A multitask deep learning approach for pulmonary embolism detection and identification

Pulmonary embolism (PE) is a blood clot traveling to the lungs and is associated with substantial morbidity and mortality. Therefore, rapid diagnoses and treatments are essential. Chest computed tomographic pulmonary angiogram (CTPA) is the gold standard for PE diagnoses. Deep learning can enhance the radiologists’workflow by identifying PE using CTPA, which helps to prioritize important cases and hasten the diagnoses for at-risk patients. In this study, we propose a two-phase multitask learning method that can recognize the presence of PE and its properties such as the position, whether acute or chronic, and the corresponding right-to-left ventricle diameter (RV/LV) ratio, thereby reducing false-negative diagnoses. Trained on the RSNA-STR Pulmonary Embolism CT Dataset, our model demonstrates promising PE detection performances on the hold-out test set with the window-level AUROC achieving 0.93 and the sensitivity being 0.86 with a specificity of 0.85, which is competitive with the radiologists’sensitivities ranging from 0.67 to 0.87 with specificities of 0.89–0.99. In addition, our model provides interpretability through attention weight heatmaps and gradient-weighted class activation mapping (Grad-CAM). Our proposed deep learning model could predict PE existence and other properties of existing cases, which could be applied to practical assistance for PE diagnosis

Risk Factors for Pediatric Ischemic Stroke and Intracranial Hemorrhage: A National Electronic Health Record Based Study

BACKGROUND: Stroke is an important cause of morbidity in pediatrics. Large studies are needed to better understand the epidemiology, pathogenesis and risk factors associated with pediatric stroke. Large administrative datasets can provide information on risk factors in perinatal and childhood stroke at low cost. The aim of this hypothesis-generating study was to use a large administrative dataset to assess for prevalence and odds-ratios of rare exposures associated with pediatric stroke. METHODS: The data for patients aged 0-18 with a diagnosis of either ischemic stroke or intracranial hemorrhage were extracted from the Cerner Health Facts EMR Database from 2000 to 2018. Prevalence of various possible risk factors for pediatric and adult stroke was assessed using ICD 9 and 10 codes. Odds ratios were calculated using a control group of patients without stroke. RESULTS: CONCLUSION: This is the largest retrospective study of pediatric stroke of its kind from hospitals across the US in both academic and non-academic clinical settings. Much of our data was consistent with prior studies. ICD codes for tobacco exposure, hyperlipidemia, diabetes, and hypertension all had high odds ratios for stroke in children, which suggest a relationship between these conditions and pediatric stroke. However, ascertainment bias is a major concern with electronic health record-based studies. More focused study is needed into the role of these exposures into the pathogenesis of pediatric stroke

A National, Electronic Health Record-Based Study of Perinatal Hemorrhagic and Ischemic Stroke

BACKGROUND: Perinatal stroke occurs in approximately 1 in 1100 live births. Large electronic health record (EHR) data can provide information on exposures associated with perinatal stroke in a larger number of patients than is achievable through traditional clinical studies. The objective of this study is to assess prevalence and odds ratios of known and theorized comorbidities with perinatal ischemic and hemorrhagic stroke. METHODS: The data for patients aged 0-28 days with a diagnosis of either ischemic or hemorrhagic stroke were extracted from the Cerner Health Facts Electronic Medical Record (EMR) database. Incidence of birth demographics and perinatal complications were recorded. Odds ratios were calculated against a control group. RESULTS: A total of 535 (63%) neonates were identified with ischemic stroke and 312 (37%) with hemorrhagic stroke. The most common exposures for ischemic stroke were sepsis (n = 82, 15.33%), hypoxic injury (n = 61, 11.4%), and prematurity (n = 49, 9.16%). The most common comorbidities for hemorrhagic stroke were prematurity (n = 81, 26%) and sepsis (n = 63, 20%). No perinatal ischemic stroke patients had diagnosis codes for cytomegalovirus disease. Procedure and diagnosis codes related to critical illness, including intubation and resuscitation, were prominent in both hemorrhagic (n = 46, 15%) and ischemic stroke (n = 45, 8%). CONCLUSION: This electronic health record-based study of perinatal stroke, the largest of its kind, demonstrated a wide variety of comorbid conditions with ischemic and hemorrhagic stroke. Sepsis, prematurity, and hypoxic injury are associated with perinatal hemorrhagic and ischemic stroke, though prevalence varies between types. Much of our data were similar to prior studies, which lends validity to the electronic health record database in studying perinatal stroke

Peripheral Blood Monocytes as a Therapeutic Target for Marrow Stromal Cells in Stroke Patients

BACKGROUND: Systemic administration of marrow stromal cells METHODS: Peripheral blood from stroke patients was collected at 5-7 days ( RESULTS: Our results show that there is a higher release of IFN-γ and IL-10 from monocytes isolated from peripheral blood at day 5-7 after stroke compared with monocytes from healthy controls. In trans-well co-cultures of MSCs and monocytes isolated from stroke patients, we found statistically significant increased levels of IL-4 and MCP-1, and decreased levels of IL-6, IL-1β, and TNF-α. Addition of MSCs to monocytes increased the secretions of Fractalkine, IL-6, and MCP-1, while the secretions of TNF-α decreased, as compared to the secretions from monocytes alone. When MSCs were added to monocytes from stroke patients, they decreased the levels of IL-1β, and increased the levels of IL-10 significantly more as compared to when they were added to monocytes from control patients. CONCLUSION: The systemic circulation of stroke patients may differentially interact with MSCs to release soluble factors integral to their paracrine mechanisms of benefit. Our study finds that the effect of MSCs on Mϕ is different on those derived from stroke patients blood as compared to healthy controls. These findings suggest immunomodulation of peripheral immune cells as a therapeutic target for MSCs in patients with acute stroke

An Interpretable Framework to Identify Responsive Subgroups From Clinical Trials Regarding Treatment Effects: Application to Treatment of Intracerebral Hemorrhage

Randomized Clinical trials (RCT) suffer from a high failure rate which could be caused by heterogeneous responses to treatment. Despite many models being developed to estimate heterogeneous treatment effects (HTE), there remains a lack of interpretable methods to identify responsive subgroups. This work aims to develop a framework to identify subgroups based on treatment effects that prioritize model interpretability. The proposed framework leverages an ensemble uplift tree method to generate descriptive decision rules that separate samples given estimated responses to the treatment. Subsequently, we select a complementary set of these decision rules and rank them using a sparse linear model. To address the trial\u27s limited sample size problem, we proposed a data augmentation strategy by borrowing control patients from external studies and generating synthetic data. We apply the proposed framework to a failed randomized clinical trial for investigating an intracerebral hemorrhage therapy plan. The Qini-scores show that the proposed data augmentation strategy plan can boost the model\u27s performance and the framework achieves greater interpretability by selecting complementary descriptive rules without compromising estimation quality. Our model derives clinically meaningful subgroups. Specifically, we find those patients with Diastolic Blood Pressure≥70 mm hg and Systolic Blood Pressuresubgroups, our framework can contribute to developing personalized treatment strategies for patients more efficiently

Sex Disparities in Access to Acute Stroke Care: Can Telemedicine Mitigate this Effect?

Background: Women have more frequent and severe ischemic strokes than men, and are less likely to receive treatment for acute stroke. Primary stroke centers (PSCs) have been shown to utilize treatment more frequently. Further, as telemedicine (TM) has expanded access to acute stroke care we sought to investigate the association between PSC, TM and access to acute stroke care in the state of Texas. Methods: Texas hospitals and resources were identified from the 2009 American Hospital Association Annual Survey. Hospitals were categorized as: (1) stand-alone PSCs not using telemedicine for acute stroke care, (2) PSCs using telemedicine for acute stroke care (PSC-TM), (3) non-PSC hospitals using telemedicine for acute stroke care, or (4) non-PSC hospitals not using telemedicine for acute stroke care. The proportion of the population who could reach a PSC within 60 minutes was determined for stand-alone PSCs, PSC-TM, and non-PSCs using TM for stroke care. Results: Overall, women were as likely to have 60-minute access to a PSC or PSC-TM as their male counterparts (POR 1.02, 95% CI 1.02-1.03). Women were also just as likely to have access to acute stroke care via PSC or PSC-TM or TM as men (POR 1.03, 95% CI 1.02-1.04). Discussion: Our study found no sex disparities in access to stand alone PSCs or to hospitals using TM in the state of Texas. The results of this study suggest that telemedicine can be used as part of an inclusive strategy to improve access to care equally for men and women

Necrostatin-1 Reduces Histopathology and Improves Functional Outcome after Controlled Cortical Impact in Mice

Necroptosis is a newly identified type of programmed necrosis initiated by the activation of tumor necrosis factor alpha (TNF?)/Fas. Necrostatin-1 is a specific inhibitor of necroptosis that reduces ischemic tissue damage in experimental stroke models. We previously reported decreased tissue damage and improved functional outcome after controlled cortical impact (CCI) in mice deficient in TNF? and Fas. Hence, we hypothesized that necrostatin-1 would reduce histopathology and improve functional outcome after CCI in mice. Compared with vehicle-/inactive analog-treated controls, mice administered necrostatin-1 before CCI had decreased propidium iodide-positive cells in the injured cortex and dentate gyrus (6 h), decreased brain tissue damage (days 14, 35), improved motor (days 1 to 7), and Morris water maze performance (days 8 to 14) after CCI. Improved spatial memory was observed even when drug was administered 15 mins after CCI. Necrostatin-1 treatment did not reduce caspase-3-positive cells in the dentate gyrus or cortex, consistent with a known caspase-independent mechanism of necrostatin-1. However, necrostatin-1 reduced brain neutrophil influx and microglial activation at 48 h, suggesting a novel anti-inflammatory effect in traumatic brain injury (TBI). The data suggest that necroptosis plays a significant role in the pathogenesis of cell death and functional outcome after TBI and that necrostatin-1 may have therapeutic potential for patients with TBI

Non-Invasive Arterial Blood Pressure Measurement and SpO2 Estimation Using PPG Signal: A Deep Learning Framework

BACKGROUND: Monitoring blood pressure and peripheral capillary oxygen saturation plays a crucial role in healthcare management for patients with chronic diseases, especially hypertension and vascular disease. However, current blood pressure measurement methods have intrinsic limitations; for instance, arterial blood pressure is measured by inserting a catheter in the artery causing discomfort and infection. METHOD: Photoplethysmogram (PPG) signals can be collected via non-invasive devices, and therefore have stimulated researchers\u27 interest in exploring blood pressure estimation using machine learning and PPG signals as a non-invasive alternative. In this paper, we propose a Transformer-based deep learning architecture that utilizes PPG signals to conduct a personalized estimation of arterial systolic blood pressure, arterial diastolic blood pressure, and oxygen saturation. RESULTS: The proposed method was evaluated with a subset of 1,732 subjects from the publicly available ICU dataset MIMIC III. The mean absolute error is 2.52 ± 2.43 mmHg for systolic blood pressure, 1.37 ± 1.89 mmHg for diastolic blood pressure, and 0.58 ± 0.79% for oxygen saturation, which satisfies the requirements of the Association of Advancement of Medical Instrumentation standard and achieve grades A for the British Hypertension Society standard. CONCLUSIONS: The results indicate that our model meets clinical standards and could potentially boost the accuracy of blood pressure and oxygen saturation measurement to deliver high-quality healthcare

Enhanced Cerebroprotection of Xenon-Loaded Liposomes in Combination with rtPA Thrombolysis for Embolic Ischemic Stroke

Xenon (Xe) has shown great potential as a stroke treatment due to its exceptional ability to protect brain tissue without inducing side effects. We have previously developed Xe-loaded liposomes for the ultrasound-activated delivery of Xe into the cerebral region and demonstrated their therapeutic efficacy. At present, the sole FDA-approved thrombolytic agent for stroke treatment is recombinant tissue plasminogen activator (rtPA). In this study, we aimed to investigate the potential of combining Xe-liposomes with an intravenous rtPA treatment in a clinically relevant embolic rat stroke model. We evaluated the combinational effect using an in vitro clot lysis model and an in vivo embolic middle cerebral artery occlusion (eMCAO) rat model. The treatment groups received intravenous administration of Xe-liposomes (20 mg/kg) at 2 h post-stroke onset, followed by the administration of rtPA (10 mg/kg) at either 2 or 4 h after the onset. Three days after the stroke, behavioral tests were conducted, and brain sections were collected for triphenyltetrazolium chloride (TTC) and TUNEL staining. Infarct size was determined as normalized infarct volume (%). Both in vitro and in vivo clot lysis experiments demonstrated that Xe-liposomes in combination with rtPA resulted in effective clot lysis comparable to the treatment with free rtPA alone. Animals treated with Xe-liposomes in combination with rtPA showed reduced TUNEL-positive cells and demonstrated improved neurological recovery. Importantly, Xe-liposomes in combination with late rtPA treatment reduced rtPA-induced hemorrhage, attributing to the reduction of MMP9 immunoreactivity. This study demonstrates that the combined therapy of Xe-liposomes and rtPA provides enhanced therapeutic efficacy, leading to decreased neuronal cell death and a potential to mitigate hemorrhagic side effects associated with late rtPA treatment

Enhanced Cerebroprotection of Xenon-Loaded Liposomes in Combination with rtPA Thrombolysis for Embolic Ischemic Stroke

Xenon (Xe) has shown great potential as a stroke treatment due to its exceptional ability to protect brain tissue without inducing side effects. We have previously developed Xe-loaded liposomes for the ultrasound-activated delivery of Xe into the cerebral region and demonstrated their therapeutic efficacy. At present, the sole FDA-approved thrombolytic agent for stroke treatment is recombinant tissue plasminogen activator (rtPA). In this study, we aimed to investigate the potential of combining Xe-liposomes with an intravenous rtPA treatment in a clinically relevant embolic rat stroke model. We evaluated the combinational effect using an in vitro clot lysis model and an in vivo embolic middle cerebral artery occlusion (eMCAO) rat model. The treatment groups received intravenous administration of Xe-liposomes (20 mg/kg) at 2 h post-stroke onset, followed by the administration of rtPA (10 mg/kg) at either 2 or 4 h after the onset. Three days after the stroke, behavioral tests were conducted, and brain sections were collected for triphenyltetrazolium chloride (TTC) and TUNEL staining. Infarct size was determined as normalized infarct volume (%). Both in vitro and in vivo clot lysis experiments demonstrated that Xe-liposomes in combination with rtPA resulted in effective clot lysis comparable to the treatment with free rtPA alone. Animals treated with Xe-liposomes in combination with rtPA showed reduced TUNEL-positive cells and demonstrated improved neurological recovery. Importantly, Xe-liposomes in combination with late rtPA treatment reduced rtPA-induced hemorrhage, attributing to the reduction of MMP9 immunoreactivity. This study demonstrates that the combined therapy of Xe-liposomes and rtPA provides enhanced therapeutic efficacy, leading to decreased neuronal cell death and a potential to mitigate hemorrhagic side effects associated with late rtPA treatment