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Background: Maternal and infant health outcomes in low- and middle-income countries (LMICs) remain below global targets. Greater integration of health services within routine antenatal care and infant immunization is a priority but has had variable success when implemented. We aimed to understand coexisting health needs for integrated services among women and infants and elevate women's views on health service delivery and planning.

Methods: We conducted a longitudinal study of 699 pregnant women and their infants in Papua New Guinea from first antenatal visit to 1 year postpartum. We collected clinical and laboratory data on health at five time points and assessed women's experience of and preferences for integrated care.

Findings: Pregnant and postpartum women and infants had a high prevalence of multiple health issues identified by clinical reporting or screening tests, including anemia, malaria, and reproductive tract infections in women and stunting, anemia, and infections in infants. Many needs coexisted, requiring an integrated approach. Women expressed broadly positive attitudes toward integrating services, prioritizing infant illness care, growth monitoring, vaccination information, maternal illness care, family planning, and maternal or infant nutrition. Women suggested more services for infants than themselves or other family members. Their health priorities changed over time from pregnancy into the postpartum period.

Conclusions: Antenatal and postpartum services in LMICs will have more impact if they identify and respond to the full spectrum of coexisting health issues affecting women and infants and better incorporate women's health needs and preferences into health service planning and delivery.

Funding: Details are provided in the acknowledgments section.

Background: Patients with systemic lupus erythematosus (SLE) complicated by immune thrombocytopenia (SLE-ITP) exhibit an increased incidence of bleeding events and significantly reduced long-term survival, with poor responses to conventional therapies as well as biologic agents.

Methods: In an investigator-initiated, single-arm, dose-escalation trial, six patients with refractory SLE-ITP received anti-CD19 chimeric antigen receptor (CAR) T cells after lymphodepleting chemotherapy. The primary outcome was safety. Secondary outcomes included overall response rate at time points (complete remission [CR]: platelet count ≥ 100 × 10⁹/L; partial remission [PR]: ≥30 × 10⁹/L with 2-fold baseline increase).

Findings: All patients achieved clinical response (CR or PR)-with three attaining CR-and discontinued immunosuppressants, with a median follow-up of 12 months. Treatment-related adverse events were limited to grade 1 cytokine release syndrome in two patients, and no immune effector cell-associated neurotoxicity syndrome (ICANS) occurred. Continuously accumulating bone marrow plasma cells, overactivated bone marrow B cell signaling pathways, and weakened activity of the megakaryocyte maturation pathway, along with dysregulated transcription factors, were observed in three PR patients by exploratory single-cell multi-omics.

Conclusion: These results preliminarily support CD19 CAR T cell therapy as a promising and safe treatment for refractory SLE-ITP. Large-scale trials are needed to verify these conclusions (ClinicalTrials.gov: NCT05930314).

Funding: This study was supported by the Chinese National Key Technology R&D Program, Ministry of Science and Technology (2021YFC2501300); the CAMS Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-005); and National High Level Hospital Clinical Research Funding (2025-PUMCH-D-001, 2022-PUMCH-B-013, D-009). This study was also funded and supported by Juventas Cell Therapy Ltd.

Background: We integrate longitudinal health outcomes from the UK Biobank (UKBB) with our own Human Phenotype Project (HPP) cohort. The HPP contains a range of data per participant that are not found in the UKBB, including microbiome, liver ultrasound, continuous glucose monitoring, and more. Conversely, the UKBB includes a much larger cohort and longer follow-up durations with large numbers of disease outcomes already tracked.

Methods: To leverage the scale and extended follow-up of the UKBB in our study, we model disease outcomes in the UKBB to predict pseudo-outcomes in the HPP. Correlating these predicted pseudo-outcomes with unique measurements in the HPP study, we identify individual biomarkers for those conditions, including those from gut microbiome, liver ultrasound, and other modalities. Multivariate analysis identifies the contribution of each modality in predicting each pseudo-outcome.

Findings: Our method enabled us to recapitulate known biomarkers across the spectrum of diseases studied as well as to reveal less-attested biomarkers in a range of different modalities. We further identify systemic biomarkers correlated with many diseases and sex-specific biomarkers with higher correlation to a pseudo-outcome for one sex as compared to the other.

Conclusions: Our method enables analysis of biomarkers leveraging both the scale and follow-up of the UKBB and the unique measurements of the HPP. This analysis provides a broad perspective across the landscape of many diseases through the lens of many modalities, providing a framework for transferring knowledge from large longitudinal cohorts to smaller, more deeply phenotyped cohorts, advancing discovery across modalities.

Funding: E.S. is supported by the European Research Council and the Israel Science Foundation.

Ongoing trials for hepatocellular carcinoma (HCC) screening and treatment have the potential to transform management. Screening trials are comparing novel imaging and blood-based strategies versus abdominal ultrasound for early HCC detection. Immune checkpoint inhibitors have transformed the therapeutic landscape, with trials evaluating potential benefit in early-stage or intermediate-stage HCC as well as new regimens to improve survival for advanced-stage HCC.

Background: The effectiveness and safety of combining intravenous tirofiban with methylprednisolone as an adjunct to endovascular thrombectomy (EVT) for acute ischemic stroke due to large-vessel occlusion are unknown.

Methods: This pooled analysis of randomized clinical trials included adult patients with large-vessel occlusion stroke within 24 h and an Alberta Stroke Program Early Computed Tomography Score of ≥6. Patients were grouped into EVT alone (control group), EVT plus tirofiban (tirofiban group), EVT plus methylprednisolone (methylprednisolone group), and EVT plus tirofiban and methylprednisolone (tirofiban-methylprednisolone group). The primary effectiveness outcome was 90-day disability as measured by the overall distribution of the modified Rankin scale scores (range, 0 [no symptoms] to 6 [death]). Safety outcomes included 90-day mortality and incidence of symptomatic intracranial hemorrhage within 48 h.

Findings: The pooled cohort contained 1,761 patients (median age, 68.0 years [interquartile range (IQR), 58.0-75.0]; 1,025 men [58.2%]). The median 90-day modified Rankin scale score was 2 (IQR, 1-4) in the tirofiban-methylprednisolone group, compared with 3 (IQR, 1-4) in the control group (adjusted common odds ratio, 1.34 [95% confidence interval [CI], 1.19-1.51]; p < 0.001). The tirofiban-methylprednisolone group had a lower mortality (15.9% vs. 18.4%; adjusted odds ratio, 0.76 [95% CI, 0.64-0.91], p = 0.008) and symptomatic intracranial hemorrhage (4.0% vs. 8.1%; adjusted odds ratio, 0.61 [95% CI, 0.47-0.80], p = 0.001) compared with the control group. No differences in these outcomes were found between tirofiban or methylprednisolone monotherapy compared with control.

Conclusions: Adjunctive tirofiban plus methylprednisolone during EVT improved functional outcomes in patients with large-vessel occlusion stroke undergoing EVT, without major safety concerns.

Funding: This work was funded by National Natural Science Foundation of China grants 82425021 and 82271349 and Noncommunicable Chronic Diseases-National Science and Technology Major Project 2024ZD0527905.

There has been much interest in the potential role of diet as a therapeutic option in Crohn's disease (CD). Several recent dietary clinical trials have been reported in "mild" Crohn's disease. Herein, we highlight several methodological pitfalls from these short-term dietary trials in mild CD that should be considered to enable appropriate interpretation by patients and clinicians.

Recent hallmarks of cancer iterations¹ posit that durable control requires mechanism-guided co-targeting of hallmark capabilities rather than single-pathway inhibition. Translating this systems-level precision oncology framework at scale remains challenging. Sicklick et al.² show that N-of-1, molecularly matched multi-drug regimens are feasible without traditional phase 1 trials; survival scales linearly with matching score, not number of drugs or dose.

Background: Pharmacotyping, the ex vivo measurement of tumor cell responses to drugs, is particularly important for cancers lacking actionable genomic markers. However, current pharmacotyping methods are not clinically feasible due to prolonged drug incubations (days to weeks), extensive manual handling, and analytical limitations, including overlooking single-cell characteristics. Addressing these hurdles is critical for pediatric T cell acute lymphoblastic leukemia (T-ALL), an aggressive cancer with limited therapeutic options.

Methods: We developed μPharma, a pharmacotyping platform that predicts single-cell drug sensitivity without direct drug exposure by quantifying pretreatment biomarkers associated with therapeutic response. μPharma integrates an automated digital microfluidic immunofluorescence assay, optimized for suspension cells, with machine learning models trained on comprehensive single-cell features. We validated μPharma using T-ALL cell lines and patient-derived xenografts, predicting sensitivity to dasatinib and venetoclax by quantifying their target proteins, LCK and BCL2, respectively, including protein expression, phosphorylation status, spatial distribution, and cellular morphology.

Findings: We confirmed that phospho-LCK is predictive of dasatinib sensitivity, consistent with prior studies, and identified phospho-BCL2 as a previously unreported biomarker for venetoclax sensitivity. Integrating multiple biomarkers into machine learning models significantly enhanced predictive accuracy compared to single-marker analyses. Key informative features included spatial protein distribution and integrated protein-morphology metrics. Additionally, single-cell analysis revealed distinct cell subpopulations, suggesting intratumor heterogeneity in drug responses.

Conclusions: μPharma provides rapid (4-h assay), accurate, and automated prediction of drug sensitivity at single-cell resolution using minimal clinical samples, potentially enabling same-day precision oncology decision-making.

Funding: This work was supported by institutional start-up funds from the University of Utah, including internal supplements provided through the Immunology, Inflammation & Infectious Disease (3i) Initiative and the Diabetes & Metabolism Research Center (DMRC).

The clinical success of cell-based immunotherapies has revolutionized treatment of cancer and other diseases by enabling precise and durable tumor targeting. However, while traditional ex vivo engineering of immune cells has demonstrated promise, these approaches are constrained by logistical, economic, and manufacturing challenges that hinder broad clinical adoption. In vivo immune engineering, which directly reprograms immune cells within the patient's body, is emerging as an attractive alternative to overcome these limitations and directly reshape the tumor microenvironment (TME) in situ and restore antitumor immunity. This review surveys current approaches to overcoming them through in vivo delivery platforms and therapeutic constructs to achieve direct in vivo gene editing. We further discuss key safety and efficacy considerations, such as biodistribution, gene expression control, immunogenicity, and tumorigenicity. Finally, we examine early clinical efforts and translational hurdles in bringing in vivo immune engineering strategies to the bedside.