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.

Abstract We conducted this systematic review to evaluate outcomes of thrombolysis followed by anticoagulation vs anticoagulation alone in pediatric patients with venous thromboembolism (VTE). This systematic review addresses mortality, VTE resolution, recurrence, bleeding, and organ-specific outcomes in 5 PICO (population, intervention, comparison, outcomes) questions on thrombolysis across pulmonary embolism (PE), extremity deep vein thrombosis (DVT), right atrial thrombosis (RAT), cerebral sinus venous thrombosis (CSVT), and renal vein thrombosis (RVT). Meta-analysis reported risk ratios or differences (95% confidence intervals [CIs]), and absolute effects per 1000 patients. Certainty of evidence was assessed using GRADE (Grading of recommendation, assessment, Development, and Evaluation) guidelines. Thirteen nonrandomized studies were included and no randomized clinical trials addressed these questions. Thrombolysis might be associated with a higher risk of major bleeding, clinically relevant nonmajor bleeding, or unspecified bleeding with risk differences of 0.09 (95% CI, −0.06 to 0.23), 0.06 (95% CI, −0.11 to 0.22), and 0.09 (95% CI, −0.04 to 0.23), respectively. In PE with hemodynamic compromise, thrombolysis might be associated with a lower risk of mortality but conclusions on PE progression were uncertain in submassive PE. In DVT, thrombolysis may have little to no effect on mortality or thrombus resolution but might be associated with lower risk of postthrombotic syndrome. In RAT, thrombolysis might have little to no effect on thrombus resolution but a higher risk of major bleeding and mortality. For CSVT and RVT, the evidence was very limited. These findings were based on very-low-certainty evidence because of confounding and imprecision from small sample sizes. This systematic review highlights key challenges in developing recommendations for thrombolysis in children with VTE.

ABSTRACT Bipolar disorder’s (BD) clinical heterogeneity has an unresolved genetic basis. We meta-analyzed genome-wide association studies (GWAS) of 16 BD subphenotypes in 226,032 individuals from 57 cohorts (38,022 cases); 10 advanced to multivariate and multi-trait analyses. Four factors (compulsive, psychotic, dysregulated, internalizing) explained 82.8% of shared genetic variance. BD1 and BD2 loaded on distinct factors despite a high genetic correlation; 87.0% of common-factor loci were significant in neither subtype. Unipolar mania aligned with psychosis over internalizing, and was distinguishable from BD1, and rapid cycling showed heritable cross-domain liability. We identified 356 risk loci, 158 novel, including the first univariate-GWAS associations for psychosis, unipolar mania, rapid cycling and schizoaffective disorder—and 249 credible genes (89 high-confidence), 12 with approved-drug or clinical-phase annotations. Cell-type association showed a midbrain dopaminergic–GABAergic gradient along the psychotic factor. BD’s genetic architecture appears hierarchical—a general liability resolving into dimensions of course and comorbidity beyond diagnostic subtypes.

Context.— Complexity of ordering and transfusing blood is particularly evident in the pediatric population. Simplification, clarification, and standardization of blood orders can decrease complexity and improve patient safety. Objective.— To improve patient safety by optimizing electronic ordering of blood components in pediatrics through a collaborative process improvement initiative. Design.— A multidisciplinary working group, formed as part of a value stream analysis to improve transfusion safety at Children’s Healthcare of Atlanta (Atlanta, Georgia), focused on decreasing variability and providing clarity when ordering, preparing, and transfusing blood using the electronic health record. Through benchmarking with other pediatric institutions and a collaborative design process with multiple local stakeholders, an extensive redesign in the existing orders and order sets occurred. Metrics were collected to determine if a change was an improvement. Results.— Nurse and laboratory informaticists, a pathology informaticist, and a transfusion medicine specialist built the new orders based on the design. The new orders focused on the following changes: standardization, introduction of logic, naming conventions, clarifying definitions, adding calculations, improving transparency of history and laboratory data, removing aliquots, clarifying communication, and implementing additional modules to inform the provider of necessary information about the patient. Metrics included a decrease in the number of orders changed within an hour, decreased calls from the blood bank to the provider to clarify the order, and an absence of overtransfusions and transfusion-related serious safety events for a year following implementation. Conclusions.— This collaborative initiative, using standard process improvement tools, resulted in standardized blood orders improving transfusion safety.

Abstract Severe aplastic anemia (SAA) is a rare and life-threatening bone marrow failure disorder. Immunosuppressive therapy (IST) with antithymocyte globulin and cyclosporine has long been a frontline treatment option in SAA; however, its limited durability and risk of long-term complications such as secondary malignancies remain a drawback in this treatment modality. Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative option with significantly improved outcomes over the long term, particularly with HLA-matched related donors. However, the use of alternative donors, such as haploidentical, mismatched, or matched unrelated donors, has previously been limited due to increased transplant-related morbidity, particularly graft-versus-host disease (GVHD). HCTs have therefore been limited to young recipients and those with HLA-matched related donors, creating significant disparity for older adults and those who lack matched donor options. Nevertheless, more recent advances in HCT, such as posttransplant cyclophosphamide for GVHD prophylaxis, have led to improved outcomes of HCT with alternative donors; however, alternative donor HCT remains underused as up-front therapy, in part because of limited multicenter trial data. This review discusses current SAA treatment approaches, including both IST and HCT, and highlights remaining gaps. It also discusses how ongoing clinical trials such as CureAA and TransIT could help address these gaps. Furthermore, we discuss the importance of stakeholder engagement and implementation science in the integration of research-based evidence into clinical practice. Bridging these gaps is necessary for achieving equitable access for patients historically excluded from frontline HCT, including older adults and racially or ethnically diverse populations.

Abstract Context Endothelial dysfunction and altered psychological measures have been identified in women with functional hypothalamic amenorrhea (FHA). Estradiol (E2) replacement, a known vasodilator, may potentially reverse vascular dysfunction and improve psychological health. Objective To evaluate 12 weeks of physiologic E2 replacement on vascular, hormonal, and psychological outcomes in women with FHA. Methods A randomized, double-blind, placebo-controlled trial was conducted in 29 women with FHA with 0.1 mg/day transdermal E2 (n = 14) or placebo patch (n = 15) twice weekly for 12 weeks. FHA was defined as amenorrhea ≥3 consecutive months, E2 < 50 pg/mL, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) <10 mIU/L, LH:FSH <1, excluding other etiologies. Endothelial dysfunction (reactive hyperemic index ≤ 1.67) was assessed, as were hormonal and psychological measures. Results Women with FHA had a mean age of 26.2 ± 6.3 years, body mass index of 21.5 ± 3.3 kg/m2, with 63% being non-Hispanic White. Baseline characteristics did not differ between groups. After 12 weeks, E2 levels were significantly higher in the E2 group (112.0 vs 36.5 pg/mL, P = .0002). However, there were no significant differences in vascular, hormonal, or psychological outcomes between E2 and placebo groups at week 12. Cortisol levels showed a near-significant decrease in the E2 group compared to an increase with placebo (−.4 vs 3.1 µg/dL, P = .05). Conclusion In women with FHA, 12 weeks of transdermal E2 increased serum E2 levels but did not improve vascular or psychological health measures. Further studies with larger sample sizes and longer follow-up are needed to explore the long-term effects of E2 therapy on cardiovascular and mental health outcomes in this population.

AbstractINTRODUCTIONGiven the close interactions between the retina and the brain, retinal amyloid imaging may serve as a diagnostic and prognostic tool for Alzheimer's disease and related dementias. This retrospective study investigated multivariable associations between retinal perivascular amyloid and cognitive domains.METHODSIntegrated analysis of retinal perivascular amyloid imaging, neuropsychological assessment, and brain magnetic resonance imaging in adults with and without cognitive impairment (N = 26; mean age: 65 ± 7 years; 50% female). Correlations between perivascular amyloid plaque burden and cognitive domains were evaluated with linear regression and interactions with hippocampal volumetry were explored.RESULTSHigher perivascular and periarteriolar amyloid plaque count in the secondary small and tertiary branches were associated with poorer verbal and visual memory in this cohort (p = 0.005–0.009). Higher perivascular amyloid burden interacted with hippocampal atrophy to worsen visual memory (p = 0.033).DISCUSSIONRetinal perivascular amyloid may serve as a non‐invasive marker for cognitive impairment and may shed insight into pathological changes in the brain.Highlights In vivo retinal perivascular amyloid plaque counts are associated with poorer memory. Retinal perivascular amyloid interacted with hippocampal atrophy to worsen memory. Retinal amyloid imaging is a potential biomarker for neurodegenerative diseases.