Citations

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.

Background: Simultaneous carpal tunnel release (sCTR) with emergent forearm fasciotomy in the setting of acute compartment syndrome (ACS) has been reported, but the national incidence and cost of delayed carpal tunnel release (CTR) remain unknown. This large database study aims to evaluate how often sCTR is performed, the frequency of delayed CTR when not performed simultaneously, and the associated costs. Methods: The PearlDiver Mariner database was queried for patients who underwent forearm fasciotomies between January 1, 2015, and October 31, 2022. Patients were grouped based on CTR timing: simultaneous, within 2 weeks, 2 weeks to 1 year, 1 to 5 years, or no CTR. Reimbursement data were collected, and patient numbers and costs were analyzed across cohorts. Results: More than half of patients undergoing emergent forearm fasciotomy received sCTR. Among those who did not, 31% required CTR within 1 year and 35% within 5 years. The total cost was highest when CTR was performed within 1 year but not on the same day as fasciotomy. After 1 year, the additional cost of CTR was similar to that of patients who never underwent fasciotomy. Conclusions: This large database study shows that over one-third of patients who did not undergo sCTR at the time of emergent forearm fasciotomy required it within 1 year, incurring significantly higher costs. Including sCTR during initial fasciotomy may reduce delayed care and associated expenses. While these findings suggest that including sCTR during initial fasciotomy may reduce delayed care and expenses, the retrospective design precludes definitive recommendations, and clinical judgment remains essential Level of Evidence: 4

Abstract Hypoparathyroidism is an endocrine disease caused by insufficient levels of PTH, which acts directly on bone and kidney and indirectly on the intestine to regulate calcium and phosphate balance. In clinical trials, palopegteriparatide (TransCon PTH) treatment enabled independence from conventional therapy (no active vitamin D, ≤600 mg/d calcium) and maintained serum biochemistries within normal ranges. The current analyses describe patterns of change in BMD, serum bone turnover markers, and serum and urine calcium in adults with chronic hypoparathyroidism treated with palopegteriparatide through 3 years of the PaTH Forward trial. Baseline BMD Z-scores for the LS, TH, FN, and 1/3 distal radius were above zero, indicating bone mass exceeding age-adjusted normative values. BMD decreased from these elevated baseline levels with palopegteriparatide treatment, with larger reductions during the first 26 weeks and modest declines thereafter. Mean BMD Z-scores at week 162 remained above zero for all 4 sites. Participants with lower baseline BMD (Z-scores below −1 and T-scores below −2.5) generally exhibited lesser declines in BMD versus those with higher baseline BMD. Palopegteriparatide treatment was associated with early increases in bone resorption (serum C-terminal telopeptide of type I collagen, CTx) and bone formation (serum procollagen type 1 N-terminal propeptide, P1NP) that peaked at weeks 12 and 26, respectively, followed by declines to levels moderately higher than baseline at week 162. Mean CTx and P1NP in the overall population and the subgroup of postmenopausal women were below their upper limits of normal from weeks 58-162. At week 162, mean serum and median urine calcium remained within normal ranges and 91% of participants were independent from conventional therapy. These results suggest that long-term palopegteriparatide therapy in adults with chronic hypoparathyroidism gradually returns the skeleton toward its natural state thereby enhancing the skeleton’s contribution to calcium homeostasis.

Abstract Purpose: Rearranged during transfection (RET) alterations are oncogenic drivers across solid tumors. Selective RET inhibitors (SRI) selpercatinib and pralsetinib have transformed outcomes for patients with RET-altered malignancies. Limited knowledge exists on genomic mechanisms of resistance to SRI. Experimental Design: We established “RETgistry,” a global consortium of patients with advanced RET-altered solid tumors who received SRI and underwent postprogression tissue or plasma biopsies assessed by next-generation sequencing. Frequencies of secondary RET resistance mutations and acquired non-RET gene alterations were determined. Progression-free survival (PFS) and time to treatment discontinuation (TTD) on first SRI were estimated with the Kaplan–Meier method. Results: RETgistry included 109 patients with RET-altered advanced solid tumors (lung, n = 94; thyroid, n = 15) who underwent 143 post-SRI progression biopsies (tissue, 91; plasma, 52). The median PFS and TTD were 13.9 months [95% confidence interval (CI), 10.1–16.6] and 17.3 months (95% CI, 14–20.2), respectively. Secondary RET mutations were detected in 20 (14%) biopsies [lung cancer, 15 (12.4%) and thyroid carcinoma, 5 (22.7%)]. Common acquired off-target alterations involved MET (18.2%; amplification, 15%), TP53 (8.2%), APC (7.6%), KRAS (7.1%), KEAP1 (5.9%), and CDKN2A/B (5.3%). MET alterations were enriched in post-SRI versus pre-SRI specimens (full cohort, 17.6% vs. 2.0%, P = 0.022; lung cancer, 19.1% vs. 2.1%, P = 0.022). Conclusions: The prevalence of secondary RET mutations after SRI was low, underscoring a greater role for off-target resistance. Recurrent acquired alterations involving tumor suppressor genes or upstream regulators of MAPK and PI3K pathways were identified, most commonly MET amplification. Continued efforts to characterize SRI resistance biology are critical to guide the development of novel therapeutic strategies.

Summary In adults with classic Hodgkin lymphoma (cHL), metabolic tumour volume (MTV) is valuable for risk stratification. This systematic review explored the role of volumetric parameters in children, adolescents and young adults (CAYA) with cHL. This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) method. Five databases were searched on 16 October 2024. Eligible studies were peer‐reviewed manuscripts, written in English, published since database inception that included patients ≤21 years of age with a diagnosis of cHL treated with chemotherapy ± radiotherapy with a baseline 18 F‐Fluorodeoxyglucose (F‐FDG) PET/CT scan for MTV quantification. The search strategy identified 3669 studies, of which 35 were eligible for inclusion. Fifteen studies (43%) evaluated a cohort exclusively ≤21 years of age. All eight studies that explored the association of baseline PET parameters with known risk factors identified a significant correlation. Nine of 12 papers (75%) demonstrated a statistically significant correlation with disease response to therapy on PET/CT. Fifteen of 20 papers (75%) demonstrated an independent statistically significant correlation with clinical outcomes. In the CAYAHL population, volumetric PET parameters are valuable for risk stratification despite heterogeneity in results. Future harmonization of the segmentation approach will facilitate incorporation of MTV into clinical practice.

Asymptomatic aortic regurgitation (AR) has traditionally been managed conservatively until symptom onset or overt left ventricular systolic dysfunction. However, adverse myocardial remodeling—detected by myocardial strain, volumetric cardiac magnetic resonance, and fibrosis imaging—often precedes current guideline thresholds for interventions and may be irreversible. Advances in multimodal imaging now enable earlier risk stratification beyond conventional metrics. In parallel, intervention strategies are evolving, including valve repair, valve-sparing root replacement, Ross procedure, and transcatheter aortic valve replacement in selected high-risk patients. This narrative review summarizes contemporary advances in imaging and intervention for asymptomatic AR, while critically appraising current evidentiary and technical limitations that constrain earlier intervention. The review is based on a narrative synthesis of the contemporary literature, drawing from recent clinical studies, imaging advances, and guideline documents rather than a systematic evidence search.

Introduction: Adult hepatitis B vaccination coverage in the United States remains low despite updated national recommendations supporting universal adult immunization. Many adults remain unaware of their susceptibility to hepatitis B virus (HBV) infection. This quality improvement (QI) study evaluated a stepwise “Offer–Offer–Test–Vaccinate” workflow designed to improve hepatitis B vaccine uptake among vaccine-hesitant adults in a primary care setting. Methods: This retrospective QI study was conducted at a single primary care clinic in Rochester, Minnesota. Adult patients (≥19 years) seen between October 1, 2022, and October 1, 2024, were routinely offered hepatitis B vaccination during rooming. Two participating physicians implemented an enhanced workflow in which patients who declined vaccination were counseled and then offered serologic screening using the 2023 CDC-recommended triple panel (HBsAg, anti-HBs, and total anti-HBc). Patients with negative serology were notified via the patient portal and reoffered vaccination along with a link to the CDC Vaccine Information Statement. The primary endpoint was initiation of the hepatitis B vaccine series following receipt of negative serology results. Preliminary series-completion data through October 1, 2025, were also assessed. Results: Among 501 eligible adults, 104 (20.8%) accepted vaccination at the initial offer. Of the 397 who declined, 106 (26.7%) agreed to serologic testing; 91 (85.8%) were seronegative. Among seronegative patients, 41 (45.1%) subsequently accepted vaccination. Integrating serologic testing increased overall vaccination uptake from 20.8% to 28.9%, an absolute increase of 8.2 percentage points and a relative increase of 39.4%. Approximately 2.6 serologic tests were required to generate 1 additional first-dose vaccination. Preliminary series-completion rates were 74.0% among those vaccinated at the initial offer and 87.8% among those vaccinated following serologic testing. Discussion: In this primary care setting, incorporating serologic testing into the workflow was associated with modestly improved hepatitis B vaccination uptake among vaccine-hesitant adults. Serologic results may help re-engage patients by providing personalized immunity information. Implementation considerations include staffing needs, laboratory access, patient portal engagement, and insurance coverage. Conclusion: The “Offer–Offer–Test–Vaccinate” strategy was associated with a modest increase in hepatitis B vaccine uptake among hesitant adults. This EMR-integrated, stepwise approach may offer a feasible and scalable strategy to reduce missed vaccination opportunities and support HBV prevention in adult primary care.

Background and Aims: Liver transplant is a specialized treatment for a spectrum of indications that use a scarce resource. Transplant is guided by principles of justice, equity, and benefit, with a constant conflict between competing interests. Organs are a national resource with a goal of equitable distribution across sites. An AASLD guideline for the evaluation and selection of appropriate candidates for transplant has been available since 2005. Methods: A multidisciplinary writing group of liver transplant experts and a librarian convened over 24 months. The writing group reviewed the literature, generated guideline recommendations, and rated the level of evidence for each recommendation based on the Oxford Center for Evidence-Based Medicine. The group categorized the strength of recommendations based on the level of evidence, risk-benefit ratio, and patient preferences. Conclusions: Liver transplant is a lifesaving procedure that should be offered to selected patients with clear indications and a reasonable prospect of benefit. The evaluation is designed to identify those in need, to outline hurdles to a successful outcome, and to develop an effective transplant plan. The goal of this document is to provide a template for this process.

Abstract Background We performed a prospective study evaluating a baseline GA battery and clinical outcomes in fit older adults (age ≥60 years) with AML and normal cardiac and renal function in the recent E-A NCTN E2906 phase 3 study. A patient-reported outcomes (PRO) assessment of Depression, Activities of Daily Living (ADL), Cognitive Function, Social Support (SS) domains, and comorbidity was performed at study registration to evaluate the prevalence of vulnerabilities and their impact on overall survival (OS) and 30-day induction mortality rates (IM) in this cohort selected for fitness to receive IC. Methods E2906 study design and results have been presented previously [n=727, age ≥60 years, randomized 1:1 to ‘standard 7&3‘ & high dose cytarabine (Arm A) vs. single agent clofarabine (CLO, Arm B), as remission induction (Step 1) and consolidation (Step 2)]. There was no difference in composite complete remission (CCR, 50%) or IM (8.5%), and CLO was inferior for OS. A baseline GA was a key secondary protocol objective, offered to all patients, and n=532 (73%) participated. We assessed Geriatric Depression Scale (GDS, none vs. any depressive symptoms, n=524); cognitive screen using Mini-Mental Exam Section (MMES, score 8/8 vs. <8, n=516); ADL & Instrumental ADL (iADL), (need for assistances vs. not n=526); a Medical Outcomes Study SS Survey (MOS-SS, measured as per unit increase, n=527); a Comorbidity survey ( ≤4 vs. ≥5 patient-reported comorbidities, n=530), patient-reported prescription medications use (PM, 0-3 vs. ≥4, n=519); and a survey of Sexual Desire (n=491) and Sexual Activity (n=477) within 4 weeks of AML diagnosis. Association of GA domains with OS, IM, and achievement of CCR was evaluated using the Chi-squared, Fisher's exact, and Wilcoxon rank sum test. Survival analysis was performed using the Cox proportional hazards models, adjusted for treatment arm. All p-values are 2-sided. Results The median age among those participating in GA battery was 67 yrs (range 60-85), including 38% age ≥70. There were 42% females, and ECOG performance status was 0 (28%), 1 (54%), 2 (16%), or 3 (2%). Central Cytogenetic review was classified (ELN2017) as Favorable (3%), Intermediate (66%), and Adverse (31%) risk. There was a notable rate of GA scores outside ‘normal’ clinical cutoff, including Depression (GDS 31%), cognitive and functional impairment [MMSE (37%), ADL (25%) and iADL (32%)], ≥5 Comorbidities (23%), and ≥4 PM's (44%). 81% & 76%, respectively, reported no sexual activity and low/none sexual desire. MOS-SS tended to be high in this cohort [mean (SD) score 87 (17)]. We observed a significant association of GA domains with OS & IM. For OS, absence of depressive symptoms [GDS, Hazard Ratio (HR) 0.79, 95% confidence Intervals (CI) 0.64-0.97, p=0.025)], MMES 8/8 (HR 0.78, 95%CI 0.64-0.96, p=0.016), requiring no assistance with ADLs (HR 0.65, 95%CI 0.52-0.82, p<0.001) and iADLs (HR 0.69, 95%CI 0.57-0.85, p<0.001), and ≤4 Comorbidities (HR 0.68, 95%CI 0.54-0.84, p=0.001) were significant for superior OS; use of ≥4 PM's was associated with inferior OS (HR 1.32, 95%CI 1.09-1.61, p=0.005). There was no association of sexual activity/desire, BMI ≥30 kg/m2, or MOS-SS with OS. IM was significantly higher among those with any depression symptoms (GDS, p=0.005), any ADL (p=0.010) or iADL (p=0.013) impairment, ≥5 comorbidities (p=0.037) and ≥4 PM's (p=0.001); there was no association with MOS-SS or MMES. There was no significant association of GA scores with cytogenetic risk group or with CCR rates. Only ADL independence (p=0.048), and possibly Comorbidity ≤4 (p=0.071), were associated with proceeding to Step 2. Conclusions In this large prospective cohort of fit older adults with AML selected to receive IC, we observed high rates of PRO-assessed GA vulnerability, which was significantly associated with inferior OS and higher IM rates, and (for ADL impairment) lower rates of proceeding to consolidation therapy. This suggests that functional and cognitive impairments are prevalent and can significantly impact outcome even in fit older adults. Despite potential long-term OS advantages of IC previously observed in E2906, efforts to systematically recognize those at higher risk based on GA PROs are needed to help identify patients who may be more appropriate for study of lower intensity treatment options to mitigate impact on IM and OS. SImilarly we plan to evaluate the potential benefit of GA-driven supportive care to improve patients' outcomes.