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26 pages, 2555 KB  
Article
Functional and Vascular Outcomes of Posterior Acetabular Wall Osteosynthesis via the Kocher–Langenbeck Approach: A Dynamic Analysis
by Yuriy Prudnikov
J. Clin. Med. 2025, 14(21), 7749; https://doi.org/10.3390/jcm14217749 - 31 Oct 2025
Viewed by 225
Abstract
Background/Objectives: The Kocher–Langenbeck approach is widely used for surgical fixation of posterior acetabular wall fractures. While previous studies have focused on mechanical outcomes and the risk of post-traumatic osteoarthritis, the effects on peripheral circulation and neuromuscular recovery remain underexplored. This study aimed [...] Read more.
Background/Objectives: The Kocher–Langenbeck approach is widely used for surgical fixation of posterior acetabular wall fractures. While previous studies have focused on mechanical outcomes and the risk of post-traumatic osteoarthritis, the effects on peripheral circulation and neuromuscular recovery remain underexplored. This study aimed to evaluate dynamic changes in neuromuscular function and microcirculation following open reduction and internal fixation (ORIF) using this approach. Methods: A retrospective analysis was conducted on 34 patients (aged 23–75) treated for posterior acetabular wall fractures between 2014 and 2022. All patients underwent ORIF via the Kocher–Langenbeck approach. Assessments at 8 and 12 months postoperatively included electromyography (EMG), chronaximetry, and rheovasography (RVG). Asymmetry coefficients were calculated to quantify blood flow and functional differences. Results: At 12 months postoperatively, significant microcirculatory asymmetry persisted in the operated limb, with arterial and venous coefficients exceeding 25% (27.5% and 26.8%, respectively). EMG revealed sustained reductions in gluteus maximus and rectus femoris activity (asymmetry ~39%). Chronaximetry showed delayed nerve conduction recovery, particularly in the common peroneal nerve (AC = 44%). The femoral segment demonstrated the most severe impairment in both arterial inflow and venous outflow. Conclusions: ORIF via the Kocher–Langenbeck approach is associated with long-term disturbances in neuromuscular function and regional circulation. Further research should explore alternative surgical approaches (e.g., ilioinguinal, Stoppa) in prospective studies, assess vascular integrity using advanced imaging (e.g., contrast-enhanced ultrasound), and incorporate long-term functional outcomes. Studies on neurovascular-sparing techniques and optimised rehabilitation protocols may help reduce postoperative morbidity and improve recovery. Full article
(This article belongs to the Section Orthopedics)
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12 pages, 898 KB  
Article
Population-Based Genetic Assessment of Thrombophilia Polymorphisms: Allelic Frequencies and Population Linkage Dynamics
by Panagiota Tsiatsiou, Sofia Balaska, Zafeirios Tsinaris, Maria Archonti, Antonia Lanta, Vasiliki Tsaireli, Anna Takardaki, Areti Kourti, Angeliki Kassomenaki, Georgios Meletis, Dimitrios A. Tsakiris and Lemonia Skoura
Medicina 2025, 61(11), 1935; https://doi.org/10.3390/medicina61111935 - 29 Oct 2025
Viewed by 288
Abstract
Background and Objectives: Thrombophilia is a prothrombotic disorder that increases the risk of blood clotting and can pose serious health problems. It is considered a condition of gene–gene or gene–environment interactions. Variation in the prevalence of thrombophilia mutations and their interaction among [...] Read more.
Background and Objectives: Thrombophilia is a prothrombotic disorder that increases the risk of blood clotting and can pose serious health problems. It is considered a condition of gene–gene or gene–environment interactions. Variation in the prevalence of thrombophilia mutations and their interaction among populations necessitates localized genetic assessments. However, population-based genetic data remains limited for developing effective preventive strategies. Materials and Methods: This cross-sectional observational study was conducted over five years (2020–2024) at a tertiary university hospital in Northern Greece. A total of 2961 individuals aged 18–85 years (mean: 50.5) were registered based on family or medical history of venous thromboembolism (VTE) or clinical symptoms of VTE. The final analysis included 2078 participants comprising 1143 males (55%) and 935 females (45%), who met all the inclusion criteria. Inclusion criteria were absence of acute illness or malignancy, informed consent, and an adequate DNA quantity for genotyping, whereas excluded criteria included incomplete laboratory data, active inflammatory or malignant disease, and cognitive or psychiatric conditions. Peripheral blood samples were collected in 2 mL K3-EDTA tubes, and genomic DNA was analyzed using real-time polymerase chain reaction (PCR) with melting curve analysis and hybridization probes (LightMix® in vitro diagnostics, TIB MolBiol, Berlin, Germany). Five thrombophilia-related polymorphisms, Factor V Leiden (F5 G1691A), prothrombin (F2 G20210A), methylenetetrahydrofolate reductase (MTHFR C677T and MTHFR A1298C), and Plasminogen Activator Inhibitor-1 (PAI-1) 4G/5G, were examined for allele and genotype frequencies, Hardy–Weinberg equilibrium testing, pairwise linkage disequilibrium (D′ and r2), and power analysis. For subjects tested for Factor V Leiden (n = 1476), the activated protein C resistance (APC) ratio was additionally evaluated using the ACL TOP 750 analyzer. Results: Allele frequencies were 7.3% for FV Leiden and 3.7% for FII. The PAI-1 allele was distributed at 44%, while the MTHFR (C677T and A1298C) alleles were each present at 33%. Significant linkage disequilibrium was identified between MTHFR (C677T and A1298C) and between MTHFR A1298C and PAI-1. No evolutionary pressure or demographic bias was found in the Hardy–Weinberg equilibrium. The APC ratio demonstrated a high sensitivity (99.2%) and specificity (96.6%), indicating that it may serve as a reliable screening method. Conclusions: Our findings highlight informative patterns in the genetic predisposition to thrombophilia, which may help develop rule-based strategies for implementing thromboprophylaxis guidelines and personalized medical interventions. Full article
(This article belongs to the Special Issue Genetics of Human Diseases: Fishing for Causality)
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5 pages, 3207 KB  
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Hepatic Sinusoidal Obstruction Syndrome Secondary to Aplastic Anemia/Paroxysmal Nocturnal Hemoglobinuria Syndrome: A Rare Case
by Xinyue Liu, Xiaohe Li, Yanhua Chen and Rui Huang
Diagnostics 2025, 15(21), 2712; https://doi.org/10.3390/diagnostics15212712 - 27 Oct 2025
Viewed by 270
Abstract
Paroxysmal nocturnal hemoglobinuria (PNH) is associated with bone marrow failure disorders and may arise during the long-term follow-up of aplastic anemia (AA), which is named AA/PNH syndrome. Thrombosis is the most frequent clinical complication and is the main cause of mortality in PNH. [...] Read more.
Paroxysmal nocturnal hemoglobinuria (PNH) is associated with bone marrow failure disorders and may arise during the long-term follow-up of aplastic anemia (AA), which is named AA/PNH syndrome. Thrombosis is the most frequent clinical complication and is the main cause of mortality in PNH. However, thromboses tend to originate in hepatic and cerebral venous vessels, but rarely in the hepatic microvascular vein in PNH patients. Here, we report on a young man with hepatic sinusoidal obstruction syndrome (HSOS) secondary to AA/PNH syndrome. His main manifestations were hemolytic anemia, renal injury, ascites, hepatomegaly, and elevated liver enzymes. The diagnosis was confirmed by peripheral blood flow cytometry, enhanced computed tomography (CT), and liver biopsy. Initially, he received symptomatic treatments including diuretics, intermittent abdominal paracentesis, and low-molecular-weight heparin. Meanwhile, due to the occurrence of PNH activity during hospitalization, methylprednisolone 40 mg per day was administered, which was later transitioned to oral prednisolone. Subsequently, the dose of corticosteroids was gradually decreased once his hemoglobin stabilized. The association between HSOS and AA/PNH syndrome is exceptionally rare, as evidenced by the scant literature on the subject. This case underscores the critical need for awareness of HSOS secondary to AA/PNH syndrome, which needs a high index of suspicion and for which prompt treatment is needed to reduce morbidity and mortality. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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14 pages, 8136 KB  
Article
Snake Venom C-Type Lectin-like Protein Vaa-Snaclec-3/2 Efficiently Prevents Carotid Artery Thrombosis in a Mouse Model Without Compromising Blood Coagulation
by Monika C. Žužek, Igor Križaj, Miran Brvar, Tomaž Trobec, Simona Kranjc Brezar, Mojca Dobaja Borak, Adrijana Leonardi, Kity Požek, Milka Vrecl and Robert Frangež
Toxins 2025, 17(11), 523; https://doi.org/10.3390/toxins17110523 - 23 Oct 2025
Viewed by 469
Abstract
Platelets play pivotal roles in thromboembolic diseases, such as myocardial infarction and ischemic stroke. In patients envenomed by the snake Vipera a. ammodytes (Vaa), pronounced and transient thrombocytopenia without bleeding is observed. We previously showed that Vaa-snaclec-3/2, the snake venom [...] Read more.
Platelets play pivotal roles in thromboembolic diseases, such as myocardial infarction and ischemic stroke. In patients envenomed by the snake Vipera a. ammodytes (Vaa), pronounced and transient thrombocytopenia without bleeding is observed. We previously showed that Vaa-snaclec-3/2, the snake venom C-type lectin-like protein, mediates this effect ex vivo. Here, we extended our study of the antithrombotic potential of this protein in vivo using a mouse model of ferric chloride (FeCl3)-induced carotid artery thrombosis. Prior to inducing thrombus formation, the mice received 1, 5, 10, 20, or 50 μg/kg Vaa-snaclec-3/2 intravenously. Afterward, the arterial blood flow was monitored with a perivascular Doppler probe. Additionally, the platelet count in the peripheral venous blood; tail bleeding time; and liver, lung, kidney, spleen, and heart histology were evaluated. The lowest dose of Vaa-snaclec-3/2 that we showed to cause severe thrombocytopenia and completely inhibit FeCl3-induced thrombus formation was 20 µg/kg. This dose prolonged the median tail bleeding time from 86.5 to 153.5 s but did not induce acute spontaneous hemorrhage, as demonstrated by histological analysis. Histology revealed no signs of apoptosis, necrosis or other degenerative changes in the inspected organs of mice exposed to 20 μg/kg Vaa-snaclec-3/2. Platelet clusters were observed only in the lungs, which appear to be the primary site of platelet sequestration and the cause of thrombocytopenia. Taken together, our findings highlight the high potential of Vaa-snaclec-3/2 as a safe and effective antithrombotic agent for the transient prevention of thrombosis in acute clinical settings. Full article
(This article belongs to the Special Issue Animals Venom in Drug Discovery: A Valuable Therapeutic Tool)
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8 pages, 711 KB  
Case Report
Quantification of Bacterial and Drug-Resistant DNA Using dPCR in a Pediatric Patient with CVC-Related Bloodstream Infection
by Masato Kojima, Hiroki Kitagawa, Kayoko Tadera, Ryo Touge, Sho Kurihara, Mari Tanaka, Maiko Shimomura, Isamu Saeki and Hiroki Ohge
Infect. Dis. Rep. 2025, 17(5), 130; https://doi.org/10.3390/idr17050130 - 16 Oct 2025
Viewed by 294
Abstract
Background: Digital polymerase chain reaction (dPCR) is a highly sensitive molecular method that allows rapid detection of bacterial DNA and resistance genes, requiring only a small blood volume. Although not a new technology, its application in pediatric patients with suspected catheter-related bloodstream [...] Read more.
Background: Digital polymerase chain reaction (dPCR) is a highly sensitive molecular method that allows rapid detection of bacterial DNA and resistance genes, requiring only a small blood volume. Although not a new technology, its application in pediatric patients with suspected catheter-related bloodstream infection (CRBSI) remains limited. Case presentation: A 16-year-old female, diagnosed with recurrent acute myelogenous leukemia, received re-induction chemotherapy through a peripherally inserted central venous catheter (PICC). The patient developed a fever, and the blood culture (BC) drawn from the PICC was positive for methicillin-resistant S. epidermidis, leading to suspicion of CRBSI. Several antibiotics were used, and the PICC was replaced. Eventually, the fever subsided, and the BC was negative after PICC removal. The levels of S. epidermidis-specific DNA sequences and mecA genes were correlated with the results of the BC and clinical course. Turnaround time was significantly shorter in dPCR (3.5 h) than in the BC (14–21 h); dPCR was performed using only 400 µL of blood. Conclusions: This case highlights the potential of dPCR as a complementary tool to conventional BCs in the management of pediatric CRBSI. dPCR may support rapid decision-making and monitoring of the treatment response, particularly when sample volumes are limited. Full article
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12 pages, 1012 KB  
Article
Lines of Risk: Tunnel Catheter Loss Due to Bloodstream Infections in Chronic Hemodialysis Patients
by Muhammad Nauman Hashmi, Fayez Hejaili, Syed Hammad Raza and Muhammad Anwar Khan
Kidney Dial. 2025, 5(4), 49; https://doi.org/10.3390/kidneydial5040049 - 15 Oct 2025
Viewed by 608
Abstract
Background: Despite efforts to rely on arteriovenous fistulas/grafts for maintenance hemodialysis, a significant number of patients still depend on tunnel hemodialysis catheters for treatment. This poses a risk factor for central line-associated bloodstream infection (CLABSI) and, subsequently, vascular access compromise. Method: We conducted [...] Read more.
Background: Despite efforts to rely on arteriovenous fistulas/grafts for maintenance hemodialysis, a significant number of patients still depend on tunnel hemodialysis catheters for treatment. This poses a risk factor for central line-associated bloodstream infection (CLABSI) and, subsequently, vascular access compromise. Method: We conducted a retrospective study in five dialysis centers to determine the potential factors resulting in vascular access loss, CLABSI incidence, and microbe distribution patterns in Saudi Arabia at centers under the Ministry of National Guard Health Affairs. Adults who regularly received hemodialysis and had positive blood cultures between January 2019 and December 2023 were the subjects of the study. Results: Our study identified the presence of tunnel infection (p < 0.001), the presence of a Gram-negative pathogen (p = 0.036), and a high body mass index (BMI > 30) (p = 0.04) as potential risk factors leading to the loss of tunnel central venous catheters. In contrast, there was a lower probability of central venous catheter loss due to Gram-positive pathogens (p = 0.01). The CLABSI rate was 1.55 per 100 patients per month over a five-year period. Patients with CVC required more hospital treatment and had a significantly higher rate of vascular access loss (p < 0.001). Both central and peripheral blood cultures had nearly identical microbe spectra. Methicillin-sensitive Staphylococcus aureus (MSSA), Methicillin-resistant Staphylococcus aureus (MRSA), and Staphylococcus epidermidis had the highest prevalence rates among Gram-positive organisms. Among the Gram-negative bacteria, Enterobacter cloacae was the most common, followed by Klebsiella pneumonia and Pseudomonas aeruginosa. Conclusions: Our findings indicate the need for rigorous measures and interventions to prevent Gram-negative infections and decrease the reliance on central venous catheters, to decrease infections in hemodialysis patients, and decrease morbidity and cost. Strict hand hygiene, patient education, and surveillance programs are recommended to monitor these patients. Full article
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31 pages, 1203 KB  
Review
Vitamins, Vascular Health and Disease
by George Ayoub
Nutrients 2025, 17(18), 2955; https://doi.org/10.3390/nu17182955 - 15 Sep 2025
Viewed by 2976
Abstract
Vascular health relies on the proper function of endothelial cells, which regulate vascular tone, blood fluidity, and barrier integrity. Endothelial dysfunction, often aggravated by inadequate vitamin absorption, contributes to a spectrum of clinical disorders, including cardiovascular disease, cerebrovascular disease, peripheral artery disease, age-related [...] Read more.
Vascular health relies on the proper function of endothelial cells, which regulate vascular tone, blood fluidity, and barrier integrity. Endothelial dysfunction, often aggravated by inadequate vitamin absorption, contributes to a spectrum of clinical disorders, including cardiovascular disease, cerebrovascular disease, peripheral artery disease, age-related macular degeneration, lymphedema, and chronic venous insufficiency. B-group vitamins (especially folate, or vitamin B9), along with vitamins B12, B6, C, D, and E, are essential in maintaining endothelial function, supporting DNA synthesis, regulating methylation, enhancing cellular repair, mitigating oxidative stress and inflammatory signaling, and curtailing vascular damage. Folate is noted for its central function in one-carbon metabolism and in converting homocysteine to methionine, thereby reducing vascular toxicity. We cover natural dietary sources of folate, synthetic folic acid, and the biologically active forms 5-methyl-(6S)-tetrahydrofolate (L-5-MTHF, L-methylfolate) and 5-formyl-(6S)-tetrahydrofolate (levoleucovorin). Therapeutic strategies to address vascular health and prevent hyperhomocysteinemia in order to preclude follow-on disorders include targeted vitamin supplementation, dietary improvements to ensure a sufficient intake of bioavailable nutrient forms, and, in certain clinical contexts, the use of active L-methylfolate or levoleucovorin (a drug product) to bypass metabolic conversion issues. These evidence-based interventions aim to restore endothelial homeostasis, slow disease progression, and improve patient outcomes across a variety of disorders linked to poor vascular health. Full article
(This article belongs to the Special Issue Nutritional Approaches in Autism and Related Disorders)
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9 pages, 680 KB  
Case Report
Borderline Oxacillin-Resistant Staphylococcus aureus (BORSA) Bacteremia—Case Report
by Beverly Buffart, Philippe Clevenbergh, Alina Stiuliuc, Ioannis Raftakis, Mony Hing, Véronique Yvette Miendje Deyi, Olivier Denis, Delphine Martiny and Nicolas Yin
Antibiotics 2025, 14(8), 809; https://doi.org/10.3390/antibiotics14080809 - 7 Aug 2025
Viewed by 1753
Abstract
Introduction: Borderline oxacillin-resistant Staphylococcus aureus (BORSA) represents a rare and poorly characterized phenotype of S. aureus. Its detection remains challenging, even in modern clinical laboratories. Moreover, there is no consensus on the optimal therapeutic approach, and treatment strategies remain controversial. In [...] Read more.
Introduction: Borderline oxacillin-resistant Staphylococcus aureus (BORSA) represents a rare and poorly characterized phenotype of S. aureus. Its detection remains challenging, even in modern clinical laboratories. Moreover, there is no consensus on the optimal therapeutic approach, and treatment strategies remain controversial. In this report, we present a rare case of BORSA bacteremia and discuss potential approaches to improve its detection and management. Case presentation: A 39-year-old woman with systemic lupus erythematosus was admitted for a suspected exacerbation, complicated by multiple serositis and nephritis. She was on chronic treatment with methylprednisolone and hydroxychloroquine. On admission, she was afebrile. Laboratory investigations revealed elevated C-reactive protein and increased D-dimer levels. Later, she developed a septic peripheral venous thrombophlebitis, and treatment was adjusted to amoxicillin–clavulanate. Blood cultures grew S. aureus, prompting a switch to intravenous oxacillin based on a negative penicillin-binding protein 2a test. A discrepancy in the antimicrobial susceptibility test was observed, with cefoxitin showing susceptibility and oxacillin resistance. Further characterizations were carried out, confirming a BORSA infection. Treatment was switched to linezolid and ciprofloxacin with good recovery. Conclusions: This case highlights the complexity of managing a patient with an uncommon and poorly documented infection. The lack of data on BORSA infections and the difficulties in detecting and treating them led to a prolonged delay in the appropriate management of this patient. Full article
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10 pages, 1522 KB  
Article
Impact of Continuous Veno-Venous Hemodiafiltration on Thyroid Homeostasis in Critically Ill Patients
by Alicja Filipczyk, Magdalena A. Wujtewicz, Michał Okrągły and Karol P. Steckiewicz
J. Clin. Med. 2025, 14(15), 5542; https://doi.org/10.3390/jcm14155542 - 6 Aug 2025
Viewed by 519
Abstract
Background: Patients in Intensive Care Units (ICUs) often develop non-thyroidal illness syndrome. Potentially, thyroid hormones may be removed during continuous veno-venous hemodiafiltration (CVVHDF), as their molecular size is smaller than the filter pores’ cutoff. The study’s main aim was to assess whether [...] Read more.
Background: Patients in Intensive Care Units (ICUs) often develop non-thyroidal illness syndrome. Potentially, thyroid hormones may be removed during continuous veno-venous hemodiafiltration (CVVHDF), as their molecular size is smaller than the filter pores’ cutoff. The study’s main aim was to assess whether the serum concentration of thyroid hormones changes over time during CVVHDF. Methods: This was a prospective observational trial that included 30 patients treated in an ICU. All patients developed acute kidney injury (AKI) and had clinical indications for implementation of CVVHDF. Blood samples were collected before initiation of CVVHDF and at 1, 2, 3, 6, 9 and 12 days after. The last sample was collected three days after CVVHDF withdrawal. Thyroid function was evaluated by determining the serum concentration of TSH, thyrotropin-releasing hormone (TRH), free triiodothyronine (fT3), free thyroxine (fT4), total triiodothyronine (tT3), total thyroxine (tT4) and reverse triiodothyronine (rT3). We additionally calculated the total activity of peripheral deiodinases (GD) using a mathematical model. Results: TRH and TSH levels remained mostly within normal ranges. fT4 and tT4 were in normal range or slightly below. In contrast, fT3 and tT3 were undetectably low in most patients throughout. Reverse T3 levels remained within normal limits. There were no statistically significant changes in any thyroid hormone levels over the CVVHDF treatment period. The calculated peripheral GD activity was lower than normal, but importantly, it did not change significantly over time. Conclusions: Thyroid hormones are not lost due to hemodiafiltration. Decreased deiodinases activity is responsible for alterations in serum concentrations of thyroid hormones in patients during CVVHDF. Full article
(This article belongs to the Section Intensive Care)
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14 pages, 3361 KB  
Article
Bacteremia Caused by a Putative Novel Species in the Genus Erwinia: A Case Report and Genomic Analysis
by Jiwoo Lee, Taek Soo Kim, Hyunwoong Park and Jae Hyeon Park
Life 2025, 15(8), 1227; https://doi.org/10.3390/life15081227 - 3 Aug 2025
Viewed by 935
Abstract
We report a case of catheter-associated bloodstream infection caused by a putative novel species in the genus Erwinia, identified using whole-genome sequencing (WGS). A female adolescent receiving long-term home parenteral nutrition via a central venous catheter (CVC) presented with a fever. Gram-negative [...] Read more.
We report a case of catheter-associated bloodstream infection caused by a putative novel species in the genus Erwinia, identified using whole-genome sequencing (WGS). A female adolescent receiving long-term home parenteral nutrition via a central venous catheter (CVC) presented with a fever. Gram-negative rods were isolated from two CVC-derived blood culture sets, while peripheral cultures remained negative. Conventional identification methods, including VITEK 2, Phoenix M50, MALDI-TOF MS, and 16S rRNA and rpoB gene sequencing, failed to achieve species-level identification. WGS was performed on the isolate using Illumina MiSeq. Genomic analysis revealed a genome size of 5.39 Mb with 56.8% GC content and high assembly completeness. The highest average nucleotide identity (ANI) was 90.3% with Pantoea coffeiphila, and ≤85% with known Erwinia species, suggesting that it represents a distinct taxon. Phylogenetic analyses placed the isolate within the Erwinia clade but separate from any known species. Antimicrobial susceptibility testing showed broad susceptibility. This case highlights the utility of WGS for the identification of rare or novel organisms not captured by conventional methods and expands the clinical spectrum of Erwinia species. While the criteria for species delineation were met, the phenotypic characterization remains insufficient to formally propose a new species. Full article
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13 pages, 434 KB  
Article
Association of TNF-R1 with Exercise Capacity in Asymptomatic Hypertensive Heart Disease—Mediating Role of Left Ventricular Diastolic Function Deterioration
by Anna Teresa Gozdzik and Marta Obremska
J. Clin. Med. 2025, 14(15), 5391; https://doi.org/10.3390/jcm14155391 - 31 Jul 2025
Viewed by 580
Abstract
Background: TNF receptor 1 (TNF-R1) mediates the proinflammatory and proapoptotic effects of TNF-alpha, with its soluble form predicting incident heart failure (HF). While there is evidence linking TNF pathway activation to cardiac dysfunction, the mechanisms involved remain unclear. This study aimed to investigate [...] Read more.
Background: TNF receptor 1 (TNF-R1) mediates the proinflammatory and proapoptotic effects of TNF-alpha, with its soluble form predicting incident heart failure (HF). While there is evidence linking TNF pathway activation to cardiac dysfunction, the mechanisms involved remain unclear. This study aimed to investigate the association between TNF-R1, exercise capacity, and cardiac function in asymptomatic patients with hypertensive heart disease (HHD). Methods: We enrolled 80 patients (mean age 55 ± 12 years) with HHD and no clinical symptoms of HF (stages A and B). Echocardiography, including tissue Doppler and left atrial and left ventricular (LV) strain assessment, was performed at rest. Peripheral venous blood samples were collected to measure serum TNF-R1 concentration. Results: The study population was divided into two subsets based on the median exercise capacity (peak VO2) value. Patients with higher VO2 had lower serum TNF-R1 concentration and higher early peak mitral annular velocity (e’) and peak atrial longitudinal strain (PALS). After adjusting for other covariates, multivariable regression analysis identified TNF-R1 as an independent determinant of peak VO2. Mediation analysis revealed that the relationship between TNF-R1 and peak VO2 was mediated by LV diastolic function (PALS or e’), with a decrease in the beta coefficient after including mediator variables from 0.37 (p < 0.001) to 0.30 (p < 0.006) and 0.31 (p = 0.004), respectively. Conclusions: In patients with HHD, higher TNF-R1 levels are associated with lower exercise capacity, which may be mediated by impaired LV diastolic function. These findings might suggest a role of TNF signalling in early HF development, justifying further studies to evaluate TNF-R1 as a biomarker for risk of HF progression. Full article
(This article belongs to the Special Issue The Role of Biomarkers in Cardiovascular Diseases)
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13 pages, 410 KB  
Review
Steal Syndrome in Free Flap Microvascular Reconstruction of the Lower Extremity: Systematic Review of Incidence, Risk Factors, and Surgical Management
by Georgios Karamitros, Ilias Iliadis, Raymond A. Pensy and Gregory A. Lamaris
Bioengineering 2025, 12(6), 647; https://doi.org/10.3390/bioengineering12060647 - 12 Jun 2025
Viewed by 1113
Abstract
Background: Steal syndrome in the setting of microvascular reconstruction refers to a phenomenon whereby blood flow is diverted from the native tissue to the free flap, leading to ischemia and potential limb loss. In the present study, we aim to comprehensively evaluate [...] Read more.
Background: Steal syndrome in the setting of microvascular reconstruction refers to a phenomenon whereby blood flow is diverted from the native tissue to the free flap, leading to ischemia and potential limb loss. In the present study, we aim to comprehensively evaluate the occurrence and management of steal syndrome in free flap reconstruction of the lower extremities. Methods: A thorough literature search was conducted across the MEDLINE, Embase, Cochrane Library, and Scopus databases up to 29 January 2025. Studies were selected based on predefined inclusion criteria focusing on free flap microvascular reconstruction in the lower extremities with a focus on steal syndrome. Two independent reviewers assessed and extracted data. Results: Three studies were included, involving seven patients, with a mean age of 65.66 ± 5.89 years, who developed steal syndrome following free flap microvascular reconstruction. The most common revision involved below-the-knee amputation (BKA) due to ischemic complications. Comorbidities such as peripheral vascular disease (PVD), diabetes, and hypertension were present in all cases. The majority of anastomoses (85.7%) were end-to-side (ETS), with only one case utilizing a flow-through configuration. The majority of cases (n = 5, 71.4%) were reconstructed using latissimus dorsi (LD) flaps, with the remaining two cases using rectus abdominis (n = 1) and gracilis (n = 1) flaps. The recipient vessel was the anterior tibial artery in two patients (28.6%), the dorsalis pedis artery in two patients (28.6%), and the popliteal artery in three patients (42.9%). The most common salvage procedure was below-the-knee amputation (BKA), performed in four patients (57.1%). One patient required revision of the venous anastomosis and flap debridement, followed by a Chopart amputation (n = 1, 14.3%). Conclusions: The occurrence of steal syndrome in free flap microvascular reconstruction of the lower extremities is rare but can lead to significant complications, including amputation. The findings indicate that steal syndrome is more likely in patients with pre-existing vascular conditions such as PVD and diabetes. While surgical technique and flap type may influence its development, further studies are needed to identify specific anatomical and clinical predictors. The absence of a unified treatment guideline underscores the need for further investigation into effective management strategies to prevent amputation and optimize patient outcomes. Full article
(This article belongs to the Special Issue Surgical Wound Infections and Management)
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15 pages, 1345 KB  
Article
The Detection of Early Changes in Inflammatory Response After Pulmonary Vein Isolation in Patients with Paroxysmal Atrial Fibrillation Can Predict Late Atrial Fibrillation Recurrence
by Ana Lanca Bastiancic, Ivana Grgic Romic, Snjezana Hrabric Vlah, Vlatka Sotošek, Marina Klasan, Petra Baumgartner, Mate Mavric and Sandro Brusich
J. Clin. Med. 2025, 14(11), 3874; https://doi.org/10.3390/jcm14113874 - 30 May 2025
Viewed by 1039
Abstract
Background: Inflammation plays an important role in the initiation of atrial fibrillation (AF) and the development of fibrosis following pulmonary vein isolation (PVI). We aimed to investigate whether early post-PVI levels of C-reactive protein (CRP), white blood cells, tumour necrosis factor alpha [...] Read more.
Background: Inflammation plays an important role in the initiation of atrial fibrillation (AF) and the development of fibrosis following pulmonary vein isolation (PVI). We aimed to investigate whether early post-PVI levels of C-reactive protein (CRP), white blood cells, tumour necrosis factor alpha (TNF-α) and transforming growth factor beta 1 (TGF-ß1) are associated with long-term arrhythmia recurrence. Methods: This prospective observational study included 48 patients with paroxysmal AF undergoing PVI. Peripheral venous blood samples were collected on the day of hospitalisation (T0), immediately after the procedure (T1) and after 24 h (T2), seven days (T3) and one month (T4) following the procedure. Blood samples were obtained from the coronary sinus (CS) before and after PVI. CRP levels, leukocyte (LKc) and neutrophile (Neu) counts were determined. TGF-β1 and TNF-α were analysed using the enzyme-linked immunosorbent assay (ELISA). After discharge, follow-up visits were scheduled at seven days and one-, three-, six-, nine- and twelve-months post-ablation, with 24 h Holter monitoring at each visit. Results: Patients were allocated into a recurrent and a non-recurrent group. Baseline characteristics did not differ between the groups, except for the duration of AF, which was found to be a significant arrhythmia recurrence predictor. Patients in the non-recurrent group had statistically significantly higher LKc at all time points, and Neu at T2 and T3. CRP and TGF-β1 concentrations were significantly higher in the non-recurrent group, while TNF-α concentration was significantly higher in the recurrent group at the T2 time point. Significantly higher concentrations of CS TNF-α at T1 and TGF-β1 at T0 and T1 were documented in the non-recurrent group. Conclusions: The study shows that an enhanced inflammatory response early after PVI, characterised by increased CRP, WBC and TGF-β1 levels, may play a protective role against late arrhythmia recurrence. Full article
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15 pages, 1537 KB  
Article
Using the Rise and Fall of Oxidative Stress and Inflammation Post-Exercise to Evaluate the Effect of Methylsulfonylmethane Supplementation on Immune Response mRNA
by Brian K. McFarlin, John H. Curtis, Heidi N. du Preez and Meredith A. McFarlin
Nutrients 2025, 17(11), 1761; https://doi.org/10.3390/nu17111761 - 23 May 2025
Viewed by 3626
Abstract
Background: Long-duration aerobic exercise results in a similar, albeit transient rise and fall in oxidative stress and inflammation, making it a useful model to evaluate nutritional supplements targeting these physiological processes. Objective: To evaluate the impact of MSM supplementation on post-exercise immune response-related [...] Read more.
Background: Long-duration aerobic exercise results in a similar, albeit transient rise and fall in oxidative stress and inflammation, making it a useful model to evaluate nutritional supplements targeting these physiological processes. Objective: To evaluate the impact of MSM supplementation on post-exercise immune response-related mRNA expression. Methods: In the present study, we enrolled healthy, experienced runners (five MSM and five placebo) who were supplemented with Methylsulfonylmethane (MSM; 1.0 g/d) or placebo for 30 days prior to a 21.1 km running event (120 to 150 min). Venous blood samples were collected prior to (PRE) the event, as well as 2 h and 4 h after the event to measure the expression of 700 mRNAs associated with generalized immune response. Results: This study is the first to demonstrate significant effects with lower MSM doses (0.5–1.0 g/d) compared to previous work using higher doses (3 g/d). We identified 29 mRNAs in four distinct immune response pathways (peripheral tissue inflammatory response, myeloid immune cell invasion, NK cell invasion/activity, and notch signaling) whose response was statistically changed with MSM at 2 h and/or 4 h. Conclusions: Based on the physiologic actions of the mRNA that changed, some logical potential health effects of MSM may be that it helps with the following: (1) supports muscle recovery by improving macrophage response to exercise, (2) speeds up recovery and restoration of damaged muscle tissue, (3) supports innate immune responsiveness to DAMP, and (4) reduces and/or improves resistance to oxidative stress after exercise. Future research should seek to validate how the changes observed with exercise may model to various chronic inflammatory states. Full article
(This article belongs to the Section Nutrigenetics and Nutrigenomics)
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14 pages, 1258 KB  
Study Protocol
Comparison of Traditional and Ultrasound-Guided Techniques for Vascular Access in Patients with Difficult Venous Access in Emergency Departments: Randomized Clinical Trial Protocol
by Mercedes S. Peralta-Gámez, Marina Gómez de Quero Córdoba, Silvia Reverté-Villarroya and Roser Cuesta-Martínez
Nurs. Rep. 2025, 15(5), 177; https://doi.org/10.3390/nursrep15050177 - 20 May 2025
Viewed by 2564
Abstract
Background: Vascular access in emergency departments (ED) is challenging for patients with difficult venous access (DIVA), causing delays and discomfort. Ultrasound-guided techniques may offer improved outcomes, making it crucial to assess their benefits, risks, and the effectiveness of validated identification systems. Objectives [...] Read more.
Background: Vascular access in emergency departments (ED) is challenging for patients with difficult venous access (DIVA), causing delays and discomfort. Ultrasound-guided techniques may offer improved outcomes, making it crucial to assess their benefits, risks, and the effectiveness of validated identification systems. Objectives: To contribute new evidence regarding the effectiveness of validated tools for identifying DIVA and to assess the clinical benefits of ultrasound-guided vascular access in emergency care, and to assess their utility in arterial puncture for arterial blood gas sampling, from now on ABG, within the ED. Methods: This study follows the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines for protocol development and the Consolidated Standards of Reporting Trials (CONSORT) guidelines for the conduct and reporting of the randomized clinical trial (RCT). The trial will be conducted in Spain throughout 2025. The study population will consist of 114 subjects with difficult intravenous access (DIVA), identified using the DIVA scale for individuals under 14 years of age and the A-DICAVE scale for adults, along with 80 subjects from the general surgical area (GSA). Participants will be randomly assigned, in a 1:1 ratio, to either the Control Group (CG) (traditional technique) or the Experimental Group (EG) (ultrasound-guided technique). Data collected will include sociodemographic characteristics, procedure-related variables (e.g., time required, human resources, and materials used), as well as pain levels, assessed using validated scales (EVA, FLACC, PAINAD), and overall satisfaction from both patients and healthcare professionals. Ethical approval has been obtained, and the trial will be registered as an RCT through an official clinical trial registry before recruitment begins. Results: Expected results suggest ultrasound guidance will significantly improve first-attempt success rates, reduce procedural time, enhance patient comfort, and optimize resource utilization compared to traditional techniques. Conclusions: The integration of ultrasound-guided vascular access into routine emergency protocols could enhance patient safety, satisfaction, and procedural efficiency in emergency care settings. Full article
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