First-trimester 3-dimensional power Doppler of the uteroplacental circulation space: a potential screening method for preeclampsia

ObjectiveThe objective of the study was to compare 3-dimensional power Doppler (3DPD) of the uteroplacental circulation space (UPCS) in the first trimester between women who develop preeclampsia (PEC) and those who do not and to assess the 3DPD method as a screening tool for PEC.Study DesignThis was a prospective observational study of singleton pregnancies at 10 weeks 4 days to 13 weeks 6 days. The 3DPD indices, vascularization index (VI), flow index (FI), and vascularization flow index (VFI), were determined on a UPSC sphere biopsy with the virtual organ computer-aided analysis (VOCAL) program.ResultsOf 277 women enrolled, 24 developed PEC. The 3DPD indices were lower in women who developed PEC. The area under the receiver-operating characteristics curve for the prediction of PEC was 78.9%, 77.6%, and 79.6% for VI, FI, and VFI, respectively.ConclusionPatients who develop PEC have lower 3DPD indices of their UPCS during the first trimester. Our findings suggest that this ultrasonographic tool has the potential to predict the development of PEC

Development and internal validation of the multivariable CIPHER (Collaborative Integrated Pregnancy High-dependency Estimate of Risk) clinical risk prediction model

Background: Intensive care unit (ICU) outcome prediction models, such as Acute Physiology And Chronic Health Evaluation (APACHE), were designed in general critical care populations and their use in obstetric populations is contentious. The aim of the CIPHER (Collaborative Integrated Pregnancy High-dependency Estimate of Risk) study was to develop and internally validate a multivariable prognostic model calibrated specifically for pregnant or recently delivered women admitted for critical care. Methods: A retrospective observational cohort was created for this study from 13 tertiary facilities across five high-income and six low- or middle-income countries. Women admitted to an ICU for more than 24 h during pregnancy or less than 6 weeks post-partum from 2000 to 2012 were included in the cohort. A composite primary outcome was defined as maternal death or need for organ support for more than 7 days or acute life-saving intervention. Model development involved selection of candidate predictor variables based on prior evidence of effect, availability across study sites, and use of LASSO (Least Absolute Shrinkage and Selection Operator) model building after multiple imputation using chained equations to address missing data for variable selection. The final model was estimated using multivariable logistic regression. Internal validation was completed using bootstrapping to correct for optimism in model performance measures of discrimination and calibration. Results: Overall, 127 out of 769 (16.5%) women experienced an adverse outcome. Predictors included in the final CIPHER model were maternal age, surgery in the preceding 24 h, systolic blood pressure, Glasgow Coma Scale score, serum sodium, serum potassium, activated partial thromboplastin time, arterial blood gas (ABG) pH, serum creatinine, and serum bilirubin. After internal validation, the model maintained excellent discrimination (area under the curve of the receiver operating characteristic (AUROC) 0.82, 95% confidence interval (CI) 0.81 to 0.84) and good calibration (slope of 0.92, 95% CI 0.91 to 0.92 and intercept of −0.11, 95% CI −0.13 to −0.08). Conclusions: The CIPHER model has the potential to be a pragmatic risk prediction tool. CIPHER can identify critically ill pregnant women at highest risk for adverse outcomes, inform counseling of patients about risk, and facilitate bench-marking of outcomes between centers by adjusting for baseline risk.Medicine, Faculty ofOther UBCNon UBCAnesthesiology, Pharmacology and Therapeutics, Department ofFamily Practice, Department ofMedicine, Department ofObstetrics and Gynaecology, Department ofReviewedFacult

Dissecting the treatment-naive ecosystem of human melanoma brain metastasis

Melanoma brain metastasis (MBM) frequently occurs in patients with advanced melanoma; yet, our understanding of the underlying salient biology is rudimentary. Here, we performed single-cell/nucleus RNA-seq in 22 treatment-naive MBMs and 10 extracranial melanoma metastases (ECMs) and matched spatial single-cell transcriptomics and T cell receptor (TCR)-seq. Cancer cells from MBM were more chromosomally unstable, adopted a neuronal-like cell state, and enriched for spatially variably expressed metabolic pathways. Key observations were validated in independent patient cohorts, patient-derived MBM/ECM xenograft models, RNA/ATAC-seq, proteomics, and multiplexed imaging. Integrated spatial analyses revealed distinct geography of putative cancer immune evasion and evidence for more abundant intra-tumoral B to plasma cell differentiation in lymphoid aggregates in MBM. MBM harbored larger fractions of monocyte-derived macrophages and dysfunctional TOX+CD8+ T cells with distinct expression of immune checkpoints. This work provides comprehensive insights into MBM biology and serves as a foundational resource for further discovery and therapeutic exploration