University of Maryland, Baltimore

Sequestration of Plasmodium falciparum-infected erythrocytes (IE) in the microvasculature is a major virulence determinant. While the sequestration of mature stage parasites (trophozoite and schizonts) to vascular endothelium is well established, the conditions that promote ring-stage IE sequestration are less understood. Here, we observed in ring-stage parasites that febrile exposure increased transcript levels of several exported parasite genes involved in the trafficking of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) ligand responsible for adherence to the endothelium of blood vessels. Furthermore, it accelerated PfEMP1 surface display in ring-stage IEs, leading to a 2-fold increase in their binding in a perfusable 3D human brain microvessel model. Additionally, we observed that parasite exposure enhances the binding of uninfected erythrocytes in 3D brain microvessels. These findings suggest a complex interplay between fever and parasite biomass in the pathogenesis of cerebral malaria.

ABSTRACT Individuals living alone with dementia are rising rapidly, yet this group remains largely unrecognized in dementia care planning. This study aimed to explore existing and prospective programming for older adults living alone with dementia across five county-level Dementia Friendly America (DFA) initiatives in Maryland. Interviews conducted with five county DFA leads reflect three broad themes: (1) county initiatives, (2) barriers to engaging persons with dementia who reside alone, and (3) next steps/way forward. Findings inform future research, policy, and practice implications. Greater intentionality, funding, and inclusive planning are needed to ensure this growing, vulnerable population is not left behind.

Although clinical guidelines endorse enoxaparin for the prevention of venous thromboembolism in patients with orthopaedic trauma, recent evidence from a large clinical trial has demonstrated that aspirin provides comparable protection against death and pulmonary embolism. This study evaluated the cost-effectiveness of thromboprophylaxis with enoxaparin compared with that with aspirin in patients with orthopaedic trauma from the perspective of the U.S. health-care system. The study modeled a hypothetical cohort of adult patients with an operatively treated extremity, pelvic, or acetabular fracture based on data from a recent clinical trial and national databases. We used a decision analysis model to compare 30 mg of enoxaparin with 81 mg of aspirin, administered twice daily in-hospital and prescribed for 21 days after discharge. Health-care costs and quality-adjusted life-years (QALYs) within 1 year after the injury derived from published research and publicly available cost data were based on potential disease states, including death or a combination of pulmonary embolism, proximal deep vein thrombosis, distal deep vein thrombosis, or a bleeding complication. We assessed cost-effectiveness compared with a willingness-to-pay threshold of $150,000 per QALY. Our model estimated that the 1-year health-care costs among patients prescribed enoxaparin were $35,301, producing 0.6705 QALYs. Aspirin was associated with $35,067 in 1-year health-care costs and 0.6701 QALYs. The overall health-care costs were $234 higher with enoxaparin but yielded only a 0.0004 improvement in QALYs, for an incremental cost-effectiveness ratio for enoxaparin of $635,340 per QALY, indicating that enoxaparin is not cost-effective compared with aspirin. In a sensitivity analysis, the probability of enoxaparin thromboprophylaxis being cost-effective compared with aspirin was 9.8% in 10,000 iterations. The findings suggest that enoxaparin is not cost-effective relative to aspirin for thromboprophylaxis in patients with orthopaedic trauma. The results support consideration of aspirin as a preferred agent in future guidelines, especially given the consistent patient preference for its oral administration. Economic and Decision Analysis Level I . See Instructions for Authors for a complete description of levels of evidence.

PARP inhibitors (PARPi) have rapidly reshaped the treatment landscape for metastatic prostate cancer, moving from biomarker-selected monotherapy in metastatic castration-resistant prostate cancer (mCRPC) to first-line combination strategies with androgen receptor pathway inhibitors (ARPIs) and more recently, into metastatic hormone-sensitive disease (mHSPC). This review summarizes the evidence-based use of PARPi in metastatic prostate cancer, integrating the mechanistic rationale and guideline perspectives. We also highlight the resistance mechanisms that inform patient selection and underpin emerging strategies. The most consistent and clinically meaningful benefit from PARPi is observed among patients with deleterious BRCA1/2 alterations, whereas outcomes among patients with non- BRCA defective homologous recombination repair (HRR) gene subsets are heterogeneous and often modest. Pairing PARPi with ARPI in mCRPC patients bearing HRR mutations, especially BRCA1/2 mutations, not only improves clinical outcomes but also increases toxicity. Furthermore, uncertainty remains regarding the overall impact of the incremental benefit of PARPi/ARPI combinations over sequential therapy. Expansion into mHSPC further underscores the field's shift toward earlier, genomically guided treatment intensification strategies. Clinical practice is converging on early comprehensive genomic testing and prioritization of PARPi-based therapy for HRR-altered, especially BRCA1/2 -mutated, prostate cancer. Key research priorities include functional biomarkers beyond gene panels, rational combinations to prevent/overcome resistance, and optimized sequencing across disease states.