/perforated appendicitis). Factor analysis was carried out to identify communalities to put forward classificatory indices. Receiver operating characteristic (ROC) analysis was used to assess the accuracy of the predictions. Results: The cohort included 246 patients (51.6% male, mean age: 24.79 ± 19.32 years). By using their biochemical data, we generated 6 new indices whose areas under the ROC curve (AUC) ranged between 0.632 and 0.762 for complicated appendicitis and from 0.597 to 0.742 for perforated appendicitis. Inflammatory Metabolic Index (IMI) at the fixed cutoffs was a promising biomarker for both histopathological and surgical diagnoses with odds ratios (OR) of 10.45 and 5.21, respectively. The Metabolic-Inflammatory Stress Index (MISI) showed high specificity (over 72%) and significant AUC values for both diagnoses (0.742 and 0.676). These findings were reinforced by significant p-values and Youden indices. Conclusions: IMI and MISI were demonstrated to be effective biomarkers for complicated and perforated appendicitis. IMI provides predictive capability, while MISI offers specificity and significant AUC values for both histopathological and surgical diagnoses. Incorporating these biomarkers could enhance the accuracy of appendicitis diagnosis and potentially guide clinical decision-making. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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8 pages, 696 KiB  
Case Report
A Rare Case Report of Wunderlich Syndrome in a Chronic Hemodialysis Patient
by Elizabeth Artinyan, Evelina Valcheva, Marina Vaysilova and Nikolay Dimov
Reports 2025, 8(3), 121; https://doi.org/10.3390/reports8030121 - 25 Jul 2025
Viewed by 316
Abstract
Background and Clinical Significance: Spontaneous renal hematoma, also known as Wunderlich syndrome (WS), is a rare disease characterized by the acute onset of spontaneous renal hemorrhage into the subcapsular, perirenal, and/or pararenal spaces without a history of prior trauma. WS can be a [...] Read more.
Background and Clinical Significance: Spontaneous renal hematoma, also known as Wunderlich syndrome (WS), is a rare disease characterized by the acute onset of spontaneous renal hemorrhage into the subcapsular, perirenal, and/or pararenal spaces without a history of prior trauma. WS can be a life-threatening condition due to hemorrhagic shock; consequently, prompt diagnosis and a therapeutic approach are essential for favorable outcomes. Treatment ranges from conservative management to surgical intervention. The most common etiologies are neoplasms and vascular diseases, but WS can also be observed in patients undergoing hemodialysis. In patients with end-stage renal disease (ESRD), especially those on hemodialysis, acquired cystic kidney disease and renal cell carcinoma are among the primary causes of WS. Although less common, WS can develop in dialysis patients even in the absence of traditional (primary) risk factors. In general, patients with chronic kidney disease (CKD) have a paradoxical hemostatic profile, likely explaining their higher tendency to bleed, so WS can occur without existing predisposing factors. The multifactorial pathogenesis in these patients includes functional platelet abnormalities, intimal arterial fibrosis, chronic inflammation, and oxidative stress associated with ESRD. The use of hemodialysis-related antithrombotic medications could serve as another contributing factor increasing the risk of bleeding. Case Presentation: We present a case report of a 62-year-old male on chronic dialysis who developed sudden right-sided lumbar pain and hematuria during dialysis without evidence of prior trauma. Imaging revealed a large subcapsular hematoma of the right kidney. Further investigations did not reveal additional risk factors in this instance; however, his routinely used hemodialysis-related antithrombotic medications were potentially a contributing factor. Despite conservative treatment, his condition worsened, and the hematoma enlarged, requiring emergency nephrectomy. Postoperatively, his condition gradually improved. Conclusions: This case highlights the importance of considering WS in hemodialysis patients, even without the presence of traditional risk factors, as well as including WS in the differential diagnosis of acute abdominal pain. Full article
(This article belongs to the Section Nephrology/Urology)
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17 pages, 638 KiB  
Review
Systemic Impact of Platelet Activation in Abdominal Surgery: From Oxidative and Inflammatory Pathways to Postoperative Complications
by Dragos-Viorel Scripcariu, Bogdan Huzum, Cornelia Mircea, Dragos-Florin Tesoi and Oana-Viola Badulescu
Int. J. Mol. Sci. 2025, 26(15), 7150; https://doi.org/10.3390/ijms26157150 - 24 Jul 2025
Viewed by 191
Abstract
Although platelets have been traditionally thought of to be essential hemostasis mediators, new research shows how important they are for controlling cellular oxidative stress, inflammatory processes, and immunological responses—particularly during major surgery on the abdomen. Perioperative problems are largely caused by the continually [...] Read more.
Although platelets have been traditionally thought of to be essential hemostasis mediators, new research shows how important they are for controlling cellular oxidative stress, inflammatory processes, and immunological responses—particularly during major surgery on the abdomen. Perioperative problems are largely caused by the continually changing interaction of inflammatory cytokines, the formation of reactive oxygen species (ROS), and platelet activation. The purpose of this review is to summarize the most recent data regarding the complex function of platelets in abdominal surgery, with an emphasis on how they interact with inflammation and oxidative stress, and to investigate the impact on postoperative therapy and subsequent studies. Recent study data on platelet biology, redox signals, surgical stress, and antiplatelet tactics was reviewed in a systematic manner. Novel tailored therapies, perioperative antiplatelet medication, oxidative biomarkers of interest, and platelet-derived microscopic particles are important themes. In surgical procedures, oxidative stress dramatically increases the reactive capacity of platelets, spurring thromboinflammatory processes that affect cardiac attacks, infection risk, and recovery. A number of biomarkers, including soluble CD40L, thromboxane B2, and sNOX2-derived peptide, showed potential in forecasting results and tailored treatment. Antiplatelet medications are still essential for controlling risk factors for cardiovascular disease, yet using them during surgery necessitates carefully weighing the risks of thrombosis and bleeding. Biomarker-guided therapies, antioxidant adjuncts, and specific platelet inhibitors are examples of evolving tactics. In abdominal procedures, platelets strategically operate at the nexus of oxidative stress, inflammatory processes, and clotting. Improved patient classification, fewer problems, and the creation of individualized surgical care strategies could result from an increased incorporation of platelet-focused tests and therapies into perioperative processes. To improve clinical recommendations, subsequent studies may want to focus on randomized studies, biomarker verification, and using translational approaches. Full article
(This article belongs to the Special Issue New Advances in Platelet Biology and Functions: 3rd Edition)
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14 pages, 1209 KiB  
Article
Investigation of Growth Differentiation Factor 15 as a Prognostic Biomarker for Major Adverse Limb Events in Peripheral Artery Disease
by Ben Li, Farah Shaikh, Houssam Younes, Batool Abuhalimeh, Abdelrahman Zamzam, Rawand Abdin and Mohammad Qadura
J. Clin. Med. 2025, 14(15), 5239; https://doi.org/10.3390/jcm14155239 - 24 Jul 2025
Viewed by 309
Abstract
Background/Objectives: Peripheral artery disease (PAD) impacts more than 200 million individuals globally and leads to mortality and morbidity secondary to progressive limb dysfunction and amputation. However, clinical management of PAD remains suboptimal, in part because of the lack of standardized biomarkers to predict [...] Read more.
Background/Objectives: Peripheral artery disease (PAD) impacts more than 200 million individuals globally and leads to mortality and morbidity secondary to progressive limb dysfunction and amputation. However, clinical management of PAD remains suboptimal, in part because of the lack of standardized biomarkers to predict patient outcomes. Growth differentiation factor 15 (GDF15) is a stress-responsive cytokine that has been studied extensively in cardiovascular disease, but its investigation in PAD remains limited. This study aimed to use explainable statistical and machine learning methods to assess the prognostic value of GDF15 for limb outcomes in patients with PAD. Methods: This prognostic investigation was carried out using a prospectively enrolled cohort comprising 454 patients diagnosed with PAD. At baseline, plasma GDF15 levels were measured using a validated multiplex immunoassay. Participants were monitored over a two-year period to assess the occurrence of major adverse limb events (MALE), a composite outcome encompassing major lower extremity amputation, need for open/endovascular revascularization, or acute limb ischemia. An Extreme Gradient Boosting (XGBoost) model was trained to predict 2-year MALE using 10-fold cross-validation, incorporating GDF15 levels along with baseline variables. Model performance was primarily evaluated using the area under the receiver operating characteristic curve (AUROC). Secondary model evaluation metrics were accuracy, sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). Prediction histogram plots were generated to assess the ability of the model to discriminate between patients who develop vs. do not develop 2-year MALE. For model interpretability, SHapley Additive exPlanations (SHAP) analysis was performed to evaluate the relative contribution of each predictor to model outputs. Results: The mean age of the cohort was 71 (SD 10) years, with 31% (n = 139) being female. Over the two-year follow-up period, 157 patients (34.6%) experienced MALE. The XGBoost model incorporating plasma GDF15 levels and demographic/clinical features achieved excellent performance for predicting 2-year MALE in PAD patients: AUROC 0.84, accuracy 83.5%, sensitivity 83.6%, specificity 83.7%, PPV 87.3%, and NPV 86.2%. The prediction probability histogram for the XGBoost model demonstrated clear separation for patients who developed vs. did not develop 2-year MALE, indicating strong discrimination ability. SHAP analysis showed that GDF15 was the strongest predictive feature for 2-year MALE, followed by age, smoking status, and other cardiovascular comorbidities, highlighting its clinical relevance. Conclusions: Using explainable statistical and machine learning methods, we demonstrated that plasma GDF15 levels have important prognostic value for 2-year MALE in patients with PAD. By integrating clinical variables with GDF15 levels, our machine learning model can support early identification of PAD patients at elevated risk for adverse limb events, facilitating timely referral to vascular specialists and aiding in decisions regarding the aggressiveness of medical/surgical treatment. This precision medicine approach based on a biomarker-guided prognostication algorithm offers a promising strategy for improving limb outcomes in individuals with PAD. Full article
(This article belongs to the Special Issue The Role of Biomarkers in Cardiovascular Diseases)
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16 pages, 4186 KiB  
Article
Physiological and Oxidative Stress in General and Spinal Anesthesia for Elective Cesarean Section in Women: Is There Any Difference?
by Nemanja D. Dimic, Gorica D. Maric, Zorana S. Orescanin Dusic, Tanja M. Grahovac, Teodora F. Vidonja Uzelac, Marko D. Djuric, Irina B. Nenadic, Marina M. Bobos, Predrag D. Stevanovic, Sladjana J. Mihajlovic and Marina M. Stojanovic
Life 2025, 15(8), 1158; https://doi.org/10.3390/life15081158 - 22 Jul 2025
Viewed by 278
Abstract
This study evaluates the influence of general anesthesia (GA) and spinal anesthesia (SA) on physiological and oxidative stress in parturients undergoing elective cesarean section, one of the most frequently performed surgical procedures worldwide. A total of 101 pregnant women were included, categorized into [...] Read more.
This study evaluates the influence of general anesthesia (GA) and spinal anesthesia (SA) on physiological and oxidative stress in parturients undergoing elective cesarean section, one of the most frequently performed surgical procedures worldwide. A total of 101 pregnant women were included, categorized into GA (n = 51) and SA (n = 50) groups. Blood samples were collected at three time points: one hour before surgery (Measurement 1), at umbilical cord clamping (Measurement 2), and two hours post-surgery (Measurement 3). Biomarkers of oxidative stress, complete blood count, and levels of biochemical parameters were measured. In second and/or third measurement, biochemical blood analysis showed increased prolactin and cortisol levels, followed by spike of glucose and insulin in the GA group. However, levels of tri-iodothyronine were reduced in both groups in the third measurement. Glutathione S-transferase (GST) activity was increased in both groups in third measurement. The results showed increased concentrations of total SH groups and decreased concentrations of non-protein SH groups in the GA group during Measurement 2. Lymphocyte count was found to be predictor of GST levels. The results indicate more a pronounced endocrine response in GA group and speak in favor of spinal anesthesia. Both kinds of anesthesia are equally safe in terms of the oxidative status of the tissue. Full article
(This article belongs to the Section Medical Research)
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14 pages, 2459 KiB  
Article
Enhancement of Oral Mucosal Regeneration Using Human Exosomal Therapy in SD Rats
by Chien Ming Lee, Qasim Hussain, Kuo Pin Chuang and Hoang Minh
Biomedicines 2025, 13(7), 1785; https://doi.org/10.3390/biomedicines13071785 - 21 Jul 2025
Viewed by 632
Abstract
Background/Objectives: Oral cavity wound recovery presents unique challenges due to constant moisture exposure and functional mechanical stresses. Nanoscale extracellular vesicles (exosomes) with regenerative properties offer promising therapeutic potential for tissue regeneration, contributing to improved health outcomes. This study evaluated human exosomal preparations in [...] Read more.
Background/Objectives: Oral cavity wound recovery presents unique challenges due to constant moisture exposure and functional mechanical stresses. Nanoscale extracellular vesicles (exosomes) with regenerative properties offer promising therapeutic potential for tissue regeneration, contributing to improved health outcomes. This study evaluated human exosomal preparations in promoting oral mucosal regeneration. Methods: We established standardized full-thickness wounds in the buccal mucosa of SD rats and divided subjects into experimental (receiving 50 billion human exosomes) and control (receiving carrier solution only) groups. Comprehensive wound assessment occurred at predetermined intervals (days 0, 3, 7, and 10) through photographic documentation, histological examination, and quantitative measurement. Results: Exosomal-treated tissues demonstrated statistically significant acceleration in closure rates (p < 0.05), achieving 87.3% reduction by day 10 versus 64.1% in the controls. Microscopic analysis revealed superior epithelial development, reduced inflammatory infiltration, and enhanced collagen architectural organization in exosomal-treated specimens. Semi-quantitative evaluation confirmed consistently superior healing metrics in the experimental group across all assessment timepoints. Conclusions: These findings demonstrate that human exosome preparations significantly enhance oral mucosal regeneration in SD rats, suggesting potential clinical applications for accelerating recovery following oral surgical procedures. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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15 pages, 1045 KiB  
Article
Metabolomic Profiling of Erector Spinae Plane Block for Breast Cancer Surgery
by Ekin Guran, Ozan Kaplan, Serpil Savlı, Cigdem Sonmez, Lutfi Dogan and Suheyla Unver
Medicina 2025, 61(7), 1294; https://doi.org/10.3390/medicina61071294 - 18 Jul 2025
Viewed by 291
Abstract
Background and Objectives: Regional and systemic analgesic techniques, such as erector spinae plane (ESP) block and opioid administration, implemented during cancer surgery, have been shown to influence immune responses and potentially affect cancer outcomes. Surgical stress and analgesic techniques used in cancer surgery—such [...] Read more.
Background and Objectives: Regional and systemic analgesic techniques, such as erector spinae plane (ESP) block and opioid administration, implemented during cancer surgery, have been shown to influence immune responses and potentially affect cancer outcomes. Surgical stress and analgesic techniques used in cancer surgery—such as regional nerve blocks or systemic opioids—not only affect pain control but also influence immune and inflammatory pathways that may impact cancer progression. To understand the biological consequences of these interventions, metabolomic profiling has emerged as a powerful approach for capturing systemic metabolic and immunological changes, which are particularly relevant in the oncologic perioperative setting. In this study, we examined the impact of the ESP on the metabolomic profile, as well as levels of VEGF, cortisol, and CRP, in addition to its analgesic effects in breast cancer surgery. Materials and Methods: Ninety patients were placed into three different analgesia groups (morphine, ESP, and control groups). Demographic data, ASA classification, comorbidities, surgery types, and pain scores were documented. Blood samples were taken at preoperative hour 0, postoperative hour 1, and postoperative hour 24 (T0, T1, and T24). VEGF, cortisol, and CRP levels were measured, and metabolomic analysis was performed. Results: Study groups were comparable regarding demographic findings, comorbidities, and surgery types (p > 0.05). NRS scores of group ESP were lowest in the first 12 h period (p < 0.01) and ESP block reduced opioid consumption (p < 0.01). VEGF and cortisol levels of group morphine were similar to ESP at T24 (p > 0.05). Group ESP had lower VEGF and cortisol levels than the control at T24 (p = 0.025, p = 0.041, respectively.). The CRP level of group morphine was higher than both ESP and control at T24 (p = 0.022). Metabolites involved in primary bile acid, steroid hormone biosynthesis, amino acid, and glutathione metabolism were changed in group ESP. Conclusions: Metabolites in bile acid biosynthesis and steroid hormone pathways, which play a key role in immune responses, were notably lower in the ESP group. Accordingly, VEGF and cortisol peaks were more moderate in group ESP. In conclusion, we think that ESP block, which provides adequate analgesia, is an acceptable approach in terms of modulating immune responses in breast cancer surgery. Full article
(This article belongs to the Special Issue Insights and Advances in Cancer Biomarkers)
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Article
Dysregulation of Purinergic Signaling Sustains Chronic Inflammation and Oxidative Imbalance in Patients After PitNET Surgical Resection
by Geile Fistarol, Luiz A. de Oliveira, Gilnei B. da Silva, Daiane Manica, Marceli C. Hanauer, Paula Dallagnol, Rafael A. Narzetti, Maria L. Bergamini, Vitória C. de Melo, Tais Vidal, Micheli M. Pillat, Jussara de Lima, Marcelo L. V. da Cunha, Marielle L. Makiyama, Filomena Marafon, Aniela P. Kempka, Ariane Zamoner and Margarete D. Bagatini
Int. J. Mol. Sci. 2025, 26(14), 6890; https://doi.org/10.3390/ijms26146890 - 17 Jul 2025
Viewed by 234
Abstract
Pituitary neuroendocrine tumors (PitNETs) are the most common intracranial tumors. Evidence suggests that these types of tumors may have high recurrence rates. In this context, the purinergic system, oxidative stress, and inflammation are important signaling pathways involved in the cancer’s pathophysiology. This study [...] Read more.
Pituitary neuroendocrine tumors (PitNETs) are the most common intracranial tumors. Evidence suggests that these types of tumors may have high recurrence rates. In this context, the purinergic system, oxidative stress, and inflammation are important signaling pathways involved in the cancer’s pathophysiology. This study aimed to evaluate the sociodemographic and diagnostic profiles, as well as assess the purinergic signaling, immunological, and redox profiles, of patients after PitNET resection. We collected sociodemographic data and the patients’ diagnostic profiles. We also collected blood samples to analyze glycemia, triglycerides, albumin, and ATP levels. The ectonucleotidase activity was determined in peripheral blood mononuclear cells (PBMCs). In addition, we evaluated their redox and immunological profiles. There was a prevalence of gonadotropic macroadenoma derived from PIT-1 cells. We found that patients included in the PitNET group had increased glycemia, serum ATP levels, and ATP hydrolysis in PBMCs. Analyzing their immunological profiles, we found that patients had increased levels of IL-6, IL-10, and TNF, while the IL-27 level was decreased. Regarding their redox profiles, PitNET patients had increased levels of ROS and protein carbonylation. Unexpectedly, patients also showed increased levels of non-protein thiols (NPSHs), total thiols (PSHs), and ascorbic acid. Thus, the dysregulation of purinergic signaling sustained chronic inflammation and oxidative imbalance in PitNET patients for a long time after surgical resection. These data suggest that patients with PitNETs require long-term accompanying to prevent cancer recurrence prognosis. The biomarkers highlighted in this study may be good tools to help the medical approaches. Full article
(This article belongs to the Special Issue Advances in the Purinergic System)
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