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PURPOSE EA1181 (ClinicalTrials.gov identifier: NCT04266249 ) is a single-arm trial evaluating neoadjuvant taxane, trastuzumab, and pertuzumab (THP) in patients with clinical stage II/IIIa human epidermal growth factor receptor 2 (HER2)–positive breast cancer. This report focuses on the secondary end points of pathologic complete response (pCR) rates and associated factors. The primary end point—3-year recurrence-free survival among patients achieving a pCR (ypT0/Tis, ypN0)—will be reported when data mature. METHODS Patients received four cycles of trastuzumab and pertuzumab (HP) with either once per week paclitaxel (12 weeks) or docetaxel (every 3 weeks for four cycles), followed by surgery. Clinicopathologic characteristics were assessed in all patients. The HER2DX pCR score was determined using diagnostic biopsy samples in a representative subset. Logistic regression models identified factors associated with pCR. RESULTS A total of 2,175 patients were enrolled (781 HER2+/estrogen receptor‑negative [ER–]; 1,394 HER2+/ER+). Of 2,141 patients who initiated THP, the overall pCR rate was 43.8%: 63.7% in HER2+/ER– and 32.4% in HER2+/ER+ tumors. Higher pCR rates were observed in tumors that were ER-negative or low ER expressing, progesterone receptor-negative or low expressing, HER2 immunohistochemistry (IHC) 3+, and in patients treated with once per week paclitaxel. T3 disease was associated with a lower pCR rate in HER2+/ER– tumors; otherwise, tumor (T) and nodal (N) stage did not significantly affect pCR. Among 569 patients assessed for HER2DX pCR scores, a high score was independently associated with higher pCR rates, after adjustment for clinicopathologic variables. CONCLUSION Neoadjuvant THP achieved pCR in nearly two-thirds of patients with HER2+/ER– and one third with HER2+/ER+ breast cancer. Low hormone receptor expression, HER2 IHC 3+ status, once per week paclitaxel use, and a high HER2DX pCR score were independent predictors of pCR. These findings should help optimize risk stratification and treatment personalization for patients with HER2-positive breast cancer.

Background New antiamyloid therapies (AAT) for treating patients with early Alzheimer disease (AD) have become available in the past 3 years. Although AAT can be beneficial in slowing progression of AD, they also come with potentially serious side effects, particularly for patients requiring anticoagulation or thrombolysis for cardiovascular conditions. Given that most patients with AD are older and likely to have cardiovascular risk factors, there is urgent need for additional guidance for clinicians about potential risks and benefits associated with AAT for patients with cardiovascular comorbidities, best practices for management of these patients, and special considerations with respect to emergency evaluation and treatment of patients on AAT who develop acute neurological symptoms. Methods The American Heart Association convened 75 multidisciplinary experts for the Amyloid‐Related Imaging Abnormalities Summit: Cardiovascular and Stroke Considerations for β‐Amyloid Immunotherapy in AD in July 2025. These experts were divided into 8 work groups to evaluate the current evidence related to AAT usage in patients with cardiovascular risk factors and conditions and develop consensus‐based guidance for clinicians. Results This statement outlines the outcomes of the Summit, including considerations for prescribers, primary care professionals, emergency personnel, and health care system stakeholders. These considerations are intended to improve identification of patients as appropriate candidates for AAT, management of patients with co‐occurring AD and cardiovascular conditions, and their emergency evaluation and treatment. The statement also includes guidance for shared decision‐making, implementation of system changes for improving dementia care, and recommendations for future research and data collection to add to the body of evidence for treating patients with concomitant AD and cardiovascular conditions. Conclusions Building on lessons learned from the establishment of stroke systems of care, the consensus‐based considerations outlined in this document can serve as a foundation for AD systems of care aimed at ensuring optimal use of these ground‐breaking therapies.

ABSTRACT Endoluminal flow diverters are increasingly used to treat cerebral aneurysms. Despite good aneurysm occlusion efficacy, delayed ischemic complications due to side branch or perforator occlusion remain a serious concern. However, the mechanisms leading to side branch occlusion are poorly understood. To investigate these mechanisms, a combination of animal and computational models was utilized. Flow diverters were deployed in four rabbit superior mesenteric artery (SMA) and studied with computational fluid dynamics (CFD) and a previously developed fibrin dynamics model. Subject‐specific vascular models were reconstructed from 3D rotational angiography images and flow conditions were derived from Doppler ultrasound velocity measurements. Flow diverting devices were virtually deployed within the vascular models under guidance from angiography images. Coupled flow and fibrin production, transport, and adhesion simulations were carried out and the effects of fibrin accumulation at the origin of jailed side branches after flow diverter implantation were analyzed. The results of the computational models suggest significant fibrin accumulation across the struts of all flow diverting devices jailing side branches. Larger accumulation was observed at the more distal branches. However, minor flow alterations were produced which were not detectable in angiography sequences. These results were in agreement with experimental observations. On the other hand, fibrin accumulation alone did not explain complete side branch occlusions, which are likely the result of the interaction between initial fibrin accumulation and subsequent cell migration from the peripheral parent artery.

ACCESS is a prospective, multicenter phase II trial evaluating peripheral blood stem cell (PBSC) transplantation using 4-7/8 HLA-mismatched unrelated donors (MMUD) with post-transplant cyclophosphamide (PTCy), tacrolimus, and mycophenolate. Adults undergoing first HCT with myeloablative (MAC) or reduced-intensity/nonmyeloablative (RIC/NMA) conditioning were enrolled, with donors aged 18-35 years and matched at 4/8-7/8 HLA loci by high-resolution typing. This expanded analysis includes all enrolled adult PBSC recipients, including the protocol-specified RIC/NMA cohort expansion, to improve precision of outcome estimates and provide descriptive analyses by HLA match level. Among 268 adults, 183 received 7/8 and 85 received <7/8 MMUD grafts; 82.4% of the <7/8 cohort received 6/8 grafts. Median follow-up among survivors was 11.9 months. At 1-year, overall survival was 78.6% (95% CI, 71.9-83.9) in the 7/8 cohort and 85.6% (95% CI, 76.0-91.5) in the <7/8 cohort. One-year relapse, non-relapse mortality, and GVHD-free relapse-free survival were 17.1%, 13.7%, and 51.1% versus 22.8%, 8.4%, and 54.6%, respectively. The cumulative incidence of grade II-IV and grade III-IV acute GVHD by day 100 was 36.6% and 7.7% in the 7/8 cohort versus 28.3% and 5.9% in the <7/8 cohort. Moderate-to-severe chronic GVHD at 1 year was 11.3% versus 7.7%, respectively. Among adult ACCESS recipients treated on a uniform young-donor PBSC/PTCy platform, short-term outcomes with predominantly 6/8 MMUD transplantation were encouraging. Because donor match level was not prospectively assigned and between-group comparisons were exploratory, these findings are descriptive and should not be interpreted as establishing equivalence with 7/8 MMUD transplantation. (Registered as NCT04904588 at CT.gov)

Introduction Allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML) entails prolonged recovery, serious complications, functional limitations, psychological distress, and extended isolation to prevent infection. During the peak of the COVID-19 pandemic, treatment disruptions, restricted caregiver access, and intensified isolation compounded these transplant-specific burdens. The longer-term influence of the pandemic experience on HCT recovery and survivorship remains poorly understood. Methods In this qualitative descriptive study, adults with AML who underwent allogeneic HCT from March through September 2020 participated in virtual semi-structured interviews from July 2022 through April 2023, approximately two years post-transplant. Participants were identified through the Center for International Blood and Marrow Transplant Research registry. Zoom or phone interviews were recorded, transcribed verbatim, and analyzed using inductive qualitative content analysis to describe survivorship experiences and opportunities to improve supportive care. Results A total of 25 AML survivors (ages 24-78, 56% male) were interviewed approximately two years post-transplant. Three themes were found: (1) Transplant is an arduous journey; (2) The COVID-19 pandemic shaped the transplant experience in complex and far-reaching ways; (3) Transplant demands sustained personal and relational investment throughout the transplant journey. Conclusions This study enhances our understanding of the stressors associated with transplantation during periods of heightened adversity, while also identifying opportunities to strengthen healthcare systems and supportive care services for this population. Situating these experiences within the context of a global health emergency offers a rare lens into how external stressors can exacerbate the already demanding nature of HCT survivorship. By understanding survivors’ experiences, healthcare systems can better anticipate and address the evolving needs of transplant survivors.

ABSTRACT Background and Aim Significant health disparities persist in alcohol‐associated liver disease (ALD), largely driven by social determinants of health (SDOH). However, the influence of neighbourhood‐level SDOH on ALD outcomes remains underexplored. In this study, we aimed to evaluate how neighbourhood‐level SDOH are associated with disease burden, comorbid conditions, and mortality in individuals with ALD. Methods We conducted a retrospective cohort study of patients with ALD in the Banner Health System, representing hospitals across Arizona, California, Nevada, Wyoming and Colorado, from January 2012 to October 2024 using ICD codes. Neighbourhood‐level SDOH were quantified using the Social Deprivation Index (SDI). Patients were stratified into quartiles based on SDI score, with Quartile 4 representing the most socioeconomically disadvantaged neighbourhoods. Primary outcomes included incidence of mortality, cirrhosis, major adverse liver outcome (MALO), Type 2 diabetes mellitus, any cancer, and major adverse cardiovascular events (MACE). A multivariable competing risk analysis was performed adjusting for age, sex, race/ethnicity, insurance type, primary language, smoking status, Type 2 diabetes mellitus, hypertension, hyperlipidemia, aspirin use, statin use, alcohol use disorder and a composite mental‐health/substance‐use disorder variable encompassing depression, anxiety disorders, post‐traumatic stress disorder, bipolar disorder, schizophrenia, and non‐alcohol substance use disorders. Results Among 11,394 patients with ALD and available SDI data, 6747 had ≥ 365 days of follow‐up. The average age was 51 years and 65.6% were female; 68.8% were non‐Hispanic White, 19.7% Hispanic, 5.9% Native American/Alaskan Native (NA), 3.2% Black, and 0.4% Asian/Pacific Islanders. Patients residing in the most disadvantaged neighbourhoods (Quartile 4) were significantly younger, more likely to be female, had a higher median BMI, and more frequently reported a non‐English primary language compared with those in the least disadvantaged areas (Quartile 1). Patients in the most deprived neighbourhoods were more likely to be Hispanic, Black, or Native American/Alaska Native and to be uninsured or on Medicaid, whereas those in the least disadvantaged neighbourhoods predominantly had private insurance. Individuals in Quartile 4 had increased mortality (adjusted hazard ratio [aHR]: 1.48, 95% Confidence Interval [CI]: 1.09–2.01) compared with individuals in Quartile 1. Conclusions In this large and demographically diverse ALD cohort, residing in socioeconomically disadvantaged neighbourhoods was associated with increased risk of mortality. These findings support the need for contextually tailored clinical interventions and broader treatment strategies that target upstream sociocultural and environmental factors that are associated with health outcomes. Addressing neighbourhood‐level SDOH through community engagement, policy reform, and cross‐sector partnerships to improve collaborative care efforts is needed to reduce health disparities in ALD.

This study examines the patient- and hospital-level variation in time to initiation of inpatient management among patients admitted to general medical services.

BACKGROUND AND OBJECTIVES: Medical management options for nontraumatic subdural hematoma (SDH) remain limited, with only atorvastatin demonstrating benefit in a single phase 2 randomized clinical trial and mixed evidence for dexamethasone. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may benefit SDH outcomes. The objective of this study was to evaluate the association between GLP-1 RA use and rescue surgery rates and mortality in patients with medically managed nontraumatic SDH. METHODS: We conducted a retrospective cohort study using the TriNetX database from 2016 to 2025, including adults with SDH who were managed conservatively without surgical evacuation or middle meningeal artery embolization. Patients prescribed GLP-1 RAs were compared with nonusers. After propensity matching, rescue surgical evacuation, all-cause mortality at 1 year, and GLP-1 RA–associated adverse events were analyzed. RESULTS: A total of 134 901 patients with conservatively managed nontraumatic SDH were identified, of whom 1470 (1.1%) were GLP-1 RA users. After propensity score matching, 2922 patients remained, with 1461 in each group. At 1 year, GLP-1 RA users experienced significantly lower rates of rescue surgery (2.23% vs 3.51%; P = .046), culminating in an overall 38% reduction in relative hazard. All-cause mortality was also significantly lower for GLP-1 RA users at 1 year (16.1% vs 23.7%, P < .001), reflecting a 33% reduction in hazards. GLP-1 RA users did not experience different rates of adverse events, such as pancreatitis, gallbladder disease, or ileus/bowel obstruction (all P > .05). CONCLUSION: Among patients with medically managed nontraumatic SDH, GLP-1 RA use was associated with significantly lower rates of rescue surgery and all-cause mortality without significantly increased risk of common GLP-1 RA–related complications.

Abstract Introduction Fetal growth restriction (FGR) is associated with an increased risk of neonatal morbidity and mortality. Current diagnostic criteria for FGR do not discriminate between constitutionally small and pathologically restricted fetuses. Following FGR diagnosis, umbilical artery (UA) Doppler is utilized to monitor fetal well‐being, but its limitations have increased interest in investigating growth velocity as an adjunctive tool. The objective of this study is to compare the predictive ability of UA Doppler studies and growth velocity for adverse neonatal outcomes in growth‐restricted fetuses. Methods This is a secondary analysis of a cohort of pregnancies delivered in a single healthcare network from August 2017 to December 2022, diagnosed antenatally with FGR. The cohort was restricted to those with baseline estimated fetal weight (EFW) between the 3rd and 50th percentiles. All subjects had growth velocity measured (defined as EFW percentile change per week between baseline and subsequent ultrasound). The primary outcome was a composite of neonatal morbidity (neonatal intensive care unit [NICU] admission, low 5‐min Appearance, Pulse, Grimace, Activity, Respiration score [<7], intraventricular hemorrhage, necrotizing enterocolitis, or metabolic acidosis) and severe adverse perinatal events (stillbirth or neonatal death, hypoxic ischemic encephalopathy, mechanical ventilation, or severe metabolic acidosis [pH < 7.0]). Neonatal morbidity and severe adverse perinatal events were analyzed separately as secondary outcomes. Independence between growth velocity and S/D ratio was evaluated. Univariate logistic regression models were then performed, with each outcome of interest as the dependent variable and S/D ratio and growth velocity as independent variables. Receiver operating characteristic (ROC) curves were generated to compare the performance of both tests. Results A total of 172 patients were included in the analysis. UA Doppler data were available for 165 patients, 15.3% of whom had S/D ratio >95th percentile; none demonstrated absent or reversed end‐diastolic flow. There was no correlation observed between S/D ratio percentile and growth velocity, suggesting independence. ROC analysis demonstrated that the discriminatory ability of growth velocity was higher across outcomes with areas under the curve (AUC) ranging from 0.65 to 0.69 while AUC for S/D ratio percentiles ranged from 0.51 to 0.53, approximating the performance of chance. Higher growth velocity was significantly associated with reduced odds of the composite outcome (odds ratio [OR], 0.79; 95% confidence interval [CI], 0.69–0.90), and neonatal morbidity (OR, 0.84; 95% CI, 0.73–0.95). S/D ratio percentile was not associated with these outcomes. Conclusion In pregnancies complicated by growth restriction with forward UA flow, growth velocity outperformed S/D ratio percentile in predicting adverse outcomes. The two tests were independent, indicating that growth velocity may reflect a component of fetal development not captured by UA Doppler. These results suggest that growth velocity could be used in addition to UA Doppler studies for fetal risk assessment, especially in fetuses with forward arterial flow.