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Abstract Background Classic progressive supranuclear palsy RS syndrome (PSP‐RS) is characterized by early postural instability/falls and vertical supranuclear gaze palsy, although other signs/symptoms can occur, for example, axial rigidity, bradykinesia, and cognitive dysfunction. The Movement Disorders Society‐PSP (MDS‐PSP) criteria consider probable PSP‐RS a homogenous syndrome, but this has not been tested. Objectives We aim to investigate relationships between signs/symptoms of PSP‐RS beyond its core features and determine whether PSP‐RS is a homogeneous syndrome. Methods 118 participants who met MDS‐PSP criteria for probable PSP‐RS were analyzed. All participants received an independent clinical diagnosis based on clinical judgment. We first performed a Network Analysis using qgraph with Spearman's correlation to quantify relationships between 16 signs/symptoms followed by a k‐means clustering analysis using the same signs/symptoms to identify possible heterogeneity of the PSP‐RS designation. Results Five network clusters were identified, reflecting: (1) tremor, (2) sensitivity to bright light, (3) oculomotor function, (4) cognition, and (5) akinetic‐rigidity‐praxis. Worse akinetic‐rigidity was associated with better oculomotor function, but worse cognition. Cluster analysis revealed two clusters. Cluster I ( n = 89) had more severe clinical features than Cluster II ( n = 29). Cluster II had a higher frequency of participants (37.9%) clinically judged as not PSP‐RS: these participants were less likely to have PSP pathology on autopsy ( P = 0.03). Conclusions Some signs/symptoms of PSP‐RS strongly associate and are more likely to co‐occur. PSP‐RS, as defined by the MDS‐PSP criteria includes a subset of participants not clinically judged as PSP‐RS who are less likely to have PSP pathology.

ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the ASCO Guidelines Methodology Manual . ASCO Guidelines follow the ASCO Conflict of Interest Policy for Clinical Practice Guidelines . Clinical Practice Guidelines and other guidance (“Guidance”) provided by ASCO is not a comprehensive or definitive guide to treatment options. It is intended for voluntary use by clinicians and should be used in conjunction with independent professional judgment. Guidance may not be applicable to all patients, interventions, diseases or stages of diseases. Guidance is based on review and analysis of relevant literature and is not intended as a statement of the standard of care. ASCO does not endorse third-party drugs, devices, services, or therapies and assumes no responsibility for any harm arising from or related to the use of this information. See complete disclaimer in Appendix 1 and 2 (online only) for more. PURPOSE To develop a clinical practice guideline and recommendations for symptom management of patients with well-differentiated grade 1 to grade 3 metastatic gastroenteropancreatic neuroendocrine tumors. METHODS ASCO convened an Expert Panel to develop a clinical practice guideline by reviewing the literature for relevant guidelines, systematic reviews, randomized controlled trials (RCTs), and observational studies to develop recommendations for clinical practice. RESULTS The literature review identified eight guidelines, 19 systematic reviews, and three RCTs that informed the development of guideline recommendations. RECOMMENDATIONS Recommendations are included for carcinoid syndrome, carcinoid heart disease and carcinoid crisis, and functional pancreatic neuroendocrine tumor syndromes. Recommendations are provided for surgical management, liver-directed therapy, and systemic therapy options, as well as palliative care. Limited guidance is provided for sequencing of interventions. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines .

Importance Many older adults with advanced cancer never communicate goals of care or treatment preferences to their clinicians, raising the risk that care received will not match their values. Scalable models of care may help surmount this barrier. Objective To test whether a combined patient and clinician intervention increased the rate of advance care planning (ACP) documentation in large health care systems. Design, Setting, and Participants This stepped-wedge cluster randomized clinical trial using an open cohort design included patients aged 65 years or older with advanced cancer seen at oncology clinics in 3 health care systems located in the US South, Midwest, and Mid-Atlantic regions from April 1, 2020, to November 30, 2022. Data collection ended in 2024. Intervention The intervention involved delivering brief evidence-based patient-facing video decision aids available in 25 languages as well as goals-of-care communication training to oncology clinicians. Patients in the control period received usual care. Main Outcomes and Measures The primary outcome was ACP documentation, which included any electronic health record documentation of a goals-of-care conversation, palliative care, hospice, or limitation of life-sustaining treatments, identified via a validated natural language processing program. Analysis was performed on an intention-to-treat basis. Results Twenty-nine practices, comprising 13 800 unique eligible patients with a total of 29 357 repeated measurements, were included (mean [SD] age, 74.5 [6.6] years; 52.3% men [15 344 of 29 357 measurements]). The proportion of patients with ACP documentation was greater in the intervention phase compared with the usual care phase (adjusted rate difference, 6.8% [95% CI, 2.8%-10.8%]; P < .001). ACP documentation in the intervention phase occurred among 3980 of 15 754 patients (25.3%) (goals-of-care conversation, 21.4% [3377 of 15 754]; palliative care, 9.6% [1517 of 15 754]; hospice, 5.4% [847 of 15 754]; and limitation of life-sustaining treatments, 7.2% [1128 of 15 754]). In comparison, ACP documentation in the usual care phase occurred among 2834 of 13 603 patients (20.8%) (goals-of-care conversation, 16.8% [2281 of 13 603]; palliative care, 9.5% [1287 of 13 603]; hospice, 5.3% [724 of 13 603]; and limitation of life-sustaining treatments, 8.4% [1149 of 13 603]). Conclusions and Relevance In this stepped-wedge cluster randomized clinical trial for older adults with advanced cancer, a bundled evidence-based decision aid and communication training intervention increased the proportion of older patients with ACP documentation. This approach offers an innovative paradigm with a clinically meaningful increase in ACP documentation, a widely used quality metric that reflects high-quality patient-centered care delivery. Trial Registration ClinicalTrials.gov Identifier: NCT03609177

Abstract Obstetric training programs typically offer limited formal education on placental pathology; yet, in practice, obstetric providers are expected to incorporate placental pathology findings into the overall evaluation of obstetric complications. In this narrative review, we briefly review pathology classifications and then delve deeper into pathology findings that may change clinical decision‐making, specifically highlighting pathologic lesions with a recurrence risk and recommended management for subsequent pregnancies. Last, we present specific recommendations on how to improve clinical interpretability and utility of placental pathology reports for obstetrical practice.

PURPOSE The combination of the Bruton tyrosine kinase inhibitor ibrutinib with bendamustine-rituximab for first-line treatment of mantle cell lymphoma (MCL) prolonged progression-free survival (PFS), but without improvement in overall survival (OS), likely because of toxicity. Acalabrutinib was shown to be efficacious and less toxic than ibrutinib in a head-to-head trial in chronic lymphocytic leukemia and therefore might lead to better outcomes in MCL. METHODS Patients 65 years and older with previously untreated MCL received acalabrutinib (100 mg twice daily) or placebo (until disease progression or unacceptable toxicity), plus six cycles of bendamustine (90 mg/m 2 once daily; days 1 and 2) and rituximab (375 mg/m 2 as a single dose; day 1) followed by rituximab maintenance in responding patients for 2 years. Crossover to acalabrutinib at disease progression was permitted. The primary end point was PFS per the independent review committee; overall response rate and OS were secondary end points. RESULTS In total, 598 patients were randomly assigned, with 299 in each arm. At a median follow-up of 49.8 months using the reverse Kaplan-Meier method, the median PFS was 66.4 months in the acalabrutinib arm and 49.6 months in the placebo arm (hazard ratio [HR], 0.73 [95% CI, 0.57 to 0.94]; P = .0160). Benefit was seen across all subgroups, including those with high-risk features. Overall response/complete response rates were 91.0%/66.6% and 88.0%/53.5% in the acalabrutinib and placebo arms, respectively. OS was not significantly different (HR, 0.86 [95% CI, 0.65 to 1.13]; P = .27). Grade 3 or greater adverse events were reported in 88.9% and 88.2% in the acalabrutinib and placebo arms, respectively. CONCLUSION The combination of acalabrutinib with bendamustine-rituximab significantly improved PFS. Clinical benefit of acalabrutinib with bendamustine-rituximab was achieved with manageable toxicity.

Abstract Objective In utero fetal spina bifida repair decreases the risk for cerebrospinal fluid (CSF) diversion including ventriculoperitoneal (VP) shunt placement, reverses hindbrain herniation, and improves motor function with a higher likelihood of independent ambulation. Unfortunately, in utero surgery can be complicated by preterm delivery. The goal of this study was to compare pregnancy and neonatal outcomes between individuals who delivered very preterm, and those who delivered later in gestation following in utero spina bifida repair. Methods Data from the North American Fetal Therapy Network Fetal Myelomeningocele Consortium Registry collected from 2011 to 2024 were analyzed. Three cohorts of patients were categorized by gestational age at delivery and compared: <30 weeks, 30–34 weeks, and >34 weeks. Comparisons between groups for maternal and delivery outcomes were completed for the entire cohort and then analyzed for those with available CSF diversion data up to 1 year of life. Chi‐square or Fisher's exact tests were used to compare categorical variables, and Kruskal–Wallis tests were used to determine if there are significant differences between the distributions of the three groups. A p ‐value <0.05 was considered significant. Results A total of 1213 patients were analyzed (<30 weeks, n = 111 [9.2%]; 30–34 weeks, n = 323 [26.6%]; >34 weeks, n = 779 [64.2%]). Overall fetal and neonatal mortality was 2.2%, 85% of which occurred in the <30‐week cohort, where perinatal mortality was 21%. Latency from fetal surgery to delivery averaged 2.1 weeks for the <30‐week group. Rates of abruption, chorioamnionitis, and spontaneous labor were higher in the <30‐week group compared to later gestational age cohorts. Neonatal morbidity was also significantly higher in the <30‐week cohort for sepsis, apnea, respiratory distress, patent ductus arteriosus, intraventricular hemorrhage, and periventricular leukomalacia in the <30‐week cohort. CSF diversion data were available for 677 neonates (<30 weeks, n = 53; 30–34 weeks, n = 186; >34 weeks, n = 438). There was no significant difference in VP shunt placement between the different gestational age groups. Conclusion Very preterm birth following in utero spina bifida repair results in significant perinatal mortality and neonatal morbidity. Delivery prior to 30 weeks of gestation occurs in 9% of patients after in utero spina bifida repair, resulting in a 21% perinatal mortality rate. However, even among those who delivered very preterm, a reduction in VP shunt rates, a benefit of in utero repair, appears to be preserved. Further data are warranted to assess the impact of prematurity following in utero surgery on ambulation and developmental outcomes.

AbstractIntroductionActive learning engages learners in constructing knowledge through interactive strategies such as simulation, small‐group discussion, and peer instruction. Although recognized as a superior approach to traditional passive learning, its adoption has been inconsistent. Barriers include reliance on traditional lectures, lack of training, and limited time to develop materials. Simulation educators have a unique skill set that may inform and support active learning initiatives.MethodsFifteen emergency medicine simulation experts convened to define the unique skill set of simulation educators and identify transferable simulation‐based medical education (SBME) skills and concepts to promote effective active learning beyond the simulation lab. Workgroup members are simulation education directors who have undergone specialized training in SBME. During biweekly meetings over 6 months, workgroup members reviewed primary literature in SBME and active learning, along with relevant simulation educator training materials. Objectives were achieved through iterative review, group conceptualization, and expert consensus.Unique treatmentThe increasing prevalence of SBME in medical education, along with the growth of simulation fellowships, has produced a group of education experts with shared competencies. Simulation educators acquire expertise in psychological safety, facilitation, communication, and debriefing, through specialized training and extensive experience. These skills are critical for active learning environments where learners benefit from structured, engaging, and psychologically safe experiences.Implications for educatorsKey transferable SBME topics were identified for use in active learning environments outside of the simulation lab: (1) psychological safety, (2) facilitation strategies, and (3) communication techniques. Transferable tools and concepts were identified to promote efficacy and learner engagement during active learning in diverse environments. Simulation educators’ expertise is an underutilized resource for faculty development initiatives aimed at advancing active learning. This work advocates for leveraging simulation educators’ skills to close the active learning implementation gap, enhance learner outcomes, and meet the evolving needs of contemporary medical education.

Objectives: Systemic beta-blockers are highly effective for the management of infantile hemangiomas (IH), but little is known about infants who do not adequately respond. We aimed to describe the characteristics and outcomes of suboptimal responders to standard-dose systemic beta-blockers in infants with IH. Methods: This is a multicenter retrospective cohort study to evaluate demographics, IH lesion characteristics, and treatment specifics of infants with IH with suboptimal response to baseline standard-dose propranolol treatment. Clinical response was used to assess the outcome after a therapeutic change. Results: Twenty-five infants were included in this study. Seven (28%) had segmental IH, 16 (64%) focal, and 2 (8%) indeterminate. The IHs were located on the head and neck in 21 (84%) infants, with 24 (96%) having a deep or combined component. Therapy changes after standard-dose propranolol treatment failure, most commonly by escalating propranolol dose to ≥2.5 mg/kg/d (59%) or surgical interventions (29%), were associated with good therapeutic effects. Conclusion: Among suboptimal responders to standard-dose systemic propranolol, IHs with a deep or combined component and located on the head and neck were the most common. This retrospective study was largely descriptive in nature with additional exploratory analyses. However, it is still encouraging that for patients with a suboptimal clinical response, higher propranolol doses of ≥2.5–3 mg/kg/d or second-line treatments with surgical interventions or systemic steroids can be considered as potentially safe and effective alternatives. Level of evidence: Level 4 (case series).

Abstract Introduction DISTINCT is a randomized controlled trial evaluating passive recharge burst SCS compared with CMM in improving pain and pain‐related physical function in patients suffering from chronic back pain without prior lumbar surgery, and for whom corrective surgery is not an option. Sub‐analyses of outcome measures are presented for a subset implanted with paddle leads at both 6 and 12 months. Objective To investigate the treatment effect of using BurstDR‐capable SCS in nonsurgical low back pain (NSLBP) patients with paddle leads. Methods An independent board‐certified spine surgeon reviewed each case, confirming a lack of corrective surgical options. Out of 29 sites and 115 implants, 10 sites implanted 50 patients with paddle leads. Primary and secondary endpoints assessed improvements in low back pain intensity (NRS), low back pain‐related disability (ODI), pain catastrophizing (PCS), and patient global impression of change (PGIC). Results Data for patients with NSLBP and implanted with paddle leads are available for 47 and 44 patients at 6 and 12 months, respectively. Patients reported significant reductions in pain relief at 6 and 12 months, decreasing from 7.8 ± 1.2 at baseline to 2.0 ± 1.6 and 2.2 ± 2.2, respectively ( p < 0.0001). Disability was substantially reduced (> 20 points) from severe to mild at 6 and 12 months; ODI reduced from 54.4 ± 15.0 at baseline to 19.9 ± 14.1 and 22.1 ± 13.6, respectively ( p < 0.0001). Pain catastrophizing improved to reflect the average of a non‐chronic pain population; decreased from 27.6 ± 13.1 at baseline to 8.1 ± 8.2 and 7.8 ± 9.9 ( p < 0.0001). 93.2% of patients reported a moderately better‐much‐improved outcome on PGIC. Ten complications occurred in 9 patients, 3 being severe device‐related events. Two explants were required; one due to infection and one due to persistent pain at the IPG site, and one lead‐related event was resolved by surgical repositioning. Conclusions Passive recharge burst using paddle leads provides substantial relief to patients suffering from severe, debilitating, NSLBP. Patients report significant improvements in pain, function, and pain‐related emotional distress. In addition, the rate of adverse events is low, supporting a favorable safety profile.