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Search Results (601)

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20 pages, 23283 KiB  
Article
Titanium–Aluminum–Vanadium Surfaces Generated Using Sequential Nanosecond and Femtosecond Laser Etching Provide Osteogenic Nanotopography on Additively Manufactured Implants
by Jonathan T. Dillon, David J. Cohen, Scott McLean, Haibo Fan, Barbara D. Boyan and Zvi Schwartz
Biomimetics 2025, 10(8), 507; https://doi.org/10.3390/biomimetics10080507 (registering DOI) - 4 Aug 2025
Abstract
Titanium–aluminum–vanadium (Ti6Al4V) is a material chosen for spine, orthopedic, and dental implants due to its combination of desirable mechanical and biological properties. Lasers have been used to modify metal surfaces, enabling the generation of a surface on Ti6Al4V with distinct micro- and nano-scale [...] Read more.
Titanium–aluminum–vanadium (Ti6Al4V) is a material chosen for spine, orthopedic, and dental implants due to its combination of desirable mechanical and biological properties. Lasers have been used to modify metal surfaces, enabling the generation of a surface on Ti6Al4V with distinct micro- and nano-scale structures. Studies indicate that topography with micro/nano features of osteoclast resorption pits causes bone marrow stromal cells (MSCs) and osteoprogenitor cells to favor differentiation into an osteoblastic phenotype. This study examined whether the biological response of human MSCs to Ti6Al4V surfaces is sensitive to laser treatment-controlled micro/nano-topography. First, 15 mm diameter Ti6Al4V discs (Spine Wave Inc., Shelton, CT, USA) were either machined (M) or additively manufactured (AM). Surface treatments included no laser treatment (NT), nanosecond laser (Ns), femtosecond laser (Fs), or nanosecond followed by femtosecond laser (Ns+Fs). Surface wettability, roughness, and surface chemistry were determined using sessile drop contact angle, laser confocal microscopy, X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM). Human MSCs were cultured in growth media on tissue culture polystyrene (TCPS) or test surfaces. On day 7, the levels of osteocalcin (OCN), osteopontin (OPN), osteoprotegerin (OPG), and vascular endothelial growth factor 165 (VEGF) in the conditioned media were measured. M NT, Fs, and Ns+Fs surfaces were hydrophilic; Ns was hydrophobic. AM NT and Fs surfaces were hydrophilic; AM Ns and Ns+Fs were hydrophobic. Roughness (Sa and Sz) increased after Ns and Ns+Fs treatment for both M and AM disks. All surfaces primarily consisted of oxygen, titanium, and carbon; Fs had increased levels of aluminum for both M and AM. SEM images showed that M NT discs had a smooth surface, whereas AM surfaces appeared rough at a higher magnification. Fs surfaces had a similar morphology to their respective NT disc at low magnification, but higher magnification revealed nano-scale bumps not seen on NT surfaces. AM Fs surfaces also had regular interval ridges that were not seen on non-femto laser-ablated surfaces. Surface roughness was increased on M and AM Ns and Ns+Fs disks compared to NT and Fs disks. OCN was enhanced, and DNA was reduced on Ns and Ns+Fs, with no difference between them. OPN, OPG, and VEGF levels for laser-treated M surfaces were unchanged compared to NT, apart from an increase in OPG on Fs. MSCs grown on AM Ns and Ns+Fs surfaces had increased levels of OCN per DNA. These results indicate that MSCs cultured on AM Ns and AM Ns+Fs surfaces, which exhibited unique roughness at the microscale and nanoscale, had enhanced differentiation to an osteoblastic phenotype. The laser treatments of the surface mediated this enhancement of MSC differentiation and warrant further clinical investigation. Full article
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18 pages, 3020 KiB  
Article
JAK2/STAT3 Signaling in Myeloid Cells Contributes to Obesity-Induced Inflammation and Insulin Resistance
by Chunyan Zhang, Jieun Song, Wang Zhang, Rui Huang, Yi-Jia Li, Zhifang Zhang, Hong Xin, Qianqian Zhao, Wenzhao Li, Saul J. Priceman, Jiehui Deng, Yong Liu, David Ann, Victoria Seewaldt and Hua Yu
Cells 2025, 14(15), 1194; https://doi.org/10.3390/cells14151194 - 2 Aug 2025
Viewed by 49
Abstract
Adipose tissue inflammation contributes to obesity-induced insulin resistance. However, increasing evidence shows that high BMI (obesity) is not an accurate predictor of poor metabolic health in individuals. The molecular mechanisms regulating the metabolically activated M1 macrophage phenotype in the adipose tissues leading to [...] Read more.
Adipose tissue inflammation contributes to obesity-induced insulin resistance. However, increasing evidence shows that high BMI (obesity) is not an accurate predictor of poor metabolic health in individuals. The molecular mechanisms regulating the metabolically activated M1 macrophage phenotype in the adipose tissues leading to insulin resistance remain largely unknown. Although the Janus Kinase (Jak)/signal transducer and activator of transcription 3 (Stat3) signaling in myeloid cells are known to promote the M2 phenotype in tumors, we demonstrate here that the Jak2/Stat3 pathway amplifies M1-mediated adipose tissue inflammation and insulin resistance under metabolic challenges. Ablating Jak2 in the myeloid compartment reduces insulin resistance in obese mice, which is associated with a decrease in infiltration of adipose tissue macrophages (ATMs). We show that the adoptive transfer of Jak2-deficient myeloid cells improves insulin sensitivity in obese mice. Furthermore, the protection of obese mice with myeloid-specific Stat3 deficiency against insulin resistance is also associated with reduced tissue infiltration by macrophages. Jak2/Stat3 in the macrophage is required for the production of pro-inflammatory cytokines that promote M1 macrophage polarization in the adipose tissues of obese mice. Moreover, free fatty acids (FFAs) activate Stat3 in macrophages, leading to the induction of M1 cytokines. Silencing the myeloid cell Stat3 with an in vivo siRNA targeted delivery approach reduces metabolically activated pro-inflammatory ATMs, thereby alleviating obesity-induced insulin resistance. These results demonstrate Jak2/Stat3 in myeloid cells is required for obesity-induced insulin resistance and inflammation. Moreover, targeting Stat3 in myeloid cells may be a novel approach to ameliorate obesity-induced insulin resistance. Full article
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9 pages, 1013 KiB  
Article
Continuous Radiofrequency for Morton’s Neuroma: Is There Complete Ablation? A Preliminary Report
by Gabriel Camuñas-Nieves, Alejandro Fernández-Gibello, Simone Moroni, Felice Galluccio, Mario Fajardo-Pérez, Francisco Martínez-Pérez, Eduardo Simón-Pérez and Alfonso Martínez-Nova
Healthcare 2025, 13(15), 1838; https://doi.org/10.3390/healthcare13151838 - 28 Jul 2025
Viewed by 350
Abstract
Background and Objectives: Morton’s neuroma is a painful foot condition that can be treated with continuous radiofrequency. However, its efficacy is not always optimal, with failure rates of 15–20%. It has been suggested that these failures may be due to incomplete nerve ablation, [...] Read more.
Background and Objectives: Morton’s neuroma is a painful foot condition that can be treated with continuous radiofrequency. However, its efficacy is not always optimal, with failure rates of 15–20%. It has been suggested that these failures may be due to incomplete nerve ablation, allowing for nerve regeneration and persistent pain. So, the aim of this study was to assess the histological effects of continuous radiofrequency on the nerves affected by Morton’s neuroma. Materials and Methods: The effect of continuous radiofrequency was evaluated in two patients with Morton’s neuroma, which required open surgery excision. In both cases, radiofrequency with a standard protocol was applied ex vivo, following the surgical excision of the neuroma. A TLG10 RF generator (90 °C, 90 s) with a monopolar needle with a 0.5 cm active tip was used. Subsequently, the samples were histologically analyzed to determine the degree of nerve ablation. Results: Histological analysis showed homogeneous focal necrosis in both cases, with lesion depths of 2.4 mm and 3.18 mm. However, areas of intact nerve tissue were identified at the periphery of the neuroma, suggesting incomplete ablation. Conclusions: The findings indicate that continuous radiofrequency does not guarantee total nerve ablation, which could explain recurrence in some cases. Intraoperative neurophysiological monitoring could be key to optimizing the procedure, ensuring complete interruption of nerve conduction and improving treatment efficacy. Full article
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21 pages, 1208 KiB  
Review
Combination of Irreversible Electroporation and Clostridium novyi-NT Bacterial Therapy for Colorectal Liver Metastasis
by Zigeng Zhang, Guangbo Yu, Qiaoming Hou, Farideh Amirrad, Sha Webster, Surya M. Nauli, Jianhua Yu, Vahid Yaghmai, Aydin Eresen and Zhuoli Zhang
Cancers 2025, 17(15), 2477; https://doi.org/10.3390/cancers17152477 - 26 Jul 2025
Viewed by 268
Abstract
Colorectal liver metastasis (CRLM) poses a significant challenge in oncology due to its high incidence and poor prognosis in unresectable cases. Current treatments, including surgical resection, systemic chemotherapy, and liver-directed therapies, often fail to effectively target hypoxic tumor regions, which are inherently more [...] Read more.
Colorectal liver metastasis (CRLM) poses a significant challenge in oncology due to its high incidence and poor prognosis in unresectable cases. Current treatments, including surgical resection, systemic chemotherapy, and liver-directed therapies, often fail to effectively target hypoxic tumor regions, which are inherently more resistant to these interventions. This review examines the potential of a novel therapeutic strategy combining irreversible electroporation (IRE) ablation and Clostridium novyi-nontoxic (C. novyi-NT) bacterial therapy. IRE is a non-thermal tumor ablation technique that uses high-voltage electric pulses to create permanent nanopores in cell membranes, leading to cell death while preserving surrounding structures, and is often associated with temporary tumor hypoxia due to disrupted perfusion. C. novyi-NT is an attenuated, anaerobic bacterium engineered to selectively germinate and proliferate in hypoxic tumor regions, resulting in localized tumor cell lysis while sparing healthy, oxygenated tissue. The synergy between IRE-induced hypoxia and hypoxia-sensitive C. novyi-NT may enhance tumor destruction and stimulate systemic antitumor immunity. Furthermore, the integration of advanced imaging and artificial intelligence can support precise treatment planning and real-time monitoring. This integrated approach holds promise for improving outcomes in patients with CRLM, though further preclinical and clinical validation is needed. Full article
(This article belongs to the Section Cancer Metastasis)
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9 pages, 671 KiB  
Article
Comparative Effects of Pulsed Field and Radiofrequency Ablation on Blood Cell Parameters During Pulmonary Vein Isolation
by Lucio Addeo, Federica Di Feo, Mario Vaccariello, Alfonso Varriale, Benedetta Brescia, Davide Bonadies, Stefano Nardi, Luigi Argenziano, Vittoria Marino, Vincenza Abbate, Luigi Cocchiara, Pasquale Guarini, Laura Adelaide Dalla Vecchia and Francesco Donatelli
Biomedicines 2025, 13(8), 1828; https://doi.org/10.3390/biomedicines13081828 - 25 Jul 2025
Viewed by 430
Abstract
Background: Pulsed field ablation (PFA) is a novel non-thermal modality for pulmonary vein isolation (PVI) in atrial fibrillation (AF), offering myocardial selectivity through irreversible electroporation while sparing surrounding structures. However, concerns have emerged regarding potential subclinical hemolysis, reflected by alterations in biochemical markers [...] Read more.
Background: Pulsed field ablation (PFA) is a novel non-thermal modality for pulmonary vein isolation (PVI) in atrial fibrillation (AF), offering myocardial selectivity through irreversible electroporation while sparing surrounding structures. However, concerns have emerged regarding potential subclinical hemolysis, reflected by alterations in biochemical markers such as lactate dehydrogenase (LDH). Methods: We conducted a retrospective, single-center study involving 249 patients undergoing PVI: 121 treated with PFA (PulseSelect or FARAPULSE) and 128 with radiofrequency (RF) ablation (PVAC catheter). Laboratory parameters were assessed at baseline, post-procedure, and at discharge, including hemoglobin, hematocrit, red blood cell (RBC) count, platelet count, creatinine, and LDH. The primary endpoint was the variation in blood cell indices; the secondary endpoint was the evaluation of LDH and hematocrit changes. Statistical analysis included t-tests and chi-square tests. Results: Baseline characteristics and pre-procedural labs did not differ significantly between groups. No significant changes in hemoglobin, hematocrit, RBC count, platelet count, or creatinine were observed post-ablation or at discharge. However, LDH levels significantly increased in the PFA group both post-procedurally and at discharge (p < 0.001), without concurrent changes in other blood cell parameters. Conclusions: PFA and RF ablation yield comparable hematological profiles after PVI, with no significant impact on key blood cell parameters. Nonetheless, the consistent rise in LDH levels in the PFA group suggests mild, subclinical hemolysis or tissue injury due to more extensive lesions. While supporting the hematologic safety of PFA, these findings underscore the need for further studies to assess the clinical significance of these biochemical alterations, particularly in high-risk patients or extensive ablation settings. Full article
(This article belongs to the Section Cell Biology and Pathology)
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20 pages, 3005 KiB  
Review
EUS-Guided Pancreaticobiliary Ablation: Is It Ready for Prime Time?
by Nina Quirk, Rohan Ahuja and Nirav Thosani
Immuno 2025, 5(3), 30; https://doi.org/10.3390/immuno5030030 - 25 Jul 2025
Viewed by 260
Abstract
Despite advances in surgery, chemotherapy, and radiation treatments for pancreatic ductal adenocarcinoma (PDAC), 5-year survival rates remain at nearly 11%. Cholangiocarcinoma, while not as severe, also possesses similar survival rates. Fewer than 20% of patients are surgical candidates at time of diagnosis; therefore, [...] Read more.
Despite advances in surgery, chemotherapy, and radiation treatments for pancreatic ductal adenocarcinoma (PDAC), 5-year survival rates remain at nearly 11%. Cholangiocarcinoma, while not as severe, also possesses similar survival rates. Fewer than 20% of patients are surgical candidates at time of diagnosis; therefore, it is imperative that alternative therapies are effective for non-surgical patients. There are several thermal ablative techniques, including radiofrequency ablation (RFA), high-intensity focused ultrasound (HIFU), microwave ablation (MWA), alcohol ablation, stereotactic body radiotherapy (SBRT), cryoablation, irreversible electroporation (IRE), biliary intraluminal brachytherapy, and biliary photodynamic therapy (PDT). Emerging literature in animal models and human patients has demonstrated that endoscopic ultrasound (EUS)-guided RFA (EUS-RFA) prevents tumor progression through coagulative necrosis, protein denaturation, and activation of anticancer immunity in local and distant tumor tissue (abscopal effect). RFA treatment has been shown to not only reduce tumor-associated immunosuppressive cells but also increase functional T cells in distant tumor cells not treated with RFA. The remarkable ability to reduce tumor progression and promote tumor microenvironment (TME) remodeling makes RFA a very promising non-surgical therapy technique that has the potential to reduce mortality in this patient population. EUS-RFA offers superior precision and safety compared to other ablation techniques for pancreatic and biliary cancers, due to real-time imaging capabilities and minimally invasive nature. Future research should focus on optimizing RFA protocols, exploring combination therapies with chemotherapy or immunotherapy, and expanding its use in patients with metastatic disease. This review article will explore the current data and underlying pathophysiology of EUS-RFA while also highlighting the role of ablative therapies as a whole in immune activation response. Full article
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54 pages, 12628 KiB  
Review
Cardiac Mechano-Electrical-Fluid Interaction: A Brief Review of Recent Advances
by Jun Xu and Fei Wang
Eng 2025, 6(8), 168; https://doi.org/10.3390/eng6080168 - 22 Jul 2025
Viewed by 264
Abstract
This review investigates recent developments in cardiac mechano-electrical-fluid interaction (MEFI) modeling, with a focus on multiphysics simulation platforms and digital twin frameworks developed between 2015 and 2025. The purpose of the study is to assess how computational modeling methods—particularly finite element and immersed [...] Read more.
This review investigates recent developments in cardiac mechano-electrical-fluid interaction (MEFI) modeling, with a focus on multiphysics simulation platforms and digital twin frameworks developed between 2015 and 2025. The purpose of the study is to assess how computational modeling methods—particularly finite element and immersed boundary techniques, monolithic and partitioned coupling schemes, and artificial intelligence (AI)-enhanced surrogate modeling—capture the integrated dynamics of cardiac electrophysiology, tissue mechanics, and hemodynamics. The goal is to evaluate the translational potential of MEFI models in clinical applications such as cardiac resynchronization therapy (CRT), arrhythmia classification, atrial fibrillation ablation, and surgical planning. Quantitative results from the literature demonstrate <5% error in pressure–volume loop predictions, >0.90 F1 scores in machine-learning-based arrhythmia detection, and <10% deviation in myocardial strain relative to MRI-based ground truth. These findings highlight both the promise and limitations of current MEFI approaches. While recent advances improve physiological fidelity and predictive accuracy, key challenges remain in achieving multiscale integration, model validation across diverse populations, and real-time clinical applicability. The review concludes by identifying future milestones for clinical translation, including regulatory model certification, standardization of validation protocols, and integration of patient-specific digital twins into electronic health record (EHR) systems. Full article
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7 pages, 2064 KiB  
Brief Report
Catheter Ablation of Premature Ventricular Contractions from Right Ventricular Outflow Tract: Concept and Application of Very-High-Power, Very-Short-Duration as a First-Line Ablation Strategy
by Shaojie Chen, Ramin Ebrahimi, Piotr Futyma, Sebastian Graeger, Gozal Mirzayeva, Anna Neumann, Daniel Schneppe, Luiz Vinícius Sartori, Sarah Janschel, Márcio Galindo Kiuchi, Martin Martinek and Helmut Pürerfellner
J. Clin. Med. 2025, 14(14), 5118; https://doi.org/10.3390/jcm14145118 - 18 Jul 2025
Viewed by 418
Abstract
This technical report presents a compelling case for the use of very-high-power, very-short-duration (VHPSD) radiofrequency ablation as a promising and efficient strategy for treating symptomatic premature ventricular contractions (PVCs) originating from the right ventricular outflow tract (RVOT). The patient with frequent, symptomatic PVCs [...] Read more.
This technical report presents a compelling case for the use of very-high-power, very-short-duration (VHPSD) radiofrequency ablation as a promising and efficient strategy for treating symptomatic premature ventricular contractions (PVCs) originating from the right ventricular outflow tract (RVOT). The patient with frequent, symptomatic PVCs and a 24% burden underwent successful ablation using a 90 W/4 s recipe via the QDOT MICRO™ catheter. The procedure resulted in immediate and sustained elimination of PVCs, with only 4 s of ablation time, near-zero fluoroscopy, no complications, and no PVC recurrence at 6 months. VHPSD ablation, though originally developed for atrial fibrillation, demonstrated remarkable procedural efficiency, precision, and lesion efficacy in this case. Compared to standard power, long-duration (SPLD) ablation, VHPSD offers the potential to significantly reduce procedural time, minimize tissue edema, and lower complication risk, particularly advantageous in anatomically challenging areas or in situations where maintaining stable catheter contact for extended periods is difficult or unfeasible. This technical report suggests the transformative potential of VHPSD as a first-line ablation strategy for RVOT-PVCs, provided careful mapping and appropriate technique are used. It underscores the need for further prospective studies to validate its broader safety, efficacy, and role in PVC management, particularly in cases involving intramural origins. Full article
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12 pages, 241 KiB  
Review
Recombinant Human TSH Versus Thyroid Hormone Withdrawal: The Role in the Preparation for RAI Therapy in Differentiated Thyroid Cancer: A Comprehensive Evidence-Based Review
by Motaz Daraghma and Michael M. Graham
J. Clin. Med. 2025, 14(14), 5000; https://doi.org/10.3390/jcm14145000 - 15 Jul 2025
Viewed by 391
Abstract
Radioactive iodine (RAI) therapy plays a fundamental role in the management of differentiated thyroid cancer (DTC) following appropriate surgical intervention. High levels of TSH are required in order to achieve maximum RAI uptake in residual thyroid tissue or metastatic cells. The two techniques [...] Read more.
Radioactive iodine (RAI) therapy plays a fundamental role in the management of differentiated thyroid cancer (DTC) following appropriate surgical intervention. High levels of TSH are required in order to achieve maximum RAI uptake in residual thyroid tissue or metastatic cells. The two techniques that are most commonly used are thyroid hormone withdrawal (THW), which induces endogenous TSH elevation by creating a hypothyroid state, and exogenous stimulation with recombinant human TSH (rhTSH). This review compares both approaches over a range of DTC risk categories. Extensive evidence demonstrates that rhTSH and THW yield equivalent oncological outcomes, including remnant ablation success, recurrence-free survival, and overall survival, in low-, intermediate-, and high-risk disease. Additionally, rhTSH maintains quality of life by avoiding hypothyroid symptoms. While THW continues to be an excellent option when there is a lack of availability of rhTSH, its disadvantages, particularly the transient hypothyroid state, must be carefully weighed against the demonstrated equivalence in efficacy. In current clinical practice, rhTSH is frequently the preferred option for its convenience, safety, and patient-centered benefits; however, the selection of the optimal approach should be based on individual clinical circumstances and patients’ preferences, as well as resource considerations. Full article
(This article belongs to the Section Nuclear Medicine & Radiology)
14 pages, 1172 KiB  
Article
Laser-Mediated Hemostasis for Older Patients Receiving Routine Dental Treatment
by Suwat Tanya, Saengsome Prajaneh, Piyachat Patcharanuchat and Sajee Sattayut
Dent. J. 2025, 13(7), 315; https://doi.org/10.3390/dj13070315 - 11 Jul 2025
Viewed by 280
Abstract
Background/Objective: Laser therapy has gained attention in dental practice to minimize bleeding and enhance blood clot formation. This study aimed to explore the utilization and to compare the clinical efficacy of laser-mediated hemostasis for older patients receiving routine dental treatment. Methods: A prospective [...] Read more.
Background/Objective: Laser therapy has gained attention in dental practice to minimize bleeding and enhance blood clot formation. This study aimed to explore the utilization and to compare the clinical efficacy of laser-mediated hemostasis for older patients receiving routine dental treatment. Methods: A prospective observational study was conducted across research networks between October 2023 and August 2024, involving 60 patients aged 50 years and older (average = 63.35 years) at risk of postoperative bleeding following dental treatments. Additionally, laser therapy for hemostasis was selected and provided among calibrated operators. A single researcher performed data collection. Before statistical analysis, data verification and clinical assessment were conducted by the operators and researcher. A clinical cut-off for hemostasis was set at 5 min. Two diode laser machines were used namely, an 810 nm and dual wavelengths of 635 nm and 980 nm. Results: There were 94 extraction sockets, 28 procedures of scaling and root planing and 18 procedures of minor oral surgery. Combining laser ablating sulcular fiber and photobiomodulation initiating blood clot formation was a preferable hemostatic technique for extraction socket, while photobiomodulation alone was a preferred technique for soft tissue hemostasis (p < 0.001). All operators confirmed that 97.86 percent of bleeding events achieved more rapid hemostasis. 61.43 percent of bleeding events clinically achieved hemostasis within 5 min by using laser-mediated hemostasis alone (p = 0.092). Full recovery of the extraction socket was significantly observed during the 2- to 4-week follow-up period (p = 0.005). No clinical complications were reported. Conclusions: Laser-mediated hemostasis effectively reduced hemostatic duration, prevented postoperative bleeding and promoted wound healing in older patients undergoing routine dental treatment. Full article
(This article belongs to the Special Issue Laser Dentistry: The Current Status and Developments)
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14 pages, 685 KiB  
Systematic Review
Association Between Left Atrial Epicardial Adipose Tissue Attenuation Assessed by Cardiac Computed Tomography and Atrial Fibrillation Recurrence Following Catheter Ablation: A Systematic Review and Meta-Analysis
by Karol Momot, Kamil Krauz, Michal Pruc, Lukasz Szarpak, Dariusz Rodkiewicz and Artur Mamcarz
J. Clin. Med. 2025, 14(13), 4771; https://doi.org/10.3390/jcm14134771 - 6 Jul 2025
Viewed by 505
Abstract
Background: Epicardial adipose tissue (EAT) may contribute to the pathogenesis of atrial fibrillation (AF). The attenuation of EAT assessed by means of computed tomography (CT) may reflect the severity of local tissue inflammation. This study aimed to systematically analyze the relationship between the [...] Read more.
Background: Epicardial adipose tissue (EAT) may contribute to the pathogenesis of atrial fibrillation (AF). The attenuation of EAT assessed by means of computed tomography (CT) may reflect the severity of local tissue inflammation. This study aimed to systematically analyze the relationship between the attenuation of EAT surrounding the left atrium (LA-EAT) and AF recurrence after catheter ablation (CA). Methods: Five databases were searched up to April 10, 2025. Original studies involving adult patients with paroxysmal or persistent AF undergoing CA were included if they provided quantitative measurements of LA-EAT attenuation on cardiac CT before ablation. Results: A total of seven retrospective observational studies with 2440 patients were included in the analysis. The percentage of male participants ranged from 60.9% to 73.0%, and the mean or median age of patients varied from 57.5 to 68.2 years. The mean body mass index across studies ranged from 24.0 to 32.4 kg/m2. A pooled analysis of all included trials demonstrated that the mean LA-EAT attenuation in the AF recurrence group was −78.97 ± 15.34 HU, which was less negative compared to the non-recurrence group (−81.37 ± 15.46 HU; mean difference [MD] = 2.22; 95% confidence interval [CI]: 0.84 to 3.61; p = 0.002). Conclusions: LA-EAT attenuation is significantly more positive in patients experiencing AF recurrence compared to those without recurrence following CA procedures. Full article
(This article belongs to the Special Issue Cardiac Electrophysiology: New Insights and Future Directions)
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20 pages, 90560 KiB  
Article
A Hybrid MIL Approach Leveraging Convolution and State-Space Model for Whole-Slide Image Cancer Subtyping
by Dehui Bi and Yuqi Zhang
Mathematics 2025, 13(13), 2178; https://doi.org/10.3390/math13132178 - 3 Jul 2025
Viewed by 266
Abstract
Precise identification of cancer subtypes from whole slide images (WSIs) is pivotal in tailoring patient-specific therapies. Under the weakly supervised multiple instance learning (MIL) paradigm, existing techniques frequently fall short in simultaneously capturing local tissue textures and long-range contextual relationships. To address these [...] Read more.
Precise identification of cancer subtypes from whole slide images (WSIs) is pivotal in tailoring patient-specific therapies. Under the weakly supervised multiple instance learning (MIL) paradigm, existing techniques frequently fall short in simultaneously capturing local tissue textures and long-range contextual relationships. To address these challenges, we introduce ConvMixerSSM, a hybrid model that integrates a ConvMixer block for local spatial representation, a state space model (SSM) block for capturing long-range dependencies, and a feature-gated block to enhance informative feature selection. The model was evaluated on the TCGA-NSCLC dataset and the CAMELYON16 dataset for cancer subtyping tasks. Extensive experiments, including comparisons with state-of-the-art MIL methods and ablation studies, were conducted to assess the contribution of each component. ConvMixerSSM achieved an AUC of 97.83%, an ACC of 91.82%, and an F1 score of 91.18%, outperforming existing MIL baselines on the TCGA-NSCLC dataset. The ablation study revealed that each block contributed positively to performance, with the full model showing the most balanced and superior results. Moreover, our visualization results further confirm that ConvMixerSSM can effectively identify tumor regions within WSIs, providing model interpretability and clinical relevance. These findings suggest that ConvMixerSSM has strong potential for advancing computational pathology applications in clinical decision-making. Full article
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7 pages, 606 KiB  
Communication
Identification of Two Distinct Stem Cell Clusters, Lrig1-Derived and Wnt/CD44-Dependent, in Corneal Epithelium
by Laurent Barnes, Evangelia Konstantinou, Jean-Hilaire Saurat, Alexandre Moulin and Gürkan Kaya
Int. J. Mol. Sci. 2025, 26(13), 6383; https://doi.org/10.3390/ijms26136383 - 2 Jul 2025
Viewed by 261
Abstract
We previously showed that selective suppression of CD44 in the corneal epithelium leads to structural abnormalities in the mouse cornea. Our comparative studies of young and aged ocular biopsies revealed that CD44 expression is downregulated in aged corneas, while leucine-rich repeats and immunoglobulin-like [...] Read more.
We previously showed that selective suppression of CD44 in the corneal epithelium leads to structural abnormalities in the mouse cornea. Our comparative studies of young and aged ocular biopsies revealed that CD44 expression is downregulated in aged corneas, while leucine-rich repeats and immunoglobulin-like domain 1 (Lrig1+) stem cells remain preserved in the peripheral limbus. These findings suggest an age-related shift in the corneal stem cell compartmentalization, characterized by impaired CD44 expression in the central cornea and preservation of Lrig1+ stem cells in the limbus, which become the main stem cells in the senescent cornea. To investigate this further, we performed topical tamoxifen-inducible, diphtheria toxin-mediated ablation of Lrig1+ stem cells in mouse corneas. We then assessed both activated and non-activated beta-catenin expression in wild-type (WT) and CD44 knockout (CD44KO) mice, given that CD44 modulates the Wingless-related integration site (Wnt) pathway. Our results indicate that two distinct stem cell populations operate in the mouse cornea: Lrig1-derived stem cells and Wnt-activity/CD44-dependent stem cells. The Lrig1-derived cells act as a reservoir of quiescent stem cells that regenerate the cornea upon injury, whereas under homeostatic conditions, the Wnt-activity/CD44-dependent stem cells are primarily responsible for corneal renewal. In the aged cornea, the loss of CD44 expression leads to reduced Wnt signaling, making the tissue increasingly dependent on Lrig1+ stem cells for regeneration. In mice, Lrig1+ stem cells are capable of sustaining permanent corneal renewal, even in the absence of CD44. Full article
(This article belongs to the Special Issue Molecular Research Progress of Skin and Skin Diseases: 2nd Edition)
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9 pages, 2559 KiB  
Case Report
Endocardial Ablation of Atrial Flutter with Involvement of the Vein of Marshall: A Case Report
by Lucio Addeo, Konstantinos Triantafyllou, Hellen Dockx, Monika Shumkova, Antonio Rapacciuolo, Stefano Nardi, Vittoria Marino, Luigi Argenziano, Pasquale Guarini, Laura Adelaide Dalla Vecchia, Francesco Donatelli and Tom De Potter
J. Clin. Med. 2025, 14(13), 4598; https://doi.org/10.3390/jcm14134598 - 29 Jun 2025
Viewed by 414
Abstract
Background: Atypical atrial flutter (AFL) is a complex clinical challenge, particularly in patients with prior atrial fibrillation (AF) treated with pulmonary vein isolation (PVI). Arrhythmias involving the vein of Marshall (VOM) often require extensive lesion sets, including ethanol infusion, to effectively target the [...] Read more.
Background: Atypical atrial flutter (AFL) is a complex clinical challenge, particularly in patients with prior atrial fibrillation (AF) treated with pulmonary vein isolation (PVI). Arrhythmias involving the vein of Marshall (VOM) often require extensive lesion sets, including ethanol infusion, to effectively target the epicardial substrate. To minimize tissue damage, an alternative strategy has been proposed, emphasizing advanced electroanatomical mapping, entrainment maneuvers, and highly targeted ablation techniques. Case Presentation: We describe a 72-year-old woman with recurrent atrial arrhythmias following pulmonary vein isolation (PVI), who presented with palpitations as her primary symptom. After ineffective pharmacological therapy, she underwent a catheter ablation procedure. Electroanatomical mapping revealed significant left atrial scarring and suggested a macroreentrant circuit involving the VOM. Entrainment maneuvers confirmed the VOM’s involvement. A single targeted endocardial ablation guided by the ablation index terminated the arrhythmia within 12 s, without the need for ethanol infusion or extensive lesion sets. Discussion: This case underscores the VOM’s role in sustaining atypical AFL post-PVI and highlights the effectiveness of precise electroanatomical mapping combined with targeted endocardial ablation. Unlike broader ablation or ethanol infusion strategies, a focused lesion at the critical isthmus achieved arrhythmia termination with minimal tissue damage. Conclusions: Endocardial ablation at the site of entrainment can safely and effectively treat VOM-related AFL, offering symptom relief and restoration of sinus rhythm. This approach may reduce procedural risks and expand the feasibility of VOM-related arrhythmia management in centers without access to ethanol infusion. Full article
(This article belongs to the Section Cardiology)
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11 pages, 2077 KiB  
Technical Note
Laparoscopic-Assisted Percutaneous Cryoablation of Abdominal Wall Desmoid Fibromatosis: Case Series and Local Experience
by Kadhim Taqi, Jaymie Walker, Cecily Stockley, Antoine Bouchard-Fortier, Stefan Przybojewski and Lloyd Mack
Surg. Tech. Dev. 2025, 14(3), 20; https://doi.org/10.3390/std14030020 - 24 Jun 2025
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Abstract
Background: Desmoid tumors (DTs) are rare, non-metastatic but locally aggressive connective tissue neoplasms. While standard treatments include surgery, radiation, and ablation, current guidelines advocate active surveillance unless tumors progress or symptoms worsen. Cryotherapy has shown promise in treating DTs; however, its application in [...] Read more.
Background: Desmoid tumors (DTs) are rare, non-metastatic but locally aggressive connective tissue neoplasms. While standard treatments include surgery, radiation, and ablation, current guidelines advocate active surveillance unless tumors progress or symptoms worsen. Cryotherapy has shown promise in treating DTs; however, its application in rectus abdominis DTs has been limited due to proximity to critical intra-abdominal structures. Methods: This case series describes a novel approach involving laparoscopic-assisted cryoablation in three patients with rectus abdominis DTs. Laparoscopic visualization was employed to improve tumor localization and procedural safety during percutaneous cryoablation. Results: The average tumor size was 7.4 cm, and a mean of 14 cryoprobes were used per case. All patients experienced complete symptom resolution. One patient developed a complication—injury to the inferior epigastric artery—requiring embolization. Follow-up imaging at three months showed significant tumor shrinkage and necrosis in two patients. The third patient had increased lesion volume due to post-procedural hematoma, although radiological markers of cryoablation efficacy were present. Conclusions: Laparoscopic-assisted cryoablation appears to be a feasible and effective technique for treating rectus abdominis DTs, providing symptom relief and favorable early tumor response. Further studies are warranted to evaluate long-term outcomes and validate this approach in broader clinical settings. Full article
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