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OBJECTIVES: We aimed to develop deep learning models using longitudinal chest X-rays (CXRs) and clinical data to predict in-hospital mortality of COVID-19 patients in the intensive care unit (ICU). METHODS: Six hundred fifty-four patients (212 deceased, 442 alive, 5645 total CXRs) were identified across two institutions. Imaging and clinical data from one institution were used to train five longitudinal transformer-based networks applying five-fold cross-validation. The models were tested on data from the other institution, and pairwise comparisons were used to determine the best-performing models. RESULTS: A higher proportion of deceased patients had elevated white blood cell count, decreased absolute lymphocyte count, elevated creatine concentration, and incidence of cardiovascular and chronic kidney disease. A model based on pre-ICU CXRs achieved an AUC of 0.632 and an accuracy of 0.593, and a model based on ICU CXRs achieved an AUC of 0.697 and an accuracy of 0.657. A model based on all longitudinal CXRs (both pre-ICU and ICU) achieved an AUC of 0.702 and an accuracy of 0.694. A model based on clinical data alone achieved an AUC of 0.653 and an accuracy of 0.657. The addition of longitudinal imaging to clinical data in a combined model significantly improved performance, reaching an AUC of 0.727 (p = 0.039) and an accuracy of 0.732. CONCLUSIONS: The addition of longitudinal CXRs to clinical data significantly improves mortality prediction with deep learning for COVID-19 patients in the ICU. KEY POINTS: ⢠Deep learning was used to predict mortality in COVID-19 ICU patients. ⢠Serial radiographs and clinical data were used. ⢠The models could inform clinical decision-making and resource allocation.
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COVID-19 , Aprendizaje Profundo , Humanos , Unidades de Cuidados Intensivos , Radiografía , Rayos XRESUMEN
While COVID-19 diagnosis and prognosis artificial intelligence models exist, very few can be implemented for practical use given their high risk of bias. We aimed to develop a diagnosis model that addresses notable shortcomings of prior studies, integrating it into a fully automated triage pipeline that examines chest radiographs for the presence, severity, and progression of COVID-19 pneumonia. Scans were collected using the DICOM Image Analysis and Archive, a system that communicates with a hospital's image repository. The authors collected over 6,500 non-public chest X-rays comprising diverse COVID-19 severities, along with radiology reports and RT-PCR data. The authors provisioned one internally held-out and two external test sets to assess model generalizability and compare performance to traditional radiologist interpretation. The pipeline was evaluated on a prospective cohort of 80 radiographs, reporting a 95% diagnostic accuracy. The study mitigates bias in AI model development and demonstrates the value of an end-to-end COVID-19 triage platform.
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OBJECTIVES: Early recognition of coronavirus disease 2019 (COVID-19) severity can guide patient management. However, it is challenging to predict when COVID-19 patients will progress to critical illness. This study aimed to develop an artificial intelligence system to predict future deterioration to critical illness in COVID-19 patients. METHODS: An artificial intelligence (AI) system in a time-to-event analysis framework was developed to integrate chest CT and clinical data for risk prediction of future deterioration to critical illness in patients with COVID-19. RESULTS: A multi-institutional international cohort of 1,051 patients with RT-PCR confirmed COVID-19 and chest CT was included in this study. Of them, 282 patients developed critical illness, which was defined as requiring ICU admission and/or mechanical ventilation and/or reaching death during their hospital stay. The AI system achieved a C-index of 0.80 for predicting individual COVID-19 patients' to critical illness. The AI system successfully stratified the patients into high-risk and low-risk groups with distinct progression risks (p < 0.0001). CONCLUSIONS: Using CT imaging and clinical data, the AI system successfully predicted time to critical illness for individual patients and identified patients with high risk. AI has the potential to accurately triage patients and facilitate personalized treatment. KEY POINT: ⢠AI system can predict time to critical illness for patients with COVID-19 by using CT imaging and clinical data.
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COVID-19 , Inteligencia Artificial , Humanos , Estudios Retrospectivos , SARS-CoV-2 , Tomografía Computarizada por Rayos XRESUMEN
To explore the role of chronic liver disease (CLD) in COVID-19. A total of 1439 consecutively hospitalized patients with COVID-19 from one large medical center in the United States from March 16, 2020 to April 23, 2020 were retrospectively identified. Clinical characteristics and outcomes were compared between patients with and without CLD. Postmortem examination of liver in 8 critically ill COVID-19 patients was performed. There was no significant difference in the incidence of CLD between critical and non-critical groups (4.1% vs 2.9%, p = 0.259), or COVID-19 related liver injury between patients with and without CLD (65.7% vs 49.7%, p = 0.065). Postmortem examination of liver demonstrated mild liver injury associated central vein outflow obstruction and minimal to moderate portal lymphocytic infiltrate without evidence of CLD. Patients with CLD were not associated with a higher risk of liver injury or critical/fatal outcomes. CLD was not a significant comorbid condition for COVID-19.
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COVID-19/epidemiología , Hepatopatías/epidemiología , Lesión Pulmonar Aguda/epidemiología , Lesión Pulmonar Aguda/patología , Anciano , COVID-19/mortalidad , Enfermedad Crónica , Comorbilidad , Femenino , Humanos , Hepatopatías/patología , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estados Unidos/epidemiologíaRESUMEN
AIMS: To determine if neurologic symptoms at admission can predict adverse outcomes in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: Electronic medical records of 1053 consecutively hospitalized patients with laboratory-confirmed infection of SARS-CoV-2 from one large medical center in the USA were retrospectively analyzed. Univariable and multivariable Cox regression analyses were performed with the calculation of areas under the curve (AUC) and concordance index (C-index). Patients were stratified into subgroups based on the presence of encephalopathy and its severity using survival statistics. In sensitivity analyses, patients with mild/moderate and severe encephalopathy (defined as coma) were separately considered. RESULTS: Of 1053 patients (mean age 52.4 years, 48.0% men [n = 505]), 35.1% (n = 370) had neurologic manifestations at admission, including 10.3% (n = 108) with encephalopathy. Encephalopathy was an independent predictor for death (hazard ratio [HR] 2.617, 95% confidence interval [CI] 1.481-4.625) in multivariable Cox regression. The addition of encephalopathy to multivariable models comprising other predictors for adverse outcomes increased AUCs (mortality: 0.84-0.86, ventilation/ intensive care unit [ICU]: 0.76-0.78) and C-index (mortality: 0.78 to 0.81, ventilation/ICU: 0.85-0.86). In sensitivity analyses, risk stratification survival curves for mortality and ventilation/ICU based on severe encephalopathy (n = 15) versus mild/moderate encephalopathy (n = 93) versus no encephalopathy (n = 945) at admission were discriminative (p < 0.001). CONCLUSIONS: Encephalopathy at admission predicts later progression to death in SARS-CoV-2 infection, which may have important implications for risk stratification in clinical practice.
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Encefalopatías/diagnóstico , Encefalopatías/mortalidad , COVID-19/diagnóstico , COVID-19/mortalidad , Admisión del Paciente/tendencias , Adulto , Anciano , Encefalopatías/terapia , COVID-19/terapia , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios RetrospectivosRESUMEN
OBJECTIVE: To develop a machine learning (ML) pipeline based on radiomics to predict Coronavirus Disease 2019 (COVID-19) severity and the future deterioration to critical illness using CT and clinical variables. MATERIALS AND METHODS: Clinical data were collected from 981 patients from a multi-institutional international cohort with real-time polymerase chain reaction-confirmed COVID-19. Radiomics features were extracted from chest CT of the patients. The data of the cohort were randomly divided into training, validation, and test sets using a 7:1:2 ratio. A ML pipeline consisting of a model to predict severity and time-to-event model to predict progression to critical illness were trained on radiomics features and clinical variables. The receiver operating characteristic area under the curve (ROC-AUC), concordance index (C-index), and time-dependent ROC-AUC were calculated to determine model performance, which was compared with consensus CT severity scores obtained by visual interpretation by radiologists. RESULTS: Among 981 patients with confirmed COVID-19, 274 patients developed critical illness. Radiomics features and clinical variables resulted in the best performance for the prediction of disease severity with a highest test ROC-AUC of 0.76 compared with 0.70 (0.76 vs. 0.70, p = 0.023) for visual CT severity score and clinical variables. The progression prediction model achieved a test C-index of 0.868 when it was based on the combination of CT radiomics and clinical variables compared with 0.767 when based on CT radiomics features alone (p < 0.001), 0.847 when based on clinical variables alone (p = 0.110), and 0.860 when based on the combination of visual CT severity scores and clinical variables (p = 0.549). Furthermore, the model based on the combination of CT radiomics and clinical variables achieved time-dependent ROC-AUCs of 0.897, 0.933, and 0.927 for the prediction of progression risks at 3, 5 and 7 days, respectively. CONCLUSION: CT radiomics features combined with clinical variables were predictive of COVID-19 severity and progression to critical illness with fairly high accuracy.
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COVID-19/diagnóstico , Aprendizaje Automático , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X/métodos , Enfermedad Crítica , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Estudios Retrospectivos , SARS-CoV-2/patogenicidadRESUMEN
BACKGROUND: Chest x-ray is a relatively accessible, inexpensive, fast imaging modality that might be valuable in the prognostication of patients with COVID-19. We aimed to develop and evaluate an artificial intelligence system using chest x-rays and clinical data to predict disease severity and progression in patients with COVID-19. METHODS: We did a retrospective study in multiple hospitals in the University of Pennsylvania Health System in Philadelphia, PA, USA, and Brown University affiliated hospitals in Providence, RI, USA. Patients who presented to a hospital in the University of Pennsylvania Health System via the emergency department, with a diagnosis of COVID-19 confirmed by RT-PCR and with an available chest x-ray from their initial presentation or admission, were retrospectively identified and randomly divided into training, validation, and test sets (7:1:2). Using the chest x-rays as input to an EfficientNet deep neural network and clinical data, models were trained to predict the binary outcome of disease severity (ie, critical or non-critical). The deep-learning features extracted from the model and clinical data were used to build time-to-event models to predict the risk of disease progression. The models were externally tested on patients who presented to an independent multicentre institution, Brown University affiliated hospitals, and compared with severity scores provided by radiologists. FINDINGS: 1834 patients who presented via the University of Pennsylvania Health System between March 9 and July 20, 2020, were identified and assigned to the model training (n=1285), validation (n=183), or testing (n=366) sets. 475 patients who presented via the Brown University affiliated hospitals between March 1 and July 18, 2020, were identified for external testing of the models. When chest x-rays were added to clinical data for severity prediction, area under the receiver operating characteristic curve (ROC-AUC) increased from 0·821 (95% CI 0·796-0·828) to 0·846 (0·815-0·852; p<0·0001) on internal testing and 0·731 (0·712-0·738) to 0·792 (0·780-0 ·803; p<0·0001) on external testing. When deep-learning features were added to clinical data for progression prediction, the concordance index (C-index) increased from 0·769 (0·755-0·786) to 0·805 (0·800-0·820; p<0·0001) on internal testing and 0·707 (0·695-0·729) to 0·752 (0·739-0·764; p<0·0001) on external testing. The image and clinical data combined model had significantly better prognostic performance than combined severity scores and clinical data on internal testing (C-index 0·805 vs 0·781; p=0·0002) and external testing (C-index 0·752 vs 0·715; p<0·0001). INTERPRETATION: In patients with COVID-19, artificial intelligence based on chest x-rays had better prognostic performance than clinical data or radiologist-derived severity scores. Using artificial intelligence, chest x-rays can augment clinical data in predicting the risk of progression to critical illness in patients with COVID-19. FUNDING: Brown University, Amazon Web Services Diagnostic Development Initiative, Radiological Society of North America, National Cancer Institute and National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health.
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Inteligencia Artificial , COVID-19/fisiopatología , Pronóstico , Radiografía Torácica , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X , Estados Unidos , Adulto JovenRESUMEN
PURPOSE: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma. Currently, there is a lack of noninvasive methods to stratify ccRCC prognosis prior to any invasive therapies. The purpose of this study was to preoperatively predict the tumor stage, size, grade, and necrosis (SSIGN) score of ccRCC using MRI-based radiomics. METHODS: A multicenter cohort of 364 histopathologically confirmed ccRCC patients (272 low [< 4] and 92 high [≥ 4] SSIGN score) with preoperative T2-weighted and T1-contrast-enhanced MRI were retrospectively identified and divided into training (254 patients) and testing sets (110 patients). The performance of a manually optimized radiomics model was assessed by measuring accuracy, sensitivity, specificity, area under receiver operating characteristic curve (AUROC), and area under precision-recall curve (AUPRC) on an independent test set, which was not included in model training. Lastly, its performance was compared to that of a machine learning pipeline, Tree-Based Pipeline Optimization Tool (TPOT). RESULTS: The manually optimized radiomics model using Random Forest classification and Analysis of Variance feature selection methods achieved an AUROC of 0.89, AUPRC of 0.81, accuracy of 0.89 (95% CI 0.816-0.937), specificity of 0.95 (95% CI 0.875-0.984), and sensitivity of 0.72 (95% CI 0.537-0.852) on the test set. The TPOT using Extra Trees Classifier achieved an AUROC of 0.94, AUPRC of 0.83, accuracy of 0.89 (95% CI 0.816-0.937), specificity of 0.95 (95% CI 0.875-0.984), and sensitivity of 0.72 (95% CI 0.537-0.852) on the test set. CONCLUSION: Preoperative MR radiomics can accurately predict SSIGN score of ccRCC, suggesting its promise as a prognostic tool that can be used in conjunction with diagnostic markers.
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Carcinoma de Células Renales , Neoplasias Renales , Carcinoma de Células Renales/diagnóstico por imagen , Carcinoma de Células Renales/cirugía , Humanos , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/cirugía , Imagen por Resonancia Magnética , Necrosis , Estudios RetrospectivosRESUMEN
Background Coronavirus disease 2019 (COVID-19) and pneumonia of other diseases share similar CT characteristics, which contributes to the challenges in differentiating them with high accuracy. Purpose To establish and evaluate an artificial intelligence (AI) system for differentiating COVID-19 and other pneumonia at chest CT and assessing radiologist performance without and with AI assistance. Materials and Methods A total of 521 patients with positive reverse transcription polymerase chain reaction results for COVID-19 and abnormal chest CT findings were retrospectively identified from 10 hospitals from January 2020 to April 2020. A total of 665 patients with non-COVID-19 pneumonia and definite evidence of pneumonia at chest CT were retrospectively selected from three hospitals between 2017 and 2019. To classify COVID-19 versus other pneumonia for each patient, abnormal CT slices were input into the EfficientNet B4 deep neural network architecture after lung segmentation, followed by a two-layer fully connected neural network to pool slices together. The final cohort of 1186 patients (132 583 CT slices) was divided into training, validation, and test sets in a 7:2:1 and equal ratio. Independent testing was performed by evaluating model performance in separate hospitals. Studies were blindly reviewed by six radiologists without and then with AI assistance. Results The final model achieved a test accuracy of 96% (95% confidence interval [CI]: 90%, 98%), a sensitivity of 95% (95% CI: 83%, 100%), and a specificity of 96% (95% CI: 88%, 99%) with area under the receiver operating characteristic curve of 0.95 and area under the precision-recall curve of 0.90. On independent testing, this model achieved an accuracy of 87% (95% CI: 82%, 90%), a sensitivity of 89% (95% CI: 81%, 94%), and a specificity of 86% (95% CI: 80%, 90%) with area under the receiver operating characteristic curve of 0.90 and area under the precision-recall curve of 0.87. Assisted by the probabilities of the model, the radiologists achieved a higher average test accuracy (90% vs 85%, Δ = 5, P < .001), sensitivity (88% vs 79%, Δ = 9, P < .001), and specificity (91% vs 88%, Δ = 3, P = .001). Conclusion Artificial intelligence assistance improved radiologists' performance in distinguishing coronavirus disease 2019 pneumonia from non-coronavirus disease 2019 pneumonia at chest CT. © RSNA, 2020 Online supplemental material is available for this article.
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Inteligencia Artificial , Infecciones por Coronavirus/diagnóstico por imagen , Neumonía Viral/diagnóstico por imagen , Radiólogos , Tomografía Computarizada por Rayos X/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Betacoronavirus , COVID-19 , Niño , Preescolar , China , Diagnóstico Diferencial , Femenino , Humanos , Lactante , Recién Nacido , Pulmón/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Pandemias , Philadelphia , Neumonía/diagnóstico por imagen , Radiografía Torácica , Radiólogos/normas , Radiólogos/estadística & datos numéricos , Estudios Retrospectivos , Rhode Island , SARS-CoV-2 , Sensibilidad y Especificidad , Adulto JovenRESUMEN
Background Despite its high sensitivity in diagnosing coronavirus disease 2019 (COVID-19) in a screening population, the chest CT appearance of COVID-19 pneumonia is thought to be nonspecific. Purpose To assess the performance of radiologists in the United States and China in differentiating COVID-19 from viral pneumonia at chest CT. Materials and Methods In this study, 219 patients with positive COVID-19, as determined with reverse-transcription polymerase chain reaction (RT-PCR) and abnormal chest CT findings, were retrospectively identified from seven Chinese hospitals in Hunan Province, China, from January 6 to February 20, 2020. Two hundred five patients with positive respiratory pathogen panel results for viral pneumonia and CT findings consistent with or highly suspicious for pneumonia, according to original radiologic interpretation within 7 days of each other, were identified from Rhode Island Hospital in Providence, RI. Three radiologists from China reviewed all chest CT scans (n = 424) blinded to RT-PCR findings to differentiate COVID-19 from viral pneumonia. A sample of 58 age-matched patients was randomly selected and evaluated by four radiologists from the United States in a similar fashion. Different CT features were recorded and compared between the two groups. Results For all chest CT scans (n = 424), the accuracy of the three radiologists from China in differentiating COVID-19 from non-COVID-19 viral pneumonia was 83% (350 of 424), 80% (338 of 424), and 60% (255 of 424). In the randomly selected sample (n = 58), the sensitivities of three radiologists from China and four radiologists from the United States were 80%, 67%, 97%, 93%, 83%, 73%, and 70%, respectively. The corresponding specificities of the same readers were 100%, 93%, 7%, 100%, 93%, 93%, and 100%, respectively. Compared with non-COVID-19 pneumonia, COVID-19 pneumonia was more likely to have a peripheral distribution (80% vs 57%, P < .001), ground-glass opacity (91% vs 68%, P < .001), fine reticular opacity (56% vs 22%, P < .001), and vascular thickening (59% vs 22%, P < .001), but it was less likely to have a central and peripheral distribution (14% vs 35%, P < .001), pleural effusion (4% vs 39%, P < .001), or lymphadenopathy (3% vs 10%, P = .002). Conclusion Radiologists in China and in the United States distinguished coronavirus disease 2019 from viral pneumonia at chest CT with moderate to high accuracy. © RSNA, 2020 Online supplemental material is available for this article. A translation of this abstract in Farsi is available in the supplement. ترج٠٠ÚÚ©Ûد٠اÛÙ Ù ÙاÙ٠ب٠ÙارسÛØ Ø¯Ø± ض٠ÛÙ Ù Ù ÙجÙد است.
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Betacoronavirus , Competencia Clínica , Infecciones por Coronavirus/diagnóstico por imagen , Neumonía Viral/diagnóstico por imagen , Radiólogos/normas , Adulto , Anciano , COVID-19 , Prueba de COVID-19 , Técnicas de Laboratorio Clínico/métodos , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/patología , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/patología , Neumonía Viral/virología , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , SARS-CoV-2 , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X/métodosRESUMEN
Haploinsufficiency of progranulin (PGRN) due to mutations in the granulin (GRN) gene causes frontotemporal lobar degeneration (FTLD), and complete loss of PGRN leads to a lysosomal storage disorder, neuronal ceroid lipofuscinosis (NCL). Accumulating evidence suggests that PGRN is essential for proper lysosomal function, but the precise mechanisms involved are not known. Here, we show that PGRN facilitates neuronal uptake and lysosomal delivery of prosaposin (PSAP), the precursor of saposin peptides that are essential for lysosomal glycosphingolipid degradation. We found reduced levels of PSAP in neurons both in mice deficient in PGRN and in human samples from FTLD patients due to GRN mutations. Furthermore, mice with reduced PSAP expression demonstrated FTLD-like pathology and behavioural changes. Thus, our data demonstrate a role of PGRN in PSAP lysosomal trafficking and suggest that impaired lysosomal trafficking of PSAP is an underlying disease mechanism for NCL and FTLD due to GRN mutations.