Citations

Purpose of review Anaphylaxis is a severe type 1 hypersensitivity reaction which is the result of mast cell degranulation causing multiorgan dysfunction. Currently, the most accepted biomarker measurement for mast cell mediated anaphylaxis is serum tryptase measurement. Serum tryptase measurement has limitations including an ideal window of collection during anaphylaxis and must be obtained by venipuncture collection. Urinary mast cell mediators are emerging mast cell biomarkers that can be used for evaluation of mast cell mediated anaphylaxis and mast cell activation. This review will highlight biomarker measurement with urinary mast cell mediators in anaphylaxis. Recent findings This review will highlight biomarker measurement of urinary mast cell mediators including N-methylhistamine, leukotriene E4, and 2,3-dinor-11beta-prostaglandin F2 alpha and their role in anaphylaxis. Summary Urine mast cell mediator collection obtained during acute anaphylaxis and compared to baseline measurements are emerging biomarkers for the detection of mast cell mediated anaphylaxis. Further research is needed to validate the utility of urinary mast cell mediators in anaphylaxis.

Introduction Out‐of‐hospital community births account for 1.6% to 2% of births in the United States and are associated with fewer obstetric interventions but increased neonatal risk. Little is known about how maternity care providers’ characteristics, values, and prior exposure to community birth influence attitudes toward community birth. Methods We conducted an observational cross‐sectional survey using a 40 to 43 item Research Electronic Data Capture questionnaire distributed October 2 to 30, 2024. Eligible participants (“providers”) included in‐hospital physicians, midwives, community birth providers, and registered nurses. The survey assessed demographics, practice characteristics, provider values, prior community birth experience, and attitudes toward community birth. Descriptive statistics were used to summarize characteristics. Group comparisons between in‐hospital and community birth providers were conducted using analysis of variance and χ 2 or Fisher exact tests. Associations between attitudes and provider values were evaluated using linear models with Bonferroni correction. Results Sixty‐seven providers completed the survey (51 in hospital, 16 community based). Most respondents were female (89.6%) and White (77.6%), with a median of 7 years in practice (IQR, 3‐14.5). Attitudes significantly differed by role ( P = .007) and credentials ( P = .002). In‐hospital providers reported safety concerns about community birth and perceived antenatal counseling to be inadequate. Perceived patient distrust during transfer was common among both in‐hospital and community‐based providers (69% and 81%, respectively). After adjustment for provider role and multiple comparisons, no significant differences in personal values were noted by attitude group; however, providers with positive attitudes toward community birth were more likely to believe that patients value compassion (β = 2.3, P = .004). Discussion Provider attitudes toward community birth appear to be shaped more by professional role and clinical experience than by differences in underlying value systems. High levels of perceived patient distrust during transfer highlight the need for interventions that strengthen compassion across maternity care settings.

Abstract Cerebrospinal fluid (CSF) is the biofluid most proximal to the central nervous system (CNS), yet its proteomic organization across neurological disease remains unresolved. We assembled a meta-atlas of 35 CSF proteomic datasets (2016–2026) comprising 10,560 quality-controlled samples spanning neurodegenerative, neuroinflammatory, neuro-oncological, infectious and structural-injury contexts. Meta-analysis of cross-cohort detection defined a 747-protein core mass-spectrometry-accessible CSF proteome that generalizes to held-out cohorts. We derived thirteen consensus meta-programs that transfer across independent cohorts and span the major neural, barrier, immune and plasma compartments. Unexpectedly, these programs are dominated by a single axis of variation opposing complement- and plasma-associated inflammation against neuronal-synaptic homeostasis. This injury–homeostasis axis is diagnosis-spanning and tracks clinical severity and disease activity across diverse neurological conditions. We show that a two-protein C5–NRCAM model can approximate the injury–homeostasis axis, bridging deep proteomic profiling toward bedside assessment.

Amyloid-targeting therapies (ATTs), including donanemab and lecanemab, are FDA-approved disease-modifying therapies for Alzheimer’s disease in the mild cognitive impairment or mild dementia stages. Early initiation is important for optimal outcomes. This article summarizes practical strategies for implementing ATTs in clinical practice, focusing on leadership alignment and infrastructure development, as well as patient identification, diagnosis, and monitoring protocols. Key recommendations include establishing appropriate patient tracking systems, infusion and imaging protocols, and interprofessional collaboration. Approaches for systematic patient routing (e.g., hub-and-spoke models, fast-track mechanisms) and biomarker-integrated assessments are critical to facilitating timely diagnosis and treatment. Education for patients, care partners, and clinicians is crucial for managing the risks associated with amyloid-related imaging abnormalities. Successful ATT implementation requires coordinated systems, timely diagnosis, and robust safety monitoring. These measures can enable frameworks for ATT administration to optimize outcomes for patients, care partners, and health systems.

Photodynamic priming (PDP), a fallout of photodynamic therapy, transiently modulates the tumor microenvironment (TME), enhances therapeutic susceptibility, and promotes immunogenic cell death through the release of damage-associated molecular patterns (DAMPs). Pancreatic ductal adenocarcinoma (PDAC) remains non-responsive to current therapies with a desmoplastic and immunosuppressive TME that limits drug delivery and blunts responses to immune checkpoint blockade. We investigated whether PDP could enhance anti-PD1 therapy responses in PDAC using patient-derived organoids (PDOs). PDOs were treated with Visudyne and red light (25, 75, and 100 J/cm²), followed by assessment of cytotoxicity, DAMP expression (HSP60, calreticulin, HMGB1), and transcriptomic changes. Monocyte-derived dendritic cells (mDCs) from healthy donors were cocultured with PDP-treated (25 J/cm 2 ) PDOs, then with matched naïve T cells. mDC and T cell activation markers were analyzed. Pembrolizumab (anti-PD1) was added to PDO-mDC-T cell cocultures to evaluate combined effects on PDO viability and T cell activation. PDP induced dose-dependent cytotoxicity and upregulated DAMPs. Gene profiling in PDOs showed increased IFN-γ , TNF-α , and CXCL12 , with reduced PD-L1 , TGF-β1 , and FOXP1 expression. mDCs exposed to PDP-treated PDOs upregulated CD40, CD86, and MHC-II, driving activation of CD4 + and CD8 + T cells, evidenced by elevated PD1 expression. Addition of pembrolizumab further decreased PDO viability and amplified effector cytokines ( IFN-γ , TNF-α , FASLG , granzyme B, IL-2 , IL-21 ). PDP was associated with modulation of the PDAC TME toward a more immunogenic phenotype by enhancing tumor immunogenicity, activating dendritic cells and T cells, and potentiating PD1 blockade. These findings provide mechanistic support for further preclinical and clinical evaluation of PDP combined with checkpoint inhibition in PDAC.

Background Intensive care units are high-acuity environments characterized by time pressure, medical complexity, and organizational demands. These conditions may influence clinicians’ ability to provide patient-centered care and contribute to forms of care perceived as fragmented or dehumanizing. Objective To examine how ICU clinicians describe and make sense of the pressures shaping everyday critical care practice, and how these pressures give rise to interacting patterns of care, including those described as hurry, blur, burden, and cruelty. Methods We conducted a qualitative study using focus groups with ICU clinicians from a large academic health system. Discussions were informed by the concept of the pathologies of care as sensitizing concepts. Four focus groups were held with physicians, nurses, advanced practice nurses, and a social worker ( N = 14). Transcripts were analyzed using directed content analysis with both deductive and inductive coding. Results Clinicians described these patterns not as discrete phenomena but as interrelated, context-dependent processes shaped by shared operational pressures such as time constraints, workload, and information demands. These dynamics were often viewed as inherent to the structure and culture of ICU care and were described as co-occurring and compounding. Communication emerged as both a contributor to and a potential mechanism for mitigation, alongside system-level strategies such as reducing documentation burden and leveraging artificial intelligence to support care delivery. Conclusions Patterns reflected in hurry, blur, burden, and cruelty are best understood as emergent properties of complex care systems. Addressing these dynamics may require system-level approaches to improve communication, reduce workload pressures, and support more patient-centered, humanizing care.

ABSTRACT TAR DNA‐binding protein 43 (TDP‐43) inclusions are defining pathological features of frontotemporal lobar degeneration (FTLD) but are also often observed in Alzheimer's disease ( AD ) and primary age‐related tauopathy (PART). TDP‐43 in AD is either associated with cognitive impairment or a protective‐life prolonging impact, and yet the localization, cellular and fragment characteristics of TDP‐43 need to be determined. We investigated the relationships between TDP‐43 volumetric inclusion burden in low likelihood AD (lAD) and definite PART by immunostaining against phosphorylated TDP‐43 (pTDP‐43), TDP‐43 C terminal (TDP‐C) and TDP‐43 N‐terminal (TDP‐N) fragments combined with 3D confocal imaging taken from eight regions: amygdala (basolateral [amygdala‐BL] and centromedial amygdala [amygdala‐CM]), the hippocampus (Cornu Ammonis [CA]‐1, CA2/3, CA4, dentate gyrus [DG] and subiculum [SUB]) and entorhinal cortex (ERC) and artificial intelligence (AI)–based segmentation via object recognition, reconstruction and quantification. We found amygdala‐CM in lAD and PART to have the overall greatest burden of pTDP‐43 whereas TDP‐N burden in amygdala‐BL of PART cases was greater than other TDP‐43 fragments. There was no difference in TDP‐43 burden in hippocampal subfields in PART. However, CA2/3 region showed greater pTDP‐43 burden while TDP‐N stood out in DG and SUB. Multiple comparisons among the groups revealed that TDP‐C was the only fragment showing differences among PART and lAD in CA2/3, DG and SUB regions. Overall, unbiased AI‐based volumetric burden analysis pipeline demonstrated unique fragment aggregation patterns in the neurodegenerative processes of PART and AD .

Healthcare Systems Science (HSS) is an important part of medical education because it helps physicians understand how healthcare systems work and how to improve them. However, it is not commonly included in graduate medical training. This manuscript describes the creation and use of a radiation oncology (RO) HSS curriculum that was built with medical school faculty and adapted to the needs of residents in our residency program. The curriculum included sixteen sessions over ten months and covered six domains: person centered care, population centered care, team-based care, high value care, leadership, and health policy economics and technology. Each session included a short lecture and a case discussion on topics such as financial toxicity, telemedicine, workflow improvement, burnout, health equity, and billing. The curriculum was used successfully with regular participation from residents and faculty, showing that it can fit into an existing residency schedule. Residents completed pre- and post-intervention surveys assessing understanding, consideration, confidence, and satisfaction related to HSS domains using 5-point Likert-scale items. Among residents with paired survey data, scores for understanding of HSS, incorporation of HSS into care planning, confidence applying HSS principles, and satisfaction with HSS integration all improved following curriculum completion. This experience shows that adding HSS to RO residency training is practical and useful, and it may also be a helpful model for other residency programs.