Citations

BACKGROUND: Childbirth can have a substantial impact on maternal health-related quality of life. Cesarean delivery is the most performed inpatient operation, yet little is known about normal postpartum recovery profiles. The primary aim of our study was to longitudinally evaluate global health visual analog scale (GHVAS; 0–100) scores up to 12 weeks after scheduled cesarean delivery and identify the time to plateau of scores. The secondary aims were to evaluate different domains of postpartum recovery using validated patient-reported outcome measures (Obstetric Quality of Recovery score [ObsQoR-10] and 5-level 5-dimensional EuroQol questionnaire [EQ-5D]). METHODS: After institutional review board approval, this single-center, prospective longitudinal study enrolled healthy women scheduled for cesarean delivery. Women were excluded for gestational age <32 weeks, neonatal demise, neonatal intensive care unit admission, inability to read or understand English, and if general anesthesia was used. Women completed baseline surveys before delivery and then at 24 and 48 hours after delivery. After hospital discharge, women completed surveys (including GHVAS, OBsQoR-10, EQ-5D, Edinburgh Postnatal Depression Scale, and activities of daily living) at 1 week, 3 weeks, 6 weeks, and 12 weeks postpartum. One-way repeated measures analysis of variance (ANOVA) was used to detect the difference in GHVAS and postpartum recovery outcomes with different follow-up time points. RESULTS: We enrolled 66 parturients and 3 were withdrawn. Response rates were 95%, 84%, 83%, and 76% at 1, 3, 6, and 12 weeks, respectively. Mean ± standard deviation [SD] GHVAS scores were 78 ± 16 at baseline, 64 ± 17 at 24 hours, 69 ± 15 at 48 hours, 75 ± 19 at 1 week, 88 ± 11 at 3 weeks, 88 ± 15 at 6 weeks, and 90 ± 12 at 12 weeks postpartum ( P < .001). The global health VAS improved up until week 3 and then plateaued close to the maximum score between 3 weeks and 12 weeks postpartum. Mean ± SD ObsQoR-10 scores were 75 ± 15 at 24 hours, 85 ± 10 at 48 hours, and 81 ± 28 at 1 week postpartum ( P = .003). The mean ± SD EQ-5D composite scores improved at 6 weeks (4.9 ± 2.9) and 3 months (4.2 ± 2.6) compared to baseline (6.5 ± 1.8) with usual activities ( P = .001) and pain/discomfort ( P < .001) showing significant improvement over time. ObsQoR-10 score at 24 hours correlated with ObsQoR-10 scores at 48 hours (r = 0.629, P < .001) and 1 week (r = 0.429, P < .001) but did not correlate with EQ-5D scores at 6 weeks and 12 weeks. CONCLUSIONS: Our study demonstrates that GHVAS after scheduled CD plateaus at week 3. This data can be used to inform patients about the anticipated trajectory of key postpartum recovery domains up to 12 weeks postpartum.

BACKGROUND: Patients presenting with cervical artery dissection (CAD) are at risk for subsequent ischemic events. We aimed to identify characteristics that are associated with increased risk of ischemic stroke after initial presentation of CAD and to evaluate the differential impact of anticoagulant versus antiplatelet therapy in these high-risk individuals. METHODS: This was a preplanned secondary analysis of the STOP-CAD study (Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection), a multicenter international retrospective observational study (63 sites from 16 countries in North America, South America, Europe, Asia, and Africa) that included patients with CAD predominantly between January 2015 and June 2022. The primary outcome was subsequent ischemic stroke by day 180 after diagnosis. Clinical and imaging variables were compared between those with versus without subsequent ischemic stroke. Significant factors associated with subsequent stroke risk were identified using stepwise Cox regression. Associations between subsequent ischemic stroke risk and antithrombotic therapy type (anticoagulation versus antiplatelets) among patients with identified risk factors were explored using adjusted Cox regression. RESULTS: In all, 4023 patients (mean age was 47.4 years; 44.5% were women) were included. By day 180, subsequent ischemic stroke occurred in 5.3% of the cohort. In adjusted Cox regression, factors associated with increased risk of subsequent ischemic stroke were prior history of ischemic stroke (adjusted hazard ratio [aHR], 7.31 [95% CI, 1.61–33.13]; P =0.010), presentation within 7 days from first symptoms (aHR, 3.04 [95% CI, 1.04–8.91]; P =0.043), infarct on baseline imaging (aHR, 9.85 [95% CI, 3.65–26.58]; P <0.001), and occlusive dissection (aHR, 2.34 [95% CI, 1.03–5.34]; P =0.043). Only patients with occlusive dissection demonstrated a reduced risk of subsequent ischemic stroke when treated with anticoagulation versus antiplatelets (aHR, 0.36 [95% CI, 0.16–0.80]; P =0.01). CONCLUSIONS: In this post hoc analysis of the STOP-CAD study, several factors associated with subsequent ischemic stroke were identified among patients with CAD. Furthermore, we identified a potential benefit of anticoagulation in patients with CAD with occlusive dissection. These findings require validation by meta-analyses of prior studies to formulate optimal treatment strategies for specific high-risk CAD subgroups.

Hypertension is the leading modifiable risk factor for atrial fibrillation (AF) and is estimated to be present in >70% of AF patients. This Frontiers Review was prepared by 29 expert members of the AF-SCREEN International Collaboration to summarize existing evidence and knowledge gaps on links between hypertension, AF, and their cardiovascular sequelae; simultaneous screening for hypertension and AF; and the prevention of AF through antihypertensive therapy. Hypertension and AF are inextricably connected. Both are easily diagnosed, often silent, and frequently treated inadequately. Together, they additively increase the risk of ischemic stroke, heart failure, and many types of dementia, resulting in greater all-cause mortality, considerable disease burden, and increased health care expenditures. Automated upper arm cuff blood pressure devices with implemented technology can be used to simultaneously detect both hypertension and AF. However, positive screening for AF with an oscillometric blood pressure monitor still requires ECG confirmation. The current evidence suggests that high-risk individuals aged ≥65 years or with treatment-resistant hypertension could benefit from AF screening. Since antihypertensive therapy effectively lowers AF risk, particularly in individuals with left ventricular dysfunction, hypertension should be the key target for AF prediction and prevention rather than merely a comorbidity of AF. Nevertheless, several important gaps in knowledge need to be filled over the next years, including the ideal method and selection of patients for simultaneous screening of hypertension and AF and the optimal antihypertensive drug class and blood pressure targets for AF prevention.

Abstract Increasing evidence suggests that Alzheimer’s disease (AD) pathogenesis strongly correlates with neuroinflammation. Peripheral monocytes are crucial components of the human immune system that may play a role in neuroinflammation, but their contribution to AD pathogenesis is largely understudied partially due to the lack of appropriate human models. Here, we present human cortical organoid microphysiological systems (hCO-MPSs) for modeling dynamic AD neuroinflammation mediated by monocytes. By incorporating 3D printed devices into an existing cortical organoid protocol, 96 hCO-MPSs can be established with significantly reduced necrosis and hypoxia as well as enhanced viability within a commonly used 96 well plate, and each hCO-MPS consists of a doughnut-shaped hCO and a 3D printed device per well. Using this approach, monocytes from AD patients exhibit higher infiltration, decreased amyloid-beta (Aβ) clearance, and stronger inflammatory responses compared to monocytes from age-matched control donors. Moreover, pro-inflammatory effects such as elevated astrocyte activation and neuronal apoptosis were observed to be induced by AD monocytes. Furthermore, the significant increase in the expression of IL1B and CCL3, both at the transcriptional and protein levels, indicated the pivotal role of these cytokine and chemokine in monocyte-mediated AD neuroinflammation. Our findings provide insight for understanding monocytes’ role in AD pathogenesis, and the user-friendly MPS models we present are compatible with existing laboratory settings, highlighting their potential for modeling neuroinflammation and developing new therapeutics for various neuroinflammatory diseases.

Background Although intravenous thrombolysis (IVT) is safe and effective in populations with general stroke, its impact on cervical artery dissection–related acute ischemic stroke (CeAD‐AIS) remains unclear. This retrospective study used the National Inpatient Sample to compare outcomes in patients with CeAD‐AIS treated with and without IVT. Methods We included adult patients with concurrent CeAD and AIS diagnoses ( International Classification of Diseases, Tenth Revision [ ICD‐10 ], codes) hospitalized from 2016 to 2019. The primary outcome was home discharge; safety outcomes included inpatient death and intracerebral hemorrhage. We performed survey‐weighted multivariable logistic regressions comparing IVT versus no IVT, followed by interaction analyses to examine effect modifications based on age, medical history, stroke severity, carotid artery involvement, and endovascular treatment. Results Between 2016 and 2019, 1360 (12.1%) of 11 285 patients with CeAD‐AIS received IVT. IVT‐treated patients had higher median National Institutes of Health Stroke Scale scores (median [interquartile range], 8 [4–17] versus 3 [1–11]; P <0.001). Adjusted analyses showed IVT was associated with higher odds of home discharge (adjusted odds ratio [OR], 1.40 [95% CI, 1.01–1.92]; P =0.042), but not with inpatient death (adjusted OR, 1.29 [95% CI, 0.76–2.20]; P =0.347) or intracerebral hemorrhage (adjusted OR, 0.69 [95% CI, 0.32–1.48]; P =0.341). Stroke severity ( P for interaction=0.001) and carotid artery involvement ( P for interaction=0.021) significantly modified IVT's effect on home discharge, with IVT being associated with an increased likelihood of home discharge in patients with moderate to severe strokes (National Institutes of Health Stroke Scale score >4) and carotid artery involvement. Conclusions IVT improves the likelihood of home discharge in patients with CeAD‐AIS without increasing the risk of inpatient death or intracerebral hemorrhage.

Abstract Motivation Multiplex immunofluorescence (MxIF) enables the quantification of multiple protein markers at a single-cell level while preserving spatial information, offering a powerful tool for studying tissue microenvironments. However, the flexibility in MxIF panel design poses challenges in standardizing cell phenotyping. Results We present SpaFlow, an efficient, customizable pipeline for unsupervised clustering and classification of MxIF data, implemented using Nextflow. SpaFlow performs quality control, clustering, and postclustering analysis on segmented and quantified MxIF data, facilitating reproducible and scalable analyses across various computing platforms. The SpaFlow pipeline integrates three clustering and classification packages—Seurat, SCIMAP, and CELESTA—each providing unique methodologies for identifying cell types based on phenotypic markers. A novel “meta-clustering” approach condenses clusters across multiple regions of interest into common meta-clusters, streamlining the cell-type identification process in large datasets. SpaFlow’s robust quality control steps, including signal summation and cell density filtering, mitigate artifacts that may impact clustering accuracy. We demonstrate the utility of SpaFlow in a case study involving 297 ovarian tumor cores, where SpaFlow successfully identified biologically meaningful cell populations, including tumor-infiltrating lymphocytes, efficiently and rapidly. Additionally, SpaFlow’s reproducibility is validated using serial tonsil sections, confirming its capability to consistently identify distinctive cell populations across matched ROIs. Availability and implementation SpaFlow is freely available with detailed documentation and examples at https://github.com/dimi-lab/SpaFlow.