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Abstract Varlilumab is a monoclonal antibody with agonistic activity on CD27. The efficacy of single-agent PD-1 inhibitors on aggressive B-cell non-Hodkin lymphoma is limited. Preclinical and phase 1 data suggest that Varlilumab is safe and may have synergistic activity with PD-1 inhibitors. In the DIAL study, we explored whether dual immunomodulatory therapy with Varlilumab and Nivolumab in patients with relapsed/refractory aggressive B-NHL was safe and effective. We conducted a randomized phase II clinical trial on adult patients with relapsed/refractory aggressive B-NHL. Patients were randomized to receive Nivolumab monotherapy in the control group and Varlilumab combined with Nivolumab in the experimental group. Crossover to the experimental group was allowed upon progression in the control group. The primary endpoint was the overall response rate based on the Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC). 54 patients underwent randomization, and 51 received assigned intervention and were included in the intention-to-treat analysis. Objective response was observed in 6 out of 51 patients (ORR 12%). There were 4 responders (ORR 16%) in the Nivolumab group and 2 responders (ORR 7.6%) in the Nivolumab and Varlilumab combination group (p = 0.3). None of the 7 patients that crossed over to the experimental group responded to the addition of Varlilumab. The ORR of patients who were previously exposed to CAR-T cell therapy was 13% (5 out of 39) compared to 8.3% (1 out of 12) in the unexposed patients (p > 0.99). The rate of treatment emergent adverse events was similar between groups, and there was no fatal TEAE in the study. The addition of Varlilumab to Nivolumb did not improve outcomes in patients with aggressive B-NHL. Even though this trial was not designed to evaluate immunotherapy as a rescue therapy after CAR-T failure, most patients (76%) had previously received CAR-T therapy, and their outcomes were equally poor.

The NCCN Guidelines for Survivorship offer guidance for health care providers who care for survivors of adult-onset cancer. These guidelines include screening, evaluation, and treatment recommendations for common physical and psychosocial problems resulting from cancer and its treatment and provide a framework for care coordination. They also present guidance for helping cancer survivors to enhance their wellness and maintain a healthy lifestyle. This article summarizes the panel’s current recommendations and recent updates regarding anxiety, depression, distress, and trauma in cancer survivors.

Background: Total kidney volume (TKV), a prognostic biomarker in ADPKD, is used to stratify high risk individuals. eGFR measures may carry significant error in ADPKD compared to measured GFR(mGFR). This retrospective study investigates the association between height adjusted TKV (htTKV) and eGFR derived from race-free CKD-EPI equations utilizing creatinine and cystatin C. Methods: eGFR was calculated using 3 race-free CKD-EPI formulas: creatinine-based (CKD-EPI creatinine), cystatin C (CKD-EPI cys), and creatinine-cystatin C (CKD-EPI creatinine-cystatin C) equations on 697 Mayo Clinic ADPKD patients. Correlations between eGFR and TKV measures were estimated and stratified by MIC class risk groups and CKD. Linear regression models were computed to predict ln(htTKV) from the 3 eGFR data sets. The eGFR measures were compared to iothalamate-based mGFR in a subset of patients (n=50). Results: A correlation between eGFR measures and htTKV (Pearson correlation r of -0.53 to -0.54), varied by MIC stratification. Pearson correlation was -0.47 to -0.48 for MIC 1A and 1B, -0.67 to -0.71 for MIC 1C, and -0.67 to -0.68 for MIC 1D and 1E. All equations were significantly associated with htTKV levels, with similar adjusted beta values (95% CI) of -0.15 (-0.17 to -0.13), -0.14 (-0.16 to -0.12), -0.15 (-0.16 to -0.13), for CKD-EPI creatinine, CKD-EPI cystatin C, and CKD-EPI creatinine-cystatin C, respectively. Compared to mGFR, the CKD-EPI creatinine-cystatin C equation was the least biased (mean -0.86 (95% CI: -3.09 to 1.37)) versus CKD-EPI creatinine (2.31 (-0.73 to 5.34)) or CKD-EPI cystatin C (-3.54 (-5.86 to -1.21)), and most precise, with 1-P30 of 16% (95% CI 7.2% to 29.1%), compared to 18% (8.6% to 31.4%) for CKD-EPI creatinine, or 20% (10.0% to 33.7%) for CKD-EPI cystatin C. Conclusion: A moderate correlation between eGFR and htTKV associated with MIC stratification. Associations between htTKV and all 3 CKD-EPI equations were similar. CKDEPIcrcys tended to be the least biased and most precise equation when compared to mGFR and may be a reasonable alternative.

Abstract INTRODUCTION Sleep and circadian rest–activity rhythm (RAR) disruption may bidirectionally relate to Alzheimer's disease (AD). Down syndrome (DS), the most common genetic cause of AD, presents sleep disorders, yet RAR patterns across the DS‐associated AD continuum remain uncharacterized. METHODS We analyzed 7‐day wrist actigraphy in 140 adults with DS (108 asymptomatic; 32 AD dementia) and 41 unimpaired controls. General linear models, adjusted for age, sex, sleep efficiency, and obstructive sleep apnea (OSA) severity, tested group differences, with interaction terms included to evaluate group‐specific associations. RESULTS DS showed lower relative amplitude and higher nocturnal activity, already in asymptomatic individuals. Rhythm strength declined further with AD progression, while regularity and phase timing remained preserved until dementia. Findings were independent of sleep duration and OSA. DISCUSSION Adults with DS showed early RAR disturbance that progressed across the AD continuum, paralleling sporadic AD. Circadian RAR features may be scalable biomarkers of AD progression.

Summary The American Society of Clinical Psychopharmacology convened a 45-member international expert task force to identify circumstances supporting the deprescribing of core psychotropic medications for major depressive disorder (MDD) and bipolar disorders. Three Delphi survey rounds plus a selective literature review identified points of consensus (predefined as ≥75% agreement) about when antidepressant, antipsychotic, mood stabiliser and sedative-hypnotic deprescribing is warranted. Twenty out of 32 statements (63%) achieved consensus across seven thematic areas. In MDD, panellists favoured discontinuing antidepressants when mechanisms of action are duplicative, adequate trials produce ≤25% improvement or loss of prior efficacy cannot be regained through dose increases or augmentations. Indefinite antidepressant maintenance in MDD was favoured after three or more lifetime episodes. In bipolar disorder, antidepressant deprescribing was favoured in the setting of rapid cycling, mixed features or emerging mania/hypomania symptoms; and discouraged if prior antidepressant cessation led to relapse. In nonpsychotic mood disorders, panellists favoured deprescribing antipsychotics that caused significant weight gain or tardive dyskinesia over adding pharmacological antidotes. Deprescribing to achieve an eventual medication-free status was considered inappropriate, in bipolar type 1, but not necessarily bipolar type 2 disorder. Although individualised circumstances necessarily inform psychopharmacology management, clinical presentations that misalign with existing pharmacotherapies may signal the desirability of cautious deprescribing.

Key Points In a cohort of children, 79% of families with kidney cysts had a monogenic diagnosis. Resolved cases were more likely to have a family history of kidney cysts and unresolved cases more often had unilateral cysts. Broad genetic testing revealed genetic diversity and informed prognosis and clinical management in childhood kidney cysts. Background Pediatric kidney cysts may indicate an underlying genetic disorder, yet the full spectrum of causes remains incompletely defined. With advances in genetic testing enabling broader evaluation, this study assessed the diagnostic utility of comprehensive genetic testing in a broad pediatric cohort with kidney cysts and characterized the underlying etiological diversity. Methods This observational cohort study included patients younger than 18 years enrolled between January 2020 and June 2024 at a single tertiary center. Genetic testing used targeted multigene or custom curated exome/genome sequencing panels, with segregation analysis when available. Eligible participants had at least two cysts without family history, one cyst with positive family history, or enlarged echogenic kidneys on prenatal ultrasound; those with congenital anomalies of the kidney and urinary tract associated with cysts were excluded. Clinical presentation was categorized as symptomatic, incidental, prenatal, or family screening. Primary outcomes were diagnostic yield and distribution of pathogenic variants. Results Among 109 patients (median age 7.6 years, 53% female), genetic testing identified a definitive diagnosis in 81 of 100 tested patients (81%) from 72 families (79%; 14 disorders). PKD1 variants were most common (45%), while PKD2 accounted for 7%. Other causes included HNF1B or 17q12 deletions (13%), minor autosomal dominant polycystic kidney disease genes (11%; GANAB, NEK8, IFT140 ), monoallelic PKHD1 (3%), and biallelic PKHD1 (8%), while syndromic ciliopathy genes accounted for 5%. A positive family history of cystic kidney disease was more common among patients with a genetic diagnosis (54% versus 11%; P = 0.008). Patients without an identified genetic diagnosis more often had unilateral cysts (26% versus 4%; P = 0.53). Diagnosis by clinical symptoms was the most genetically diverse category. Conclusions Comprehensive genetic testing in pediatric kidney cysts achieved high diagnostic yield in a selected cohort and identified diverse causes beyond major autosomal dominant polycystic kidney disease/autosomal recessive polycystic kidney disease genes, supporting early evaluation to improve diagnostic accuracy, inform prognosis, and guide management, even in the absence of family history.

Importance There is a need for greater recognition of clinical psychopharmacology endpoints, including instances where specific psychotropic medications may become unnecessary, redundant, contradictory, or otherwise inappropriate and therefore merit deprescribing. Objective To address circumstances warranting psychotropic medication deprescribing. Evidence Review The American Society of Clinical Psychopharmacology convened a panel of 45 international psychopharmacology experts who developed and completed a multiround Delphi survey and conducted a focused literature review between January and May of 2025, in order to identify areas of consensus or disagreement on key aspects of the deprescribing of psychotropic medications. These included collaborative risk-benefit assessments with patients; pharmacokinetic and pharmacodynamic factors; pharmacogenomics; distinguishing redundant or conflictual from complementary mechanisms of action; managing adverse effects; assuring medication adherence; drug tolerance or tachyphylaxis; medication misuse; and the psychological context and ramifications of deprescribing. Findings Consensus was achieved on 44 of 50 final Delphi statements (88%). Panelists unanimously agreed that components of a pharmacotherapy regimen should undergo periodic review to ensure that treatments target relevant symptoms and have favorable risk-benefit ratios. Key points of consensus were that deprescribing: (1) should not occur without first assessing medication adherence; (2) merits consideration if less than partial therapeutic response is apparent, or if treatment goals have been reached and relapse prevention is not a long-term objective; (3) involves psychological ramifications that warrant attention; (4) should be followed by close clinical monitoring; and (5) risk-benefit decisions should ideally involve active patient participation within a shared decision-making model. Conclusions and Relevance Through this Consensus Statement, the Task Force identified circumstances in which the selective elimination of certain psychotropic medications may be clinically indicated. Empirical trials are needed to assess the implementation of deprescribing protocols and gauge their safe, effective, and acceptable outcomes.

Abstract Response Assessment in Pediatric Neuro-Oncology (RAPNO) is an international working group dedicated to developing standardized recommendations for response assessment in children with central nervous system tumors enrolled on clinical trials. This standardization facilitates easier and more reliable comparison of responses across trials. Since the first RAPNO publication in 2013, response guidelines have been issued for medulloblastoma (MB), low-grade glioma (LGG), high-grade glioma (HGG), diffuse intrinsic pontine glioma, ependymoma, and craniopharyngioma. Many of these guidelines have already been incorporated into clinical trials to evaluate their effectiveness and accuracy. RAPNO has always been predicated on the idea that these consensus recommendations will require updates over time as they are applied in practice given technological advancements, evolving treatment approaches, and growing knowledge of disease pathology. A half-day RAPNO symposium sponsored by the Society of Neuro-Oncology was held in San Diego, California, United States, on May 15, 2025. This event coincided with the 8th Biennial Pediatric Society of Neuro-Oncology meeting. The main objectives were to identify ongoing RAPNO challenges, discuss potential updates, and plan future initiatives across 3 specific groups: (1) LGG/Craniopharyngioma, (2) HGG/diffuse midline glioma (DMG)/Ependymoma, and (3) MB and other seeding tumors. This manuscript reviews the symposium proceedings and highlights key topics and challenges discussed, as well as outlining future RAPNO initiatives.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Hodgkin lymphoma provide expert, multidisciplinary recommendations for the diagnosis and treatment of Hodgkin lymphoma. The panel convenes annually to update recommendations based on a review of recently published clinical trials. This selection from the NCCN Guidelines for Hodgkin Lymphoma focuses on the management of newly diagnosed and relapsed/refractory classic Hodgkin lymphoma in adults aged 18 to 60 years.

What was done? A review of artificial intelligence (AI) applications for the imaging of uterine fibroids, endometriosis, and adenomyosis. What was found? AI models can assist with the recognition, segmentation, and localization of uterine fibroids, and the differentiation of benign fibroids and sarcomas. Models can aid in the diagnosis of adenomyosis and endometriosis, and the prediction of the impact of endometriosis on fertility. What the findings mean? Deployed thoughtfully, AI tools could reduce variability, shorten read times, and add objective measurements to routine care. Studies evaluating these models are limited by single-institution designs and continued reliance on expert sonologists and radiologists.