<p>(A–C) Qualitative comparison of unprocessed sample, centrifuged sample, and sample proce... more <p>(A–C) Qualitative comparison of unprocessed sample, centrifuged sample, and sample processed with the Centrifuge Chip. Immunofluorescent images of Cytokeratin (CK, red – epithelial cells), CD45 (green – leukocytes), and DAPI (blue – nucleus). Insets show well-plate color: yellow (fresh specimen), red (indicating bloody) and colorless (after processing with device). Arrows indicate CK+/DAPI+ epithelial cells. (D) Purity increases upon processing with the Centrifuge Chip. Purity is defined as the presence of CK+/DAPI+ (epithelial and mesothelial cells) over the total number of cells. All samples (N = 66) were seen to increase in purity after processing with the Centrifuge Chip. Red and blue bars represent the average purity.</p
<p>(A) Normalized frequency distributions of nucleated cells in relation to cell diameter a... more <p>(A) Normalized frequency distributions of nucleated cells in relation to cell diameter are plotted for pleural effusions analyzed within 24 hours of collection and diagnosed as negative (blue, solid), inflammation (chronic and acute, green, dashed), or malignant (red, dotted). Relative to negative pleural effusions, malignant samples contain a larger population fraction of cells greater than 15 µm, and cases of inflammation contain a larger population of cells between 10–15 µm. N = 13, 9, and 10 for negative, inflammation, and malignant cases. (B) The frequency distributions of the same samples after processing through the Centrifuge Chip were subtracted by the distributions before processing to observe enrichment. The device enriches for cell populations greater than 15 µm and depletes smaller cells.</p
<p>(A) RT-PCR was performed on non-spiked, unprocessed spiked samples (0.1% purity), and pr... more <p>(A) RT-PCR was performed on non-spiked, unprocessed spiked samples (0.1% purity), and processed spiked samples. KRAS* ΔCt decreased in all cases (n = 7), demonstrating an improved signal for the KRAS mutation. Compared to non-spiked samples, processed spiked samples exhibit a clearer KRAS* ΔCt which is more distinct than for unprocessed spiked samples. The dotted black line shows a 12.2 Ct cut-off threshold for the KRAS mutation. (B) Receiver operating characteristic curves are plotted based on a Gaussian distribution of samples shown in part A. Processed samples show higher area under curve (AUC) values at 0.998 (blue, solid), compared with 0.905 (red, dashed) for unprocessed samples.</p
<p>(A) A photograph of the Centrifuge Chip device. Only a single inlet and outlet is requir... more <p>(A) A photograph of the Centrifuge Chip device. Only a single inlet and outlet is required. (B) A schematic of the massively parallel microfluidic device that selectively traps large cells in individual microscale vortices. (C) A photograph of the device connected to an automated fluidic instrument to deliver patient pleural samples and saline wash through the Centrifuge Chip into the waste bottle or collection plate. Trapped epithelial and mesothelial cells are made readily available i) into a collection tube for further cytology slide comparisons with the original and/or ii) into a well-plate for immunolabeling, imaging and analysis. (D) High-speed microscopic image showing trapping of larger single and clumped cells while smaller red and white blood cells pass through.</p
<p>Unprocessed patient samples are prepared with traditional cytological techniques using P... more <p>Unprocessed patient samples are prepared with traditional cytological techniques using Papanicolaou (Pap) and May-Grunwald–Giemsa (MGG) stains. Cells collected from samples processed with Centrifuge Chip were also made into cytology slides. In all samples, malignant and mesothelial cells are found amongst a cellular background of immune cells in standard slides while little background is observed in the Centrifuge Chip slide. In samples diagnosed as ‘positive for malignancy’, single and clumped malignant cells (red arrows) are retrieved following the Centrifuge Chip. In patients diagnosed as ‘negative for malignancy’, mesothelial cells (green arrows) were found amongst a background of blood cells in standard slides, compared to no blood cell background upon Centrifuge Chip Processing. Samples diagnosed as atypical contained cells which resembled either malignant or mesothelial cells (blue arrows). Images obtained at 200× magnification.</p
Objective The US Food and Drug Administration (FDA) regulates the marketing of medical devices ba... more Objective The US Food and Drug Administration (FDA) regulates the marketing of medical devices based on the premarket approval (PMA) or 510(k) pathway. We investigated the relationship among the regulatory pathway of otolaryngologic devices, the number of recalls, and the recall characteristics. Study Design Retrospective cross-sectional analysis. Setting Publicly available FDA databases. Methods The FDA Ear, Nose, and Throat Devices Panel database was queried for 510(k) clearances and PMA approvals from 1976 to 2019. Device recalls from 2003 to 2019 were reviewed. Devices were then categorized by subspecialty, type, supporting evidence, and PMA supplement type. Logistic regression characterized the odds of recall for each device type and subspeciality. Results A total of 1061 (57.8%) 510(k) and 778 (42.3%) PMA device applications and modifications were approved. There were 120 (11.3%) recall events associated with 42 unique otolaryngologic devices cleared via the 510(k) pathway, as...
Preoperative cardiopulmonary exercise testing (CPET) is well validated for prognostication before... more Preoperative cardiopulmonary exercise testing (CPET) is well validated for prognostication before advanced surgical heart failure therapies, but its role in prognostication after LVAD surgery has never been studied. VE/VCO2 slope is an important component of CPET which has direct pathophysiologic links to right ventricular (RV) performance. We hypothesized that VE/VCO2 slope would prognosticate RV dysfunction after LVAD. All CPET studies from a single institution were collected between September 2009 and February 2019. Patients who ultimately underwent LVAD implantation were selectively analyzed. Peak VO2 and VE/VCO2 slope were measured for all patients. We evaluated their association with hemodynamic, echocardiographic and clinical markers of RV dysfunction as well mortality. Patients were stratified into those with a ventilatory class of III or greater. (VE/VCO2 slope of ≥ 36, n = 43) and those with a VE/VCO2 slope < 36 (n = 27). We compared the mortality between the 2 groups, as well as the hemodynamic, echocardiographic and clinical markers of RV dysfunction. 570 patients underwent CPET testing. 145 patients were ultimately referred to the advanced heart failure program and 70 patients later received LVAD implantation. Patients with VE/VCO2 slope of ≥ 36 had higher mortality (30.2% vs. 7.4%, p = 0.02) than patients with VE/VCO2 slope < 36 (n = 27). They also had a higher incidence of clinically important RVF (Acute severe 9.3% vs. 0%, Severe 32.6% vs 25.9%, p = 0.03). Patients with a VE/VCO2 slope ≥ 36 had a higher CVP than those with a lower VE/VCO2 slope (11.2 ± 6.1 vs. 6.0 ± 4.8 mmHg, p = 0.007), and were more likely to have a RA/PCWP ≥ 0.63 (65% vs. 19%, p = 0.008) and a PAPI ≤ 2 (57% vs. 13%, p = 0.008). In contrast, peak VO2 < 12 ml/kg/min was not associated with postoperative RV dysfunction or mortality. Elevated preoperative VE/VCO2 slope is a predictor of postoperative mortality, and is associated with postoperative clinical and hemodynamic markers of impaired RV performance.
Proceedings of the 42nd International ACM SIGIR Conference on Research and Development in Information Retrieval, 2019
Automatically generating accurate summaries from clinical reports could save a clinician's time, ... more Automatically generating accurate summaries from clinical reports could save a clinician's time, improve summary coverage, and reduce errors. We propose a sequence-to-sequence abstractive summarization model augmented with domain-specific ontological information to enhance content selection and summary generation. We apply our method to a dataset of radiology reports and show that it significantly outperforms the current state-of-the-art on this task in terms of rouge scores. Extensive human evaluation conducted by a radiologist further indicates that this approach yields summaries that are less likely to omit important details, without sacrificing readability or accuracy.
The use of filters and editing tools for perfecting selfies is increasing. While some aesthetic e... more The use of filters and editing tools for perfecting selfies is increasing. While some aesthetic experts have touted the ability of this technology to help patients convey their aesthetic goals, others have expressed concerns about the unrealistic expectations that may come from the ability for individuals to digitally alter their own photos in these so-called “super-selfies.” The aim of the study is to determine the changes that individuals seek when enhancing selfies. Twenty subjects participated in this study between July 25 and September 24, 2019. Subjects had two sets of headshots taken (neutral and smile) and were provided an introduction on the use of the Facetune2 app. Subjects received a digital copy of their photographs and were asked to download the free mobile app. After 1 week of trialing the different tools for enhancing their appearance, subjects submitted their self-determined most attractive edited photographs. Changes in marginal reflex distance (MRD) 1 and 2, nose ...
The Journal of Heart and Lung Transplantation, 2019
Oversizing (ACPA ratio > 1) increased grade 3 PGD risk (adjusted OR 2.3 [95% CI 1.0-5.2], p = 0.0... more Oversizing (ACPA ratio > 1) increased grade 3 PGD risk (adjusted OR 2.3 [95% CI 1.0-5.2], p = 0.04). Conclusion: Oversizing via CXR was associated with increased PGD risk. CXR measurement appears to serve as an estimate of true TLC. D-R ACPA ratio shows promise as a size matching tool in donor allocation and requires further investigation.
Process variability during the acquisition of magnetic resonance imaging (MRI) can lengthen exami... more Process variability during the acquisition of magnetic resonance imaging (MRI) can lengthen examination times and introduce unexpected exam differences which can negatively impact the cost and quality of care provided to patients. Digital Imaging and Communications in Medicine (DICOM) metadata can provide more accurate study data and granular series-level information that can be used to increase operational efficiency, optimize patient care, and reduce costs associated with MRI examinations. Systematic use of such data analysis could be used as a continuous operational optimization and quality control mechanism.
Pleural effusions-fluids that build up surrounding the lungs-can harbor malignant cells which are... more Pleural effusions-fluids that build up surrounding the lungs-can harbor malignant cells which are important to identify for diagnosis of cancer. However, rare malignant cells may lead to misleading diagnoses and a large background of leukocytes can prevent accurate identification of mutations of interest for targeted anti-cancer therapies. We developed a miniaturized microfluidic system that employs microscale vortices for the size-based isolation of malignant cancer cells and mesothelial cells. By processing mL volumes of pleural effusions and enriching target cells over a background of blood cells, we replace the traditional centrifugation step in the clinical lab. We demonstrate higher purity in 100% of the samples (n=30) where cells are made readily available for immunolabeling, standard cytology analysis and molecular analysis.
The presentation of radiology exams can be enhanced through the use of dynamic images. Dynamic im... more The presentation of radiology exams can be enhanced through the use of dynamic images. Dynamic images differ from static images by the use of animation and are especially useful for depicting real-time activity such as the scrolling or the flow of contrast to enhance pathology. This is generally superior to a collection of static images as a representation of clinical workflow and provides a more robust appreciation of the case in question. Dynamic images can be shared electronically to facilitate teaching, case review, presentation, and sharing of interesting cases to be viewed in detail on a computer or mobile devices for education. The creation of movies or animated images from radiology data has traditionally been challenging based on technological limitations inherent in converting the Digital Imaging and Communications in Medicine (DICOM) standard to other formats or concerns related to the presence of protected health information (PHI). The solution presented here, named Cinebot, allows a simple "one-click" generation of anonymized dynamic movies or animated images within the picture archiving and communication system (PACS) workflow. This approach works across all imaging modalities, including stacked cross-sectional and multi-frame cine formats. Usage statistics over 2 years have shown this method to be well-received and useful throughout our enterprise.
Evaluation of pleural fluids for metastatic cells is a key component of diagnostic cytopathology.... more Evaluation of pleural fluids for metastatic cells is a key component of diagnostic cytopathology. However, a large background of smaller leukocytes and/or erythrocytes can make accurate diagnosis difficult and reduce specificity in identification of mutations of interest for targeted anti-cancer therapies. Here, we describe an automated microfluidic system (Centrifuge Chip) which employs microscale vortices for the size-based isolation and concentration of cancer cells and mesothelial cells from a background of blood cells. We are able to process non-diluted pleural fluids at 6 mL/min and enrich target cells significantly over the background; we achieved improved purity in all patient samples analyzed. The resulting isolated and viable cells are readily available for immunostaining, cytological analysis, and detection of gene mutations. To demonstrate the utility towards aiding companion diagnostics, we also show improved detection accuracy of KRAS gene mutations in lung cancer cell...
<p>(A–C) Qualitative comparison of unprocessed sample, centrifuged sample, and sample proce... more <p>(A–C) Qualitative comparison of unprocessed sample, centrifuged sample, and sample processed with the Centrifuge Chip. Immunofluorescent images of Cytokeratin (CK, red – epithelial cells), CD45 (green – leukocytes), and DAPI (blue – nucleus). Insets show well-plate color: yellow (fresh specimen), red (indicating bloody) and colorless (after processing with device). Arrows indicate CK+/DAPI+ epithelial cells. (D) Purity increases upon processing with the Centrifuge Chip. Purity is defined as the presence of CK+/DAPI+ (epithelial and mesothelial cells) over the total number of cells. All samples (N = 66) were seen to increase in purity after processing with the Centrifuge Chip. Red and blue bars represent the average purity.</p
<p>(A) Normalized frequency distributions of nucleated cells in relation to cell diameter a... more <p>(A) Normalized frequency distributions of nucleated cells in relation to cell diameter are plotted for pleural effusions analyzed within 24 hours of collection and diagnosed as negative (blue, solid), inflammation (chronic and acute, green, dashed), or malignant (red, dotted). Relative to negative pleural effusions, malignant samples contain a larger population fraction of cells greater than 15 µm, and cases of inflammation contain a larger population of cells between 10–15 µm. N = 13, 9, and 10 for negative, inflammation, and malignant cases. (B) The frequency distributions of the same samples after processing through the Centrifuge Chip were subtracted by the distributions before processing to observe enrichment. The device enriches for cell populations greater than 15 µm and depletes smaller cells.</p
<p>(A) RT-PCR was performed on non-spiked, unprocessed spiked samples (0.1% purity), and pr... more <p>(A) RT-PCR was performed on non-spiked, unprocessed spiked samples (0.1% purity), and processed spiked samples. KRAS* ΔCt decreased in all cases (n = 7), demonstrating an improved signal for the KRAS mutation. Compared to non-spiked samples, processed spiked samples exhibit a clearer KRAS* ΔCt which is more distinct than for unprocessed spiked samples. The dotted black line shows a 12.2 Ct cut-off threshold for the KRAS mutation. (B) Receiver operating characteristic curves are plotted based on a Gaussian distribution of samples shown in part A. Processed samples show higher area under curve (AUC) values at 0.998 (blue, solid), compared with 0.905 (red, dashed) for unprocessed samples.</p
<p>(A) A photograph of the Centrifuge Chip device. Only a single inlet and outlet is requir... more <p>(A) A photograph of the Centrifuge Chip device. Only a single inlet and outlet is required. (B) A schematic of the massively parallel microfluidic device that selectively traps large cells in individual microscale vortices. (C) A photograph of the device connected to an automated fluidic instrument to deliver patient pleural samples and saline wash through the Centrifuge Chip into the waste bottle or collection plate. Trapped epithelial and mesothelial cells are made readily available i) into a collection tube for further cytology slide comparisons with the original and/or ii) into a well-plate for immunolabeling, imaging and analysis. (D) High-speed microscopic image showing trapping of larger single and clumped cells while smaller red and white blood cells pass through.</p
<p>Unprocessed patient samples are prepared with traditional cytological techniques using P... more <p>Unprocessed patient samples are prepared with traditional cytological techniques using Papanicolaou (Pap) and May-Grunwald–Giemsa (MGG) stains. Cells collected from samples processed with Centrifuge Chip were also made into cytology slides. In all samples, malignant and mesothelial cells are found amongst a cellular background of immune cells in standard slides while little background is observed in the Centrifuge Chip slide. In samples diagnosed as ‘positive for malignancy’, single and clumped malignant cells (red arrows) are retrieved following the Centrifuge Chip. In patients diagnosed as ‘negative for malignancy’, mesothelial cells (green arrows) were found amongst a background of blood cells in standard slides, compared to no blood cell background upon Centrifuge Chip Processing. Samples diagnosed as atypical contained cells which resembled either malignant or mesothelial cells (blue arrows). Images obtained at 200× magnification.</p
Objective The US Food and Drug Administration (FDA) regulates the marketing of medical devices ba... more Objective The US Food and Drug Administration (FDA) regulates the marketing of medical devices based on the premarket approval (PMA) or 510(k) pathway. We investigated the relationship among the regulatory pathway of otolaryngologic devices, the number of recalls, and the recall characteristics. Study Design Retrospective cross-sectional analysis. Setting Publicly available FDA databases. Methods The FDA Ear, Nose, and Throat Devices Panel database was queried for 510(k) clearances and PMA approvals from 1976 to 2019. Device recalls from 2003 to 2019 were reviewed. Devices were then categorized by subspecialty, type, supporting evidence, and PMA supplement type. Logistic regression characterized the odds of recall for each device type and subspeciality. Results A total of 1061 (57.8%) 510(k) and 778 (42.3%) PMA device applications and modifications were approved. There were 120 (11.3%) recall events associated with 42 unique otolaryngologic devices cleared via the 510(k) pathway, as...
Preoperative cardiopulmonary exercise testing (CPET) is well validated for prognostication before... more Preoperative cardiopulmonary exercise testing (CPET) is well validated for prognostication before advanced surgical heart failure therapies, but its role in prognostication after LVAD surgery has never been studied. VE/VCO2 slope is an important component of CPET which has direct pathophysiologic links to right ventricular (RV) performance. We hypothesized that VE/VCO2 slope would prognosticate RV dysfunction after LVAD. All CPET studies from a single institution were collected between September 2009 and February 2019. Patients who ultimately underwent LVAD implantation were selectively analyzed. Peak VO2 and VE/VCO2 slope were measured for all patients. We evaluated their association with hemodynamic, echocardiographic and clinical markers of RV dysfunction as well mortality. Patients were stratified into those with a ventilatory class of III or greater. (VE/VCO2 slope of ≥ 36, n = 43) and those with a VE/VCO2 slope < 36 (n = 27). We compared the mortality between the 2 groups, as well as the hemodynamic, echocardiographic and clinical markers of RV dysfunction. 570 patients underwent CPET testing. 145 patients were ultimately referred to the advanced heart failure program and 70 patients later received LVAD implantation. Patients with VE/VCO2 slope of ≥ 36 had higher mortality (30.2% vs. 7.4%, p = 0.02) than patients with VE/VCO2 slope < 36 (n = 27). They also had a higher incidence of clinically important RVF (Acute severe 9.3% vs. 0%, Severe 32.6% vs 25.9%, p = 0.03). Patients with a VE/VCO2 slope ≥ 36 had a higher CVP than those with a lower VE/VCO2 slope (11.2 ± 6.1 vs. 6.0 ± 4.8 mmHg, p = 0.007), and were more likely to have a RA/PCWP ≥ 0.63 (65% vs. 19%, p = 0.008) and a PAPI ≤ 2 (57% vs. 13%, p = 0.008). In contrast, peak VO2 < 12 ml/kg/min was not associated with postoperative RV dysfunction or mortality. Elevated preoperative VE/VCO2 slope is a predictor of postoperative mortality, and is associated with postoperative clinical and hemodynamic markers of impaired RV performance.
Proceedings of the 42nd International ACM SIGIR Conference on Research and Development in Information Retrieval, 2019
Automatically generating accurate summaries from clinical reports could save a clinician's time, ... more Automatically generating accurate summaries from clinical reports could save a clinician's time, improve summary coverage, and reduce errors. We propose a sequence-to-sequence abstractive summarization model augmented with domain-specific ontological information to enhance content selection and summary generation. We apply our method to a dataset of radiology reports and show that it significantly outperforms the current state-of-the-art on this task in terms of rouge scores. Extensive human evaluation conducted by a radiologist further indicates that this approach yields summaries that are less likely to omit important details, without sacrificing readability or accuracy.
The use of filters and editing tools for perfecting selfies is increasing. While some aesthetic e... more The use of filters and editing tools for perfecting selfies is increasing. While some aesthetic experts have touted the ability of this technology to help patients convey their aesthetic goals, others have expressed concerns about the unrealistic expectations that may come from the ability for individuals to digitally alter their own photos in these so-called “super-selfies.” The aim of the study is to determine the changes that individuals seek when enhancing selfies. Twenty subjects participated in this study between July 25 and September 24, 2019. Subjects had two sets of headshots taken (neutral and smile) and were provided an introduction on the use of the Facetune2 app. Subjects received a digital copy of their photographs and were asked to download the free mobile app. After 1 week of trialing the different tools for enhancing their appearance, subjects submitted their self-determined most attractive edited photographs. Changes in marginal reflex distance (MRD) 1 and 2, nose ...
The Journal of Heart and Lung Transplantation, 2019
Oversizing (ACPA ratio > 1) increased grade 3 PGD risk (adjusted OR 2.3 [95% CI 1.0-5.2], p = 0.0... more Oversizing (ACPA ratio > 1) increased grade 3 PGD risk (adjusted OR 2.3 [95% CI 1.0-5.2], p = 0.04). Conclusion: Oversizing via CXR was associated with increased PGD risk. CXR measurement appears to serve as an estimate of true TLC. D-R ACPA ratio shows promise as a size matching tool in donor allocation and requires further investigation.
Process variability during the acquisition of magnetic resonance imaging (MRI) can lengthen exami... more Process variability during the acquisition of magnetic resonance imaging (MRI) can lengthen examination times and introduce unexpected exam differences which can negatively impact the cost and quality of care provided to patients. Digital Imaging and Communications in Medicine (DICOM) metadata can provide more accurate study data and granular series-level information that can be used to increase operational efficiency, optimize patient care, and reduce costs associated with MRI examinations. Systematic use of such data analysis could be used as a continuous operational optimization and quality control mechanism.
Pleural effusions-fluids that build up surrounding the lungs-can harbor malignant cells which are... more Pleural effusions-fluids that build up surrounding the lungs-can harbor malignant cells which are important to identify for diagnosis of cancer. However, rare malignant cells may lead to misleading diagnoses and a large background of leukocytes can prevent accurate identification of mutations of interest for targeted anti-cancer therapies. We developed a miniaturized microfluidic system that employs microscale vortices for the size-based isolation of malignant cancer cells and mesothelial cells. By processing mL volumes of pleural effusions and enriching target cells over a background of blood cells, we replace the traditional centrifugation step in the clinical lab. We demonstrate higher purity in 100% of the samples (n=30) where cells are made readily available for immunolabeling, standard cytology analysis and molecular analysis.
The presentation of radiology exams can be enhanced through the use of dynamic images. Dynamic im... more The presentation of radiology exams can be enhanced through the use of dynamic images. Dynamic images differ from static images by the use of animation and are especially useful for depicting real-time activity such as the scrolling or the flow of contrast to enhance pathology. This is generally superior to a collection of static images as a representation of clinical workflow and provides a more robust appreciation of the case in question. Dynamic images can be shared electronically to facilitate teaching, case review, presentation, and sharing of interesting cases to be viewed in detail on a computer or mobile devices for education. The creation of movies or animated images from radiology data has traditionally been challenging based on technological limitations inherent in converting the Digital Imaging and Communications in Medicine (DICOM) standard to other formats or concerns related to the presence of protected health information (PHI). The solution presented here, named Cinebot, allows a simple "one-click" generation of anonymized dynamic movies or animated images within the picture archiving and communication system (PACS) workflow. This approach works across all imaging modalities, including stacked cross-sectional and multi-frame cine formats. Usage statistics over 2 years have shown this method to be well-received and useful throughout our enterprise.
Evaluation of pleural fluids for metastatic cells is a key component of diagnostic cytopathology.... more Evaluation of pleural fluids for metastatic cells is a key component of diagnostic cytopathology. However, a large background of smaller leukocytes and/or erythrocytes can make accurate diagnosis difficult and reduce specificity in identification of mutations of interest for targeted anti-cancer therapies. Here, we describe an automated microfluidic system (Centrifuge Chip) which employs microscale vortices for the size-based isolation and concentration of cancer cells and mesothelial cells from a background of blood cells. We are able to process non-diluted pleural fluids at 6 mL/min and enrich target cells significantly over the background; we achieved improved purity in all patient samples analyzed. The resulting isolated and viable cells are readily available for immunostaining, cytological analysis, and detection of gene mutations. To demonstrate the utility towards aiding companion diagnostics, we also show improved detection accuracy of KRAS gene mutations in lung cancer cell...
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