High-grade pulmonary neuroendocrine carcinoma (HGNEC-L), including SCLC and LCNEC, is aggressive and usually treated according to SCLC paradigms. The clinical relevance of de novo actionable genomic alterations (AGA) remains incompletely defined.

We performed a retrospective multicenter analysis of advanced HGNEC-L with de novo AGA, assessing rwORR, rwDCR, rwPFS, and OS. Findings were contextualized by a structured literature review and exploratory pooled reconstructed-IPD Cox analysis, with targeted therapy modeled as a source-stratified time-dependent covariate.

Ten patients from four tertiary centers were included. Most were women (90.0%) and never-smokers (70.0%); histology was LCNEC in 60.0% and SCLC/mixed SCLC in 40.0%. AGA included EGFR mutations (n = 6), EML4-ALK fusions (n = 2), KIF5B-RET fusion (n = 1), and KRAS p.G12C (n = 1). Targeted-containing regimens achieved rwORR 77.8%, rwDCR 88.9%, and median rwPFS 9.0 months (95% CI, 2.0-18.7), as opposed to 3.7 months for ICI-containing regimens and 2.6 months for chemotherapy alone. Median OS for the entire cohort was 17.2 months (95% CI, 4.8-36.3); overall survival did not differ significantly between patients with and without targeted-containing exposure (19.0 vs. 17.2 months; log-rank p = 0.50). In pooled reconstructed-IPD time-dependent Cox analysis (72 patients, 39 deaths), targeted therapy showed a favorable but non-significant OS association (HR, 0.89; 95% CI, 0.31-2.56; p = 0.831), maintained directionally in the age/sex-adjusted subset (HR, 0.54; 95% CI, 0.16-1.77; p = 0.306).

De novo AGA-positive HGNEC-L represents a clinically relevant subgroup with potential sensitivity to genotype-matched targeted therapy, supporting comprehensive molecular profiling and early targeted therapy consideration.

Breast cancer is the most frequent malignant neoplasm in women and presents marked biological heterogeneity. The androgen receptor (AR) has emerged as a biomarker with important prognostic and therapeutic implications, its effect varying according to the molecular subtype. The objective of this study was to analyze AR expression in breast carcinoma samples and its relationship with the different molecular subtypes and clinicopathological variables.

An observational, descriptive, cross-sectional, and prospective study was conducted based on the immunohistochemical analysis of 215 formalin-fixed, paraffin-embedded breast carcinoma samples. AR expression was digitally evaluated as the percentage of positive tumor cells after incubation with an anti-AR monoclonal antibody.

A high frequency of AR expression was demonstrated in the cohort, with a median of 53.3%. There were statistically significant differences between molecular subtypes (p < 0.001), detecting greater expression in luminal tumors and markedly low levels in triple-negative breast cancer (TNBC) (median 0.41%). A significant negative correlation was evidenced between AR expression and the Ki-67 proliferation index (ρ = -0.272; p < 0.001), both in the overall sample and in the TNBC subgroup.

The androgen receptor is associated with specific molecular subtypes and lower tumor proliferation, suggesting a less aggressive phenotype and supporting its role as a biological biomarker and potential therapeutic target in the management of breast cancer.

Background: Large loop excision of the transformation zone (LLETZ) is an established surgical procedure for cervical intraepithelial neoplasia; however, secondary postoperative bleeding may lead to unplanned outpatient visits, hospitalization, or surgical intervention. This study aimed to evaluate the incidence and risk factors of postoperative bleeding after LLETZ. Methods: We conducted a retrospective single-center cohort study comprising 1493 patients who underwent LLETZ for the treatment of cervical dysplasia between January 2008 and May 2023 at the Medical University of Vienna. Postoperative bleeding was defined as an unscheduled outpatient presentation for bleeding from the operative site within eight weeks after LLETZ requiring additional treatment. Clinical, surgical and histopathological parameters were analyzed. Univariable logistic regression was performed to identify factors associated with postoperative bleeding, with additional stratified analyses according to the use of intraoperative cervical infiltration. Results: Postoperative bleeding occurred in 56 patients (3.8%). The median time to bleeding was 13.5 days (IQR 9.0-17.0). Among patients with postoperative bleeding, 20 (35.7%) required hospitalization, 10 (50.0%) underwent operative intervention, and 2 (10.0%) required blood transfusion. In logistic regression, increasing cone length was associated with higher odds of postoperative bleeding (OR 1.83 per cm, 95% CI 1.06-3.18, p = 0.031). Anticoagulation and/or antiplatelet therapy was also associated with an increased bleeding risk (OR 3.61, 95% CI 1.46-8.96, p = 0.006). Higher BMI was associated with lower odds of postoperative bleeding (BMI per +5 kg/m²: OR 0.62, 95% CI 0.43-0.90, p = 0.011). Conclusions: LLETZ is associated with a low risk of clinically relevant postoperative bleeding, with an unplanned outpatient re-presentation rate of 3.8% and a re-operation rate of 0.7%. Increased cone length and anticoagulation and/or antiplatelet therapy were associated with higher bleeding rates. Larger prospective studies are needed to validate these findings and improve individualized perioperative risk assessment.

Background/Objectives: Actinic keratosis is an intraepithelial lesion that may progress into squamous cell carcinoma; therefore, all lesions should be treated. The study aimed to investigate the potential correlations between patient and lesion characteristics, treatment option choice, and clinical outcomes, analyzing long-term real-world data. Methods: A retrospective study was conducted in a specialized hospital in Milan. Data on patients with actinic keratoses were collected from January 2018 to July 2024. Results: A total of 369 patients were included, with normal weight (58%), higher educational level (83%), personal skin cancer history (51%), childhood sunburns (68%), and face localization (70%), with multiple contiguous distribution (54%) of lesions. In total, 45.5% received multiple treatments. Field-directed therapies were prescribed in 84% of cases (32% of complete clearance). A total of 43% were lost to follow-up. Higher educational level, personal and familiar skin cancer history, previous atypical naevus excision, higher naevus count, and multiple treatments (p < 0.05) were associated with regularity in visit attendance. In multivariable analysis, immunosuppression (OR = 5.01 [0.97, 29.5], p = 0.056) and multiple contiguous lesions (OR = 4.62 [1.75, 14.7], p = 0.004) were found to be significantly associated with incomplete clinical response. Conclusions: Real-world data on patients with actinic keratoses may help identify more personalized management strategies that influence treatment outcomes and adherence to follow-up.

Background: Endoscopic risk assessment of glottic lesions is examiner-dependent. This prospective single-center diagnostic evaluation study assessed the real-time analytical performance of the CE-MDR Class IIb-certified Zeno AI system during structured flexible laryngoscopy. Methods: A total of 109 patients underwent protocol-based flexible laryngoscopy. Post-epiglottic visualization of the glottic level and additional acquisition characteristics were documented systematically. Three experienced examiners independently classified each case as morphologically unremarkable, benign, or malignant/suspicious; majority vote served as the expert reference. Zeno AI classified findings as unremarkable, benign, malignant, or uncertain. The system was evaluated in shadow mode, and AI outputs were included only when the same classification remained stable for at least three seconds. The primary analysis assessed agreement between Zeno AI and the expert majority using Cohen's κ. Interobserver agreement among the examiners was assessed using Fleiss' κ. Diagnostic performance against histopathology was evaluated secondarily in operated patients using a primary intent-to-diagnose analysis and a secondary definitive-output analysis. Results: Expert majority classified 64/109 findings as unremarkable, 34/109 as benign, and 11/109 as malignant/suspicious. AI classified 65/109 as unremarkable, 26/109 as benign, 12/109 as malignant, and 6/109 as uncertain. Excluding uncertain outputs, AI and the expert majority agreed in 99/103 cases (96.1%; κ = 0.927). Histopathology was available in 36 patients, with 27 findings negative for malignancy and 9 positive for malignancy. In the primary intent-to-diagnose analysis, treating uncertain outputs as test-negative, sensitivity was 88.9%, specificity 92.6%, PPV 80.0%, and NPV 96.2%. In the secondary analysis restricted to definitive AI outputs, sensitivity was 100%, specificity 91.7%, PPV 80.0%, and NPV 100%. No finding positive for malignancy was classified as benign; one high-grade dysplasia was classified as uncertain. Conclusions: Zeno AI showed high agreement with expert assessment during structured flexible laryngoscopy. However, its potential clinical benefit was not evaluated in this shadow-mode study. Uncertain outputs should be regarded as non-definitive and require expert assessment, while histopathology remains essential for definitive diagnosis.

Breast and ovarian cancer are among the most common neoplasms in women, and germline variants in the BRCA1 gene markedly increase the risk of developing them. Despite existing studies, the frequency and spectrum of BRCA1 variants in women from Jalisco, Mexico, remain underexplored.

To identify and characterize BRCA1 variants in a cohort of Mexican women with breast and ovarian cancer, and to assess their functional and splicing consequences through computational analysis.

Genomic DNA from 228 women with breast and/or ovarian cancer, selected by clinical criteria suggestive of hereditary cancer, was analyzed by next-generation sequencing. The functional impact of point variants was predicted with Ensembl VEP, SIFT, PolyPhen-2, REVEL, CADD, and AlphaMissense, and their effect on splicing was evaluated with SpliceAI, using the MANE Select canonical transcript (NM_007294.4).

BRCA1 variants were identified in 14.0% of this screening-enriched cohort, with carrier proportions of 16.2% in ovarian and 13.6% in breast cancer; these figures reflect a selected series and do not represent population prevalence. Breast cancer carriers showed a younger age at diagnosis, a higher proportion of the triple-negative phenotype, and a stronger family history. Fourteen-point variants and four large rearrangements were detected, with a predominance of truncating loss-of-function alterations. The recurrent missense variant c.5123C>A (p.Ala1708Glu), located in the BRCT1 domain, was the most relevant finding, present in 28.1% of carriers (9/32). The computational analysis did not reclassify variants on its own but provided complementary evidence (PP3/BP4) consistent with current classifications: it allowed reannotation of c.5243G>A from nonsense to missense, supported the pathogenic nature of the intronic splice variant c.4987-3C>A, and was concordant with the likely benign interpretation of c.2735A>G, while c.3367G>T remained of uncertain significance.

This cohort from Western Mexico harbors a distinctive spectrum of BRCA1 variants, including the recurrent c.5123C>A variant, which may reflect a regional founder effect warranting haplotype analysis. These findings underscore the need for local evidence and for genetic panels adapted to the Mexican population, to enable accurate and equitable variant interpretation and access to targeted therapies such as PARP inhibitors.

Osteochondroma is the most common benign bone tumor in childhood. Although most lesions are asymptomatic, surgical treatment is indicated in patients with pain, mechanical symptoms, cosmetic concerns, restricted range of motion, or neurovascular compression. This study evaluated the clinical characteristics and surgical outcomes of osteochondromas in children and adolescents treated at a single tertiary pediatric surgery center.

This retrospective study included 75 pediatric patients who underwent surgical excision of osteochondroma between January 2015 and January 2026. Demographic, clinical, radiological, operative, histopathological, and follow-up data were analyzed. Lesion-related variables were assessed at the level of individual exostoses. The primary outcome was surgical treatment outcome, while secondary outcomes included lesion localization, symptoms, hospital stay, postoperative complications, recurrence, and associations between clinical and morphological variables.

A total of 75 patients with 76 solitary osteochondromas were included. The median age was 13 years, and 64.0% of patients were male. Most lesions were located distally (73.7%), with the femur being the most common site (48.7%), followed by the tibia (22.4%). Pain was the most frequent symptom, present in 63.2% of exostoses, followed by cosmetic concern in 32.9%. Standard radiography was used in nearly all cases (98.7%). Radiographic measurements significantly underestimated lesion size compared with intraoperative measurements, with median diameters of 3.0 cm and 4.0 cm, respectively (p < 0.001). A strong positive correlation was observed between radiographic and intraoperative lesion diameter (ρ = 0.77; p < 0.001), while symptom duration showed a weak but significant correlation with lesion diameter (ρ = 0.28; p = 0.013). No significant association was found between lesion diameter and symptomatic presentation, and logistic regression did not identify age, sex, lesion location, or diameter as significant predictors of symptoms. Postoperative outcomes were favorable: 94.6% of patients had no complications, wound infection and hematoma occurred in 2.7% each, and no recurrences or reoperations were recorded during a median follow-up of 63 months. Histopathological examination confirmed osteochondroma in all cases.

Surgical excision of symptomatic pediatric osteochondromas was associated with favorable postoperative outcomes, a low complication rate, and no observed recurrence during follow-up. Standard radiography correlates well with intraoperative findings but may underestimate true lesion size, likely due to limited visualization of the cartilaginous cap. Symptom development appears multifactorial and cannot be reliably predicted by lesion size or location alone.

Background: Socioeconomic deprivation is a well-established determinant of participation in colorectal cancer (CRC) screening. However, less is known about the geographic clustering of screening adherence and whether spatial inequalities mirror regional patterns of socioeconomic disadvantage. This study investigated the association between socioeconomic deprivation and adherence to CRC screening across Italian regions and explored the presence of spatial autocorrelation using geographic analytical methods. Methods: We conducted a nationwide ecological cross-sectional study including 21 Italian regional units. Pearson correlation analysis was performed to explore associations between colorectal cancer (CRC) screening adherence, primary care physician (PCP) workload and socioeconomic deprivation. Multivariable linear regression was used after assessment of multicollinearity using variance inflation factors (VIFs). Sensitivity analyses included alternative deprivation indicators and leave-one-region-out analyses. Spatial dependence was evaluated using Global Moran's I and Local Indicators of Spatial Association (LISA). Results: CRC screening adherence showed substantial geographic variability across Italy, with higher participation in northern regions and lower participation in southern areas. Screening adherence was inversely associated with socioeconomic deprivation. Sensitivity analyses confirmed the robustness of the association across alternative deprivation measures and sequential exclusion of each regional unit. Spatial analysis demonstrated significant positive spatial autocorrelation (Moran's I = 0.275; p = 0.039), indicating that neighbouring regions tended to exhibit similar screening behaviours. LISA analysis identified significant High-High clusters in northern Italy, Low-Low clusters in southern and insular regions, and isolated spatial outliers, highlighting persistent territorial inequalities in preventive healthcare utilisation. Conclusions: Regional disparities in CRC screening participation were associated with socioeconomic deprivation and modest but significant spatial clustering. These findings provide a regional-level description of inequalities in screening participation and may help inform future public health strategies aimed at reducing disparities in organised colorectal cancer screening.

Although cervical cancer is a highly preventable malignancy, Romania continues to report critical mortality rates. This paradox is largely attributable to the suboptimal implementation of clinical guidelines and a passive, "opt-in" administrative framework. This cross-sectional study investigates the cognitive and behavioural determinants-specifically, human papillomavirus (HPV) knowledge, institutional trust in healthcare systems, and digital misinformation exposure-that modulate female attitudes toward HPV immunisation.

An observational cross-sectional study was conducted between December 2025 and March 2026 across four obstetrics and gynaecology clinics. Data were collected via digital questionnaires administered to adult female patients aged 18 to 65 years. The assessment tool evaluated four primary domains: HPV knowledge, perceived vaccine safety, immunisation intention, and the degree of exposure to social media misinformation.

The cohort demonstrated a substantially low vaccination rate (28.6%). Statistical analysis elucidated significant positive correlations between HPV knowledge, trust in health authorities, and vaccination intention. Furthermore, reliance on official information sources strongly correlated with perceived vaccine safety. Conversely, exposure to negative online content exhibited a weak negative association with knowledge levels, yet it did not directly influence vaccination intention.

Health literacy and institutional trust emerge as fundamental pillars for HPV vaccine acceptance. To overcome patient vaccine hesitancy, the national healthcare system must initiate a strategic paradigm shift, prioritising the neutralization of digital misinformation and transitioning from a passive model to a proactive, "opt-out" infrastructure.

Osteoradionecrosis of the jaw (ORNJ) remains a major late complication of head and neck radiotherapy, and risk assessment relies mainly on clinical and dosimetric factors. We constructed the Host Tissue Repair Vulnerability Index (HTRVI), a composite biomarker integrating inflammatory, immune-nutritional, and oxygenation-related parameters, to estimate biological susceptibility to ORNJ in locally advanced nasopharyngeal carcinoma (LA-NPC).

This retrospective cohort included 261 LA-NPC patients treated with definitive concurrent chemoradiotherapy between 2010 and 2021. HTRVI was calculated as (CRP × platelet × neutrophil)/(albumin × lymphocyte × hemoglobin). HTRVI was compared with hemoglobin (Hb) and the Global Immune-Nutrition-Inflammation Index (GINI) using receiver operating characteristic analysis. Multivariable logistic regression, restricted cubic spline analysis (RCS), and bootstrap resampling assessed independent association, continuous risk relationship, and internal validation.

During a median follow-up of 63.8 months, 24 patients (9.2%) developed ORNJ. HTRVI showed superior discrimination (AUC, 0.864; 95% CI, 0.769-0.932) compared with Hb (AUC, 0.785; p = 0.001) and GINI (AUC, 0.759; p = 0.045). HTRVI remained independently associated with ORNJ after adjustment for mandibular mean dose and post-CCRT tooth extraction burden (OR per standard deviation increase, 4.81; 95% CI, 1.10-20.99; p = 0.037). RCS analysis showed a significant continuous association between HTRVI and ORNJ risk (P_overall < 0.001) without nonlinearity (P_nonlinear = 0.736). Internal validation showed minimal optimism (bootstrap-corrected AUC, 0.993).

HTRVI was independently associated with ORNJ and provided additional predictive information beyond established clinical and dosimetric factors in this single-center cohort. The continuous HTRVI-ORNJ association supports a biological continuum model of host tissue repair vulnerability. However, HTRVI should currently be regarded as an investigational biomarker requiring independent external and prospective validation before clinical implementation.