Citations

BACKGROUND: Hemorrhagic risk in dural arteriovenous fistulas (dAVFs) is largely determined by venous anatomy, but the contribution of systemic cardiovascular factors and their medical therapy remains poorly defined. This study examined associations between cardiovascular risk factors and antithrombotic use and hemorrhagic presentation, angiographic obliteration, and early functional outcomes after treatment. METHODS: We analyzed 1350 adults with intracranial dAVFs from the international Consortium for Dural Arteriovenous Fistula Outcomes Research registry, which retrospectively accrued cases across 14 centers in 4 countries between 1990 and 2017. Demographics, cardiovascular comorbidities, antithrombotic use, angioarchitectural features, treatment strategies, and follow-up outcomes were collected from prospectively maintained databases. Primary end points were hemorrhagic presentation, angiographic obliteration, and 90-day functional status after treatment. Univariable and multivariable logistic regressions were performed with model-specific adjustments. RESULTS: Hemorrhage occurred in 375 patients (27.8%) and was most strongly associated with high-grade dAVF classification and male sex; antithrombotic therapy was associated with lower odds of hemorrhagic presentation. Other cardiovascular risk factors showed no independent relationship with bleeding. Angiographic obliteration was achieved in 621 of 845 patients (73.5%). Hemorrhagic onset, high dAVF grade, and surgical treatment were independently associated with angiographic obliteration, whereas smoking and embolization demonstrated only nonsignificant trends after adjustment. At 90 days, 934 patients (88.9%) were functionally independent. Baseline modified Rankin Scale score was the strongest factor associated with 90-day functional outcome, while neither cardiovascular comorbidities nor treatment modality independently influenced functional status. CONCLUSIONS: In this large multicenter dAVF cohort, hemorrhagic presentation was most strongly associated with venous angioarchitecture. Male sex and antithrombotic therapy were also independently associated with hemorrhagic presentation. Angiographic obliteration was common, particularly among surgically treated lesions, and 90-day functional outcome was most strongly associated with baseline functional status.

ABSTRACT Myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) are clonal myeloid neoplasms shaped by genetic lesions and immune dysregulation, both of which contribute to disease progression and poor outcomes. Existing prognostic systems, such as IPSS‐R and IPSS‐M, do not incorporate immune alterations. We assessed the biological and clinical relevance of an immune dysfunction signature (IDS) across multi‐center MDS and CMML cohorts. IDS scores, derived from bulk transcriptomic data, were significantly associated with inferior leukemia‐free and overall survival. In multivariable analyses, IDS retained independent prognostic value alongside IPSS‐R, IPSS‐M, and bi‐allelic TP53 inactivation. Incorporation of IDS into existing models improved prognostic discrimination and time‐dependent predictive accuracy. Longitudinal analyses revealed that rising IDS scores paralleled disease progression and acute transformation, whereas declining scores were observed in remission. Biologically, IDS‐high cases demonstrated reduced cytotoxic T‐cell activity, expansion of regulatory T cells, enrichment of primitive progenitor signals, and increased expression of checkpoint pathway genes. These findings were validated across multiple independent MDS cohorts and consistently reproduced in CMML, where IDS also stratified risk and tracked disease evolution. Finally, integration with drug response signatures from the BeatAMLv2 cohort suggested potential therapeutic vulnerability of IDS‐high cases to multikinase and NF‐κB pathway inhibitors. These results establish IDS as a robust and dynamic biomarker in MDS and CMML, with applications in refined risk stratification, longitudinal disease monitoring, and guiding personalized therapeutic strategies targeting immune dysfunction. Trial Registration: #201709072RINC, #202109078RINB, #202207050RINB

Abstract Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) and alveolar macrophage pneumonia (AMP) are two rare but closely related conditions within the spectrum of smoking-related interstitial pneumonias. Both share characteristic histopathologic features, including the accumulation of pigmented alveolar macrophages alongside varying degrees of interstitial inflammation and fibrosis. RB-ILD is typically a localized, bronchiolocentric process often found in smokers, whereas AMP represents a more diffuse and clinically significant disease that may arise not only from tobacco smoke but also from other causes such as occupational exposures, autoimmune diseases, and drug reactions. This review highlights the clinical presentation, imaging findings, histopathology, and treatment of both entities, emphasizing their overlapping features as well as key distinctions. We further discuss the pathogenic mechanisms driven by cigarette smoke—including oxidative stress, immune activation, and fibrosis—that underlie these diseases. A clear understanding of the similarities and differences between RB-ILD and AMP is essential for accurate diagnosis, effective management, and prognostication, particularly in patients with a history of smoking and diffuse parenchymal lung involvement.

ABSTRACT Background This exploratory analysis of the NEURO‐TTRansform Phase 3 trial evaluated the efficacy of eplontersen in patients with hereditary transthyretin (ATTRv) amyloidosis with polyneuropathy by genetic variant. Methods Changes from baseline in NEURO‐TTRansform primary endpoints serum transthyretin (TTR) at Week 65, modified Neuropathy Impairment Score+7 (mNIS+7) composite score, and Norfolk Quality of Life‐Diabetic Neuropathy (Norfolk QoL‐DN) total score at Week 66 were evaluated in patients with early‐onset (aged < 50 years) and late‐onset (aged ≥ 50 years) Val30Met (p.Val50Met) or non‐Val30Met ATTRv amyloidosis with polyneuropathy. Secondary endpoints from NEURO‐TTRansform were also evaluated by genetic variant. Results In total, 144 patients with early‐onset ( n = 54) or late‐onset ( n = 31) Val30Met or non‐Val30Met ( n = 59), ATTRv amyloidosis with polyneuropathy were randomized to eplontersen. A further 60 patients from NEURO‐TTR with early‐onset ( n = 16) or late‐onset ( n = 17) Val30Met or non‐Val30Met ( n = 27), served as a historical placebo group. The mean percentage difference (95% confidence interval) in serum TTR was −79.9 (−87.8, −72.0), −85.0 (−93.3, −76.6), and −70.6 (−77.7, −63.5) with eplontersen versus placebo in the early‐ and late‐onset Val30Met, and non‐Val30Met groups, respectively. Across subgroups, the change from baseline to Week 66 in mNIS+7 composite score was generally well maintained, and the Norfolk QoL‐DN total score improved with eplontersen versus worsening with placebo. The Polyneuropathy Disability score was maintained in most patients. From baseline to Week 65, the modified body mass index was maintained with eplontersen compared to a marked reduction (worsening) for placebo. Conclusions Findings were suggestive of consistent benefits in reducing neuropathy impairment and improving QoL with eplontersen versus historical placebo, across TTR variants. Trial Registration ClinicalTrials.gov: NCT04136184, NCT01737398

Abstract Background Photon‐counting‐detector (PCD) CT systems offer ultra‐high spatial resolution, yet the visual spatial resolution on clinical images often constrained by large pixel size, yielding resolutions below system capabilities. While reducing pixel size and using sharp kernels enhance visual spatial resolution, it increases noise, compromising image quality. Purpose To investigate the combined effects of pixel size and reconstruction kernels on visual spatial resolution using phantom and clinical images and to develop a dedicated high‐resolution deep convolutional neural network (HR‐CNN) to better utilize the intrinsic high spatial resolution of PCD‐CT in clinical imaging. Methods The relationship between spatial resolution, reconstruction kernel, and pixel size was investigated to identify strategies for utilizing the full spatial resolution potential of PCD‐CT. To overcome the increased noise associated with high‐resolution settings, a dedicated HR‐CNN was developed to push the limit of spatial resolution in routine PCD‐CT exams. The HR‐CNN was trained using patient exams acquired with ultra‐high‐resolution (UHR) mode and reconstructed with a 150‐mm field of view (FOV), matrix size of 1024×1024 (0.15‐mm pixel size) and sharpest quantitative kernel (Qr89). The impact of FOV, kernel, and denoising on spatial resolution was studied using bar‐pattern phantoms and a pilot clinical evaluation including 5 patients with interstitial lung diseases. Two thoracic radiologists evaluated 4 different FOV/reconstruction conditions: (1) FOV‐410/Qr56‐Iterative reconstruction (IR), (2) FOV‐410/Qr89‐IR, (3) FOV‐150/Qr89‐IR, and (4) FOV‐150/Qr89‐HR‐CNN in terms of overall image quality, noise, visual spatial resolution, and overall preference. Results With a FOV of 410 mm, the Qr89 sharp kernel displayed bar‐patterns up to 14 lp/cm, not much higher than the routine lung kernel Qr56. When the FOV was reduced to 150 mm, Qr89‐IR allowed for the visualization of line pair patterns ranging from 18 to 20 lp/cm, with 20 lp/cm being moderately discernible. The application of Qr89‐HR‐CNN yielded further improvement, enabling the display of line pair patterns as high as 20–22 lp/cm. In patient cases, both radiologists consistently ranked the FOV‐150 images processed with HR‐CNN as superior across metrics including overall image quality, noise reduction, visual spatial resolution, and overall preference. The HR‐CNN reduced the noise in patients’ images by 93.0 ± 0.6% and 44.9 ± 5.3% in comparison with the original FBP and IR images, respectively. Conclusions The spatial resolution of PCD‐CT is not maximized in routine practice due to the large FOV and high noise levels at sharp kernels. The proposed HR‐CNN denoising method, along with small pixel size, may allow the high spatial resolution toward the system limit to be implemented in practice, which is beneficial in the diagnosis of many diseases, including interstitial lung disease.

PURPOSE Chronic myelomonocytic leukemia (CMML) is a rare myeloid neoplasm characterized by clinical heterogeneity and is associated with poor outcomes. To date, limited molecular information has been incorporated into disease classification and risk stratification. We aimed to integrate genomic features into the clinical decision-making process for CMML. PATIENTS AND METHODS We analyzed a retrospective cohort of 3013 patients with CMML (training set) and a prospective population of 516 patients (validation set). Using an innovative framework for multimodal data analysis, we developed molecular-based disease taxonomy and prognostication. RESULTS Unsupervised clustering identified nine entities with distinct genomic features and outcomes ( P < .001), including splicing machinery, transcription factors, signal transduction and tyrosine kinase pathways aberrations, and high-risk molecular signatures. Notably, 15% of patients showed molecular/clinical overlap with other myeloid neoplasms. We integrated molecular and clinical information to build the international CMML Prognostic Scoring System (iCPSS), incorporating mutations in nine genes together with hematologic parameters and cytogenetic abnormalities. The iCPSS identified five groups with distinct probability of overall and leukemia-free survival in both training and validation cohorts ( P < .001), outperforming existing prognostic models. Importantly, 55% of patients were reassigned to higher or lower risk groups by the iCPSS. Decision analysis demonstrated that iCPSS could refine the optimal timing of allogeneic transplantation at the individual level; compared with conventional prognostic tools, iCPSS-based decision modeling changed transplantation strategy in 31% of cases, resulting in a significant gain-in-life expectancy for eligible patient population ( P < .001). A federated learning platform was implemented to enable continuous, privacy-preserving model update across multiple centers. CONCLUSION Molecular information improves CMML classification and prognostication, supports more effective clinical decision making, and potentially refines the design of clinical trials.

Background: ASCO recommends extended venous thromboembolism (VTE) prophylaxis with low-molecular-weight heparin (LMWH) or direct oral anticoagulants (DOACs) following cancer surgery. However, these recommendations were based on trials using routine venography, which detects asymptomatic VTEs, and real-life efficacy is not well studied. We aimed to assess the association of extended VTE prophylaxis with the incidence of clinically significant VTE after elective cancer surgery. Patients and Methods: In this retrospective, population-based cohort study, we identified patients who underwent surgical resection for lung, breast, esophageal, gastric, pancreas, and colon cancer from 2010 to 2017 using the SEER–Medicare linked dataset. Patients were divided into 1 of 2 main groups for comparative analyses: those who received extended VTE prophylaxis after cancer surgery and those who did not. Patients who received extended VTE prophylaxis after cancer surgery were identified as those prescribed prophylactic doses of LMWH or a DOAC within 7 days of discharge, as captured in Medicare Part D files. Results: A total of 113,739 Medicare beneficiaries were identified, of whom 1,570 (1.4%) received extended VTE prophylaxis. There was a year-over-year increase in the use of extended VTE prophylaxis during the study period, rising from 0.6% in 2010 to 3.3% in 2017. The overall incidence of VTE was 1.6% at 1 month, 4.3% at 6 months, 5.7% at 12 months, with significant differences observed across cancer types ( P <.001). However, patients who received extended VTE prophylaxis had a higher 1-year cumulative incidence of postoperative VTE compared with those who did not (11.4% vs 5.3%; P <.001), an association that was consistent across cancer sites. In adjusted analyses, extended VTE prophylaxis was independently associated with an increased risk of VTE (hazard ratio, 1.6; 95% CI, 1.3–2.0; P <.001). Extended prophylaxis was also associated with a higher 1-year incidence of bleeding events compared with patients who did not receive prophylaxis (12.0% vs 8.5%; P <.001). Conclusions: The utilization of extended VTE prophylaxis after cancer surgery remains low, although it has increased every year. Paradoxically, patients who received extended VTE prophylaxis had higher incidences of clinically significant VTE and bleeding compared with those who did not, likely reflecting patient selection and surveillance bias after surgery. In light of these findings, national guidelines recommending postoperative extended VTE prophylaxis, and its use as a surrogate for quality of care, should continue to be re-examined.

BACKGROUND: Patients with locally advanced rectal cancer face substantial costs related to multimodal therapy. However, the extent of this burden is poorly characterized. OBJECTIVE: To characterize the prevalence and predictors of patient-reported financial toxicity after treatment for locally advanced rectal cancer. DESIGN: Multicenter retrospective cohort study with a cross-sectional survey administered to assess patients’ financial concerns as well as clinicodemographic data. SETTING: Three high-volume tertiary academic centers. PATIENTS: Patients who completed treatment for pathological stage II to III rectal adenocarcinoma between 2000 and 2019 and were alive. MAIN OUTCOME MEASURES: Patient-reported financial toxicity and risk factors associated with financial toxicity. RESULTS: A total of 523 patients were identified, 190 (36.3%) responded to the survey, and 2 were excluded for incomplete surveys. Of the responders, 163 (86.7%) were identified as having financial toxicity related to their cancer diagnosis, and most (96.8%) had insurance. Patients with financial toxicity were less likely to have fully paid medical leave (39.8% vs 75%; p = 0.03) compared to patients without financial toxicity. They also reported increased difficulty paying bills ( p < 0.001) and decreased monthly household income ( p < 0.001) due to their diagnosis. Furthermore, these patients reported increased difficulty paying for transportation to medical appointments ( p = 0.002) and were less likely to be completely satisfied with their insurance coverage ( p = 0.003). Feeling well informed regarding treatment-related costs was associated with decreased odds of financial toxicity (OR 0.14; 95% CI, 0.02–0.78; p = 0.02), whereas taking unpaid leave for treatment was associated with increased odds of financial toxicity (OR 4.71; 95% CI, 1.36–16.34; p = 0.01). LIMITATIONS: Cross-sectional design and moderate response rate may introduce selection and recall bias. CONCLUSIONS: Patients undergoing treatment for locally advanced rectal cancer, including those insured, are at risk for financial toxicity due to direct and indirect costs. Effective communication between these patients and physicians regarding the economic implications of treatment is essential to reducing financial toxicity. See Video Abstract . TOXICIDAD FINANCIERA TRAS EL TRATAMIENTO DEL CÁNCER RECTAL LOCALMENTE AVANZADO ANTECEDENTES: Los pacientes con cáncer de recto localmente avanzado enfrentan costos sustanciales relacionados con la terapia multimodal. Sin embargo, la magnitud de esta carga está poco caracterizada. OBJETIVO: Caracterizar la prevalencia y los predictores de la toxicidad financiera reportada por los pacientes después del tratamiento para el cáncer de recto localmente avanzado. DISEÑO: Estudio de cohorte retrospectivo multicéntrico con una encuesta transversal para evaluar las preocupaciones financieras de los pacientes, así como datos clínico-demográficos. ESCENARIO: Tres centros académicos terciarios de alto volumen. PACIENTES: Pacientes que completaron el tratamiento para el adenocarcinoma de recto en estadio patológico II-III entre 2000 y 2019 y estaban vivos. PRINCIPALES MEDIDAS DE RESULTADOS: Toxicidad financiera reportada por los pacientes y factores de riesgo asociados con la toxicidad financiera. RESULTADOS: Se identificó a un total de 523 pacientes, 190 (36,3%) respondieron a la encuesta y 2 fueron excluidos por encuestas incompletas. De los encuestados, 163 (86,7 %) presentaron toxicidad financiera relacionada con su diagnóstico de cáncer, y la mayoría (96,8 %) contaba con seguro médico. Los pacientes con toxicidad financiera tuvieron menos probabilidades de tener licencia médica con goce de sueldo completo (39,8 % frente a 75 %; p = 0,03) en comparación con los pacientes sin toxicidad financiera. También informaron mayor dificultad para pagar facturas ( p < 0,001) y una disminución de los ingresos familiares mensuales ( p < 0,001) debido a su diagnóstico. Además, estos pacientes informaron mayor dificultad para pagar el transporte a las citas médicas ( p = 0,002) y menor probabilidad de estar completamente satisfechos con su cobertura médica ( p = 0,003). Sentirse bien informado sobre los costos relacionados con el tratamiento se asoció con una menor probabilidad de toxicidad financiera (OR: 0,14; IC del 95 %: 0,02-0,78; p = 0,02), mientras que tomar una licencia sin sueldo para el tratamiento se asoció con una mayor probabilidad de toxicidad financiera (OR: 4,71; IC del 95 %: 1,36-16,34; p = 0,01). LIMITACIONES: El diseño transversal y la tasa de respuesta moderada pueden introducir sesgos de selección y de recuerdo. CONCLUSIONES: Los pacientes en tratamiento para el cáncer de recto localmente avanzado, incluidos los asegurados, corren el riesgo de sufrir toxicidad financiera debido a los costos directos e indirectos. Una comunicación eficaz entre estos pacientes y los médicos sobre las implicaciones económicas del tratamiento es esencial para reducir la toxicidad financiera. ( AI-generated translation )

Background and Aims: Liver transplantation has evolved from a treatment restricted to patients with end-stage liver disease to a therapeutic option for selected patients with primary and metastatic liver malignancies. This review explores the rapidly expanding field of transplant oncology, highlighting its role in hepatocellular carcinoma, colorectal liver metastasis, neuroendocrine liver metastasis, and intrahepatic and perihilar cholangiocarcinoma. Emphasis is placed on strategies to broaden eligibility, optimize donor organ use, and improve oncologic outcomes. Approach and Results: We synthesized current evidence from clinical series, registries, and experimental protocols to evaluate patient selection criteria, outcomes, and peri-transplant management. Key topics include downstaging approaches to meet transplant criteria, such as locoregional therapies and systemic regimens, and their prognostic implications. Advances in donor utilization have been analyzed for their capacity to expand the graft pool. In addition, the review addresses the integration of oncologic principles into immunosuppression regimens, balancing graft protection with cancer control. Collectively, the reported studies demonstrate improved survival and reduced recurrence when stringent selection and multimodal therapy were applied. Conclusions: Transplant oncology reshapes the therapeutic landscape of liver malignancies, with growing evidence supporting liver transplantation in carefully selected patients beyond traditional indications. Optimized downstaging, innovative donor strategies, and tailored immunosuppression are pivotal for safe expansion. Continued collaboration between the transplant and oncology disciplines, along with prospective trials, is essential to further define standardized protocols and solidify transplantation as a cornerstone of multidisciplinary cancer care.