Statistical Mapping of PFOA and PFOS in Groundwater throughout the Contiguous United States.

Per-and polyfluoroalkyl substances (PFAS) are synthetic chemicals that are increasingly being detected in groundwater. The negative health consequences associated with human exposure to PFAS make it essential to quantify the distribution of PFAS in groundwater systems. Mapping PFAS distributions is particularly challenging because a national patchwork of testing and reporting requirements has resulted in sparse and spatially biased data. In this analysis, an inhomogeneous Poisson process (IPP) modeling approach is adopted from ecological statistics to continuously map PFAS distributions in groundwater across the contiguous United States. The model is trained on a unique data set of 8910 PFAS groundwater measurements, using combined concentrations of two PFAS analytes. The IPP model predictions are compared with results from random forest models to highlight the robustness of this statistical modeling approach on sparse data sets. This analysis provides a new approach to not only map PFAS contamination in groundwater but also prioritize future sampling efforts.

Clinical Outcome of Patients with Poor-Grade Aneurysmal Subarachnoid Hemorrhage with Bundled Treatments: A Propensity Score-Matched Analysis.

BACKGROUND: Poor-grade aneurysmal subarachnoid hemorrhage (aSAH), defined as Hunt and Hess (HH) grades IV and V, is a challenging disease because of its high mortality and poor functional outcomes. The effectiveness of bundled treatments has been demonstrated in critical diseases. Therefore, poor-grade aSAH bundled treatments have been established. This study aims to evaluate whether bundled treatments can improve long-term outcomes and mortality in patients with poor-grade aSAH. METHODS: This is a comparative study using historical control from 2008 to 2022. Bundled treatments were introduced in 2017. We compared the rate of favorable outcomes (modified Rankin Scale score 0-2) at 6 months and mortality before and after the introduction of the bundled treatments. To eliminate confounding bias, the propensity score matching method was used. RESULTS: A total of 90 consecutive patients were evaluated. Forty-three patients received bundled treatments, and 47 patients received conventional care. The proportion of patients with HH grade V was higher in the bundle treatment group (41.9% vs. 27.7%). Conversely, the proportion of patients with fixed pupils on the initial examination was higher in the conventional group (30.2% vs. 38.3%). After 1:1 propensity score matching, 31 pairs were allocated to each group. The proportion of patients with 6-month favorable functional outcomes was significantly higher in the bundled treatments group (46.4% vs. 20.7%, p = 0.04). The 6-month mortality rate was 14.3% in the bundled treatments group and 27.3% in the conventional group (p = 0.01). Bundled treatments (odd ratio 14.6 [95% confidence interval 2.1-100.0], p < 0.01) and the presence of an initial pupil reflex (odd ratio 12.0 [95% confidence interval 1.4-104.6], p = 0.02) were significantly associated with a 6-month favorable functional outcome. CONCLUSIONS: The bundled treatments improve 6-month functional outcome and mortality in patients with poor-grade aSAH.

Extended monitoring of re-coiled cerebral aneurysms after initial postcoiling recanalization: Safety and durability of repeat coil embolization.

PURPOSE: In the endovascular era, postcoiling recanalization of cerebral aneurysms is occurring with greater frequency. Repeat coiling is usually done to prevent rebleeding, although long-term outcomes of re-embolization have yet to be adequately investigated. The present study was undertaken to assess clinical and radiographic outcomes of re-embolization in recanalized aneurysms, focusing on procedural safety, efficacy, and durability. METHOD: In this retrospective review, we examined 308 patients with 310 recurrent aneurysms. All lesions were re-coiled, once major recanalization (after initial coil embolization) was established. Medical records and radiologic data amassed during extended follow-up were then subject to review. Cox proportional hazards regression analysis was undertaken to identify risk factors for subsequent recurrence. RESULT: During a lengthy follow-up (mean, 40.2 ± 33.0 months), major recanalization developed again in 87 aneurysms (28.1%). Multivariable Cox regression analysis linked re-recanalization to initial saccular neck width (p=.003) and autosomal dominant polycystic kidney disease (ADPKD; p<.001). Stent implantation (p=.038) and successful occlusion at second coiling (p=.012) were protective against later recanalization in this setting. The more recent the second embolization was performed, the lower the risk of further recurrence (p=.023). Procedure-related complications included asymptomatic thromboembolism (n = 9), transient ischemic neurologic deficits (n = 2), procedural bleeding (n = 1), and coil migration (n = 1), but there were no residual effects or deaths. CONCLUSION: Repeat coil embolization is a safe therapeutic option for recanalized cerebral aneurysms. Wide-necked status and ADPKD emerged as risks for subsequent recanalization, whereas successful occlusion and stent implantation seemed to reduce the likelihood of recurrence after re-embolization procedures.

Genome-wide association study identifies novel susceptibilities to adult moyamoya disease.

Genome-wide association study has limited to discover single-nucleotide polymorphisms (SNPs) in several ethnicities. Here, we investigated an initial GWAS to identify genetic modifiers predicting with adult moyamoya disease (MMD) in Koreans. GWAS was performed in 216 patients with MMD and 296 controls using the large-scale Asian-specific Axiom Precision Medicine Research Array. A subsequent fine-mapping analysis was conducted to assess the causal variants associated with adult MMD. A total of 489,966 out of 802,688 SNPs were subjected to quality control analysis. Twenty-one SNPs reached a genome-wide significance threshold (p = 5 × 10-8) after pruning linkage disequilibrium (r2 < 0.8) and mis-clustered SNPs. Among these variants, the 17q25.3 region including TBC1D16, CCDC40, GAA, RNF213, and ENDOV genes was broadly associated with MMD (p = 3.1 × 10-20 to 4.2 × 10-8). Mutations in RNF213 including rs8082521 (Q1133K), rs10782008 (V1195M), rs9913636 (E1272Q), rs8074015 (D1331G), and rs9674961 (S2334N) showed a genome-wide significance (1.9 × 10-8 < p < 4.3 × 10-12) and were also replicated in the East-Asian populations. In subsequent analysis, RNF213 mutations were validated in a fine-mapping outcome (log10BF > 7). Most of the loci associated with MMD including 17q25.3 regions were detected with a statistical power greater than 80%. This study identifies several novel and known variations predicting adult MMD in Koreans. These findings may good biomarkers to evaluate MMD susceptibility and its clinical outcomes.

Discussion on "Instrumented difference-in-differences" by Ting Ye, Ashkan Ertefaie, James Flory, Sean Hennessy & Dylan S. Small.

We reinterpret the instrumented difference-in-differences (iDID) under a linear instrumental variables (IV) model. Under the linear IV model, we show why iDID is a clear improvement over two existing methods, difference-in-differences (DID) and a cross-sectional, IV analysis. We also re-express some of the assumptions of iDID using familiar, regression-based identification assumptions. We conclude with a method inspired by the linear IV model that can potentially remedy the weak identification problem in iDID.

Geometric versus Hemodynamic Indexes for Rupture-Destined Aneurysms: A Retrospective Cohort and a Repeated-Measures Study.

INTRODUCTION: A proper stratification of intracranial aneurysms is critical in identifying rupture-destined aneurysms and unruptured intracranial aneurysms. We aimed to determine the utility of geometric and hemodynamic indexes in differentiating two types of aneurysms and to examine the characteristics of natural evolutionary changes of unruptured aneurysms. METHODS: Rupture-destined aneurysm refers to an aneurysm that undergoes subsequent aneurysmal subarachnoid hemorrhage (SAH). On the other hand, an unruptured intracranial aneurysm is characterized by an aneurysm that does not experience rupture during serial time-of-flight magnetic resonance angiography (TOF-MRA). In addition to geometric indexes, signal intensity gradient (SIG), an in vivo approximated wall shear stress from TOF-MRA, was measured in aneurysms. The difference between the maximum and minimum values of SIG in an aneurysm compared to parent arterial values was designated as the delta-SIG ratio. RESULTS: This study analyzed 20 rupture-destined aneurysms in 20 patients and 45 unruptured intracranial aneurysms in 41 patients with follow-up TOF-MRA. While geometric indexes did not show differences between the two groups, the delta-SIG ratio was higher in the rupture-destined aneurysms (1.5 ± 0.6 vs. 1.1 ± 0.3, p = 0.032). The delta-SIG ratio showed a higher area under the receiver operating characteristic curve for SAH than the size ratio (0.72 [95% CI, 0.58-0.87] vs. 0.56 [95% CI, 0.41-0.72], p = 0.033). The longitudinal re-examination of TOF-MRA in the unruptured intracranial aneurysms revealed evidence of aneurysmal growth, while concurrently exhibiting hemodynamic stability. CONCLUSION: The delta-SIG ratio showed higher discriminatory results between the two groups compared to geometric indexes. Aneurysmal rupture risk should be assessed by considering both geometric and hemodynamic information. This study was registered on ClinicalTrials.gov (NCT05450939).

Population-Attributable Risk Fractions for Antiplatelets and Anticoagulants in Spontaneous Intracranial Hemorrhages.

INTRODUCTION: Concerns about spontaneous intracranial hemorrhages (sICHs) have increased over time with the increasing use of antithrombotic agents. Hence, we aimed to analyze the risk and risk fractions for antithrombotics in sICHs in South Korea. METHODS: From the National Health Insurance Service-National Sample Cohort including 1,108,369 citizens, 4,385 cases, aged 20 years or more and newly diagnosed as sICHs between 2003 and 2015, were included in this study. A total of 65,775 sICH-free controls were randomly selected at a ratio of 1:15 from individuals with the same birth year and sex according to a nested case-control study design. RESULTS: Although the incidence rate of sICHs started to decrease from 2007 onward, the use of antiplatelets, anticoagulants, and statins continued to increase. Antiplatelets (adjusted odds ratio [OR] 3.59, 95% confidence interval [CI] 3.18-4.05), anticoagulants (adjusted OR 7.46, 95% CI 4.92-11.32), and statins (adjusted OR 1.98, 95% CI 1.79-2.18) were significant risk factors for sICHs even after adjusting for hypertension, alcohol intake, and cigarette smoking. From 2003-2008 to 2009-2015, the population-attributable fractions changed from 28.0% to 31.3% for hypertension, from 2.0% to 3.2% for antiplatelets, and from 0.5% to 0.9% for anticoagulants. CONCLUSION: Antithrombotic agents are significant risk factors for sICHs, and their contribution is increasing over time in Korea. These findings are expected to draw the attention of clinicians to precautions to be taken when prescribing antithrombotic agents.

Delayed ischemic events with low-dose prasugrel medication for stent-assisted coil embolization in intracranial aneurysm patients.

OBJECTIVE: Much emphasis has been put on the use of antiplatelet medication for the prevention of ischemic events in the treatment of cerebral aneurysms with stent assistance. In this regard, the effectiveness and safety of a low-dose prasugrel regimen during the periprocedural period was recently reported. The purpose of this study was to present the outcomes of patients on low-dose prasugrel regimens during the follow-up period after stent-assisted coil embolization (SACE) of cerebral aneurysms. METHODS: For the 396 consecutive patients undergoing SACE procedures, low-dose prasugrel therapy (5 mg of prasugrel and 100 mg of aspirin) was recommended for 3 months after the endovascular treatment. The authors performed a retrospective review of a single-center experience focusing on delayed ischemic events beyond 1 month after treatment. The mean follow-up period was 24.6 ± 11.3 months. RESULTS: In this cohort of patients on a low-dose prasugrel regimen, cerebral infarction occurred in 1 patient (0.3%, 95% CI 0%-1.8%) beyond 1 month after SACE. No intracranial hemorrhage occurred. Overall ischemic events occurred in 14 patients (3.5%, 95% CI 2.1%-5.9%), all within 6 months of the coiling procedure. All patients had transient symptoms. The events occurred within 2 months after cessation of prasugrel in 11 patients (78.6%). Prasugrel maintenance for 6 months was found to result in lower ischemic events compared with maintenance for 3 months. CONCLUSIONS: For patients undergoing SACE, a low-dose prasugrel regimen was a safe and reliable treatment option for the prevention of delayed ischemic events. Transient ischemic events often occurred within 2 months of stopping prasugrel medication.

Tuning Random Forests for Causal Inference under Cluster-Level Unmeasured Confounding.

Recently, there has been growing interest in using machine learning methods for causal inference due to their automatic and flexible ability to model the propensity score and the outcome model. However, almost all the machine learning methods for causal inference have been studied under the assumption of no unmeasured confounding and there is little work on handling omitted/unmeasured variable bias. This paper focuses on a machine learning method based on random forests known as Causal Forests and presents five simple modifications for tuning Causal Forests so that they are robust to cluster-level unmeasured confounding. Our simulation study finds that adjusting the default tuning procedure with the propensity score from fixed effects logistic regression or using variables that are centered to their cluster means produces estimates that are more robust to cluster-level unmeasured confounding. Also, when these parametric propensity score models are mis-specified, our modified machine learning methods remain robust to bias from cluster-level unmeasured confounders compared to existing parametric approaches based on propensity score weighting. We conclude by demonstrating our proposals in a real data study concerning the effect of taking an eighth-grade algebra course on math achievement scores from the Early Childhood Longitudinal Study.

Is it safe to discontinue antiplatelet medication after stent-assisted coil embolization? If so, when is the best time?

PURPOSE: Antiplatelet maintenance after stent-assisted coil embolization (SACE) is generally considered essential to avoid post-procedural thromboembolic complications. However, there is still debate as to whether it is safe to discontinue antiplatelet drugs after SACE or when is the best time to do so. We investigate herein the clinical outcomes experienced by patients who discontinue antiplatelet agents after SACE. METHODS: From a prospective database, we retrieved the data for 120 consecutive patients (harboring 130 aneurysms) in whom antiplatelet agents were discontinued after SACE between January 2010 and December 2019. We defined thromboembolic complications associated with discontinuation as neurologic or radiographic ischemia that occurred within 6 months of discontinuation of antiplatelet agents; the lesion was required to be correlated with the stented artery. RESULTS: The mean time of discontinuation of antiplatelet medication was 31.4 ± 18.3 months after SACE (median, 26 months). The majority of patients stopped antiplatelet medication between 18 and 36 months after SACE (74 patients, 61.6%). Laser-cut closed-cell stent was most commonly applied in 91 aneurysms (70.0%), followed by braided closed-cell (n=29; 22.3 %) and laser-cut open-cell stent 10 (7.7 %). No patients experienced cerebral ischemia related to discontinuation of antiplatelet medication. CONCLUSION: Our preliminary study suggests that it may be safe to discontinue antiplatelet medication after SACE in patients at low risk for ischemia. The optimal time to discontinue might be around 18 to 36 months after SACE. Large cohort-based studies or randomized clinical trials are warranted to confirm these results.

Weak-instrument robust tests in two-sample summary-data Mendelian randomization.

Mendelian randomization (MR) has been a popular method in genetic epidemiology to estimate the effect of an exposure on an outcome using genetic variants as instrumental variables (IV), with two-sample summary-data MR being the most popular. Unfortunately, instruments in MR studies are often weakly associated with the exposure, which can bias effect estimates and inflate Type I errors. In this work, we propose test statistics that are robust under weak-instrument asymptotics by extending the Anderson-Rubin, Kleibergen, and the conditional likelihood ratio test in econometrics to two-sample summary-data MR. We also use the proposed Anderson-Rubin test to develop a point estimator and to detect invalid instruments. We conclude with a simulation and an empirical study and show that the proposed tests control size and have better power than existing methods with weak instruments.

Two robust tools for inference about causal effects with invalid instruments.

Instrumental variables have been widely used to estimate the causal effect of a treatment on an outcome. Existing confidence intervals for causal effects based on instrumental variables assume that all of the putative instrumental variables are valid; a valid instrumental variable is a variable that affects the outcome only by affecting the treatment and is not related to unmeasured confounders. However, in practice, some of the putative instrumental variables are likely to be invalid. This paper presents two tools to conduct valid inference and tests in the presence of invalid instruments. First, we propose a simple and general approach to construct confidence intervals based on taking unions of well-known confidence intervals. Second, we propose a novel test for the null causal effect based on a collider bias. Our two proposals outperform traditional instrumental variable confidence intervals when invalid instruments are present and can also be used as a sensitivity analysis when there is concern that instrumental variables assumptions are violated. The new approach is applied to a Mendelian randomization study on the causal effect of low-density lipoprotein on globulin levels.

Nonparametric bounds in two-sample summary-data Mendelian randomization: Some cautionary tales for practice.

Recently, in genetic epidemiology, Mendelian randomization (MR) has become a popular approach to estimate causal exposure effects by using single nucleotide polymorphisms from genome-wide association studies (GWAS) as instruments. The most popular type of MR study, a two-sample summary-data MR study, relies on having summary statistics from two independent GWAS and using parametric methods for estimation. However, little is understood about using a nonparametric bound-based analysis, a popular approach in traditional instrumental variables frameworks, to study causal effects in two-sample MR. In this article, we explore using a nonparametric, bound-based analysis in two-sample MR studies, focusing primarily on implications for practice. We also propose a framework to assess how likely one can obtain more informative bounds if we used a different MR design, notably a one-sample MR design. We conclude by demonstrating our findings through two real data analyses concerning the causal effect of smoking on lung cancer and the causal effect of high cholesterol on heart attacks. Overall, our results suggest that while a bound-based analysis may be appealing due to its nonparametric nature, it is far more conservative in two-sample settings than in one-sample settings to get informative bounds on the causal exposure effect.

Endovascular treatment of medullary bridging vein-draining dural arteriovenous fistulas: foramen magnum vs. craniocervical junction lesions.

PURPOSE: Dural arteriovenous fistulas (AVFs) draining to medullary bridging vein (MBV) are located at foramen magnum (FM) and craniocervical junction (CCJ). Such fistulas are rare but pose a challenge to endovascular management. This study was undertaken to assess clinical manifestations, angiographic features, and outcomes of endovascular treatment in patients with MBV dural AVFs. METHODS: A number of our patients (N = 22) were diagnosed with MBV dural AVF and treated by endovascular means. There were 9 FM lesions and 13 CCJ lesions. We reviewed clinical records and imaging studies to define clinical characteristics, vascular anatomic details, and treatment outcomes, comparing FM- and CCJ-level subsets. RESULTS: Subjects ranged from 37 to 74 years of age (mean, 57.7 years) with male predominance (2.7:1). They presented with intracranial hemorrhage (11/22, 50%), myelopathy (8/22, 36%), or nonspecific symptoms (3/22, 14%). In 17 patients (77.3%), the shunts showed complete or near-complete occlusion following endovascular treatment (FM, 100%; CCJ, 61.5%). However, seven patients experienced ischemic events (FM, 11.1%; CCJ, 46.2%) and one patient sustained a hemorrhagic complication. No hemorrhages recurred during follow-up monitoring, and myelopathic symptoms abated. CONCLUSION: MBV dural AVFs are highly aggressive lesions for which proper diagnosis and treatment are of utmost importance. Although transarterial embolization proved highly successful in FM lesions, shunt occlusion was less frequent in the CCJ subset, with greater risk of ischemic complications.

An introduction to spillover effects in cluster randomized trials with noncompliance.

In some cluster randomized trials, subjects may not comply with their assigned treatment status. Such treatment noncompliance can create opportunities for spillover effects within clusters. Little research has focused on what can be learned in such context. This article provides a non-technical review of recent work on the complications that arise in cluster randomized trials where some units within treated clusters do not comply with treatment but the treatment spillovers over to these units. We motivate concepts using a hypothetical vaccine cluster randomized trial. We review that standard instrumental variable methods cannot recover the complier average causal effect in the presence of these spillovers. In fact, we review that without additional assumptions, little can be learned about compliance effects or spillover effects. We discuss one additional assumption that allows for bounds on a key causal effect. We also outline an estimator for these bounds.

Genome-wide association study reveals sex-specific genetic architecture of facial attractiveness.

Facial attractiveness is a complex human trait of great interest in both academia and industry. Literature on sociological and phenotypic factors associated with facial attractiveness is rich, but its genetic basis is poorly understood. In this paper, we conducted a genome-wide association study to discover genetic variants associated with facial attractiveness using 4,383 samples in the Wisconsin Longitudinal Study. We identified two genome-wide significant loci, highlighted a handful of candidate genes, and demonstrated enrichment for heritability in human tissues involved in reproduction and hormone synthesis. Additionally, facial attractiveness showed strong and negative genetic correlations with BMI in females and with blood lipids in males. Our analysis also suggested sex-specific selection pressure on variants associated with lower male attractiveness. These results revealed sex-specific genetic architecture of facial attractiveness and provided fundamental new insights into its genetic basis.

Clinical Factors Associated with the Risk of Intracranial Aneurysm Rupture in Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: The occurrence of intracranial aneurysms is higher in patients with autosomal dominant polycystic kidney disease (ADPKD) than in the healthy population. However, research concerning the factors related to the risk of intracranial aneurysm rupture in patients with ADPKD is still insufficient. OBJECTIVES: The aim of the study was to investigate the prevalence of intracranial aneurysms and aneurysmal subarachnoid hemorrhage (SAH) and to analyze the systemic factors associated with high-risk aneurysms in patients with ADPKD. METHODS: We screened patients who underwent cerebral angiography between January 2007 and May 2017 in the ADPKD registry. Patients were examined for the presence of intracranial aneurysms and subsequently reclassified into 3 groups based on the risk of aneurysmal rupture: the aneurysm-negative (group 1), low-risk aneurysm (group 2), or high-risk aneurysm (group 3). Various systemic factors were compared, and independent factors associated with high-risk aneurysms were analyzed. RESULTS: Among the 926 patients, 148 (16.0%) had intracranial aneurysms and 11 (1.2%) had previous aneurysmal SAH. Patients with intracranial aneurysms were further classified into group 2 (low-risk aneurysms, 15.5%) or group 3 (high-risk aneurysms, 84.5%). Age (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.01-1.05, p = 0.004), female sex (OR 3.13, 95% CI 1.94-5.0 6, p < 0.001), dolichoectasia (OR 8.57, 95% CI 1.53-48.17, p = 0.015), and mitral inflow deceleration time (DT) (OR 1.01, 95% CI 1.00-1.01, p = 0.046) were independently associated with high-risk aneurysms, whereas hypercholesterolemia (OR 0.46, 95% CI 0.29-0.72, p = 0.001) was negatively associated. CONCLUSION: In the present study among patients with ADPKD, the prevalence of intracranial aneurysms and aneurysmal SAH was 16 and 1.2%, respectively. Age, female sex, dolichoectasia, and mitral inflow DT were positively associated with high-risk aneurysms, whereas hypercholesterolemia was negatively associated. A subsequent large-scaled longitudinal study is needed to define the plausibility of the clinical parameters.

Random Forests Approach for Causal Inference with Clustered Observational Data.

There is a growing interest in using machine learning (ML) methods for causal inference due to their (nearly) automatic and flexible ability to model key quantities such as the propensity score or the outcome model. Unfortunately, most ML methods for causal inference have been studied under single-level settings where all individuals are independent of each other and there is little work in using these methods with clustered or nested data, a common setting in education studies. This paper investigates using one particular ML method based on random forests known as Causal Forests to estimate treatment effects in multilevel observational data. We conduct simulation studies under different types of multilevel data, including two-level, three-level, and cross-classified data. Our simulation study shows that when the ML method is supplemented with estimated propensity scores from multilevel models that account for clustered/hierarchical structure, the modified ML method outperforms preexisting methods in a wide variety of settings. We conclude by estimating the effect of private math lessons in the Trends in International Mathematics and Science Study data, a large-scale educational assessment where students are nested within schools.

Retrograde stenting through anterior communicating artery in coil embolization of the posterior communicating artery aneurysm: contralateral approach.

During coil embolization of wide-necked posterior communicating artery (PcomA) aneurysms, stent assistance is sometimes limited if PcomA is acutely angled at its origins from saccular neck. Herein, we present two instances where retrograde stenting was used for coil embolization of PcomA aneurysms. Both procedures involved a contralateral approach via anterior communicating artery (AcomA). To achieve this, the stent-delivery microcatheter was inserted retrograde from contralateral to ipsilateral internal carotid artery (ICA) across AcomA, arriving at ipsilateral PcomA. A separate microcatheter, passed through ipsilateral ICA, was then used to select the aneurysm sac for coil delivery. Coil embolization ultimately took place under protection of a horizontally placed stent extending from PcomA to terminal ICA. Each aneurysm was properly coiled and occluded, without procedural complications. This stenting technique is a reasonable option, offering a means of strategic coil embolization in wide-necked PcomA aneurysms and providing complete neck coverage through contralateral access.

Neurological Pupil Index as an Indicator of Neurological Worsening in Large Hemispheric Strokes.

BACKGROUND/OBJECTIVE: Cerebral herniation due to brain edema is the major cause of neurological worsening in patients suffering large hemispheric strokes. In this study, we investigated whether quantitative pupillary response could help identify the neurological worsening due to brain swelling in patients with large hemispheric strokes. METHODS: Quantitative pupillary assessment using an automated pupillometer (NPi-100) was performed between April 2017 and August 2019 for patients suffering large hemispheric strokes. Consecutive pupillary responses were measured every 2 or 4 h as a part of routine clinical care. We compared the mean neurological pupil index (NPi) values, NPi value at the time of neurological deterioration, and percentage change in NPi from the immediate previous value between patients with and without neurological worsening. RESULTS: In this study, 2442 quantitative pupillary assessments were performed (n = 30; mean age, 67.9 years; males, 60.0%). Among the included patients, 10 (33.3%) experienced neurological worsening. Patients with neurological worsening had a significantly lower mean value of NPi and a sudden decrease in the NPi value as compared to those without neurological worsening during the whole monitoring period (3.88 ± 0.65 vs. 4.45 ± 0.46, P < 0.001; and 29.5% vs. 11.1%, P = 0.006, respectively). All patients with NPi values below 2.8 showed neurological deterioration. CONCLUSIONS: Quantitative monitoring of the pupillary response using an automated pupillometer could be a useful and noninvasive tool for detecting neurological deterioration due to cerebral edema in large hemispheric stroke patients.