Citations

The translation of AI-generated brain metastases (BM) segmentation into clinical practice relies heavily on diverse, high-quality annotated medical imaging datasets. The BraTS-METS 2023 challenge has gained momentum for testing and benchmarking algorithms using rigorously annotated internationally compiled real-world datasets. This study presents the results of the segmentation challenge and characterizes the challenging cases that impacted the performance of the winning algorithms. Untreated brain metastases on standard anatomic MRI sequences (T1, T2, FLAIR, T1PG) from eight contributed international datasets were annotated in stepwise method: published UNET algorithms, student, neuroradiologist, final approver neuroradiologist. Segmentations were ranked based on lesion-wise Dice and Hausdorff distance (HD95) scores. False positives (FP) and false negatives (FN) were rigorously penalized, receiving a score of 0 for Dice and a fixed penalty of 374 for HD95. The mean scores for the teams were calculated. Eight datasets comprising 1303 studies were annotated, with 402 studies (3076 lesions) released on Synapse as publicly available datasets to challenge competitors. Additionally, 31 studies (139 lesions) were held out for validation, and 59 studies (218 lesions) were used for testing. Segmentation accuracy was measured as rank across subjects, with the winning team achieving a LesionWise mean score of 7.9. The Dice score for the winning team was 0.65 ± 0.25. Common errors among the leading teams included false negatives for small lesions and misregistration of masks in space. The Dice scores and lesion detection rates of all algorithms diminished with decreasing tumor size, particularly for tumors smaller than 100 mm3. In conclusion, algorithms for BM segmentation require further refinement to balance high sensitivity in lesion detection with the minimization of false positives and negatives. The BraTS-METS 2023 challenge successfully curated well- annotated, diverse datasets and identified common errors, facilitating the translation of BM segmentation across varied environments and providing the tools for future development of personalized volumetric reports to patients undergoing BM treatment.

Background and Aims: Reducing avoidable readmissions in cirrhosis is challenging. Enhanced engagement using health information technology (HIT) interventions and caregivers lowered readmissions in an open-label study of the Patient Buddy App (PBA). Aim : Multicenter trial of PBA versus standard of care (SOC) to reduce avoidable readmissions. Approach and Results: An open-label, randomized clinical trial was performed at 3 sites to study the effect of PBA (HIT) versus SOC in cirrhosis inpatients with adult caregivers (dyads). Initial randomization was 1:1:1 between SOC, HIT only, and HIT+ visits. However, due to COVID-19, an unplanned study redesign required a combined HIT versus SOC. Primary outcome : Avoidable readmissions (decided by a blinded monitoring board). Secondary outcomes were all-cause readmission and stakeholder input. PBA focused on medication adherence, cognitive testing, and symptoms, and was remotely monitored by study staff. In all, 464 subjects (232 dyads) were enrolled [Virginia Commonwealth University (VCU): 120, Mayo: 40, Department of Veterans Affairs (VA): 72; 116 dyads/group]. Avoidable readmissions were significantly higher in SOC versus HIT (19.8% vs. 10.3%, p =0.04) with OR of 2.14 (95% CI 1.01–4.54) and remained significant even after removing pre-COVID HIT+ visits patients (19.8% vs. 9.3%, p =0.040) with OR of 2.41 (95% CI 1.02–5.69). All-cause readmissions were higher in SOC versus HIT (48% vs. 30%, p =0.005). App evaluation/engagemen t : 1660 alerts were sent; mostly related to HE. Most dyads were satisfied with the app. Conclusions: In a multicenter randomized clinical trial of 464 cirrhosis inpatients and their CGs across several practice settings, the PBA was associated with lower avoidable readmissions at 30 days post-discharge compared to SOC.

11pt, fleqn, a4paper, ]LegrandOrangeBook Background: Early catheter ablation for atrial fibrillation (AF) improves outcomes, but the optimal timing, especially in heart failure (HF) subtypes, remains unclear. Objective: To evaluate the impact of ablation timing on outcomes in patients with HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). Methods: We used the TriNetX database (2010–2024) to identify HF patients with AF who underwent ablation. Patients were classified as early ablation (≤1 year of first AF diagnosis) or delayed ablation (1–3 years), with propensity score matching (PSM) applied to balance the baseline characteristics. The primary outcome was AF recurrence, defined by repeat ablation, direct current cardioversion (DCCV), or antiarrhythmic drug (AAD) use after a 3-month blanking period. Secondary outcomes included stroke, hospitalization, and mortality over 5 years. Results: After PSM, delayed ablation was associated with higher AF recurrence in both HFrEF (HR 1.25, p < 0.001) and HFpEF (HR 1.27, p = 0.01), as seen in multivariate analysis. In HFrEF, delayed ablation was associated with higher incidence of re-do ablation, AAD use, and DCCV, while in HFpEF, higher recurrence with delayed ablation was associated with increased AAD use. Both cohorts had similar stroke and mortality rates between early and delayed ablation. CONCLUSIONS: Delayed ablation in HFrEF and HFpEF was linked to higher AF recurrence, driven by increased redo ablations, DCCV, AAD use in HFrEF, and higher AAD use in HFpEF. Stroke and mortality rates were similar, suggesting earlier ablation may enhance rhythm control without affecting long-term survival. Condensed Abstract Delayed atrial fibrillation (AF) ablation was associated with higher (AF) recurrence in both HFrEF and HFpEF. In HFrEF, delayed ablation led to increased use of re-do ablation, cardioversion and antiarrhythmic drugs (AADs). In HFpEF, only AAD use was significantly higher with delayed ablation. Stroke and mortality rates were similar between early and delayed ablation groups.

Pediatric metabolic dysfunction–associated steatotic liver disease (MASLD) has become more prevalent on a global scale over the last decades and is associated with significant comorbidities in childhood and a 40-fold higher risk of early mortality in young adulthood. MASLD has now become the leading indication for liver transplantation in young adults in the United States. However, pediatric MASLD is still perceived as an indolent condition by many patients, families, and clinicians. In this Call to Action, we aim to raise awareness of pediatric MASLD as a public health crisis. Herein, we describe insufficient screening and disease staging practices, and a lack of accurate non-invasive tests and effective pharmacotherapy, both stemming from a paucity of multicenter clinical trials in pediatric MASLD. We provide clear steps to address this public health emergency by promoting awareness campaigns, educating and empowering patients and families, addressing barriers including access to care, nutritional and exercise support programs, establishing multidisciplinary care, launching community initiatives, and conducting clinical trials in pediatric MASLD for an age-based evaluation of novel diagnostic and therapeutic options. We conclude by highlighting the urgent need for comprehensive public health policies to control the tide of pediatric MASLD and call upon stakeholders to act now.

Goals: Our aim was to perform a national survey of provider attitudes, practices, and knowledge regarding weight loss and MASLD medications in patients with MASLD. Background: While weight loss is a cornerstone in the management of metabolic dysfunction-associated steatotic liver disease (MASLD), FDA-approved medications for weight loss remain underutilized. Results: We conducted a survey before resmetirom approval of hepatology and gastroenterology providers practicing in 44 states. Surveys were sent to 747 providers with 304 complete responses (41%), of whom 260 (86%) work at a liver transplant center. While nearly all respondents (96%) believed that weight loss medications could benefit patients with MASLD, 77% have never/rarely prescribed them due to low comfort (81%). Among weight loss medication prescribers, glucagon-like peptide-1 (GLP-1) receptor agonists were preferred (66%). In contrast, 63% had prescribed off-label medications for MASLD in the past 12 months, most commonly vitamin E (30%) and GLP-1 receptor agonists (25%). The top reported barriers to prescribing weight loss medications were lack of training/unfamiliarity, cost/insurance coverage, and side-effects, which may be explained by low formal obesity education and lack of knowledge (only 33% of FDA-approved medications for weight loss were correctly identified by >50% of providers). Overall, there was reasonable provider-reported adherence to the 2023 AASLD practice guidance for MASLD. Conclusions: This nationwide survey of hepatology and gastroenterology providers before resmetirom demonstrates that while off-label prescribing for MASLD was common, weight loss medication prescription rates remain very low due to low comfort possibly from insufficient education despite strong beliefs that they can benefit patients with MASLD.

Objective: Diabetes is a defining disease of the 21st century because of its rising prevalence, association with obesity, and enormous health impact. Abundant evidence shows that lifestyle interventions can delay or prevent type 2 diabetes (T2D) in adults, offer relief, and sometimes achieve complete remission. Despite this empowering message, there are no clinical practice guidelines that focus primarily on lifestyle interventions as first-line management of prediabetes and T2D. Our objective, therefore, is to offer pragmatic, trustworthy, and evidence-based guidance for clinicians in using the 6 pillars of lifestyle medicine—nutrition, physical activity, stress management, sleep, social connectedness, avoidance of risky substances—for managing adults with T2D and in preventing T2D in adults with prediabetes or a history of gestational diabetes mellitus. Methods: We used well-established, peer-reviewed guideline methodology to develop evidence-based key action statements (recommendations) that facilitate quality improvement in clinical practice. The guideline development group included 20 members representing consumers, advanced practice nursing, cardiology, clinical pharmacology, behavioral medicine, endocrinology, family medicine, lifestyle medicine, nutrition and dietetics, health education, health and wellness coaching, sleep medicine, sports medicine, and obesity medicine. Recommendation strength was based on the aggregate evidence supporting a key action statement plus a comparison of associated benefits vs harms/costs. Multiple literature searches, conducted by an information specialist, identified 8 relevant guidelines, 118 relevant systematic reviews, and 112 randomized clinical trials. The guideline underwent extensive internal, external, and public review and comment prior to publication. Results: We developed 14 key action statements and associated evidence profiles, each with a distinct quality improvement goal in the context of lifestyle interventions for T2D. Strong recommendations were made regarding advocacy for lifestyle interventions; assessing baseline lifestyle habits; establishing priorities for lifestyle change; prescribing aerobic and muscle strength physical activity; reducing sedentary time; identifying sleep disorders; prescribing nutrition plans for prevention and treatment; promoting peer/familial support and social connections; counseling regarding tobacco, alcohol, and recreational drugs, and establishing a plan for continuity of care. Recommendations were made regarding identifying the need for psychological interventions and for adjusting (deprescribing) pharmacologic therapy. We include numerous tables and figures to facilitate implementation, a plain-language summary for consumers, and an executive summary for clinicians as separate publications. Conclusions: There is robust research evidence supporting the efficacy of lifestyle interventions in preventing, treating, and achieving remission of T2D in adults. Our multidisciplinary guideline development group successfully synthesized this evidence into 14 key action statements that can be used by clinicians and other healthcare professionals to improve quality of care for adults with, or at-risk for, T2D. Despite the research gaps and implementation challenges we highlight in the guideline we believe strongly that our recommendations have immediate relevance and can help raise awareness and shift the paradigm of T2D management towards optimal use of lifestyle interventions.

This executive summary highlights evidence-based recommendations for using lifestyle interventions in the treatment and remission of type 2 diabetes (T2D) and prediabetes in adults. The summary and guideline are intended for any clinician or healthcare professional in a community or non-inpatient healthcare setting involved in managing non-pregnant adults with T2D, prediabetes or a history of gestational diabetes mellitus (GDM). The purpose of this executive summary is to provide a succinct overview of the key action statements (recommendations) from Lifestyle Interventions for Treatment and Remission of Type 2 Diabetes and Prediabetes in Adults: A Clinical Practice Guideline from the American College of Lifestyle Medicine. This is the first diabetes guideline to emphasize lifestyle interventions as the foundation of management and is also the first to focus on all six pillars of lifestyle medicine (plant-predomination nutrition, regular physical activity, restorative sleep, stress reduction, social connectedness, and avoiding risky substances), including behavior change strategies. This summary is not intended to substitute for the full guideline, which should be read before taking the recommended actions. The guideline on which this summary is based was developed with a priori methodology that has been previously published, refined, and used in over 20 multidisciplinary, trustworthy, and evidence-based national guidelines. The guideline development group included 20 members representing consumers, advanced practice nursing, cardiology, clinical pharmacology, behavioral medicine, endocrinology, family medicine, lifestyle medicine, nutrition and dietetics, health education, health and wellness coaching, sleep medicine, sports medicine, and obesity medicine. We developed 14 key action statements and associated evidence profiles, each with a distinct quality improvement goal in the context of lifestyle interventions for T2D. Strong recommendations were made regarding advocacy for lifestyle interventions; assessing baseline lifestyle habits; establishing priorities for lifestyle change; prescribing aerobic and muscle strength physical activity; reducing sedentary time; identifying sleep disorders; prescribing nutrition plans for prevention and treatment; promoting peer/familial support and social connections; counseling regarding tobacco, alcohol, and recreational drugs, and establishing a plan for continuity of care. Recommendations were made regarding identifying the need for psychological interventions and for adjusting (deprescribing) pharmacologic therapy. We include numerous tables and figures to facilitate implementation, a plain-language summary for consumers, and an executive summary for clinicians as separate publications. Although not a substitute for the full clinical practice guideline, this executive summary can provide insight into the key guideline recommendations, to whom they apply, and to how they might alter care. These recommendations offer detailed, explicit, and evidence-based strategies for successful lifestyle behavior change, making them relevant not only to our guideline but to other guidelines and standards that advocate for lifestyle change in managing adults with T2D.

Background The effectiveness of endovascular thrombectomy (EVT) for low Alberta Stroke Program Early CT score (ASPECTS) stroke patients with occlusion of the second segment of the middle cerebral artery (M2) is unclear. Methods This was a multicenter retrospective study. Patients with M1 or M2 occlusions and low ASPECTS (<6) who underwent successful EVT (modified treatment in cerebral ischemia score of 2b or higher) were included. Primary outcome was futile EVT reperfusion (defined as 90-day modified Rankin scale of 5 or 6). Other outcomes of interest include acceptable outcomes (modified Rankin scale of 3 or less) and intracranial hemorrhage (ICH), and all-cause 90-day mortality. Outcomes for M1 patients were compared to M2 patients with multivariable logistic regression models accounting for potential confounders. Results 173 patients with M1 or M2 occlusions and low ASPECTS (<6) who underwent successful EVT were identified. After multivariable adjustments, M2 patients had significantly higher odds of futile reperfusion (OR 5.48 [95%CI 1.91 to 15.7], p = 0.002), lower odds of acceptable outcomes (OR 0.33 [95%CI 0.12 to 0.89], p = 0.028), and higher odds of all-cause mortality (OR 4.90 [95%CI 1.65 to 14.5], p = 0.004). These findings suggest that EVT's efficacy for low-ASPECTS stroke patients may be diminished for patients with M2 occlusions. M2 occlusion was not significantly associated with ICH. Conclusions Among low-ASEPCTS stroke patients who underwent successful EVT, those with M2 occlusions had significantly higher odds of poor outcome compared to those with M1 occlusions.

PURPOSE Neoadjuvant immunotherapy (IO) has become the standard of care for early-stage triple-negative breast cancer (TNBC), but not yet for other subtypes. We previously developed a clinical-grade mRNA-based immune classifier (ImPrint) predicting response to IO that is now being used in I-SPY2.2 as part of the response predictive subtypes. We report the performance of ImPrint in hormone receptor–positive and human epidermal growth factor receptor 2–negative (HR+HER2–) patients from five IO arms. METHODS A total of 204 HR+HER2– (MammaPrint high-risk) patients from five IO arms (anti–PD-1, anti–PD-L1/poly [ADP-ribose] polymerase inhibitor combination, anti–PD-1/toll-like receptor 9 dual-IO combination, and anti–PD-1 ± lymphocyte activation gene 3 dual-IO combination) and 191 patients from the chemotherapy-only control arm were included in this analysis. Patients were classified as ImPrint+ (likely sensitive) versus ImPrint– (likely resistant), using pretreatment mRNA. Performance of ImPrint for predicting pathologic complete response (pCR) to IO-containing arms was characterized and compared with tumor grade (III), MammaPrint (ultra) High2 risk (MP2), and estrogen receptor (ER)-low (ER ≤ 10%). RESULTS Overall, the pCR rate across the five IO arms was 33%. 26% of HR+HER2– patients were ImPrint+, and pCR rates with IO were 75% in ImPrint+ versus 17% in ImPrint–, with the highest pCR rate >90% in a dual-IO arm. In the control arm, pCR rates were 33% in ImPrint+ and 8% in ImPrint–. Tumor grade (III), MP2, and ER-low showed pCR rates in IO of 45%, 56%, and 63%, respectively, with lower pCR odds ratios (OR < 7.5) compared with ImPrint (OR = 14.5). CONCLUSION Using an accurate selection strategy, HR+HER2– patients could achieve pCR rates similar to what is seen with best neoadjuvant therapies in TNBC and HER2+ (ie, pCR rate >65%-70%). ImPrint, an Food and Drug Administration IDE-enabled assay, may represent a way to identify HR+HER2– patients for IO that best balances likely benefit versus risk of serious immune-related adverse events.