Citations

Abstract Purpose: Head and neck (HN) radiotherapy contour quality directly impacts local control (LC) and survival; however, few departments peer review (PR) contours prior to radiotherapy planning (RTP). This study reports outcomes of a single institution’s formal HN contour PR process. Methods: A formal HN contour PR process was implemented. Prior to RTP, HN radiation oncologists reviewed contours, provided feedback and assigned contour grades as follows: R0 (no change), R1 (minor revision, not high risk) or R2 (major revision; high risk). The PR task was completed and the contour grade was recorded. Cochran-Armitage trend test was performed. Results: Pilot PR process was performed over a 7-month period for 88 patients, followed by a maintenance phase. Contours were graded as follows: R0 ( N = 51), R1 ( N = 20) and R2 ( N = 17). Over time, the number of R2 revisions decreased ( p = 0.0001); month 1 ( N = 7), month 2 ( N = 3), month 3 ( N = 5), month 4 ( N = 2) and months 5–7 ( N = 0). Conversely, the number of R0 revisions improved over time ( p = 0.0203); month 1 ( N = 5), months 2–3 ( N = 9), month 4 ( N = 5), month 5 ( N = 8), month 6 ( N = 12) and month 7 ( N = 3). Each radiation oncologist demonstrated reduction in R2 revisions during the pilot. During maintenance, all 3 radiation oncologists demonstrated low rates of R2 revisions of less than 3 cases per year. Conclusion: Incorporation of HN contour PR into routine clinical workflow is feasible. The collective experience of multiple high-volume HN radiation oncologists led to improved contour quality in the pilot for each radiation oncologist and continued to ensure high quality in the maintenance phase.

Abstract Objective: Outpatient parenteral antimicrobial therapy (OPAT) is a mainstay of clinical infectious diseases practice, and OPAT-related publications continue to be prominent in journals. The objective of this article is to summarize ten clinically important OPAT-related publications from 2024. Design: Narrative review. Methods: Eighty-one articles were found in a literature search, and 56 met inclusion criteria. A survey containing 25 articles was sent to an email listserv of clinicians with OPAT experience. Results: This article summarizes the top 10 OPAT articles published in 2024, based on those survey results. Conclusions: Common themes from the top 10 OPAT articles published in 2024 included OPAT clinician workload, patient perspectives of OPAT, tools for OPAT work, and dalbavancin use.

Abstract: AIM: The purpose of this study is to investigate the safety and effectiveness of remote ischemic conditioning (RIC) as a therapeutic intervention for cerebral ischemia in patients with Takayasu arteritis (TA). METHODS: TARIC-1 is a randomized, double-blind, parallel-group pilot trial conducted at Xuanwu Hospital, Capital Medical University. Participants with TA and reduced cerebral blood perfusion are randomly allocated to either the RIC or sham-RIC groups. Both the groups receive conventional medical care, with the RIC group receiving twice-daily sessions of 200 mmHg inflation pressure and the sham-RIC group receiving 60 mmHg inflation pressure, for 24 consecutive weeks. OUTCOMES: The primary outcome is the change in mean cerebral blood flow across the entire brain and regions of interest following the 24-week RIC treatment. Secondary outcomes include clinical assessments using the Indian Takayasu Clinical Activity Score 2010, Vasculitis Damage Index, and Birmingham Vasculitis Activity Score at 24 weeks postintervention. Changes in arterial transit time and the incidence of major adverse cerebrovascular events are additional secondary outcomes. Safety outcomes include mortality and any adverse events, including skin changes and pain ratings, within the 24-week period. SAMPLE SIZE ESTIMATES: This pilot study plans to enroll 22 patients per group, totaling 44 participants. CONCLUSIONS: In individuals with TA, RIC may be a well-tolerated treatment that enhances cerebral perfusion and lowers the risk of ischemic cerebrovascular episodes. TRIAL REGISTRATION: http://www.clinicaltrials.gov (identifier: NCT06178419).

Abstract Esophageal squamous cell carcinoma (ESCC) remains a leading cause of cancer-related mortality worldwide, and there are limited molecular screening options. Following a prior discovery and validation studies in subjects from the United States, China, and Iran, we aimed to validate methylated DNA markers (MDM) for ESCC detection in Malawi, a country with one of the highest ESCC incidence. Fourteen MDMs were tested on 177 tissue samples. Ten MDMs showed excellent performance (AUCs ≥ 0.85); a random forest model achieved an AUC of 0.97. The consistent cross-population performance suggests potential for universal application of these MDMs and further justifies exploring nonendoscopic sampling methods, such as swallowed cell collection devices in combination with MDMs, for efficient and cost-effective screening in high-incidence populations. Prevention Relevance: This study validates MDMs for early detection of ESCC in Malawi, supporting their potential role in noninvasive, population-based screening strategies in Africa to enable early detection and timely intervention for cancer interception, potentially reducing cancer burden in high-incidence, resource-limited regions.

Extracorporeal membrane oxygenation (ECMO) represents an established modality of intraoperative circulatory and respiratory support during lung transplantation (LTx). Systemic anticoagulation with unfractionated heparin (UFH) remains essential to prevent circuit thrombosis; however, the optimal monitoring strategy during this procedure remains uncertain. Conventional assays, including antifactor Xa activity (anti-Xa), activated partial thromboplastin time (aPTT), aPTT ratio (aPTTr), and activated clotting time (ACT), demonstrate variable sensitivity and reliability, particularly at low UFH concentrations where ACT is often inadequate. This study aimed to evaluate the interrelationship between standard coagulation monitoring methods and to assess the feasibility of using viscoelastic testing, specifically the ROTEM INTEM/HEPTEM clotting time ratio (I/Hr), as a bedside alternative to ACT. A total of 79 patients undergoing LTx with intraoperative ECMO support were analyzed. Unfractionated heparin was administered in all cases, and coagulation parameters were assessed preoperatively, before ECMO cannulation, and during ECMO support. A strong correlation was observed between I/Hr and anti-Xa, with satisfactory agreement with aPTT and aPTTr. Bland–Altman analysis confirmed narrower limits of agreement for I/Hr-derived versus ACT-derived anti-Xa predictions. These findings support I/Hr as a reliable and practical bedside surrogate for UFH monitoring during ECMO-assisted LTx.

ABSTRACT Neurodegenerative diseases are characterised by the assembly of a limited number of disease-specific proteins into amyloid filaments, which form intracellular inclusions or extracellular deposits in the central nervous system (CNS) 1,2 . We previously found that amyloid filaments of TATA-binding protein-associated factor 15 (TAF15) characterise a subtype of frontotemporal lobar degeneration with FET protein-immunoreactive inclusions (FTLD-FET) 3 , termed atypical FTLD with ubiquitin-positive inclusions (aFTLD-U) 4 , which causes early-onset, rapidly progressive behavioural variant frontotemporal dementia (FTD). However, it was not clear if TAF15 proteinopathy was more widespread in neurodegenerative diseases. Two additional FTLD-FET subtypes have been proposed, neuronal intermediate filament inclusion body disease (NIFID) and basophilic inclusion body disease (BIBD) 5,6 , which have more heterogenous clinical presentations including FTD, motor neuron diseases (MND) and movement disorders. Here, we used electron cryo-microscopy (cryo-EM) to determine a total of 32 amyloid filament structures from the brains of 17 individuals encompassing all three proposed subtypes of FTLD-FET and their diverse clinical presentations. All cases were characterised by TAF15 filaments, in the absence of filaments of the other FET proteins, fused in sarcoma (FUS) and Ewing’s sarcoma (EWS). All three aFTLD-U cases had the previously-reported TAF15 fold 3 . Unexpectedly, we found four distinct TAF15 folds among 11 NIFID cases. Eight of these cases shared a common fold, while the remaining three were each distinct. Furthermore, we found distinct TAF15 folds for each of the three BIBD cases. Neuropathological reassessment of the neocortical TAF15 inclusion pathology of these cases distinguished the NIFID cases with the common fold from the others. Thus, TAF15 filament structures form the basis of a new, expanded classification of FTLD-FET subtypes. Moreover, we discovered a TAF15 Y38C variant in the filament fold of one of the individuals with BIBD. The structure is unable to incorporate wild-type TAF15, despite the individual being heterozygous, suggesting that this variant drives TAF15 filament assembly. This study provides structural and genetic evidence that TAF15 amyloid filaments underlie the diverse group of neurodegenerative diseases currently termed FTLD-FET, which we therefore rename FTLD-TAF15.

Cholangiocarcinoma (CCA) represents a biologically and clinically heterogeneous group of biliary tract malignancies. Growing evidence underscores that the 3 major anatomic subtypes—intrahepatic (iCCA), perihilar (pCCA), and distal (dCCA)—are distinct tumor entities rather than a single disease. Each subtype differs in embryologic origin, carcinogenesis mechanisms, molecular landscape, and immunogenic profile, all of which contribute to variability in diagnosis, treatment responsiveness, and prognosis. The importance of understanding these distinctions is reinforced by the rising global incidence of CCA, which highlights the need for precision medicine approaches based on these subtypes. Recent advances have deepened our insight into subtype-specific risk factors, including chronic biliary diseases and metabolic conditions, while artificial intelligence–driven tools are improving diagnostic accuracy and risk stratification. Surgical innovations now allow for more tailored resections and perioperative care, and therapeutic strategies are increasingly guided by molecular and immune profiling. Emerging strategies for early diagnosis and chemoprevention in high-risk populations further emphasize the significance of recognizing the unique biology of each subtype. In this review, we provide a comprehensive overview of the distinct anatomic subsets of CCA, integrating their molecular and biological foundations with clinical management to inform practice and guide future research.

Abstract Background Coronary computed tomography angiography (CCTA) is a non-invasive diagnostic modality for assessing coronary artery disease (CAD), with a growing global trend favouring a "CT-first" approach. However, this strategy strains healthcare systems as demand for CCTA increases. Pre-test probability (PTP) models for obstructive CAD are used to optimize the usage of CCTA. However, these models perform inconsistently across different subpopulations and offer limited discriminatory accuracy, with low positive predictive values (PPV). This study aims to enhance the PTP models with explainable artificial intelligence (XAI) on electrocardiogram (ECG) data. Methods Patients who underwent CCTA for suspected CAD with both CAD-Reporting and Data System (CAD-RADS) classification and Coronary Artery Calcium Score (CACS) were included. Obstructive CAD was defined as CAD-RADS 3 or above. Missing values were imputed. The Risk Factor Weighted Clinical Likelihood (RF-CL) model, based on clinical variables (age, sex, symptom type, smoking, hypertension, dyslipidaemia, diabetes, and family history) was computed. Two gradient descent decision tree models, "AI-ECG" and "AI-CAC," were developed for the pilot study. AI-ECG used clinical risk factors and ECG classification as abnormal, borderline or normal, while AI-CAC further incorporated CACS. We used a cutoff value of 15%, reflecting current guidelines. Comparative analysis was performed using area under the curve (AUC) analysis, the DeLong test for statistical comparison, and feature importance using SHAP values. We intend to develop and present a model based on ECG signal data during the conference. Pilot results We identified 6 178 patients who underwent CCTA between 2022 and 2024 at the Cardiology Centers Netherlands (CCN), of which 2 083 were included (mean age 57.4 ± 10.2 years; 48.1% male). Obstructive CAD was found in 413 (19.8%) patients. The RF-CL model was outperformed by both AI-ECG (AUC: 0.69 vs. 0.80, p<0.001) and AI-CACS (AUC: 0.69 vs. 0.90, p<0.001). Sensitivity increased in both AI models, from 0.46 to 0.87 for AI-ECG and to 0.83 for AI-CACS, while PPV improved only in the AI-CACS model (from 0.37 to 0.61). Key predictive features were CACS, age, sex, ECG classification, and family history. Conclusion and Discussion Our pilot study shows that integrating XAI with clinical risk factors and ECG classification enhances PTP estimation for obstructive CAD. Implementing this model can better stratify patients at risk of obstructive CAD, support more focused CCTA use and reduce unnecessary testing. Nonetheless, further external validation is needed to assess model performance in real-world, prospective clinical settings. Additionally, models based on raw ECG signals have the potential to extract more detailed information.Reciever Operating Characteristic CurvesFeature Importance