Intensive multiagent treatment regimens have substantially improved outcomes in advanced-stage classic Hodgkin lymphoma (cHL). Brentuximab vedotin (BV), etoposide, cyclophosphamide, doxorubicin, dacarbazine and dexamethasone (BrECADD) demonstrated the highest efficacy in cHL reported to date in a randomised phase III trial. Cytotoxic agents are conventionally administered during the first 4 days of a 21-day cycle. A total of four cycles are applied to patients with a complete response after two cycles, otherwise six cycles. We developed a condensed BrECADD protocol, reducing intravenous administration days to only three (-25%). Between January 2024 and July 2026, 30 patients received 132 cycles of 3-day BrECADD at our institution. Primary objective was to describe feasibility and safety; secondary objectives included response, progression-free survival (PFS) and overall survival (OS). Grade ≥3 adverse events occurred in 23 patients (77%), predominantly haematological. Six patients (20%) had grade ≥3 infections (four viral, two bacterial) and six (20%) had pathogen-unspecified febrile neutropenia. Twenty-four patients (80%) required only four BrECADD cycles. There were no treatment discontinuations. After a median follow-up of 18 months (range 4-29), 1-year PFS and OS rates were both 100%. Based on these encouraging results, the condensed 3-day protocol is considered feasible and we recommend it for future BrECADD use.

Background and Study Aims A papilla located on the left wall of a periampullary diverticulum creates a mechanically unfavourable axis for biliary cannulation that is not readily corrected from the conventional endoscopist position. We describe the Extreme Anticlockwise Bileduct Cannulation Diverticulum (ABCD) technique, where "Extreme" qualifies the degree of anticlockwise rotation applied-an endoscopist-repositioning manoeuvre designed to address this constraint without additional instrumentation. Patients and Methods Following observations in two index cases, the technique was adopted pre-emptively in consecutive patients with a confirmed left-wall periampullary papilla. Twenty-four patients were prospectively enrolled between July 2021 and February 2026. The endoscopist repositioned to the patient's head end and applied extreme anticlockwise duodenoscope rotation to realign the instrument axis. The primary outcome was successful biliary cannulation. Adverse events were graded using the Cotton consensus criteria. Results Successful biliary cannulation was achieved in 23/24 patients (95.8%), all within 5 min of adopting the repositioned stance. Primary guidewire cannulation was achieved in 20/24 (83.3%); the remaining three required needle-knife fistulotomy, performed from the same repositioned stance. Trainees were involved in 22 cases and cannulated independently in 16 (72.7%). Then, 3 of 24 patients (12.5%) experienced post-sphincterotomy bleeding, graded as AGREE Grade I. No post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis or other major complications were observed. Conclusions The Extreme ABCD technique is a simple, equipment-independent repositioning strategy for ERCP in left-wall periampullary diverticular anatomy. In this prospective series, it was associated with a high rate of biliary cannulation without rescue accessories and was feasible in a supervised training environment. Multicentre evaluation is warranted.

Advanced systemic mastocytosis (AdvSM), comprising aggressive systemic mastocytosis, mast cell leukemia, and systemic mastocytosis with an associated hematological neoplasm, is a heterogeneous myeloid neoplasm with poor prognosis. Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only potentially curative treatment, yet its benefit across AdvSM subtypes in the era of KIT-targeted tyrosine kinase inhibitors (TKIs) such as midostaurin and avapritinib remains unclear. To identify patient subgroups benefiting from allo-HCT and to define prognostic factors for post-transplant survival, we analyzed 631 AdvSM patients from the European Competence Network on Mastocytosis registry, including 69 who underwent allo-HCT. Treatment effects were assessed using time-dependent Cox regression in a transplant-eligible complete-case cohort (n = 419). In this cohort, allo-HCT showed no overall survival (OS) benefit (hazard ratio [HR] 1.21, 95% CI 0.80-1.84; p = 0.37), whereas TKI response emerged as a strong independent predictor of survival (HR 0.42; p<0.001). Subtype-stratified analysis revealed an allo-HCT benefit exclusively in patients with systemic mastocytosis associated with acute myeloid leukemia (n = 30; HR 0.20; p = 0.020). Among the 69 transplanted patients, median OS was 49.6 months with 2-year and 5-year survival of 63% and 46%, respectively. The International Prognostic Scoring System for Mastocytosis (IPSM) at transplantation independently predicted both OS (HR per category 1.68; p = 0.026) and progression-free survival (HR 1.99; p = 0.003), whereas the Mutation-Adjusted Risk Score and diagnostic subtype did not reach statistical significance. Competing risk analysis demonstrated that higher IPSM captured both relapse-related and transplant-related mortality. These findings suggest that the survival benefit of allo-HCT in AdvSM is driven primarily by control of the associated myeloid neoplasm. Accordingly, allo-HCT should be prioritized in patients with SM-AML, whereas TKI-directed strategies may be preferred in other subtypes, with IPSM at transplantation potentially guiding transplant selection and timing.

Magnetic resonance imaging (MRI) is essential for post-treatment surveillance of patients with intracranial central nervous system (CNS) tumours. However, interpretation is often complicated due to post radiotherapy MRI abnormalities. Current literature demonstrates substantial heterogeneity in terminology and definitions used to describe these MRI abnormalities, limiting clinical decision-making and comparability across studies. To address this, an international multidisciplinary Delphi consensus was conducted within the Radiation Imaging and Neuro-Oncology Group (RING). Questionnaires were developed by the steering committee and distributed to experts in radiation oncology, neuroradiology, neuro-oncology, medical oncology, and neurosurgery. A three-round Delphi method was employed, with consensus defined as ≥ 75% agreement. Consensus was reached on the applicability and definitions with adoption of the term Treatment-Related Imaging Abnormality (TRIA). Clear definitions for potential and confirmed TRIA were established. Subcategorization based on imaging features all demonstrated high agreement. For consistent application of the framework minimal essential elements for MRI request forms were identified. The final consensus was endorsed by ESTRO, ESNR and EORTC. This Delphi consensus provides a standardized framework for MRI abnormalities following radiotherapy for intracranial CNS tumours. The framework aims to harmonize reporting, support clinical decision-making, and improve comparability in future neuro-oncology research. Central nervous system neoplasms - Radiotherapy - Magnetic resonance imaging - Delphi Technique - Treatment-Related Imaging Abnormality (TRIA).

Adolescence marks a critical window for the emergence of mental health problems and reproductive maturation. Menstrual cycle characteristics - including pubertal timing, cycle regularity, menstrual pain, and premenstrual symptoms -may capture biological and experiential processes relevant to psychopathology. However, evidence linking menstrual features to a broad range of mental health outcomes, including ADHD symptoms, remains limited. Using data from the Adolescent Brain Cognitive Development (ABCD) Study (v6.1 N = 5,678 biological females; 17,567 post-menarche observations across 7 waves), we examined associations between reproductive timing, menstrual characteristics and symptoms of attention-deficit/hyperactivity disorder (ADHD), depression, and anxiety symptoms across repeated assessments in early adolescence using linear mixed-effects models with crossed random intercepts for site, family, and participant. Two co-primary model specifications were used: without BMI (M1, full sample) and with BMI (M2). False discovery rate correction was applied across outcomes. Earlier age at menarche was specifically associated with higher depression symptom scores (B = -0.087, pFDR < 0.001), with attenuation after BMI adjustment. Greater gynaecologic age (time since menarche TSM) also associated with higher depression scores (B = + 0.118, pFDR < 0.001) independent of chronological age and pubertal timing. Among girls with established cycles (TSM ≥ 2 years), irregular cycles were associated with higher depression and anxiety, whereas associations with ADHD did not remain after BMI adjustment. Long cycles were associated with anxiety only. Severe menstrual pain and premenstrual symptom severity showed dose-response associations with depression, anxiety, and ADHD that were robust to BMI adjustment. The association between irregular cycles and depression, and between long cycles and depression and anxiety, strengthened significantly with increasing gynaecologic age, while symptom burden associations were consistent throughout the post-menarcheal period. Menstrual symptom burden particularly severe pain and premenstrual distress and earlier menarche were consistently associated with higher levels of psychiatric symptoms in adolescent girls. These findings highlight menstrual health as a potentially informative dimension of adolescent mental health assessment. When girls present with significant menstrual symptoms, assessment of emotional wellbeing may be warranted.

Relapsed or refractory acute myeloid leukemia (R/R AML) remains a therapeutic challenge, with standard high‑dose cytarabine-based salvage regimens achieving complete remission (CR) rates of around 50%. In the phase 1/2 RELAX trial, adding venetoclax (VEN) to high‑dose cytarabine and mitoxantrone (HAM) was considered safe and resulted in CR or CR with incomplete hematologic recovery (CRi) in 75% of patients. Here, we performed a multicenter real‑world analysis of 128 R/R AML patients treated with HAM plus VEN (VEN 400 mg days 1-14, cytarabine 1000 mg/m[2] IV twice daily days 3-5, mitoxantrone 10 mg/m[2] IV days 5-7) between March 2023 and June 2025. The median age was 60 years (range, 20-74). Patients had a median of 1 prior therapy (range, 1-5), 38% had prior allogeneic hematopoietic cell transplantation (HCT), and 25% VEN exposure. Overall, 69% achieved CR/CRi; response rates were higher in patients with one prior therapy line (78%) and VEN-naïve patients (76%). Sixty-eight percent proceeded to HCT. After a median follow-up of 11.5 months, estimated 1‑year RFS and OS rates were 59% and 58%, respectively. In a prognostic classifier derived from pooled real-world and RELAX trial data (183 patients), TP53 mutation, complex karyotype, ≥2 prior therapy lines, and Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 predicted inferior outcomes. Patients without these features had a 1-year OS of 73%. HAM plus VEN retains high efficacy and encouraging survival outcomes in a real-world setting, supporting its use as an effective salvage and bridge-to-transplant strategy.

Associations between music participation and language outcomes in children have been widely reported, yet whether cortical morphometry statistically accounts for these relationships remains unclear, particularly at the population level.

Latino adolescents experience disproportionately high rates of depressive symptoms relative to other racial and ethnic groups in the United States, yet the multilevel factors shaping these disparities remain understudied. Family conflict is an important predictor of adolescent mental health, particularly within Latino communities where family relationships occupy a central role in social and emotional development. Using data from the Adolescent Brain Cognitive Development (ABCD) Study four-year follow-up (N = 1,796), we examined whether neighborhood social vulnerability moderated the association between family conflict and depressive symptoms among Latino adolescents. Multilevel models were estimated separately for each of the four Social Vulnerability Index (SVI) themes: socioeconomic status, household composition/disability, minority status/language, and housing/transportation. Family conflict was a consistent predictor of depressive symptoms across all four models (Theme 1: b = 5.36, p < .001; Theme 2: b = 4.91, p < .001; Theme 3: b = 3.00, p = .159; Theme 4: b = 3.60, p = .015), with a mean CBCL withdrawn-depressed T-score of 53.96 (SD = 6.49) across the sample. No interaction effects were statistically significant. These findings underscore the centrality of family dynamics as a driver of depressive symptoms among Latino adolescents regardless of neighborhood context. Future research should integrate opportunity-focused neighborhood metrics, investigate mediation pathways, and incorporate additional ecological factors to better understand the multilevel determinants of Latino adolescent mental health.

The pervasive rise of video gaming in adolescent life necessitates a clearer understanding of its complex impact on cognitive and mental health development, as previous research has yielded conflicting results due to small sample sizes and unaddressed confounding factors. Here we leverage the Adolescent Brain Cognitive Development (ABCD) Study dataset (N = 9,712; mean age 9.92 years) to examine relationships between varying video gaming exposure levels and neurocognitive, behavioral, and neural outcomes. Controlling for critical environmental and demographic covariates, we show that associations between gaming and developmental outcomes are not uniform. Moderate gaming (<1 h/day) was associated with enhanced cognitive performance, including elevated fluid and total IQ, and lower externalizing and aggressive behavior scores compared to non-gamers. Conversely, excessive gaming (≥3 h/day) correlated with significantly higher attention problems and ADHD scores. Notably, all gaming cohorts outperformed non-gamers on the N-back task, with heavy gamers exhibiting significantly increased BOLD activation in the right precuneus and right middle frontal gyrus. These findings provide a comprehensive neurodevelopmental framework, supporting the hypothesis that while excessive use presents behavioral risks, moderate video gaming may be associated with enhanced cognitive and mental health profiles.

BackgroundRates of mental illness in adolescents are increasing at an alarming rate. At the same time, youth participation in physical activity is continually declining. International public health guidelines recommend that children spend at least 60 min/day in moderate-to-vigorous physical activity for optimal development of brain health. This study aimed to disentangle within-person effects of physical activity on mental health symptoms from stable, between-person differences using a four-wave random-intercepts cross-lagged panel model (RI-CLPM).MethodsData from the longitudinal Adolescent Brain Cognitive Development (ABCD) Study were used to follow pre-adolescent children (N = 6361) across development (10-14.2 years old). Physical activity was measured by youth-report. Internalizing and externalizing mental health behaviors were measured by the parent-reported Child Behavior Checklist. Bidirectional relationships between mental health and physical activity were assessed using RI-CLPM.ResultsFor internalizing symptoms, cross-lagged (within-person) random effects showed that higher physical activity at year 2 predicted fewer internalizing symptoms at year 3 (β= -0.037 [-0.062 to -0.012]), and from year 3 to year 4 (β = -0.045 [-0.068 to -0.022]). More internalizing symptoms at baseline predicted less physical activity from year 2 to year 3 (β = -0.076 [-0.125 to -0.027]), and from year 3 to year 4 (β = -0.075 [-0.118 to -0.031]). For externalizing symptoms, there were no significant cross-lagged or between-person effects.ConclusionIn this large, multi-wave longitudinal cohort, more physical activity was associated with fewer internalizing symptoms across early adolescent development. Additionally, higher internalizing symptoms were associated with lower physical activity across development. No associations were found with externalizing symptoms. Findings suggest that physical activity may alleviate internalizing symptoms during early adolescence, underscoring the need for promoting adherence to international physical activity guidelines in the complex management of adolescent mental health.

Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer and remains the most lethal malignancy of the digestive system. Despite recent advances, surgical treatment remains the only potentially curative option. Most patients are diagnosed with locally advanced or disseminated disease, and chemotherapy is the only indicated treatment. Pancreatic resection rates in centers that do not perform vascular resection are around 15-20% of diagnosed cases, while in specialized centers with vascular expertise, they may reach 30-45%. Ablative therapies have been investigated as local alternatives for unresectable tumors. Radiofrequency ablation (RFA) has proven efficacy in the treatment of hepatic neoplasms, and has recently been explored in PDAC. Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) represents a minimally invasive alternative for thermal ablation of pancreatic tumors. Early experience suggests that may serve as a palliative modality for pain or obstruction control, and to facilitate chemotherapy. However, this treatment is considered experimental and requires procedural standardization. Careful patient selection is essential, prioritizing cases without metastatic spread, with tumors accessible by EUS and without extensive vascular invasion. Endoscopic ultrasound-guided radiofrequency ablation should not replace surgery in resectable pancreatic ductal adenocarcinoma. The endoscopic ultrasound-guided radiofrequency ablation should be considered as a palliative option within multidisciplinary protocols. Endoscopic ultrasound-guided radiofrequency ablation is an isolated palliative modality, and considered an option to treat the pancreatic ductal adenocarcinoma.