Pathophysiology : the official journal of the International Society for Pathophysiology最新文献

{"title":"Neuromuscular Electrical Stimulation Plus Nutritional Counseling Attenuates Thigh Muscle Thickness Loss in Hospitalized Cancer Patients.","authors":"Tatyanne L N Gomes, Thaís C Borges, Jessica F M Ivo, Lara G Mainardi, Renata G C Abadio, Benjamin T Wall, Gustavo D Pimentel","doi":"10.3390/pathophysiology32040068","DOIUrl":"10.3390/pathophysiology32040068","url":null,"abstract":"<p><strong>Background and aims: </strong>This study aimed to determine whether neuromuscular electrical stimulation (NMES) combined with nutritional counseling promotes an increase in thigh muscle thickness (MT), as well as to assess changes in the relationship between MT and intracellular water (ICW). Body composition methods such as ultrasound may overestimate muscle mass, depending on the context, because they cannot distinguish the contractile protein component from body fluids, including intra- and extracellular water.</p><p><strong>Methods: </strong>A pilot randomized parallel trial was conducted with 25 hospitalized patients with unselected cancer, who were divided into two groups: NMES + Diet and Diet. Both groups received nutritional counseling, but only one group received NMES. NMES was applied bilaterally to the origin and insertion points of the quadriceps twice daily, with a 3 h interval between sessions, for 7 consecutive days. MT and ICW were measured before and after the intervention. Food consumption was assessed using a 24 h dietary recall at baseline and at the end of the study to quantify and adjust macronutrient intake during the intervention.</p><p><strong>Results: </strong>Both treatment groups (Diet × NMES + Diet) showed similar dropout rates which means participants in the more intensive treatment did not quit more frequently, once intervention with NMES was feasible and well tolerated. In addition, both groups showed a reduction in carbohydrate intake (<i>p</i> = 0.012) and an increase in leucine intake (<i>p</i> < 0.001) post-intervention. The increase in leucine intake was significantly greater in the NMES + Diet group (<i>p</i> < 0.001), and the reduction in carbohydrate intake was also greater in this group (<i>p</i> = 0.012). In the delta analysis, the NMES + Diet group showed an increase in thigh MT, whereas the Diet group experienced a decrease (Diet group: ∆ = -2.53 ± 3.73 mm vs. NMES + Diet group: ∆ = 2.09 ± 2.27 mm, <i>p</i> = 0.001). Moreover, the MT/ICW ratio was higher in the NMES + Diet group post-intervention (Diet group: ∆ = -0.15 ± 0.19 mm/L vs. NMES + Diet group: ∆ = 0.11 ± 0.09 mm/L, <i>p</i> < 0.001), while no significant difference in ICW was observed between groups.</p><p><strong>Conclusions: </strong>short-term intervention combining nutritional counseling with NMES increased thigh MT and the MT/ICW ratio, possibly due to NMES-induced extracellular water expansion.</p>","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"32 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12735726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145822666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulating Role of Resveratrol in Metabolic and Inflammatory Dysregulation Caused by Surgical and Psychoemotional Stress in Rats.","authors":"Roman Ryabushko, Heorhii Kostenko, Oleh Akimov, Vitalii Kostenko","doi":"10.3390/pathophysiology32040067","DOIUrl":"10.3390/pathophysiology32040067","url":null,"abstract":"<p><p><b>Objectives:</b> This study investigates the effects of resveratrol on systemic inflammatory, oxidative, and metabolic responses in a rat model that combines surgical trauma with prior exposure to Single Prolonged Stress (SPS), an established experimental protocol for modeling post-traumatic stress disorder (PTSD). <b>Methods:</b> Male Wistar rats (n = 21) were randomly assigned to three groups: (I) control (polyvinylpyrrolidone, PVP), (II) SPS + laparotomy + PVP), and (III) SPS + laparotomy + resveratrol. Resveratrol (5 mg/kg of body weight/day) or vehicle was administered intragastrically for seven days. Serum concentrations of cortisol, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), glucose, insulin, lipid fractions, and thiobarbituric acid-reactive substances (TBA-RS) were determined by enzyme-linked immunosorbent assay and spectrophotometric methods. Insulin resistance was assessed using the homeostatic model assessment of insulin resistance (HOMA-IR) index. <b>Results:</b> Combined SPS and surgical trauma induced a pronounced systemic inflammatory response characterized by elevated cortisol (+138%), TNF-α (+83%), IL-6 (+465%), and ceruloplasmin (+71%), as well as hyperglycemia, hyperinsulinemia, increased HOMA-IR, and atherogenic dyslipidemia with reduced high-density lipoprotein cholesterol (HDL-CH; -64%), elevated triglycerides (TGs; +216%), and very low-density lipoprotein cholesterol (VLDL-CH; +218%). Marked activation of lipid peroxidation was observed, as indicated by increased TBA-RS levels before and after incubation. Resveratrol administration significantly decreased cortisol (-45%), TNF-α (-47%), and IL-6 (-85%), normalized the IL-10/IL-6 ratio, and reduced ceruloplasmin levels (-13%). The compound improved insulin sensitivity (HOMA-IR -50%), elevated HDL-CH (+115%), and lowered TGs and VLDL-CH (-44%). It also attenuated both basal and inducible lipid peroxidation (TBA-RS -11% and -13%), indicating restoration of antioxidant capacity. <b>Conclusions:</b> Thus, resveratrol effectively counteracts the neuroendocrine, inflammatory, and metabolic disturbances induced by combined PTSD-like stress and surgical trauma.</p>","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"32 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12736161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145822667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calcification in Vascular Smooth Muscle Cells Is Associated with Elevated GCLm and Impaired Contraction: Insights into Osteogenic Transdifferentiation and Therapeutic Approaches.","authors":"Luisa F Delgadillo, Nabil A Rashdan, Hunter Hamilton, Jack H Pattillo, Shuai Yuan, Randa S Eshaq, Norman R Harris, Jonathan S Alexander, Christopher B Pattillo","doi":"10.3390/pathophysiology32040066","DOIUrl":"10.3390/pathophysiology32040066","url":null,"abstract":"<p><strong>Background: </strong>Vascular calcification is a strong predictor of cardiovascular morbidity and mortality. Oxidative stress plays a key role in promoting vascular calcification. Glutathione (GSH), as a major cellular antioxidant, is produced in response to oxidative stress and is regulated by the enzyme glutamate-cysteine ligase (GCL). In this study, we examined the role of the GCL modifier subunit (GCLm) in regulating vascular smooth muscle cell (VSMC) calcification.</p><p><strong>Methods: </strong>Human coronary artery VSMCs were exposed to phosphate-rich media to induce calcification.</p><p><strong>Results: </strong>Calcification led to a decrease in the GSH:GSSG ratio (reduced glutathione to oxidized glutathione), and elevated GCLm expression, coincident with mobilization of osteogenic genes and loss of contractile phenotype. KEGG pathway analysis of human unstable atherosclerotic plaques similarly showed increased GCLm expression and activation of reactive oxygen species (ROS)-related pathways. Notably, forced overexpression of GCLm in murine VSMCs (MOVAS cells) significantly accelerated calcification. These findings implicate GCLm upregulation in promoting VSMC calcification, potentially by disrupting redox homeostasis and driving phenotypic switching. Further mechanistic studies are warranted to evaluate GCLm as a potential therapeutic target in vascular calcification.</p>","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"32 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12736360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145822661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diffusion Tensor Tractography Shows White Matter Tract Changes in Breast Cancer Survivors with Balance Impairment.","authors":"Alexandra Nikolaeva, Maria Pospelova, Mark Voynov, Varvara Krasnikova, Albina Makhanova, Samvel Tonyan, Aleksandr Efimtsev, Fionik Olga, Anatoliy Levchuk, Gennadiy Trufanov, Konstantin Samochernykh, Tatyana Alekseeva, Stephanie E Combs, Maxim Shevtsov","doi":"10.3390/pathophysiology32040063","DOIUrl":"10.3390/pathophysiology32040063","url":null,"abstract":"<p><p><b>Objectives</b>: Breast cancer survivors often experience long-term neurological complications, including balance impairments, following treatment. This study aimed to investigate microstructural changes in white matter tracts in breast cancer survivors with balance impairment using diffusion tensor tractography. <b>Methods</b>: An open, single-center, prospective study was conducted including two groups-healthy age-matched volunteers (<i>n</i> = 28) and breast cancer survivors (<i>n</i> = 35) with balance impairment. All participants underwent diffusion tensor tractography at baseline and at the end of the follow-up period of six months. Quantitative anisotropy was analyzed using DSI Studio to assess white matter integrity. <b>Results</b>: At baseline, patients with balance impairment exhibited significantly reduced quantitative anisotropy values in the middle cerebellar peduncles (<i>p</i> = 0.046) and cerebellar hemispheres (<i>p</i> = 0.024, 0.055) compared to healthy controls. At the end of the follow-up, quantitative anisotropy values were increased across most tracts, though some differences persisted between groups (<i>p</i> < 0.001). <b>Conclusions</b>: Breast cancer survivors with balance impairment demonstrate sustained microstructural white matter changes, particularly in cerebellar and vestibular pathways. These findings suggest that diffusion tensor tractography can provide valuable insights into central nervous system alterations contributing to post-treatment balance dysfunction and may serve as a potential tool for early diagnosis and rehabilitation planning.</p>","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"32 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12641777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145592616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and Laboratory Parameters After Drowning and Diving Accidents and Their Association with Survival.","authors":"Anne Petzold, Jan Dreßler, Anne Schrimpf, André Gries","doi":"10.3390/pathophysiology32040065","DOIUrl":"10.3390/pathophysiology32040065","url":null,"abstract":"<p><p><b>Introduction</b>: The prognosis for patients admitted to emergency departments (ED) after drowning or diving accidents is often uncertain. In this study, we evaluated a range of clinical and laboratory parameters as potential indicators of survival. Many of these markers have previously been investigated in the context of survival prediction in both trauma-related and non-trauma-related clinical scenarios. <b>Methods</b>: We conducted a retrospective analysis of 25 patients aged >17 years who were admitted to the ED of the University Hospital Leipzig after drowning or diving accidents between 2012 and 2024. Clinical and laboratory parameters were compared between survivors and non-survivors, with survival defined as discharge from the hospital. <b>Results</b>: Of all cases analyzed-comprising 19 drowning and six diving incidents-10 patients (40%) survived, while 15 (60%) did not. Age, sex, or etiology of the accident were not statistically associated with survival. Compared to survivors, non-survivors were significantly more likely to have received prehospital cardiopulmonary resuscitation (CPR; 20% vs. 86.7%) and to have exhibited lower Glasgow Coma Scale scores and lower pH values (7.4 vs. 6.7). They were also more likely to have shown increased levels of lactate (4.3 mmol/L vs. 14.8 mmol/L), CK-MB quotient (9.7% vs. 51.8%), myoglobin (188.9 µg/L vs. 1930.9 µg/L), and blood glucose (6.6 mmol/L vs. 14.3 mmol/L). <b>Conclusions</b>: The need for CPR appears to be the most significant risk factor for not surviving a drowning or diving accident. Furthermore, certain laboratory parameters, such as pH and lactate, may provide supportive information regarding the severity of hypoxia and could be cautiously considered as indicators of survival likelihood in these patients. Our findings offer a rationale for future prospective studies, aiming to incorporate additional clinical and biochemical markers and potentially develop new prognostic scoring systems for patients following drowning or diving accidents. This study examines the association between clinical and laboratory parameters and survival in patients following drowning and diving accidents. A total of 25 cases from 2012 to 2024 were retrospectively analyzed. The results showed that patients who required CPR had significantly poorer outcomes. Certain laboratory markers; such as pH and lactate levels; were closely related to survival status in this patient group.</p>","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"32 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12641767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145592599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyperferritinemia Is Associated with Higher Adiposity, Metabolic Syndrome, and Hepatic Dysfunction, Mainly Affecting Men: A Study in Southern Brazil.","authors":"Késia Zanuzo, Márcia Fernandes Nishiyama, Eloá Angélica Koehnlein, Sabrina Grassiolli","doi":"10.3390/pathophysiology32040064","DOIUrl":"10.3390/pathophysiology32040064","url":null,"abstract":"<p><p><b>Objectives</b>: Serum ferritin (SF) reflects iron homeostasis, in addition to being an acute phase reactant protein. Since its levels are altered in the obesity state, we compared body composition, metabolic profile, liver alterations, and dietary patterns in adults stratified by SF levels (normal vs. high). <b>Methods</b>: A cross-sectional study was conducted using secondary data from 113 adults (≥18 years) of both sexes, attended at an outpatient nutrition clinic in southern Brazil and categorized for normal or high SF. Socioeconomic, anthropometric, blood pressure, dietary, biochemical, and liver parameters were assessed and statistical analyses performed. <b>Results</b>: Participants with high SF were more frequently male (<i>p</i> < 0.0001), married or in a civil union (<i>p</i> = 0.012), and had lower educational levels (<i>p</i> = 0.009). Moreover, higher rates of obesity (<i>p</i> = 0.003), cardiovascular risk (<i>p</i> = 0.004), increased body fat percentage (BF%; <i>p</i> = 0.002) and metabolic disturbances such as elevated glucose (<i>p</i> = 0.023), triglycerides (<i>p</i> = 0.003), insulin resistance (<i>p</i> = 0.027), hypertension (<i>p</i> = 0.001), and metabolic syndrome (MS) (<i>p</i> = 0.001) were noted in this group. Liver-related findings comprised increased ALT (<i>p</i> = 0.008), uric acid (<i>p</i> = 0.016), and indicators of steatosis (<i>p</i> = 0.022). Logistic regression demonstrated a higher likelihood of elevated SF among men (OR = 16.82) and individuals with increased BF% (OR = 7.5), without significant influence of diet. <b>Conclusions</b>: Adults with elevated SF were predominantly obese men with excess adiposity, insulin resistance, and metabolic and hepatic dysfunctions, conditions that increase the risk of MS and liver injury. These findings suggest that SF and other iron biomarkers may serve as valuable tools for diagnosing metabolic dysfunctions and obesity-related liver diseases, particularly Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).</p>","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"32 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12641791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145592590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased Mortality with Intermediate Ascitic Polymorphonuclear Cell Counts Amongst Patients with Cirrhosis: Time to Redefine the Care Approach.","authors":"Shahid Habib, Michael Ball, Chris Thomas, Traci Murakami, Nehali Patel, Sandeep Yarlagadda, Sarah Patel, Courtney Walker, Varun Takyar, Krunal Patel, Christian Domingues, Chiu-Hsieh Hsu","doi":"10.3390/pathophysiology32040062","DOIUrl":"10.3390/pathophysiology32040062","url":null,"abstract":"<p><strong>Background: </strong>Spontaneous bacterial peritonitis (SBP) is a serious complication in patients with decompensated cirrhosis and ascites. Diagnosis typically relies on an ascitic polymorphonuclear (A-PMN) cell count ≥ 250 cells/high-power field (HPF).</p><p><strong>Methods: </strong>In this retrospective cohort study, 117 hospitalized patients with acute decompensation of chronic liver disease and a diagnostic paracentesis were evaluated. Clinical, laboratory, and imaging data were collected. Patients were stratified by A-PMN counts of ≤50, 51-249, or ≥250 cells/HPF. Additional analysis was performed with patients stratified by ascitic white blood cell (WBC) count and albumin. Mortality risk was assessed at 28, 90, and 365 days.</p><p><strong>Results: </strong>Patients with A-PMN ≤ 50 cells/HPF had the lowest 28-day mortality (8%). At 90 and 365 days, mortality risk was significantly higher for the A-PMN 51-249 cells/HPF group (90-day hazard ratio (HR) 3.55, <i>p</i> = 0.01; 365-day HR 2.43, <i>p</i> = 0.02), but not A-PMN ≥ 250 cells/HPF group (90-day HR 2.95, <i>p</i> = 0.1; 365-day HR 2.95, <i>p</i> = 0.2). Ascitic WBC count did not significantly predict mortality, though higher counts were associated with extraperitoneal infections. Ascitic fluid albumin ≤ 1.0 g/dL was independently associated with increased 365-day mortality (HR 3.53, <i>p</i> = 0.03).</p><p><strong>Conclusions: </strong>Binary SBP A-PMN thresholds may not adequately capture mortality risk in cirrhotic patients with ascites. Low ascitic albumin and intermediate A-PMN counts are associated with increased long-term mortality, suggesting the need for more nuanced diagnostic and prognostic criteria in SBP evaluation.</p>","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"32 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12641635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145592612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunopathogenesis of Systemic Lupus Erythematosus: Interplay of Innate and Adaptive Immunity, Microbiome Dysbiosis, and Emerging Therapeutic Targets.","authors":"Arslan Ahmed, Siru Li, Jane J Yu, Wen-Hai Shao","doi":"10.3390/pathophysiology32040061","DOIUrl":"10.3390/pathophysiology32040061","url":null,"abstract":"<p><p>Systemic lupus erythematosus is a multifactorial autoimmune disease characterized by the dysregulation of both innate and adaptive immunity, resulting in chronic inflammation, autoantibody production, and multi-organ damage. Innate immune dysfunction involves macrophages, neutrophils, plasmacytoid dendritic cells, natural killer cells, and the complement system, which collectively amplify autoimmunity through defective clearance of apoptotic cells, overproduction of pro-inflammatory cytokines, and abnormal type I interferon signaling. Adaptive immune abnormalities, including skewed T-cell subsets, impaired regulatory T and B cells, and autoreactive B-cell hyperactivity, further perpetuate pathogenic autoantibody generation. Gut microbiota dysbiosis contributes to SLE pathogenesis via Th17 activation, loss of mucosal tolerance, and molecular mimicry mechanisms. This review synthesizes current knowledge on the immunopathogenesis of SLE, emphasizing the interplay between innate and adaptive immunity and integrating evidence from both human and experimental murine models to provide a comprehensive understanding of disease mechanisms.</p>","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"32 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12641968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145592605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pulsed-Field Ablation Is Associated with Lower Endothelial Injury and Procedure Time Compared to Cryoballoon Ablation in Paroxysmal Atrial Fibrillation.","authors":"Josip Katic, Ante Anic, Toni Breskovic, Josip Andelo Borovac, Branka Kresic, Daniela Supe-Domic, Marko Kumric, Josko Bozic, Zrinka Jurisic","doi":"10.3390/pathophysiology32040060","DOIUrl":"10.3390/pathophysiology32040060","url":null,"abstract":"<p><strong>Background: </strong>Thromboembolic events, though infrequent, remain a significant complication of atrial fibrillation (AF) ablation, largely related to endothelial damage. Cryoballoon (CB) and radiofrequency ablation can induce pro-coagulant responses, whereas pulsed-field ablation (PFA), a novel non-thermal electroporation-based technique, has shown tissue selectivity with potential endothelial-sparing effects.</p><p><strong>Methods: </strong>We aimed to compare PFA and second-generation CB ablation regarding endothelial injury in patients with paroxysmal AF. In this single-center prospective observational study, 25 patients with paroxysmal drug-refractory AF underwent pulmonary vein isolation using either a pentaspline PFA catheter (n = 14) or a second-generation CB catheter (n = 11). Circulating von Willebrand factor antigen (vWF) levels were assessed before and after ablation as a biomarker of endothelial damage, alongside routine laboratory and echocardiographic parameters. Procedural characteristics were also analyzed.</p><p><strong>Results: </strong>Baseline demographic, clinical, and echocardiographic data were comparable between groups. PFA was associated with significantly shorter skin-to-skin procedure time (59 vs. 94 min, <i>p</i> = 0.005) and left atrial dwell time (44 vs. 79 min, <i>p</i> < 0.001) compared with CB ablation. Importantly, vWF levels decreased significantly after PFA (-7.6%, <i>p</i> = 0.007), while CB ablation showed a non-significant increase (+9.5%, <i>p</i> = 0.155). The between-group difference in percent change of vWF was statistically significant (-5.6% vs. +8.3%, <i>p</i> = 0.006).</p><p><strong>Conclusions: </strong>PFA was associated with reduced endothelial injury and shorter procedural times compared with CB ablation, suggesting a potential advantage in lowering thromboembolic risk. These findings support the concept of PFA as an \"endothelial sparing\" ablation modality. However, the PFA procedure was associated with a significantly greater extent of myocardial injury, as reflected in circulating high-sensitivity cardiac troponin T values, compared to CB ablation (<i>p</i> = 0.007). Larger, randomized studies are warranted to confirm these results and evaluate long-term clinical outcomes.</p>","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"32 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12641627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145592589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polymicrobial Infection (Gram-Positive and Gram-Negative) Exacerbates Systemic Inflammatory Response Syndrome in a Conscious Swine Extremity Trauma Model.","authors":"Catharina C Gaeth, Travis R Madaris, Jamila M Duarte, Amber M Powers, Christina M Sandoval, Stefanie M Shiels, Randolph Stone","doi":"10.3390/pathophysiology32040059","DOIUrl":"10.3390/pathophysiology32040059","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Extremity trauma represents a significant proportion of battlefield injuries and is prevalent in polytraumatized patients from accidents. Delayed antibiotic treatment and surgical intervention can lead to wound infections, contributing to preventable mortality. This preliminary study aimed to develop a conscious swine model of complex extremity trauma that induces systemic inflammatory response syndrome (SIRS). <b>Methods</b>: All surgical procedures were conducted under anesthesia with sufficient analgesia. All swine were instrumented with a telemetry device and catheters at least 3 days prior to any injury. In phase 1 of model development, a complex extremity injury was performed that consisted of skin and muscle loss, bone defect, severe hemorrhage, and 2 h tourniquet application. In phase 2, multi-drug resistant Gram-positive and Gram-negative bacteria were inoculated topically at the injury site to exacerbate pathophysiological changes towards SIRS. Post-injury, conscious animals were assessed a minimum of twice daily, including pain assessment, neurological response, and vital signs. Blood samples were collected for microbiological testing, complete blood cell counts, and biochemical analysis. <b>Results</b>: After establishing SIRS criteria for Sinclair swine, we developed a model of severe extremity trauma leading to SIRS. During phase 1, resuscitative fluids were reduced and discontinued, with animals surviving 24 h and maintaining SIRS for up to 4 h post-recovery. Phase 2 showed that Gram-negative and Gram-positive pathogens can exacerbate and prolong SIRS. After 72 h, localized infection at the injury site was observed in all animals. <b>Conclusions</b>: We established a new swine model of complex extremity trauma with SIRS. Our model is consistent, reproducible, and relevant to prolonged care scenarios, providing a platform for future research into the evaluation of preventative and therapeutic strategies.</p>","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"32 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12641754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145592582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}