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15 pages, 1448 KB  
Article
Evolving Clinicopathological Characteristics of Women with Locally Advanced Cervical Cancer Treated with Definitive Chemoradiation Before and After Implementation of Organized Cervical Cancer Screening in Serbia
by Jelena Stanić, Marija Popović-Vuković, Predrag Nikić, Ivana Šović, Luka Jovanović, Predrag Petrašinović, Marko Jovanović, Tatjana Arsenijević and Aleksandar Tomašević
Cancers 2026, 18(17), 2891; https://doi.org/10.3390/cancers18172891 - 7 Sep 2026
Abstract
Background: Organized cervical cancer screening aims to reduce the burden of advanced disease through earlier detection. However, a substantial proportion of women continue to present with locally advanced cervical cancer (LACC) requiring definitive chemoradiation. This study evaluated temporal changes in the demographic and [...] Read more.
Background: Organized cervical cancer screening aims to reduce the burden of advanced disease through earlier detection. However, a substantial proportion of women continue to present with locally advanced cervical cancer (LACC) requiring definitive chemoradiation. This study evaluated temporal changes in the demographic and clinicopathological characteristics of women with LACC treated with definitive chemoradiation before and after implementation of the organized cervical cancer screening program in Serbia. Methods: This retrospective single-center cohort study included 200 consecutive women with histologically confirmed LACC treated with definitive chemoradiation at the Institute of Oncology and Radiology of Serbia. Two cohorts were analyzed: a pre-screening cohort (2010–2011, n = 100) and a post-screening cohort (2022–2023, n = 100). Demographic and clinicopathological characteristics, including age, histopathology, FIGO stage, lymph node involvement, and geographic distribution, were compared. For study purposes, all patients were retrospectively restaged according to the FIGO 2018 classification using the best available clinical, radiological, and pathological data. Results: Women in the post-screening cohort were significantly older at diagnosis than those in the pre-screening cohort (mean age 54.9 vs. 49.7 years, p = 0.0046), with a substantially higher proportion of patients older than 64 years (28% vs. 2%, p < 0.0001). Although the overall distribution of FIGO stages II–IV did not differ significantly, a marked redistribution of FIGO 2018 substages was observed (p < 0.0001), characterized by an increased proportion of stage IIIC disease and significantly more frequent lymph node involvement (63% vs. 41%, p = 0.0018). Geographic distribution remained stable, with most patients referred from the Belgrade administrative district. Conclusions: This study demonstrated clinically relevant temporal changes in the demographic and clinicopathological characteristics of women requiring definitive chemoradiation for LACC in Serbia. More than a decade after implementation of organized cervical cancer screening, tertiary referral centers continue to manage a substantial burden of patients with locally advanced disease requiring complex, resource-intensive treatment. These findings should not be interpreted as a direct evaluation of the national screening program but may provide valuable insights for healthcare planning in Serbia and other countries with similarly resource-constrained healthcare systems. Strengthening participation in organized screening, ensuring timely diagnostic evaluation, and improving HPV vaccination uptake remain essential to reduce the burden of advanced cervical cancer. Full article
(This article belongs to the Section Cancer Epidemiology and Prevention)
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15 pages, 839 KB  
Article
Impact of Residual Mediastinal Nodal Disease After Neoadjuvant Chemoimmunotherapy for Non-Small Cell Lung Cancer
by Berta Mosleh, Anastasia Papaporfyriou, Thorsten Fuereder, Helmut Prosch, Joachim Widder, Felicitas Oberndorfer, Clemens Aigner, Marco Idzko, Daniela Gompelmann and Mir Alireza Hoda
Cancers 2026, 18(17), 2871; https://doi.org/10.3390/cancers18172871 - 5 Sep 2026
Viewed by 193
Abstract
Background/Objectives: In recent years, neoadjuvant chemoimmunotherapy followed by surgery has improved outcomes in patients with stage II/III non-small cell lung cancer (NSCLC). However, the prognostic impact of residual mediastinal nodal disease after chemoimmunotherapy remains insufficiently defined, particularly with the introduction of the Union [...] Read more.
Background/Objectives: In recent years, neoadjuvant chemoimmunotherapy followed by surgery has improved outcomes in patients with stage II/III non-small cell lung cancer (NSCLC). However, the prognostic impact of residual mediastinal nodal disease after chemoimmunotherapy remains insufficiently defined, particularly with the introduction of the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) 9th edition nodal subclassification. Methods: In this retrospective study, 90 consecutive patients with clinically node-positive (cN1-2) resectable locally advanced NSCLC who underwent neoadjuvant chemoimmunotherapy followed by curative-intent resection were included. Disease-free survival (DFS) was analyzed according to postoperative pathologic nodal status. Nodal status was assessed using the UICC/AJCC 8th edition (ypN0, ypN1, ypN2) and reclassified according to the 9th edition (ypN0, ypN1, ypN2a, ypN2b). Residual postoperative nodal disease was defined as residual pathologic nodal involvement (ypN+) in patients with clinically node-positive (cN+) disease at baseline. Results: The cohort comprised 90 patients (60% male, median age 63 years [interquartile range (IQR) 58–69]). Following neoadjuvant therapy, surgery revealed pathologic nodal clearance in 53 (58.9%) and residual nodal disease in 37 (41.1%) patients (ypN1, n = 16 [17.8%]; ypN2a, n = 15 [16.7%]; and ypN2b, n = 6 [6.7%]). DFS differed significantly by postoperative nodal status (global log-rank p < 0.001), with progressively poorer outcomes with increasing residual nodal burden. Conclusions: Residual nodal disease after neoadjuvant chemoimmunotherapy and surgery is associated with progressively inferior DFS according to its anatomic extent. The UICC/AJCC 9th-edition staging system provides clinically relevant prognostic granularity, supporting further investigation of mediastinal restaging and postoperative treatment strategies. Full article
(This article belongs to the Collection Diagnosis and Treatment of Primary and Secondary Lung Cancers)
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13 pages, 532 KB  
Article
OnabotulinumtoxinA Improves Sleep Quality in Patients with Chronic Migraine: A Prospective Real-World Study
by Giovanna Viticchi, Lorenzo Falsetti, Marco Bartolini, Sergio Salvemini, Gioacchino De Vanna, Eleonora Beccacece, Najdi Tanuzi and Mauro Silvestrini
Toxins 2026, 18(9), 379; https://doi.org/10.3390/toxins18090379 - 3 Sep 2026
Viewed by 174
Abstract
Sleep disturbances are highly prevalent in patients with chronic migraine (CM) and are increasingly recognized as major contributors to disease burden and headache chronification. Growing evidence suggests that dysregulation of calcitonin gene-related peptide (CGRP) signaling and central sensitization may represent common biological mechanisms [...] Read more.
Sleep disturbances are highly prevalent in patients with chronic migraine (CM) and are increasingly recognized as major contributors to disease burden and headache chronification. Growing evidence suggests that dysregulation of calcitonin gene-related peptide (CGRP) signaling and central sensitization may represent common biological mechanisms linking migraine and sleep impairment. OnabotulinumtoxinA (OBT-A), an established preventive treatment for CM, inhibits the release of CGRP and other nociceptive mediators from trigeminal sensory neurons, thereby reducing peripheral and central sensitization. However, its effects on sleep quality remain incompletely characterized. The aim of this prospective real-world observational pilot study was to evaluate the impact of OBT-A treatment on sleep quality in patients with CM. Consecutive patients initiating OBT-A therapy at a tertiary headache center were enrolled and assessed at baseline (before the first OBT-A treatment cycle) and after three months, immediately before the second scheduled administration, using the Pittsburgh Sleep Quality Index (PSQI), alongside measures of migraine frequency, acute medication use, migraine-related disability, and headache impact. Fifteen patients completed follow-up evaluations. OBT-A treatment was associated with significant improvements across all clinical outcomes. Median monthly migraine days decreased from 18 to 10 (adjusted p = 0.006), while acute medication use, MIDAS scores, and HIT-6 scores were significantly reduced. Sleep quality improved markedly, with median PSQI scores decreasing from 10 to 6 (adjusted p = 0.006). Eleven of 15 patients (73.3%) achieved a ≥3-point reduction in PSQI, and the proportion of participants with pathological sleep quality (PSQI > 5) decreased from 86.7% to 53.3%. Although this categorical improvement did not reach statistical significance (exact p = 0.063), likely due to the limited sample size, it may nonetheless suggest a beneficial effect on sleep quality, although the lack of statistical significance warrants cautious interpretation. These findings provide preliminary real-world evidence that OBT-A treatment is associated with improved subjective sleep quality in patients with chronic migraine. Improvements in sleep quality occurred alongside reductions in migraine frequency, acute medication use, disability, and headache impact. Given the observational and uncontrolled design of the study, it remains unclear whether sleep improvement reflects a direct effect of OBT-A or occurs secondarily to improvements in migraine-related outcomes. Larger prospective controlled studies are needed to clarify the mechanisms underlying sleep improvement and its relationship with treatment response. Full article
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25 pages, 11419 KB  
Article
Benefit–Hematotoxicity Stratification in Patients with Triple-Negative Breast Cancer Receiving Platinum-Based Neoadjuvant Therapy: A Multitask Deep Learning Study
by Hao Sun, Xinglu Zhou, Jian Liang, Yujie Shi, Bao Deng, Ziqi Guo, Tong Su, Binbin Guo and Lei Zhong
Cancers 2026, 18(17), 2842; https://doi.org/10.3390/cancers18172842 - 2 Sep 2026
Viewed by 206
Abstract
Objectives: Platinum-based neoadjuvant therapy can improve pathological response in triple-negative breast cancer (TNBC), but severe hematotoxicity may compromise treatment delivery. This study developed and validated a multitask learning framework to jointly predict pathological complete response (pCR) and severe hematotoxicity and to support benefit–hematotoxicity [...] Read more.
Objectives: Platinum-based neoadjuvant therapy can improve pathological response in triple-negative breast cancer (TNBC), but severe hematotoxicity may compromise treatment delivery. This study developed and validated a multitask learning framework to jointly predict pathological complete response (pCR) and severe hematotoxicity and to support benefit–hematotoxicity stratification. Methods: This multicenter retrospective study included 2060 consecutive patients with TNBC receiving platinum-based neoadjuvant therapy at three institutions. Patients were assigned to a training cohort (n = 1406), an internal validation cohort (n = 351), or an external validation cohort (n = 303). A multitask TabNet (MT-TabNet) model was developed using pretreatment clinical, pathological, imaging, laboratory, electrocardiographic, and planned treatment exposure variables to jointly estimate pCR and severe hematotoxicity. Model performance was evaluated using discrimination, calibration, decision curve analysis, and interpretability analyses. The predicted probabilities were further integrated into a utility-based framework for benefit–hematotoxicity stratification. Results: Overall, 639 patients (31.0%) achieved pCR, and 651 (31.6%) developed severe hematotoxicity. MT-TabNet achieved AUCs of 0.874, 0.842, and 0.819 for pCR prediction and 0.859, 0.846, and 0.818 for severe hematotoxicity prediction in the training, internal validation, and external validation cohorts, respectively. The model showed generally acceptable calibration and clinical net benefit. pCR prediction was predominantly associated with tumor-related characteristics, whereas severe hematotoxicity prediction was more strongly associated with planned treatment exposure and host-related laboratory indicators. Utility-based stratification showed progressively higher pCR rates and lower severe hematotoxicity rates from the low- to high-benefit groups across all three cohorts. Survival differed significantly among benefit groups for both progression-free survival (PFS) and overall survival (OS) in the training and internal validation cohorts; in the external validation cohort, OS differed significantly, whereas PFS showed a similar but nonsignificant trend. Conclusions: MT-TabNet enabled joint estimation of pCR and severe hematotoxicity in patients with TNBC receiving platinum-based neoadjuvant therapy. The utility-based framework integrated efficacy and toxicity predictions into clinically interpretable benefit–hematotoxicity stratification and warrants further prospective evaluation for individualized risk assessment and toxicity monitoring. Full article
(This article belongs to the Special Issue Treatment Response and Predictive Factors in Breast Cancer)
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20 pages, 3529 KB  
Article
Long-Term Outcomes and Paired Immune and Genomic Exploratory Analyses After Neoadjuvant Dose-Dense MVAC in Muscle-Invasive Bladder Cancer: A Single-Centre Case Series
by Daan De Maeseneer, Alexander Decruyenaere, Joni Van der Meulen, Siebe Loontiens, Toon Rosseel, Pieter-Jan Volders, Sofie Verbeke, Valerie Fonteyne, Charles Van Praet, Camille Berquin and Sylvie Rottey
Cancers 2026, 18(17), 2839; https://doi.org/10.3390/cancers18172839 - 2 Sep 2026
Viewed by 193
Abstract
Background/Objectives: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy has been the standard of care for muscle-invasive bladder cancer (MIBC) for two decades, yet a substantial proportion of patients derive no benefit. As antibody–drug conjugates and immune checkpoint inhibitors reshape perioperative treatment, [...] Read more.
Background/Objectives: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy has been the standard of care for muscle-invasive bladder cancer (MIBC) for two decades, yet a substantial proportion of patients derive no benefit. As antibody–drug conjugates and immune checkpoint inhibitors reshape perioperative treatment, it is unclear which patients retain meaningful benefit from platinum. We describe long-term outcomes and exploratory paired immune and genomic analyses in a single-centre cohort treated with dose-dense MVAC (dd-MVAC). Methods: We retrospectively identified 54 consecutive patients with MIBC treated with neoadjuvant dd-MVAC between November 2013 and November 2019. Forty-two underwent radical cystectomy and are assessable for pathologic response. Immunohistochemistry for CD3, CD8, FOXP3, PD-1, PD-L1, PD-L2, and NY-ESO-1 was evaluable in 31 baseline specimens and 22 paired specimens; paired genomic profiling was evaluable in 12 cases, with paired tumour mutational burden (TMB) in 10 by whole-exome sequencing and 7 by TSO-500. Paired analyses necessarily exclude patients achieving a pathologic complete response (pCR), who have no residual tumour, and most early progressors. Results: pCR was achieved in 11/42 operated patients (26%, 95% CI 15–41). Median follow-up was 87 months (IQR 24–104). Hydronephrosis was the only baseline factor associated with absence of pCR (p = 0.016). Within the operated cohort, pCR was associated with longer recurrence-free survival (log-rank p = 0.017), but the difference in overall survival did not reach significance (p = 0.121). NAC reduced intratumoral FOXP3 (q = 0.001), NY-ESO-1 (q = 0.013), PD-L2 (q = 0.013), and CD3 (q = 0.043) after correction for multiple comparisons, whereas TMB showed no significant change (TSO-500 p = 0.67; WES p = 0.86). No statistically significant association was detected between any baseline immune marker, including PD-L1, and pCR. The mutational landscape was largely concordant before and after NAC. Conclusions: This study was exploratory and was not powered to validate predictive biomarkers. In this long-term cohort, dd-MVAC was associated with measurable depletion of intratumoral immune populations in chemoresistant tumours, while paired genomic profiles remained broadly concordant. No pre-treatment biomarker identified platinum-refractory patients, but the small evaluable subsets mean these are hypothesis-generating rather than negative findings, and prospective studies with pre-specified biomarker endpoints are required. Full article
(This article belongs to the Special Issue Advances in Treatment of Bladder Cancer)
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21 pages, 2400 KB  
Article
Early Nutritional–Immune Biomarker Trajectories Following Gastrectomy for Gastric Cancer: A Prospective Longitudinal Cohort Study
by Catalin Dumitru Cosma, Vlad Olimpiu Butiurca, Dragos Molnar, Cosmin Nicolescu, Calin Molnar and Marian Botoncea
Nutrients 2026, 18(17), 2862; https://doi.org/10.3390/nu18172862 - 2 Sep 2026
Viewed by 208
Abstract
Background: Nutritional deterioration is a common consequence of gastrectomy for gastric cancer and may persist despite standardized perioperative care. However, prospective longitudinal evidence describing the early course of postoperative nutritional recovery remains limited. This study aimed to characterize nutritional recovery trajectories following curative [...] Read more.
Background: Nutritional deterioration is a common consequence of gastrectomy for gastric cancer and may persist despite standardized perioperative care. However, prospective longitudinal evidence describing the early course of postoperative nutritional recovery remains limited. This study aimed to characterize nutritional recovery trajectories following curative gastrectomy and to evaluate the influence of the extent of gastric resection on postoperative recovery. Methods: A prospective cohort of 239 consecutive patients undergoing curative-intent subtotal or total gastrectomy for gastric adenocarcinoma was followed between January 2022 and December 2025. The longitudinal complete-case analysis included 217 patients with available assessments at all three predefined time points: preoperatively (T0), at hospital discharge (T1), and three months after surgery (T3). Nutritional–immune biomarker trajectories were assessed preoperatively (T0), at hospital discharge (T1), and three months after surgery (T3) using serum albumin, total cholesterol, absolute lymphocyte count, and the Controlling Nutritional Status (CONUT) score. Longitudinal changes were evaluated using linear mixed-effects models with patient-specific random intercepts. Results: All evaluated nutritional–immune biomarkers changed significantly in an adverse direction after surgery, reaching their most unfavorable values at hospital discharge (all p < 0.001), followed by partial biochemical recovery at three months. Because albumin, lymphocyte count, and CONUT are influenced by the acute inflammatory and metabolic response to surgery, the discharge changes should not be interpreted as direct evidence of acute malnutrition. Nevertheless, none of the evaluated biomarkers returned to its preoperative value. Recovery between discharge and three months represented 65.6% of the initial decline for serum albumin, 50.5% for absolute lymphocyte count, 51.7% for total cholesterol, and 60.9% for the CONUT score. After adjustment for age, sex, neoadjuvant chemotherapy, baseline body mass index, ASA status, pathological T3–T4 stage, and major postoperative morbidity, total gastrectomy was associated with a greater early decline in absolute lymphocyte count at hospital discharge (β = −165.7 cells/mm3; 95% CI, −204.9 to −126.6; p < 0.001). This difference was no longer present at three months (p = 0.955). No significant time-by-gastrectomy interactions were observed for albumin, cholesterol, or corrected CONUT. Conclusions: Nutritional recovery following gastrectomy is a dynamic and prolonged process characterized by marked early nutritional–inflammatory biomarker changes and incomplete biochemical restoration at three months. Resection extent was not independently associated with persistently less favorable albumin, cholesterol, or corrected CONUT trajectories. The findings describe early biochemical changes and should not be extrapolated to body composition, functional recovery, micronutrient status, quality of life, or long-term survivorship. These findings apply primarily to patients who survived and completed the three-month follow-up. Full article
(This article belongs to the Section Clinical Nutrition)
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21 pages, 32278 KB  
Article
The Stiff Elbow Revisited: How Much Motion Can Surgery Really Restore?
by Mihai Tudor Gavrila, Traian Eduard Stanescu and Dinu Gartonea
Medicina 2026, 62(9), 1658; https://doi.org/10.3390/medicina62091658 - 29 Aug 2026
Viewed by 192
Abstract
Background and Objectives: Post-traumatic elbow stiffness is a disabling condition often resulting from a combination of capsular contracture, osseous impingement, and residual instability, rendering it exceptionally challenging to treat. The aim of this study was to evaluate the outcomes of a comprehensive [...] Read more.
Background and Objectives: Post-traumatic elbow stiffness is a disabling condition often resulting from a combination of capsular contracture, osseous impingement, and residual instability, rendering it exceptionally challenging to treat. The aim of this study was to evaluate the outcomes of a comprehensive surgical approach for the treatment of post-traumatic elbow stiffness. Materials and Methods: A retrospective case series of 20 consecutive patients treated between 2018 and 2025 was conducted. Etiologies included distal humeral fractures (n = 9), terrible triad injuries (n = 4), elbow dislocations (n = 3), olecranon fractures (n = 2), and neglected radial head fractures (n = 2). All patients underwent anterior and posterior arthrolysis with triceps tenolysis. Additional procedures included ligament reconstruction, radial head arthroplasty, anterior capsule repair, tricepsplasty, and ulnar nerve transposition when indicated. Elbow range of motion was assessed preoperatively and during follow-up at 2 weeks, 6 weeks, 3 months, 6 months, and 1 year postoperatively. Results: Mean flexion improved from 81.0° to 125.3°, while the extension deficit improved from 66.5° to 16.5°. Mean supination increased from 54.8° to 82.8°, and mean pronation from 67.0° to 84.5°. The mean flexion–extension arc improved from 14.5° to 108.8°, representing a mean gain of 94.3°. One transient sensory ulnar neuropathy and one case of postoperative triceps insufficiency requiring revision surgery were observed; one patient developed postoperative skin blistering following a posterior approach. Conclusions: Comprehensive, pathology-oriented surgical treatment resulted in substantial improvement in elbow motion and restoration of a functional range of movement. Full article
(This article belongs to the Special Issue Advances in Diagnosis and Treatment of Orthopedic Disorders)
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38 pages, 10323 KB  
Article
Automated Detection and Ordinal Severity Grading of Periapical Lesions on Panoramic Radiographs Using a Lesion-Preserving Tiling and Ordinal-Aware YOLO Framework
by Faruk Oztekin, Oguzhan Katar, Nurefsan Avci and Furkan Konus
Diagnostics 2026, 16(17), 2778; https://doi.org/10.3390/diagnostics16172778 - 29 Aug 2026
Viewed by 248
Abstract
Background/Objectives: Apical periodontitis is among the most prevalent dental pathologies, and its radiographic severity is graded on panoramic radiographs using the ordinal periapical index (PAI 3 < 4 < 5). Existing computer-aided systems typically treat these grades as unrelated classes and down-sample the [...] Read more.
Background/Objectives: Apical periodontitis is among the most prevalent dental pathologies, and its radiographic severity is graded on panoramic radiographs using the ordinal periapical index (PAI 3 < 4 < 5). Existing computer-aided systems typically treat these grades as unrelated classes and down-sample the radiograph to a fixed input, which erases the small periradicular radiolucencies that define early disease. This study evaluated a lesion-preserving, ordinal-aware YOLO framework for the simultaneous detection and severity grading of periapical lesions. Methods: A total of 3924 expert-annotated panoramic radiographs (PAI 3/4/5) were processed with an adaptive lesion-preserving tiling algorithm that mapped each radiograph onto native-resolution 640 × 640 tiles so that every lesion appeared intact within exactly one tile, yielding 4641 tiles. Six consecutive YOLO generations (YOLOv8, YOLOv9, YOLOv10, YOLO11, YOLO12, and YOLO26) were benchmarked under one identical pipeline on a locked hold-out test set of 985 lesions, of which 628 were PAI 3, 274 PAI 4, and 83 PAI 5. YOLO12m, which attained the highest point estimates and the smallest run-to-run variation, was then progressively augmented with an ordinal-aware detection loss, a high-resolution P2 head, severity class-weighting and test-time augmentation. Localization was measured with COCO mAP and severity grading with severity-weighted average precision (Sev-wAP), quadratic weighted kappa (QWK), a catastrophic off-by-two error rate, and per-grade recall. Results: Lesion-preserving tiling improved detection for every generation, raising the mAP@0.50 of YOLO12m from 0.494 to 0.615, the highest point estimate among the six generations, although the margin over the next two was within the resolution of this test set. Cumulatively adding the ordinal loss, the P2 head, severity weighting, and test-time augmentation raised mAP@0.50 to 0.664, mAP@0.50:0.95 to 0.333, Sev-wAP to 0.704, and QWK to 0.780. PAI 5 average precision rose from 0.268 to 0.331 and PAI 5 recall from 0.602 to 0.663, 55 of 83 severe lesions, while catastrophic confusion between mild and severe lesions stood at 0.41%, 4 of the 985 reference lesions. Conclusions: Coupling lesion-preserving tiling with ordinal severity-aware detection improves localization and severity-weighted precision by resolvable margins, shifts every severe-grade measure in a clinically preferable direction, and provides a reproducible reference protocol for comparing detector architectures on this task. Full article
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20 pages, 992 KB  
Article
Beyond the Operating Room? Cytology-Based Yield and Resource Utilization of Outpatient Versus Operating Room EBUS-TBNA Pathways
by Paolo Albino Ferrari, Cosimo Bruno Salis, Sabrina Sarais, Massimiliano Santoru, Matteo Pinna-Susnik, Sonia Nemolato, Fabiola Farci, Elisabetta Pusceddu, Alessandro Tamburrini, Oliver Harrison, Francesco Guerrera, Paraskevas Lyberis, Daniela Ledda, Graziano Carta, Laura Riva, Giuseppe Porcu, Stefano Marini, Paolo Siotto, Alessandro Giuseppe Fois and Antonio Macciò
Diagnostics 2026, 16(17), 2767; https://doi.org/10.3390/diagnostics16172767 - 28 Aug 2026
Viewed by 209
Abstract
Background/Objectives: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) can be performed via pathways that differ in anesthesia, setting, airway management, monitoring, recovery, and hospitalization. We compared an outpatient endoscopy suite pathway with sedation and spontaneous breathing, and an operating room pathway with general anesthesia [...] Read more.
Background/Objectives: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) can be performed via pathways that differ in anesthesia, setting, airway management, monitoring, recovery, and hospitalization. We compared an outpatient endoscopy suite pathway with sedation and spontaneous breathing, and an operating room pathway with general anesthesia and laryngeal mask ventilation, assessing cytology-based yield, sample adequacy, workflow, and costs. Methods: This single-center observational study included consecutive EBUS-TBNA procedures. Allocation was nonrandom and reflected workflow, operating room availability, complexity, airway/anesthetic considerations, and judgment. The primary endpoint was cytology-based diagnostic yield in the diagnostic cohort; staging outcomes included cytology distribution, sample adequacy, and positivity among adequate samples. Systematic diagnostic verification was not available for the entire cohort; however, postoperative nodal pathology was retrospectively retrieved when available in the staging cohort. Because verification remained incomplete and selectively available, sensitivity, specificity, negative predictive value, and overall diagnostic accuracy were not estimated. Results: Clinical outcome analyses included 447 procedures (319 diagnostic and 128 staging), while the administrative cost dataset included 533 completed procedures. Diagnostic yield was similar between pathways (108/229, 47.2% vs. 45/90, 50.0%; p = 0.740). In the staging cohort, sample adequacy was comparable (83/85, 97.6% vs. 39/42, 92.9%; p = 0.331), and positivity among adequate samples did not differ (21.7% vs. 20.5%; p = 1.000). Exploratory postoperative pathological nodal-stage data were available for 60/128 staging procedures; among 58 cases with interpretable EBUS-TBNA results, patient-level N-stage concordance was 44/58 (75.9%), and postoperative nodal upstaging occurred in 11/58 (19.0%). No prespecified intraprocedural composite adverse events were documented. Duration appeared shorter in operating room cases but, owing to incomplete differential recording, was descriptive only. Length of stay and costs were markedly higher in the operating room pathway. Conclusions: The pathways showed similar cytology-based outcomes but differed in hospitalization rates and costs. Nonrandom allocation and pathway heterogeneity preclude causal interpretation as a sedation-versus-general-anesthesia comparison. Prospective studies with standardized allocation, diagnostic verification, systematic capture of adverse events, and follow-up are warranted. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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16 pages, 11681 KB  
Article
Optimization of Posterior Fossa Image Quality Using Virtual Monoenergetic Reconstructions from Dual-Layer Spectral CT
by Helena Mellander Oxholm, Veronica Fransson, Björn M. Hansen, Birgitta Ramgren, Kristina Ydström, Teresa Ullberg and Johan Wassélius
Tomography 2026, 12(9), 120; https://doi.org/10.3390/tomography12090120 - 24 Aug 2026
Viewed by 154
Abstract
Background/Objectives: Beam-hardening artifacts from the skull base reduce image quality in routine non-contrast head CT, particularly in the posterior fossa. Virtual monoenergetic images (VMIs) reconstructed from dual-layer spectral CT have been shown to reduce these artifacts, but previous studies have generally been [...] Read more.
Background/Objectives: Beam-hardening artifacts from the skull base reduce image quality in routine non-contrast head CT, particularly in the posterior fossa. Virtual monoenergetic images (VMIs) reconstructed from dual-layer spectral CT have been shown to reduce these artifacts, but previous studies have generally been limited by small cohorts or evaluation of only a limited range of monoenergetic reconstructions. The aim of this study was to comprehensively evaluate image quality and posterior fossa artifact reduction across the monoenergetic spectrum in a large cohort of normal head CT examinations. Methods: Consecutive adult patients undergoing non-contrast head CT on a dual-layer spectral CT system were retrospectively included if no intracranial pathology was identified on clinical interpretation. Regions of interest were placed in predefined posterior fossa and supratentorial locations in conventional images and automatically propagated to VMIs reconstructed from 40 to 200 keV. Image noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), attenuation, and a posterior fossa artifact index were quantified. Two neuroradiologists independently performed qualitative image quality assessment. Results: A total of 188 examinations were included in the quantitative analysis and 40 in the qualitative assessment. Compared with conventional images, VMIs reconstructed at ≥50 keV demonstrated significantly reduced image noise in the posterior fossa together with a higher SNR, while the CNR was improved between 40 and 80 keV. Qualitative assessment likewise demonstrated superior overall image quality and reduced artifact severity, with the highest ratings generally obtained for reconstructions around 60 keV. Improvements became marginal above approximately 80 keV. Conclusions: Virtual monoenergetic reconstructions from dual-layer spectral CT improve posterior fossa image quality by reducing beam-hardening artifacts while maintaining favorable image noise and tissue contrast. Intermediate-energy reconstructions (approximately 50–70 keV) provide the most favorable balance between beam-hardening artifact reduction, image noise, and tissue contrast, supporting their use as an image optimization strategy for non-contrast head CT. Whether these technical improvements translate into improved diagnostic performance should be evaluated in future studies including patients with posterior fossa pathology. Full article
(This article belongs to the Section Neuroimaging)
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19 pages, 1100 KB  
Article
Repeated Exposure to Electroconvulsive Seizures Induces Autistic-Like Pathology in Mice
by Ri Jin Kang, Yujeong Kim, Dongpil Shin, Hyang-Sook Hoe, Bae Ji Hyun and Myoung Ok Kim
Clin. Transl. Neurosci. 2026, 10(3), 23; https://doi.org/10.3390/ctn10030023 - 21 Aug 2026
Viewed by 179
Abstract
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions, communication deficits, and excessive repetitive behaviors. While ASD has a strong genetic basis, growing evidence suggests that epileptic seizures may serve as environmental risk factors for ASD development. The high [...] Read more.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions, communication deficits, and excessive repetitive behaviors. While ASD has a strong genetic basis, growing evidence suggests that epileptic seizures may serve as environmental risk factors for ASD development. The high comorbidity between epilepsy and ASD (20–30%) suggests potential shared neurobiological mechanisms, yet the causal relationship remains poorly understood. To investigate the causal role of seizures in the development of ASD-like pathology, we exposed adolescent mice (3 weeks old) to electroconvulsive seizures (ECS) for 10 consecutive days. This repeated ECS exposure led to the emergence of autistic-like behaviors including significantly decreased sociability, increased repetitive self-grooming, enhanced marble burying behavior, and anxiety-like behaviors, without affecting general locomotor activity. Additionally, repeated exposure to ECS induced significant changes in glutamatergic neurotransmission in the mice’s prefrontal cortex and hippocampus, brain regions critically involved in social cognition and behavioral regulation. Interestingly, these changes occurred without alterations in other excitatory/inhibitory neuronal markers, suggesting a specific impact on glutamate receptor expression rather than a general disruption of excitatory/inhibitory balance. These findings suggest that repeated seizures may contribute to ASD-like symptoms by specifically affecting key glutamatergic neurotransmitter systems, providing insights into the neurobiological mechanisms underlying the comorbidity between epilepsy and autism. In addition, repeated ECS differentially regulated histone deacetylase (HDAC) transcripts in a region-specific manner and produced seizure-intensity-dependent transcriptomic signatures. Full article
15 pages, 1433 KB  
Article
Clinicopathological Predictors of Pathological Response and Survival in Older Patients Undergoing Perioperative FLOT Chemotherapy for Resectable Gastric and Gastroesophageal Junction Adenocarcinoma
by Aykut Özmen, Tuba Tahtalı, Gündüz Karaoğlan, Mehmet Kutlay, Ulviye Oflas, Tanju Kapağan, Nilüfer Bulut and Gökmen Umut Erdem
Medicina 2026, 62(8), 1612; https://doi.org/10.3390/medicina62081612 - 21 Aug 2026
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Abstract
Background and Objectives: Evidence regarding predictors of pathological response and long-term outcomes in older patients receiving perioperative FLOT chemotherapy for resectable gastric or gastroesophageal junction cancer remains limited. We aimed to identify factors associated with pathological response and survival in patients aged [...] Read more.
Background and Objectives: Evidence regarding predictors of pathological response and long-term outcomes in older patients receiving perioperative FLOT chemotherapy for resectable gastric or gastroesophageal junction cancer remains limited. We aimed to identify factors associated with pathological response and survival in patients aged ≥65 years treated with neoadjuvant FLOT. Materials and Methods: This retrospective single-center study included 86 consecutive patients (median age, 69 years; 72.1% male) aged ≥65 years with resectable gastric or gastroesophageal junction adenocarcinoma who underwent neoadjuvant FLOT chemotherapy followed by curative-intent gastrectomy. Major pathological response was defined as College of American Pathologists tumor regression grade (CAP TRG) 0–1. Logistic regression analyses were performed to identify predictors of pathological response. Disease-free survival (DFS) and overall survival (OS) were analyzed using the Kaplan–Meier method and Cox proportional hazards regression analyses. Results: Overall, 14 patients (16.3%) achieved a major pathological response. Body mass index (BMI) ≥ 25 kg/m2 (OR 5.13, p = 0.04) was independently associated with a major pathological response. During a median follow-up of 29.2 months, 39 patients (45.3%) developed recurrence and 35 (40.7%) died. ECOG performance status (ECOG PS) ≥ 1 was independently associated with both inferior DFS (HR = 2.76, p = 0.02) and OS (HR = 2.52, p = 0.045). In addition, ypN stage 2–3 (HR = 2.58, p = 0.008) was independently associated with worse DFS, whereas positive surgical margins were independently associated with worse OS (HR = 2.62, p = 0.02). Conclusions: In older patients with resectable gastric or gastroesophageal junction adenocarcinoma treated with perioperative FLOT chemotherapy, baseline BMI was independently associated with major pathological response, whereas ECOG PS and postoperative pathological factors were independently associated with survival. These findings highlight the importance of careful patient selection and individualized multimodal treatment in this population. Full article
(This article belongs to the Section Oncology)
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16 pages, 430 KB  
Article
Artificial Intelligence for Diagnosing Normal Anatomical Variants and Pathological Oral Mucosal Lesions: A Prospective Observational Study
by Ana Glavina, Marija Galešić, Bojan Poposki and Antonija Tadin
Medicina 2026, 62(8), 1610; https://doi.org/10.3390/medicina62081610 - 21 Aug 2026
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Abstract
Background and Objectives: Artificial intelligence (AI) is increasingly used in clinical dentistry, but its diagnostic accuracy for oral mucosal lesions based on clinical photographs remains insufficiently validated. This prospective observational study compared the Top-1 diagnostic accuracy of ChatGPT-4o and ChatGPT-5 in identifying [...] Read more.
Background and Objectives: Artificial intelligence (AI) is increasingly used in clinical dentistry, but its diagnostic accuracy for oral mucosal lesions based on clinical photographs remains insufficiently validated. This prospective observational study compared the Top-1 diagnostic accuracy of ChatGPT-4o and ChatGPT-5 in identifying normal anatomical variants and pathological oral mucosal lesions and evaluated their performance across anatomical sites. Materials and Methods: Seventy adults with either normal anatomical variants (n = 21) or pathological oral mucosal lesions (n = 49) were consecutively recruited at the Department of Dental Medicine, University Hospital of Split, Croatia. One standardized clinical photograph per patient was analyzed by ChatGPT-4o and ChatGPT-5 under image-only and image-plus-text conditions using identical prompts. The reference diagnosis was established by an oral medicine specialist, with histopathological examination (HPE) performed when clinically indicated. Diagnostic performance was assessed using Top-1 accuracy and McNemar’s test. Results: Both models showed low accuracy with image-only input, but performance improved significantly after clinical information was added (p < 0.001). Overall Top-1 accuracy increased from 19.0% to 69.0% for ChatGPT-4o and from 9.0% to 51.0% for ChatGPT-5. For normal anatomical variants, accuracy increased from 14.3% to 81.0% and from 14.3% to 76.2%, respectively. For pathological oral mucosal lesions, accuracy increased from 20.4% to 63.3% and from 6.1% to 40.8%, respectively. ChatGPT-4o showed numerically higher accuracy than ChatGPT-5, particularly for pathological oral mucosal lesions, but no statistically significant difference was found between the models in the corresponding paired comparisons. Conclusions: Diagnostic performance was limited with image-only input but improved substantially when standardized clinical information accompanied the images. The numerical differences between models, particularly for pathological oral mucosal lesions, may be clinically relevant but do not establish superiority or equivalence. Neither model can currently replace conventional clinical diagnosis, and AI should be regarded as a clinical decision-support tool for evaluating oral mucosal lesions. Full article
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16 pages, 1605 KB  
Article
Post-COVID Syndrome in Patients with Chronic Diseases: Clinical Factors Associated with Its Presence in a Real-World Clinical Cohort
by Timur Tastaibek, Nurlan Jainakbayev and Nargiza Nassyrova
COVID 2026, 6(8), 149; https://doi.org/10.3390/covid6080149 - 21 Aug 2026
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Abstract
Background/Objectives: Post-COVID syndrome (PCS) remains a clinically heterogeneous condition. In patients with chronic diseases, real-world evidence is needed to describe its frequency and to identify clinical factors associated with its current presence. This study assessed the prevalence of PCS and factors associated [...] Read more.
Background/Objectives: Post-COVID syndrome (PCS) remains a clinically heterogeneous condition. In patients with chronic diseases, real-world evidence is needed to describe its frequency and to identify clinical factors associated with its current presence. This study assessed the prevalence of PCS and factors associated with current PCS status among patients with chronic diseases. Methods: This observational cross-sectional study included a consecutively enrolled source clinical sample of 850 adults receiving inpatient or outpatient care in Almaty and the Almaty Region between June and December 2025. The primary analytic cohort comprised participants with documented prior COVID-19 (n = 250). PCS was assessed at study enrollment according to the national clinical protocol as current symptoms persisting for more than 12 weeks and not explained by an alternative diagnosis. Multivariable logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). COVID-19 vaccination was excluded from the primary model and evaluated only in a sensitivity analysis because vaccination timing relative to infection was unavailable. The exploratory association-based probability model was evaluated using the AUC with 95% CI, Brier score, calibration assessment, bootstrap internal validation with 1000 resamples, assessment of age nonlinearity, and decision curve analysis. Results: PCS was identified in 147 of 250 participants with prior COVID-19 (58.8%). In the revised primary multivariable model, age (OR = 1.24 per 10-year increase; 95% CI: 1.01–1.54; p = 0.040) and endocrine diseases (OR = 3.36; 95% CI: 1.69–6.98; p < 0.001) remained associated with current PCS status. The association with endocrine diseases persisted after adjustment for body mass index. The apparent AUC was 0.687 (95% CI: 0.620–0.753), and the Brier score was 0.218. Bootstrap internal validation yielded an optimism-corrected AUC of 0.655, a calibration intercept of 0.061, and a calibration slope of 0.816. Conclusions: PCS was frequent among patients with chronic diseases who had prior COVID-19. Older age and endocrine pathology were the most consistent factors associated with current PCS status. All model-performance estimates were obtained within the development sample; the model should not be used for individual prediction or follow-up planning without prospective external validation. Full article
(This article belongs to the Special Issue Long COVID: Pathophysiology, Symptoms, Treatment, and Management)
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16 pages, 838 KB  
Article
Clinicopathological, Molecular, and Economic Outcomes of Bethesda III and IV Thyroid Nodules Following Implementation of a Publicly Funded ThyroSeq v3 Program: A Retrospective Two-Center Cohort Study
by Gianluca Savoia, Sarah B. Payne, Matthew Vaitzner, Saruchi Bandargal, Michael P. Hier, Marco A. Mascarella, Keith Richardson, Alex Mlynarek, Nader Sadeghi, Sabrina Daniela Silva Wurzba, Rawan Azzam, Elliot J. Mitmaker, Brian M. Gilfix, Marc Pusztaszeri, Véronique-Isabelle Forest and Richard J. Payne
Cancers 2026, 18(16), 2695; https://doi.org/10.3390/cancers18162695 - 20 Aug 2026
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Abstract
Background/Objectives: Since 2021, indeterminate thyroid nodules have been routinely assessed using molecular testing through Quebec’s provincial ThyroSeq v3 pilot project. The primary objective of our study was to compare the molecular and clinicopathological characteristics of Bethesda III and Bethesda IV thyroid nodules [...] Read more.
Background/Objectives: Since 2021, indeterminate thyroid nodules have been routinely assessed using molecular testing through Quebec’s provincial ThyroSeq v3 pilot project. The primary objective of our study was to compare the molecular and clinicopathological characteristics of Bethesda III and Bethesda IV thyroid nodules evaluated through the pilot project. The secondary objective was to assess the program’s economic impact. Methods: This retrospective study included 934 patients (mean age 55.7 ± 14.3 years; 79.3% female; mean nodule size 2.2 ± 0.8 cm) from two McGill University teaching hospitals in Quebec, comprising 593 Bethesda III and 341 Bethesda IV nodules that underwent molecular testing between 2021 and 2025. Eligible nodules were TI-RADS 3 or 4, measured 1–4 cm, and Bethesda III nodules required two consecutive cytology results before testing. Clinicopathological characteristics, histopathological diagnoses, molecular findings, and mutational profiles were analyzed. A projected 10-year cost analysis was also performed. Results: Of the 934 nodules tested, 280 demonstrated a genetic alteration. The risk of malignancy among surgically resected ThyroSeq v3-positive Bethesda III and IV nodules was 68% and 78%, respectively. Compared with Bethesda III nodules, Bethesda IV nodules demonstrated significantly greater vascular invasion (p = 0.029) and prevalence of oncocytic carcinomas (p = 0.010). Molecular testing was associated with an estimated reduction of 1.49 million Canadian dollars in healthcare costs over 10 years. Conclusions: Although Bethesda IV nodules exhibited more oncocytic carcinomas and invasion, molecular mutation class distribution and the prevalence of aggressive pathological features were similar between Bethesda categories. Together with the demonstrated economic savings, these findings support continued implementation of publicly funded ThyroSeq v3 testing to improve management of indeterminate thyroid nodules while reducing unnecessary surgery. Full article
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