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Introduction/Purpose The multicenter, prospective, single‐arm, controlled, non‐randomized SCENT trial on flow diverter (FD) treatment for intracranial aneurysms (IA) was analyzed for patients’ age and IA characteristics impacting stroke and occlusion rates over 5 years. Materials and Methods Impact on major ipsilateral stroke and IA occlusion was studied by stratifying age as </= 65 years versus >65 years. Twice as many subjects treated were </= 65 years old (n=119/180). Product‐limit (Kaplan‐Meier) estimates of time to both endpoints, stratified by age group, were created. Univariate predictors of time to stroke were identified by including candidate variables in univariable proportional hazards regression models. Those variables found to be significant (p<0.10) at the univariate level were entered into a multivariable survival model to identify independent predictors. The stepwise selection produced a final reduced model with a significance level to both enter and stay set at 0.05. Results When parent artery stenosis and IA size were entered into a multiple‐stepwise survival model, only stenosis remained as an independently significant predictor of time to stroke. At 3‐year follow‐up, there were a total of 23 strokes (12.8%), with 11 (47.8%) occurring in subjects </= 65 years; there was a greater risk for seniors (HR1.96, 95% CI 0.83‐4.78, p=.122). Four patients (4/180; 2.2%) experienced aneurysm ruptured within the first week post‐treatment, with 3 being </= 65 and the fourth aged 66 years. No new strokes were reported between 3 and 5 years. Complete IA occlusion rates for seniors were 60.0% (33/55), 67.6% (25/37), and 85.7% (18/21) at 12, 36, and 60 months, respectively, as compared to 79.1% (87/110), 82.5% (66/80), and 91.8% (56/61) for younger subjects. The time to complete IA occlusion was shorter in younger patients (HR1.53, 95% CI 1.07‐2.19, p=.020). Five subjects (2.8%) underwent retreatment, 2 in 60‐year‐old patients, and one each aged 64, 70, and 75. Conclusion Stroke, early rupture risk, and aneurysm occlusion in patients treated with FD are related to age and pre‐existing parent artery stenosis, IA size, and location. With demographic shifts, future treatments need to focus on expedited and improved healing.

INTRODUCTION While prognostic understanding (PU) is important for all patients (pts) considering hematopoietic stem cell transplantation (HCT), it may be particularly important for older (&gt;65 years), medically infirm, and/or frail pts deciding whether to undergo allogeneic HCT (allo-HCT). This abstract reports on PU and concordance with transplant physician (hereafter MD) PU for pts participating in an ongoing seamless, phase II-III randomized clinical trial (ACE-BMT) comparing 4-arms: a pt-administered comorbidity management intervention (CM), specialist-administered palliative care (PC), a combined arm of CM and PC to standard of care. Here we report preliminary data on the concordance between pt and MD PU on the chance of cure 1-year (yr) post allo-HCT. METHODS Pt PU was compared to MD PU (gold standard) to determine concordance. MD and pt answers were compared on a single validated question asked at enrollment to the study (typically 2 weeks prior to HCT). Both pts and MD's estimated the chance of cure 1 yr after allo-HCT by selecting one of six possible response options: very good (more than 90%), good (75-90%), better than 50% (50-74%), worse than 50% (25-49%), bad (10-24%) or very bad (less than 10%). PU was “concordant” or “accurate” if MD and pt selected the same response option. Pts with discordant PU were labeled “pessimistic” if the pt selected a response option with a lower chance of cure than the MD (and “optimistic” if a higher chance). Response options were further simplified to greater than or less than 50% chance of cure and MD and pt PU were compared again. Descriptive statistics, chi-square for categorical and t-tests for continuous variables were used. Logistic regression was used to determine the association between pt prognostic concordance and pt socio-demographic and clinical characteristics. RESULTS All pts consented to date were included (n=358), except those who did not answer the prognosis question (n=61). 54.2% (n=194) had HCT-Comorbidity Index (HCT-CI) of ≥3, 67.9% (n=243) were older than 65 yrs and 4.5% (n=16) were frail, defined by walk speed &lt;0.8 m/s. Median age was 68 yrs (range 20-80). 39.7% (n=141) were female. 89.9% (n=322) identified as White, 4.2% (n=15) Asian, and 1% each as Black/African American and Native Hawaiian/Other Pacific Islander. 5.3% (n=19) identified Hispanic. 11.5% (n=44) had high school education or less. 54.1% (n=183) made less than $100,000/yr. 40.1% (n=136) had acute myelogenous leukemia, 25.4% (n=86) had high-risk myelodysplastic syndrome and 10.6% (n=36) had a myeloproliferative cancer. 72.1% (n=245) had matched, 82.5% (n=283) unrelated and 95.0% (n=36) peripheral blood allo-HCT. 9% (n=31) had KPS of 100%, 35% (n=121) KPS 90%, and 47.5% (n=147) KPS 80%. Pts reported having a very good, good, better than 50%, worse than 50% and bad/very bad chance of cure 1 yr post allo-HCTL 34.4% (n=123), 30.7% (n=110), 26.0% (n=93), 7.3% (n=26) and 1.7% (n=6), respectively. 91.1% (n=326) of pts felt they had a &gt;50% chance of being cured 1 yr post allo-HCT. MD answers were missing for 159/358 (44.4%) pts. MDs reported pt had a very good, good, better than 50%, worse than 50% and bad/very bad chance of being cured 1 yr post allo-HCT, 3.0% (n=6), 6.5% (n=13), 52.8% (n=105), 35.7% (n=71) and 2% (n=4) respectively. 62.3% (n=124) of MDs felt the pt had a &gt;50% chance of being cured 1 yr post allo-HCT. For the subset of pts with MD prognostic data (n=199), pt's PU was concordant 20.6% (n=41) of the time when compared across all 6 response options. Overall, 71.9% (n=143) of pts erred toward optimism, while 7.5% (n=15) of pts were pessimistic. 60.8% of MD and pts agreed on prognosis when dichotomized to better or worse than 50% chance of being cured 1 yr post allo-HCT. Prognostic concordance was not significantly associated with any pt socio-demographic factors, HCT-CI or KPS via descriptive statistics or regression analysis. CONCLUSIONS In this prospective randomized trial focusing on a population of older, medically infirm, and/or frail pts receiving allo-HCT, pts' PU was not concordant with MD prognosis approximately 80% of the time. While some pts were pessimistic, the majority overestimated the likelihood they would be cured of disease compared to MD estimates. Future studies should investigate the true accuracy of both MD and pt prognosis, as well as how to improve communication about prognosis and pt PU (if inaccurate based on best available information) prior to HCT.

Abstract BACKGROUND Patients with meningiomas that have progressed after surgery and/or radiation have limited treatments. Loss of NF2 and CDKN2A/B are common in higher-grade meningiomas and promote meningioma progression. We evaluated the efficacy of abemaciclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor, as part of Alliance A071401, a genomically-driven phase II trial in recurrent or progressive meningiomas. METHODS Eligible patients (pts) with grade 2/3 tumors and NF2 mutations or CDK pathway alterations were treated with abemaciclib 200 mg orally twice daily. Two co-primary endpoints were used: progression-free survival at 6 months (PFS6) and response rate (RR); the trial would be declared positive if either endpoint was met. Twenty-four evaluable pts provided ≥85% power to detect a PFS6 ≥41.5% (vs. null 15%; alpha=0.02), and ≥89% power to detect RR ≥20% (vs. null 2.5%; alpha=0.021). RESULTS Of 83 pts screened while the abemaciclib arm was open between September 15, 2021 and October 3, 2022, 36 eligible pts received abemaciclib. The observed PFS6 rate in the first 24 evaluable pts was 54% (95% CI 33-75%), thus the study met PFS6 endpoint. Of all 35 evaluable pts, median PFS was 7.6 months (95% CI 3.6-17.1 months), estimated 6-month PFS was 55% (95% CI 40-75%) and estimated 6-month OS was 88% (95% CI 77-100%). No objective responses were observed. Of the 36 pts who started treatment, two had a grade 4 adverse event at least possibly related to treatment which included ALT elevation(1), AST elevation(1) and vomiting(1). Patients with NF2 alterations (n=24) had favorable PFS6 outcomes (58%, 95% CI 37-78%) compared to those with CDK (n=4, 25%, 95% CI 1-81%) and CDK+NF2 alterations (n=7, 29% 95% CI 4-71%), (Fisher’s Exact p=0.036). CONCLUSIONS Abemaciclib was well-tolerated and resulted in improved PFS6, meeting the trial’s co-primary endpoint. Abemaciclib warrants further investigation for the treatment of patients with progressive meningiomas.

Abstract Chronic lymphocytic leukemia (CLL) patients are immunocompromised and highly vulnerable to serious recurrent infections. Conventional dendritic cells (cDCs) and plasmacytoid DCs (pDCs) are principal sensors of infection and are essential in orchestrating innate and adaptive immune responses to resolve infection. This study identified significant deficiencies in six functionally distinct DC subsets in blood of untreated CLL (UT-CLL) patients and selective normalization of pDCs in response to acalabrutinib (a Bruton tyrosine kinase inhibitor) therapy. DCs are continuously replenished from hematopoiesis in bone marrow (BM). Four BM developmental intermediates that give rise to cDCs and pDCs were examined and significant reductions of these were identified in UT-CLL patients supporting a precursor/progeny relationship. The deficiencies in blood DCs and BM DC progenitors were significantly associated with alterations in the Flt3/FL signaling pathway critical to DC development and function. Regarding clinical parameter, cDC subset deficiencies are associated with adverse prognostic indicators of disease progression, including IGHV mutation, CD49d, CD38, and ZAP-70 status. Importantly, UT-CLL patients with shared DC subset deficiencies had shorter time-to-first treatment (TTFT), uncovering a profound alteration in innate immunity with the potential to instruct therapeutic decision-making.

Three-dimensional reconstruction of airways has shown increased luminal area in patients with COVID-19 and post-acute sequelae of COVID-19 when compared with healthy controls. These findings suggest the role of large conducting airways in the pathogenesis of post-acute sequelae of COVID 19.

Background The most common cause of preventable death after injury is haemorrhage. Resuscitative endovascular balloon occlusion of the aorta is intended to provide earlier, temporary haemorrhage control, to facilitate transfer to an operating theatre or interventional radiology suite for definitive haemostasis. Objective To compare standard care plus resuscitative endovascular balloon occlusion of the aorta versus standard care in patients with exsanguinating haemorrhage in the emergency department. Design Pragmatic, multicentre, Bayesian, group-sequential, registry-enabled, open-label, parallel-group randomised controlled trial to determine the clinical and cost-effectiveness of standard care plus resuscitative endovascular balloon occlusion of the aorta, compared to standard care alone. Setting United Kingdom Major Trauma Centres. Participants Trauma patients aged 16 years or older with confirmed or suspected life-threatening torso haemorrhage deemed amenable to adjunctive treatment with resuscitative endovascular balloon occlusion of the aorta. Interventions Participants were randomly assigned 1 : 1 to: standard care, as expected in a major trauma centre standard care plus resuscitative endovascular balloon occlusion of the aorta. Main outcome measures Primary: Mortality at 90 days. Secondary: Mortality at 6 months, while in hospital, and within 24, 6 and 3 hours; need for haemorrhage control procedures, time to commencement of haemorrhage procedure, complications, length of stay (hospital and intensive care unit-free days), blood product use. Health economic: Expected United Kingdom National Health Service perspective costs, life-years and quality-adjusted life-years, modelled over a lifetime horizon. Data sources Case report forms, Trauma Audit and Research Network registry, NHS Digital (Hospital Episode Statistics and Office of National Statistics data). Results Ninety patients were enrolled: 46 were randomised to standard care plus resuscitative endovascular balloon occlusion of the aorta and 44 to standard care. Mortality at 90 days was higher in the standard care plus resuscitative endovascular balloon occlusion of the aorta group (54%) compared to the standard care group (42%). The odds ratio was 1.58 (95% credible interval 0.72 to 3.52). The posterior probability of an odds ratio > 1 (indicating increased odds of death with resuscitative endovascular balloon occlusion of the aorta) was 86.9%. The overall effect did not change when an enthusiastic prior was used or when the estimate was adjusted for baseline characteristics. For the secondary outcomes (3, 6 and 24 hours mortality), the posterior probability that standard care plus resuscitative endovascular balloon occlusion of the aorta was harmful was higher than for the primary outcome. Additional analyses to account for intercurrent events did not change the direction of the estimate for mortality at any time point. Death due to haemorrhage was more common in the standard care plus resuscitative endovascular balloon occlusion of the aorta group than in the standard care group. There were no serious adverse device effects. Resuscitative endovascular balloon occlusion of the aorta is less costly (probability 99%), due to the competing mortality risk but also substantially less effective in terms of lifetime quality-adjusted life-years (probability 91%). Limitations The size of the study reflects the relative infrequency of exsanguinating traumatic haemorrhage in the United Kingdom. There were some baseline imbalances between groups, but adjusted analyses had little effect on the estimates. Conclusions This is the first randomised trial of the addition of resuscitative endovascular balloon occlusion of the aorta to standard care in the management of exsanguinating haemorrhage. All the analyses suggest that a strategy of standard care plus resuscitative endovascular balloon occlusion of the aorta is potentially harmful. Future work The role (if any) of resuscitative endovascular balloon occlusion of the aorta in the pre-hospital setting remains unclear. Further research to clarify its potential (or not) may be required. Trial registration This trial is registered as ISRCTN16184981. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/199/09) and is published in full in Health Technology Assessment; Vol. 28, No. 54. See the NIHR Funding and Awards website for further award information.