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11 pages, 621 KB  
Article
Correlations of Lumbar Interspinous Distance with Neuroforaminal Dimensions, Disc Space Height, and Patient Demographic Factors
by Carson Cummings, Zachary Brandt, Kai Nguyen, Asael Isaac, Jean-Carlos Gutierrez, Ashley Kempf, David Cheng, Joel D. Carson, Emily Novak, Jacob Razzouk, Olumide Danisa and Wayne Cheng
Tomography 2025, 11(9), 100; https://doi.org/10.3390/tomography11090100 (registering DOI) - 27 Aug 2025
Abstract
Background/Objectives: A thorough understanding of spinal anatomy is essential for diagnostic assessment and surgical intervention. Interspinous distance (ISD), neuroforaminal dimensions (NFDs), and disc space height (DSH) have each been studied separately; however, their interrelationship remains unstudied. Given the use of interspinous implants as [...] Read more.
Background/Objectives: A thorough understanding of spinal anatomy is essential for diagnostic assessment and surgical intervention. Interspinous distance (ISD), neuroforaminal dimensions (NFDs), and disc space height (DSH) have each been studied separately; however, their interrelationship remains unstudied. Given the use of interspinous implants as a minimally invasive treatment for lumbar stenosis and degenerative disc disease, defining these relationships is of growing clinical significance. This study investigates the correlation between ISD and both NFDs and DSH in a normative population and whether ISD varies with demographic factors. Methods: A retrospective chart review was performed on 852 patients who underwent CT imaging of the lumbar spine. ISD was measured from L1 to L5 as the shortest distance between the most caudal tip of the superior spinous process and the inferior spinous process. DSH was measured at the anterior, middle, and posterior margins. NFDs were assessed in axial and sagittal views, including axial width, craniocaudal height, and foraminal area. Statistical analysis assessed correlations between ISD, NFDs, DSH, and demographic variables. Results: No strong correlation was observed between ISD and either NFDs or DSH. Slightly greater correlation was present at L1–L3, weakening at L4–L5, where interspinous implants are most commonly placed. Demographic analysis revealed no consistent relationship between ISD and ethnicity, sex, or BMI. While it may be expected that larger ISD correlates with greater NFDs or DSH, our findings do not support this assumption. Conclusions: ISD does not strongly correlate with NFDs or DSH, and demographic factors do not significantly influence ISD in a healthy population. Full article
(This article belongs to the Special Issue Orthopaedic Radiology: Clinical Diagnosis and Application)
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26 pages, 3815 KB  
Article
Deep Learning Method Based on Multivariate Variational Mode Decomposition for Classification of Epileptic Signals
by Shang Zhang, Guangda Liu, Shiqing Sun and Jing Cai
Brain Sci. 2025, 15(9), 933; https://doi.org/10.3390/brainsci15090933 (registering DOI) - 27 Aug 2025
Abstract
Background/Objectives: Epilepsy is a neurological disorder that severely impacts patients’ quality of life. In clinical practice, specific pharmacological and surgical interventions are tailored to distinct seizure types. The identification of the epileptogenic zone enables the implementation of surgical procedures and neuromodulation therapies. [...] Read more.
Background/Objectives: Epilepsy is a neurological disorder that severely impacts patients’ quality of life. In clinical practice, specific pharmacological and surgical interventions are tailored to distinct seizure types. The identification of the epileptogenic zone enables the implementation of surgical procedures and neuromodulation therapies. Consequently, accurate classification of seizure types and precise determination of focal epileptic signals are critical to provide clinicians with essential diagnostic insights for optimizing therapeutic strategies. Traditional machine learning approaches are constrained in their efficacy due to limited capability in autonomously extracting features. Methods: This study proposes a novel deep learning framework integrating temporal and spatial information extraction to address this limitation. Multivariate variational mode decomposition (MVMD) is employed to maintain inter-channel mode alignment during the decomposition of multi-channel epileptic signals, ensuring the synchronization of time–frequency characteristics across channels and effectively mitigating mode mixing and mode mismatch issues. Results: The Bern–Barcelona database is employed to classify focal epileptic signals, with the proposed framework achieving an accuracy of 98.85%, a sensitivity of 98.75%, and a specificity of 98.95%. For multi-class seizure type classification, the TUSZ database is utilized. Subject-dependent experiments yield an accuracy of 96.17% with a weighted F1-score of 0.962. Meanwhile, subject-independent experiments attain an accuracy of 87.97% and a weighted F1-score of 0.884. Conclusions: The proposed framework effectively integrates temporal and spatial domain information derived from multi-channel epileptic signals, thereby significantly enhancing the algorithm’s classification performance. The performance on unseen patients demonstrates robust generalization capability, indicating the potential clinical applicability in assisting neurologists with epileptic signal classification. Full article
12 pages, 964 KB  
Article
Surgical Treatment of Scaphoid Non-Union in Adolescents: A Modified Vascularized Bone Graft Technique
by Diletta Bandinelli, Alessia Pagnotta, Alessandro Piperno, Martina Marsiolo, Angelo Gabriele Aulisa and Francesco Falciglia
Children 2025, 12(9), 1135; https://doi.org/10.3390/children12091135 - 27 Aug 2025
Abstract
Background: Although adolescents are at a lower risk of developing scaphoid non-union than adults, this complication is not uncommon in younger patients. The current gold standard for surgical treatment is non-vascularized bone grafting from the iliac crest or distal radius, and it is [...] Read more.
Background: Although adolescents are at a lower risk of developing scaphoid non-union than adults, this complication is not uncommon in younger patients. The current gold standard for surgical treatment is non-vascularized bone grafting from the iliac crest or distal radius, and it is often considered the first-line option. However, non-union can persist in 10–20% of cases, and failure rates can reach up to 50% when the proximal pole is necrotic. Methods: We evaluated a modified vascularized bone graft surgical technique in selected adolescent patients, with the goal of avoiding growth-related complications. Our experience is based on three cases of scaphoid non-union treated surgically between June 2019 and June 2022. Results and Conclusions: The modified surgical technique has shown promising results in the selected cases and carries no risk of donor site morbidity. It enables preservation of severely compromised scaphoid bones, prevents early-onset wrist osteoarthritis, and facilitates the return to sports activities for young patients. Full article
(This article belongs to the Special Issue Pediatric Upper Extremity Pathology)
20 pages, 2622 KB  
Case Report
WHO Grade II or III Solitary Fibrous Tumors (Hemangiopericytomas) of the Spine: Two Case Reports with a Comprehensive Review of the Literature
by Kazuyuki Segami, Yutaro Okamura, Syu Takahashi, Yasuo Ueda, Koji Kanzaki and Yoshifumi Kudo
J. Clin. Med. 2025, 14(17), 6068; https://doi.org/10.3390/jcm14176068 (registering DOI) - 27 Aug 2025
Abstract
Solitary fibrous tumors (SFTs) of the spine are rare. SFTs, especially those classified as WHO grade II or III (previously termed hemangiopericytomas), are aggressive neoplasms with a high recurrence rate and metastatic potential. In the literature, descriptions of SFTs are limited to case [...] Read more.
Solitary fibrous tumors (SFTs) of the spine are rare. SFTs, especially those classified as WHO grade II or III (previously termed hemangiopericytomas), are aggressive neoplasms with a high recurrence rate and metastatic potential. In the literature, descriptions of SFTs are limited to case reports and small case series. To our knowledge, 157 cases, including the current case, have been reported since Schirger’s 1958 report on spinal SFTs. This report describes two cases of WHO grade II and III SFTs in the spine and presents a review of the literature. In the first case, an extradural WHO grade II SFT recurred 6 years after the first surgery, and a second surgery was performed, including wide excision of the surrounding tissue. The patient has remained recurrence-free for 16 years since the second surgery. In the second case, an intradural extramedullary WHO grade III SFT was resected, including the dura mater, and the patient has remained recurrence-free for 3 years since the surgery. Few reports have described tumor recurrence and long-term outcomes after reoperation, as in the first case, or extensive resection including the dura, as in the second case. Furthermore, the literature review not only summarizes patients’ general and surgical information, but also indicates, based on multivariate analysis, that gross total resection (GTR) is an important factor in preventing recurrence and metastasis. This is the first study to comprehensively examine previous reports and identify risk factors for recurrence and metastasis. In addition, because recurrences have been reported long after surgery, we believe that even if GTR is performed surgically, it is important to conduct follow-ups to check for long-term recurrence. Full article
(This article belongs to the Section Orthopedics)
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16 pages, 1031 KB  
Article
A Substance-Based Medical Device for Managing Hemorrhoidal Disease: Output from a Cross-Sectional Survey
by Roberto Cioeta, Paola Muti, Marta Rigoni, Roberta La Salvia, Elena Gabriele, Andrea Cossu and Emiliano Giovagnoni
J. Clin. Med. 2025, 14(17), 6069; https://doi.org/10.3390/jcm14176069 (registering DOI) - 27 Aug 2025
Abstract
Background: Hemorrhoidal disease (HD) is a common anorectal condition characterized by symptoms such as bleeding, pain, discomfort and itching. While often underdiagnosed due to patient reluctance to seek care, HD significantly impacts quality of life (QoL). Conservative treatments are preferred for low-grade HD, [...] Read more.
Background: Hemorrhoidal disease (HD) is a common anorectal condition characterized by symptoms such as bleeding, pain, discomfort and itching. While often underdiagnosed due to patient reluctance to seek care, HD significantly impacts quality of life (QoL). Conservative treatments are preferred for low-grade HD, with increasing interest in natural substance-based therapies. Materials and Methods: A large-scale survey was conducted using a digital platform to collect real-world data (RWD) from patients, pharmacists and physicians. The research assessed perceived effectiveness, safety, tolerability, quality of life (QoL) and usage patterns of NeoFitoroid BioOintment. Quantitative analysis was also performed using a global score (GS) based on Likert scale ratings and their distribution. Results: A total of 2618 participants were included. A strong concordance across the three participating cohorts in the answers provided for all items of the questionnaire was observed. The descriptive analysis revealed high grades of effectiveness, safety and tolerability. Indeed, over 90% of respondents rated the product as “good” or “excellent” in terms of effectiveness and safety. Conclusions: These findings underscore the treatment’s effectiveness, safety, tolerability and positive influence on QoL in HD patients. Full article
(This article belongs to the Special Issue Clinical Innovations in Digestive Disease Diagnosis and Treatment)
51 pages, 1043 KB  
Systematic Review
Metastatic Carcinomas at the Episiotomy Site: A Systematic Literature Review
by Andrea Palicelli, Gabriele Tonni, Federica Torricelli, Beatrice Melli, Vincenza Ylenia Cusenza, Sandra Martinelli, Eleonora Zanetti, Alessandra Bisagni, Magda Zanelli, Maria Paola Bonasoni, Teresa Rossi, Lucia Mangone, Venus Damaris Medina-Illueca, Maurizio Zizzo, Andrea Morini, Giuseppe Broggi, Rosario Caltabiano, Serena Salzano, Francesca Sanguedolce, Nektarios I. Koufopoulos, Ioannis Boutas, Aleksandra Asaturova, Chiara Casartelli, Sara Rubagotti, Matteo Crotti, Lorenzo Aguzzoli and Vincenzo Dario Mandatoadd Show full author list remove Hide full author list
Cancers 2025, 17(17), 2801; https://doi.org/10.3390/cancers17172801 - 27 Aug 2025
Abstract
Background/Objectives: Rarely, primary (PriCs) or metastatic (metECs) carcinomas occur in the episiotomy site. Methods: A systematic literature review of metECs was carried out. We reviewed the PRISMA guidelines and the Scopus, Pubmed, and Web of Science databases. Results: We found [...] Read more.
Background/Objectives: Rarely, primary (PriCs) or metastatic (metECs) carcinomas occur in the episiotomy site. Methods: A systematic literature review of metECs was carried out. We reviewed the PRISMA guidelines and the Scopus, Pubmed, and Web of Science databases. Results: We found 21 carcinomas; all of them were cervical carcinomas (11 squamous, SCC; 6 adenocarcinomas; 3 adenosquamous; 1 SCC or adenocarcinoma) diagnosed during pregnancy (38%) or 0.25–8 months postpartum (57%). SCCs were larger (mean size: 4.8 cm). At presentation, only two cases were pN+, and no distant metastases were found, excluding four episiotomy metastases (one anticipating the cervical cancer diagnosis); the remaining episiotomy metastases (mean size: 3 cm; one multifocal) were found at follow-up (these were first metastases in 86% of cases). The time range from the episiotomy/last delivery to first episiotomy metastasis was 1–66 (mean, 12.3) months. Treatment was variable: hysterectomy (71%) ± lymphadenectomy (67%) and/or adjuvant treatment (19%); chemoradiation/radiotherapy alone (24%). A total of 90% of cases recurred after 18 days to 66 months (mean, 12 months). At last follow-up, ten patients (48%) were disease-free after 12–120 (mean, 63.5) months, two patients (10%) were alive with disease, and nine (42%) patients died of disease after 6–36 (mean, 12.5) months (including two never-cleared/progressing cases). Conclusions: PriCs and metECs are rare. Iatrogenic/obstetric implantation or vascular dissemination of cervical cancer at the site of episiotomy may occur. For episiotomy lesions, accurate gynecological/perineal examination is required, and biopsy can be considered. Larger studies are required in order to determine treatment guidelines. Compared to PriCs, metECs occurred in younger (premenopausal) patients, were not associated with endometriosis, and demonstrated slightly smaller size and shorter mean time from episiotomy to episiotomy metastases, with a higher likelihood of a less favorable prognosis. Full article
(This article belongs to the Special Issue Advancements in Surgical Approaches for Gynecological Cancers)
19 pages, 6232 KB  
Article
Comparison of Open Versus Minimally Invasive Repair of Colovesical Fistula: A Case Report and Propensity-Matched National Database Analysis
by Alexis Volkert, Anmol Nigam, David Stover, Pravin Meshram, Rubeena Naaz, Chidiebere Onongaya, Sean Huu-Tien Nguyen, Jordan Sauve, Wolfgang Gaertner and James V. Harmon Jr.
J. Clin. Med. 2025, 14(17), 6065; https://doi.org/10.3390/jcm14176065 (registering DOI) - 27 Aug 2025
Abstract
Background: Colovesical fistulas are abnormal communications between the colon and urinary bladder, most commonly caused by diverticular disease. Although colovesical fistulas are rare, they should be suspected in patients presenting with recurrent urinary tract infections, pneumaturia, or fecaluria. We integrated two case reports [...] Read more.
Background: Colovesical fistulas are abnormal communications between the colon and urinary bladder, most commonly caused by diverticular disease. Although colovesical fistulas are rare, they should be suspected in patients presenting with recurrent urinary tract infections, pneumaturia, or fecaluria. We integrated two case reports with a retrospective national cohort analysis to assess the surgical treatment of colovesical fistulas. Methods: We report two cases of colovesical fistulas, both secondary to sigmoid diverticulitis, treated surgically via minimally invasive approaches. A retrospective analysis using the National Inpatient Sample database from 2016 to 2022 was conducted to compare outcomes of open surgery with those of minimally invasive surgery. Propensity score matching and multivariable regression analyses were used to evaluate clinical outcomes. Results: The first patient underwent hand-assisted laparoscopic sigmoidectomy with fistula takedown and has remained asymptomatic at 8 months, while the second patient underwent robotic-assisted sigmoidectomy with staged ileostomy reversal and has remained asymptomatic at 1 month. National data analysis showed no significant difference in mortality (<1% versus <1%, p = 0.931), wound complications (1.4% versus 1.0%; p = 0.554), or postoperative sepsis or shock (7.1% versus 5.6%; p = 0.114) between open and minimally invasive surgical approaches. However, the minimally invasive surgery group had significantly shorter length of stay than the open surgery group (6.9 versus 7.3 days, p < 0.001). Conclusions: Minimally invasive repair of colovesical fistulas was associated with shorter hospital stays than open surgery, with no significant differences in major complications. Early identification and timely surgical management are critical for achieving favorable outcomes. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
13 pages, 834 KB  
Article
Rehabilitation Outcomes Following Surgical Management of Lower-Limb Soft Tissue Sarcomas: Insights from Gait Analysis
by Marco Germanotta, Francesca Falchini, Arianna Pavan, Stefania Lattanzi, Laura Cortellini, Beniamino Brunetti, Stefania Tenna, Alice Valeri, Chiara Pagnoni, Roberto Passa, Michela Angelucci, Bruno Vincenzi, Rossana Alloni, Irene Giovanna Aprile and Sergio Valeri
J. Clin. Med. 2025, 14(17), 6061; https://doi.org/10.3390/jcm14176061 (registering DOI) - 27 Aug 2025
Abstract
Background: Soft tissue sarcomas (STSs) are rare and heterogeneous malignancies requiring a multidisciplinary approach to diagnosis and treatment. Advances in surgical techniques, chemotherapy, and radiotherapy have improved survival rates but often result in significant functional impairments, particularly in patients undergoing limb-sparing procedures. Rehabilitation [...] Read more.
Background: Soft tissue sarcomas (STSs) are rare and heterogeneous malignancies requiring a multidisciplinary approach to diagnosis and treatment. Advances in surgical techniques, chemotherapy, and radiotherapy have improved survival rates but often result in significant functional impairments, particularly in patients undergoing limb-sparing procedures. Rehabilitation is crucial for restoring mobility and independence, with recent studies emphasizing the importance of personalized rehabilitation protocols tailored to specific surgical interventions. Quantitative assessments, such as 3D motion capture and surface electromyography, provide objective insights into gait performance and motor function, enabling more precise rehabilitation strategies to optimize recovery. Methods: This study evaluated gait performance in 21 patients with lower-limb impairment following limb-sparing surgery for STS. Patients underwent two instrumented gait assessments using marker-based 3D motion capture and surface electromyography to measure spatiotemporal gait parameters, joint kinematics, and muscle activity. Independence in the activity of daily living was assessed with the modified Barthel Index in both timepoints. Results: Following rehabilitation, patients demonstrated significant improvements in functional independence, as reflected by an increase in the modified Barthel Index (p < 0.001). Gait analysis revealed increased walking speed, stride length, cadence, and improved joint range of motion at the hip, knee, and ankle, though electromyographic analysis showed no statistically significant differences in muscle activation patterns or co-contraction indices. Conclusions: These findings underscore the importance of a rehabilitation programs personalized on gait strategies. A deeper understanding of motor adaptations based on sarcoma location and surgical approach could further refine rehabilitation protocols, ultimately enhancing patient outcomes and quality of life. Full article
(This article belongs to the Section Clinical Rehabilitation)
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18 pages, 3192 KB  
Article
Dedifferentiation-Dependent Regeneration of the Biliary Ductal Epithelium in Response to Hepatic Injury in TFF1-Deficient Mice
by Taisuke Yamamoto, Junpei Yamaguchi, Toshio Kokuryo, Yukihiro Yokoyama, Takashi Mizuno, Shunsuke Onoe, Masaki Sunagawa, Taisuke Baba and Tomoki Ebata
Cells 2025, 14(17), 1323; https://doi.org/10.3390/cells14171323 - 27 Aug 2025
Abstract
The mechanisms involved in the regeneration of biliary epithelial cells (BECs) after liver injury remain unclear. In this study, we employed KRT19CreERT/LSL-tdTomato (KT) mice and KT/TFF1KO mice to clarify the regeneration and cell fate of BECs via lineage tracing. Tamoxifen (TAM) [...] Read more.
The mechanisms involved in the regeneration of biliary epithelial cells (BECs) after liver injury remain unclear. In this study, we employed KRT19CreERT/LSL-tdTomato (KT) mice and KT/TFF1KO mice to clarify the regeneration and cell fate of BECs via lineage tracing. Tamoxifen (TAM) was administered to the mice to label cytokeratin 19 (CK19)-positive BECs. The mice were subsequently fed a choline-deficient, ethionine-supplemented (CDE) diet for four weeks, after which the mouse livers were analyzed. Whereas the proportion of tdTomato+ cells in CK19-positive BECs decreased in the KT mice, it remained high in the KT/TFF1KO mice. Then, we analyzed hepatic progenitor cells (HPCs), the possible source of BECs. Although tdTomato-labeled HPCs were rarely found in the pretreatment mice, they were frequently found in the KT/TFF1KO mice after the CDE diet, suggesting the dedifferentiation of tdTomato-labeled BECs to HPCs. These results indicate not only that the loss of TFF1 accelerates the dedifferentiation of BECs into HPCs but also that HPCs are the source of BECs in TFF1KO mice. In addition, tdTomato-labeled HNF4α-positive hepatocytes were frequently found in the KT/TFF1KO mice, revealing the transdifferentiation of BECs to hepatocytes. The role of TFF1 as an inducer of biliary differentiation might be useful in the treatment of patients with hepatic or biliary dysfunction. Full article
18 pages, 1473 KB  
Article
Neutrophil to Lymphocyte Ratio a Prognostic Tool in Endometrial Cancer Among Classical Prognostic Factors
by Alexandra Timea Kirsch-Mangu, Alexandru Țîpcu, Vlad Alexandru Gâta, Diana Cristina Pop, Zsolt Fekete, Alexandru Irimie and Paul Milan Kubelac
Diagnostics 2025, 15(17), 2172; https://doi.org/10.3390/diagnostics15172172 - 27 Aug 2025
Abstract
Background: Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries. Despite advances in diagnosis and treatment, recurrence and mortality remain significant concerns. The neutrophil-to-lymphocyte ratio (NLR), a marker of systemic inflammation, has shown prognostic value in several malignancies, but its [...] Read more.
Background: Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries. Despite advances in diagnosis and treatment, recurrence and mortality remain significant concerns. The neutrophil-to-lymphocyte ratio (NLR), a marker of systemic inflammation, has shown prognostic value in several malignancies, but its utility in EC remains underexplored. Objective: To evaluate the prognostic significance of the preoperative NLR in patients with endometrial cancer undergoing primary surgical treatment. Methods: We conducted a retrospective cohort study including 398 patients with histologically confirmed endometrial adenocarcinoma surgically treated at a tertiary cancer center. Preoperative complete blood counts were used to calculate NLR, and a cutoff value of 2.27 was determined through Receiver Operating Characteristic (ROC) analysis. Survival outcomes were assessed using Kaplan–Meier analysis and Cox proportional hazards modeling. Results: Patients with NLR ≥ 2.27 had significantly reduced median overall survival (OS) compared to those with NLR < 2.27 (72.3 vs. 92.8 months, p = 0.008). In multivariate analysis, elevated NLR remained an independent predictor of poorer OS (HR = 1.87; 95% CI: 1.156–3.017; p = 0.011), alongside age ≥ 64 years, lymphovascular space invasion (LVSI), lymph node involvement, and distant metastases. ROC analysis yielded an Area Under the Curve (AUC) of 0.646 for NLR. Notably, vaginal brachytherapy was associated with improved survival (HR = 0.53; p = 0.026), while other adjuvant therapies were not independently significant. Conclusions: Preoperative NLR is an accessible, independent prognostic biomarker in endometrial cancer and may serve as a surrogate indicator of tumor-promoting inflammation and immune dysregulation. Its integration into preoperative assessment could enhance risk stratification and guide personalized treatment strategies. However, findings should be interpreted in light of the study’s retrospective design, single-center setting, and lack of molecular classification data. Prospective validation is warranted to confirm its clinical utility. Full article
(This article belongs to the Special Issue Diagnosis and Management of Gynecological Cancers: Third Edition)
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10 pages, 417 KB  
Review
The Journey of Sentinel Lymph Node Biopsy in Cutaneous Melanoma: A Brief Narrative Review from Scalpel to Smart Tech
by Rǎzvan Ioan Andrei, Silviu Cristian Voinea, Cristian Ioan Bordea, Aniela Roxana Nodiți, Teodora Mihaela Peleașă and Alexandru Blidaru
Medicina 2025, 61(9), 1542; https://doi.org/10.3390/medicina61091542 - 27 Aug 2025
Abstract
Sentinel lymph node biopsy (SLNB) has transformed the management of cutaneous melanoma, emerging as a cornerstone in evaluating regional lymphatic spread while minimizing surgical morbidity. From its theoretical foundation laid by Cabanas to its refinement and clinical validation through landmark trials, SLNB has [...] Read more.
Sentinel lymph node biopsy (SLNB) has transformed the management of cutaneous melanoma, emerging as a cornerstone in evaluating regional lymphatic spread while minimizing surgical morbidity. From its theoretical foundation laid by Cabanas to its refinement and clinical validation through landmark trials, SLNB has evolved into a standard of care with significant prognostic value. This review traces the historical trajectory of SLNB, analyzes current guidelines and controversies and explores future directions. Novel imaging technologies, such as indocyanine green fluorescence and augmented reality-assisted mapping, promise to enhance accuracy and reduce invasiveness. Furthermore, the advent of effective systemic therapies and neoadjuvant protocols is reshaping the therapeutic landscape, potentially redefining the role of SLNB in melanoma management. As precision medicine advances, SLNB remains an essential procedure, with its utility continually redefined by technological innovation and evolving oncologic strategies. Full article
(This article belongs to the Section Oncology)
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14 pages, 964 KB  
Article
Predicting COVID-19 Sepsis Outcomes: Roles of IL-6, Cardiac Biomarkers, Clinical Factors, and Vaccination Status and Exploratory Analysis of Tocilizumab Therapy in an Eastern European Cohort
by Diana-Maria Mateescu, Adrian-Cosmin Ilie, Ioana Cotet, Camelia-Oana Muresan, Ana-Maria Pah, Marius Badalica-Petrescu, Stela Iurciuc, Maria-Laura Craciun, Adrian Cote and Alexandra Enache
Viruses 2025, 17(9), 1168; https://doi.org/10.3390/v17091168 - 27 Aug 2025
Abstract
(1) Background: COVID-19 sepsis, marked by hyperinflammation and cardiac injury, poses significant challenges in high-comorbidity populations. This prospective cohort study evaluates the prognostic value of IL-6, troponin, NT-proBNP, and radiological findings for mortality and unfavorable outcomes in a post-2022 Eastern European cohort. (2) [...] Read more.
(1) Background: COVID-19 sepsis, marked by hyperinflammation and cardiac injury, poses significant challenges in high-comorbidity populations. This prospective cohort study evaluates the prognostic value of IL-6, troponin, NT-proBNP, and radiological findings for mortality and unfavorable outcomes in a post-2022 Eastern European cohort. (2) Methods: At “Victor Babes” Hospital, Timisoara, Romania (September 2022–December 2024), 207 adults with COVID-19 sepsis (Sepsis-3 criteria) were enrolled. Baseline IL-6, troponin, NT-proBNP, CRP, PCT, D-dimers, and chest CT lung involvement were measured. Unfavorable outcomes (in-hospital death, ICU transfer, mechanical ventilation, or vasopressor use) were analyzed using logistic and linear regression. (3) Results: Among 207 patients (mean age: 68.7 years, 54.1% male), 52 (25.1%) experienced unfavorable outcomes. Multivariable analysis identified IL-6 (OR 1.016 per pg/mL, p = 0.013), troponin (OR 1.013 per ng/L, p = 0.017), NT-proBNP (OR 1.009 per pg/mL, p = 0.049), >50% lung involvement (OR 1.835, p = 0.011), unvaccinated status (OR 2.312, p = 0.002), and higher BMI (OR 1.112 per kg/m2, p = 0.005) as independent predictors of unfavorable outcomes. Tocilizumab use (n = 12) was associated with reduced mortality (p = 0.041). IL-6 (cut-off 39.0 pg/mL, AUC = 0.91) and troponin (cut-off = 111.3 ng/L, AUC = 0.88) showed strong predictive accuracy. (4) Conclusions: Elevated IL-6, troponin, NT-proBNP, severe lung involvement, unvaccinated status, and higher BMI predict adverse outcomes in COVID-19 sepsis. Tocilizumab may offer survival benefits, warranting larger trials. These findings support targeted risk stratification in high-comorbidity populations. Full article
(This article belongs to the Special Issue Viral Sepsis: Pathogenesis, Diagnostics and Therapeutics)
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19 pages, 14183 KB  
Article
The Exposure to Polypropylene Micro- and Nanoplastics Impairs Wound Healing and Tissue Regeneration in the Leech Hirudo verbana
by Camilla Bon, Alice Maretti, Laura Pulze, Nicolò Paris, Orlando Santoro, Stefania Pragliola, Lorella Izzo, Nicolò Baranzini and Annalisa Grimaldi
Microplastics 2025, 4(3), 56; https://doi.org/10.3390/microplastics4030056 (registering DOI) - 27 Aug 2025
Abstract
Plastic pollution represents a persistent global issue, with catastrophic effects on ecosystems. Due to unique properties, these synthetic materials do not break down into biodegradable compounds when naturally dispersed, but degrade into smaller fragments, known as micro- (MPs) and nanoplastics (NPs), that easily [...] Read more.
Plastic pollution represents a persistent global issue, with catastrophic effects on ecosystems. Due to unique properties, these synthetic materials do not break down into biodegradable compounds when naturally dispersed, but degrade into smaller fragments, known as micro- (MPs) and nanoplastics (NPs), that easily enter the food chain. Among plastics, polypropylene (PP) is one of the most common, whose consumption has dramatically increased in recent years for single-use packaging and surgical masks. In this context, given the widespread detection of PP-MPs and NPs in various biological matrices, investigating their toxicity in living organisms is crucial. For these reasons, this study aims to assess how PP-MPs and NPs affect tissue regeneration following injury, proposing the freshwater leech Hirudo verbana as an established experimental model. Injured leeches were examined at different time points after plastic administration, and analyses were conducted using microscopy, immunofluorescence, and molecular biology techniques. The results demonstrate that plastic exposure induces fibrosis, disrupts tissue reorganization, delays wound repair, and activates the innate immune and oxidative stress responses. In summary, this project provides new insight into the adverse effects of PP particles on living organisms, highlighting for the first time their negative impact on proper tissue regeneration. Full article
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12 pages, 3806 KB  
Case Report
Case-Based Insights into Enteropathy-Associated T-Cell Lymphoma—Single-Center Experience
by Marija Elez, Lavinika Atanasković, Svetlana Mirosavljević, Mihailo Bezmarević, Dragan Živojinović, Radoslav Romanović, Jelena Djekić and Predrag Krstić
Hematol. Rep. 2025, 17(5), 43; https://doi.org/10.3390/hematolrep17050043 (registering DOI) - 27 Aug 2025
Abstract
Background: Enteropathy-associated T-cell lymphoma (EATL) is a rare subtype of mature T-cell lymphoma, accounting for fewer than 5% of peripheral T-cell lymphomas, with an aggressive course and poor prognosis. There are two types of this disease based on morphology and immunophenotype: type I, [...] Read more.
Background: Enteropathy-associated T-cell lymphoma (EATL) is a rare subtype of mature T-cell lymphoma, accounting for fewer than 5% of peripheral T-cell lymphomas, with an aggressive course and poor prognosis. There are two types of this disease based on morphology and immunophenotype: type I, which is often, but not always, associated with celiac disease (classic EATL), and type 2, monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL). Risk factors for classic EATL are poor adherence to a gluten-free diet, advanced age, male sex, and HLA-DQ2 homozygosity. The treatment options include surgery and various chemotherapy regimens with autologous stem cell transplantation, but the outcomes are discouraging, and clinical trials with targeted and biologic therapies are needed. Case Presentation: We report three cases of type 1 EATL, all with lethal outcomes, with one patient dying during initial treatment, one dying following several surgical interventions and without waiting to start chemotherapy, and one dying following a good treatment response but with severe infection. Full article
(This article belongs to the Special Issue Innovations in Hematologic Oncology: SOHO Italy Perspectives)
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Article
Profibrotic Molecules Are Reduced in CRISPR-Edited Emery–Dreifuss Muscular Dystrophy Fibroblasts
by Eleonora Cattin, Elisa Schena, Elisabetta Mattioli, Stefania Marcuzzo, Silvia Bonanno, Paola Cavalcante, Federico Corradi, Daniela Benati, Giorgia Farinazzo, Marco Cattaneo, Veronica De Sanctis, Roberto Bertorelli, Lorenzo Maggi, Melania Giannotta, Antonella Pini, Gaetano Vattemi, Denise Cassandrini, Marco Cavallo, Cristina Manferdini, Gina Lisignoli, Beatrice Fontana, Ilaria Pace, Claudio Bruno, Roberta Roncarati, Chiara Fiorillo, Manuela Ferracin, Eric C. Schirmer, Alessandra Recchia and Giovanna Lattanziadd Show full author list remove Hide full author list
Cells 2025, 14(17), 1321; https://doi.org/10.3390/cells14171321 - 27 Aug 2025
Abstract
Emery–Dreifuss muscular dystrophy (EDMD) is caused by mutations in EMD, LMNA, SYNE1, SYNE2, and other related genes. The disease is characterized by joint contractures, muscle weakening and wasting, and heart conduction defects associated with dilated cardiomyopathy. Previous studies demonstrated the [...] Read more.
Emery–Dreifuss muscular dystrophy (EDMD) is caused by mutations in EMD, LMNA, SYNE1, SYNE2, and other related genes. The disease is characterized by joint contractures, muscle weakening and wasting, and heart conduction defects associated with dilated cardiomyopathy. Previous studies demonstrated the activation of fibrogenic molecules such as TGFbeta 2 and CTGF in preclinical models of EDMD2 and increased secretion of TGFbeta 2 in patient serum. A wide screening of patient cells suggested fibrosis, metabolism, and myogenic signaling as the most affected pathways in various EDMD forms. In this study, we show that alpha-smooth muscle actin-positive myofibroblasts are overrepresented in patient fibroblast cultures carrying EMD, LMNA, or SYNE2 mutations, and profibrotic miRNA-21 is upregulated. Upon CRISPR/Cas correction of the mutated EMD or LMNA sequence in EDMD1 or EDMD2 fibroblasts, respectively, we observe a reduced expression of fibrogenic molecules. However, in patient myoblasts, neither fibrogenic proteins nor miRNA-21 were upregulated; instead, miRNA-21-5p was downregulated along with muscle-specific miRNA-133b and miRNA-206, which have a crucial role in muscle cell homeostasis. These observations suggest that the conversion of laminopathic fibroblasts into a profibrotic phenotype is a determinant of EDMD-associated muscle fibrosis, while miRNA-206-dependent defects of laminopathic myoblasts, including altered regulation of VEGF levels, contribute to muscle cell deterioration. Notably, our study provides a proof-of-principle for the application of gene correction to EDMD1 and EDMD2 and presents EDMD1 isogenic cells that exhibit an almost complete rescue of a disease-specific miRNA signature. These cells can be used as experimental models for studying muscular laminopathies. Full article
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