tbuckley/cabot-search huggingface dataset:
Deep learning interpretation of echocardiograms
Authors: Amirata Ghorbani, David Ouyang, Abubakar Abid, Bryan He, Jonathan H. Chen, Robert A. Harrington, David H. Liang, Euan A. Ashley, James Y. Zou
Journal: npj Digital Medicine (2020)

Abstract Echocardiography uses ultrasound technology to capture high temporal and spatial resolution images of the heart and surrounding structures, and is the most common imaging modality in cardiovascular medicine. Using convolutional neural networks on a large new dataset, we show that deep learning applied to echocardiography can identify local cardiac structures, estimate cardiac function, and predict systemic phenotypes that modify cardiovascular risk but not readily identifiable to human interpretation. Our deep learning model, EchoNet, accurately identified the presence of pacemaker leads (AUC = 0.89), enlarged left atrium (AUC = 0.86), left ventricular hypertrophy (AUC = 0.75), left ventricular end systolic and diastolic volumes ( $${R}^{2}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msup><mml:mrow><mml:mi>R</mml:mi></mml:mrow><mml:mrow><mml:mn>2</mml:mn></mml:mrow></mml:msup></mml:math> = 0.74 and $${R}^{2}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msup><mml:mrow><mml:mi>R</mml:mi></mml:mrow><mml:mrow><mml:mn>2</mml:mn></mml:mrow></mml:msup></mml:math> = 0.70), and ejection fraction ( $${R}^{2}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msup><mml:mrow><mml:mi>R</mml:mi></mml:mrow><mml:mrow><mml:mn>2</mml:mn></mml:mrow></mml:msup></mml:math> = 0.50), as well as predicted systemic phenotypes of age ( $${R}^{2}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msup><mml:mrow><mml:mi>R</mml:mi></mml:mrow><mml:mrow><mml:mn>2</mml:mn></mml:mrow></mml:msup></mml:math> = 0.46), sex (AUC = 0.88), weight ( $${R}^{2}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msup><mml:mrow><mml:mi>R</mml:mi></mml:mrow><mml:mrow><mml:mn>2</mml:mn></mml:mrow></mml:msup></mml:math> = 0.56), and height ( $${R}^{2}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msup><mml:mrow><mml:mi>R</mml:mi></mml:mrow><mml:mrow><mml:mn>2</mml:mn></mml:mrow></mml:msup></mml:math> = 0.33). Interpretation analysis validates that EchoNet shows appropriate attention to key cardiac structures when performing human-explainable tasks and highlights hypothesis-generating regions of interest when predicting systemic phenotypes difficult for human interpretation. Machine learning on echocardiography images can streamline repetitive tasks in the clinical workflow, provide preliminary interpretation in areas with insufficient qualified cardiologists, and predict phenotypes challenging for human evaluation.
Addressing the global cirrhosis epidemic: one size will not fit all
Authors: Peter L Wang, Jennifer A Flemming
Journal: The Lancet. Gastroenterology & hepatology (2020)

Cirrhosis is a global health concern, as the 11th most common cause of mortality worldwide that accounts for 2% of deaths annually. 1 WHOGlobal Health estimates 2016: disease burden by cause, age, sex, by country and by region. https://www.who.int/healthinfo/global_burden_disease/estimates/en/index1.htmlDate: 2000–2016 Date accessed: October 21, 2019 Google Scholar The causes of cirrhosis are largely secondary to public health and lifestyle-related exposures, including hepatitis B and C, alcohol-related liver disease, and non-alcoholic steatohepatitis (NASH). Therefore, cirrhosis epidemiology could be influenced by interventions targeted at reducing these conditions. Over the past several decades, regional and international efforts to mitigate cirrhosis risk factors have been developed, including WHO resolutions to eliminate viral hepatitis by 2030, reduce harmful alcohol consumption, and tackle the obesity epidemic by promoting physical activity and a healthy diet. To assess the efficacy of these efforts on cirrhosis disease burden and to inform future health policy initiatives, the availability of contemporary epidemiological data is paramount, especially data that are stratified by cirrhosis cause and region. The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017Cirrhosis imposes a substantial health burden on many countries and this burden has increased at the global level since 1990, partly due to population growth and ageing. Although the age-standardised death and DALY rates of cirrhosis decreased from 1990 to 2017, numbers of deaths and DALYs and the proportion of all global deaths due to cirrhosis increased. Despite the availability of effective interventions for the prevention and treatment of hepatitis B and C, they were still the main causes of cirrhosis burden worldwide, particularly in low-income countries. Full-Text PDF Open Access
Psychological Distress and Quality of Life Evaluation in Head and Neck Cancer: the Role of Family Caregiver
Authors: O. Ostellino, M. Airoldi, M. Garzaro, L. Raimondo, G. Riva, C. Bartoli, S. Carnio, G. Fora, C. Giordano, G. Pecorari
Journal: Annals of Oncology (2012)
Abstract 132: Predictive Value of Inflammation Markers With Stroke Recurrence and Cardiovascular Mortality
Authors: Yang Yunyun
Journal: Circulation (2019)

Background: Inflammation markers are associated with the risk of cardiovascular events, however, the relationships of inflammation markers with risk of post-stroke remain controversial. Objects: To investigated association of two clinical recorded inflammation markers, white blood cell count (WBC) and platelet count (PLTC) with first-onset stroke and long-term prognosis of stroke. Methods: A Chinese case-control study was conducted, comprising 2002 stroke cased (885 atherothrombosis, 565 lacunar stroke, 552 hemorrhagic stroke) and 1996 controls. Stroke patients were prospectively followed-up for a median of 4.5 years (range, 0.1-6.0). Results: The WBC and PLTS were higher in stroke patients than controls, however, the ratio of PLTS to WBC was lower in stroke patients than controls. During the follow-up, 369 recurrent strokes and 343 cardiovascular mortality were documented. Adjusted for cardiovascular disease, the increased ration of PLTC to WBC was negatively correlated with stroke recurrence (HR, 0.60, 95%CI 0.44 to 0.81, P =0.001), with no associations for PLTC and WBC. Compared with stroke patients with WBC in the first quartile (2.1-5.6х10 9 /L) , subjects in the fourth quartile (7.8-19.8х10 9 /L) had 2.10-fold risk for cardiovascular mortality (hazard ration [HR],2.10, 95% confidence interval [CI], 1.20 to 2.48, P =0.004), with no associations for PLTC. However, the increased ratio of PLTC to WBC decreased risk of cardiovascular mortality HR was 0.61 in the second quartile (2.09-17.60х10 9 /L), HR was 0.58 in the third quartile (17.61-24.04х10 9 /L) and HR was 0.48 in the fourth quartile (24.05-34.54х10 9 /L) (all P &lt;0.01). Conclusion: Higher WBC and PLTC are associated with poorer prognosis of stroke, and the ration of WBC to PLTC improved the predictive value for cardiovascular mortality and stroke recurrence.
Local microvascular leakage promotes trafficking of activated neutrophils to remote organs
Authors: Charlotte Owen-Woods, Régis Joulia, Anna Barkaway, Loïc Rolas, Bin Ma, Astrid Fee Nottebaum, Kenton P. Arkill, Monja Stein, Tamara Girbl, Matthew Golding, David O. Bates, Dietmar Vestweber, Mathieu-Benoit Voisin, Sussan Nourshargh
Journal: Journal of Clinical Investigation (2020)

Increased microvascular permeability to plasma proteins and neutrophil emigration are hallmarks of innate immunity and key features of numerous inflammatory disorders. Although neutrophils can promote microvascular leakage, the impact of vascular permeability on neutrophil trafficking is unknown. Here, through the application of confocal intravital microscopy, we report that vascular permeability-enhancing stimuli caused a significant frequency of neutrophil reverse transendothelial cell migration (rTEM). Furthermore, mice with a selective defect in microvascular permeability enhancement (VEC-Y685F-ki) showed reduced incidence of neutrophil rTEM. Mechanistically, elevated vascular leakage promoted movement of interstitial chemokines into the bloodstream, a response that supported abluminal-to-luminal neutrophil TEM. Through development of an in vivo cell labeling method we provide direct evidence for the systemic dissemination of rTEM neutrophils, and showed them to exhibit an activated phenotype and be capable of trafficking to the lungs where their presence was aligned with regions of vascular injury. Collectively, we demonstrate that increased microvascular leakage reverses the localization of directional cues across venular walls, thus causing neutrophils engaged in diapedesis to reenter the systemic circulation. This cascade of events offers a mechanism to explain how local tissue inflammation and vascular permeability can induce downstream pathological effects in remote organs, most notably in the lungs.
Lentiviral gene therapy for X-linked chronic granulomatous disease
Authors: Donald B. Kohn, Claire Booth, Elizabeth M. Kang, Sung-Yun Pai, Kit L. Shaw, Giorgia Santilli, Myriam Armant, Karen F. Buckland, Uimook Choi, Suk See De Ravin, Morna J. Dorsey, Caroline Y. Kuo, Diego Leon-Rico, Christine Rivat, Natalia Izotova, Kimberly Gilmour, Katie Snell, Jinhua Xu-Bayford Dip, Jinan Darwish, Emma C. Morris, Dayna Terrazas, Leo D. Wang, Christopher A. Bauser, Tobias Paprotka, Douglas B. Kuhns, John Gregg, Hayley E. Raymond, John K. Everett, Geraldine Honnet, Luca Biasco, Peter E. Newburger, Frederic D. Bushman, Manuel Grez, H. Bobby Gaspar, David A. Williams, Harry L. Malech, Anne Galy, Adrian J. Thrasher
Journal: Nature Medicine (2020)
IA30 Investigating and Overcoming Primary Resistance of EGFR and HER2 (ERBB2) Exon 20 Mutant NSCLC
Authors: J.P. Robichaux, Y.Y. Elamin, R.S.K. Vijayan, J. He, L. Hu, F. Zhang, A. Poteete, M. Pisegna, M.B. Nilsson, H. Sun, M.V. Negrao, X. Le, V.M. Raymond, R.B. Lanman, G.M. Frampton, V.A. Miller, A.B. Schrock, J.B. Cross, K. Wong, J.V. Heymach
Journal: Journal of Thoracic Oncology (2020)
Assessing the Time‐Dependent Impact of Performance Status on Outcomes After Liver Transplantation
Authors: David Wallace, Thomas Cowling, Mark J. McPhail, Sarah E. Brown, Varuna Aluvihare, Abid Suddle, Georg Auzinger, Michael A. Heneghan, Ian A. Rowe, Kate Walker, Nigel Heaton, Jan van der Meulen, William Bernal
Journal: Hepatology (2020)

Background and Aims Identifying how the prognostic impact of performance status (PS) differs according to indication, era, and time period (“epoch”) after liver transplantation (LT) could have implications for selection and treatment of patients on the waitlist. We used national data from the United Kingdom and Ireland to assess impact of PS on mortality separately for HCC and non‐HCC recipients. Approach and Results We assessed pre‐LT PS using the 5‐point modified Eastern Cooperative Oncology Group scale and used Cox regression methods to estimate hazard ratios (HRs) that compared posttransplantation mortality in different epochs of follow‐up (0‐90 days and 90 days to 1 year) and in different eras of transplantation (1995‐2005 and 2006‐2016). 2107 HCC and 10,693 non‐HCC patients were included. One‐year survival decreased with worsening PS in non‐HCC recipients where 1‐year survival was 91.9% (95% confidence interval [CI], 88.3‐94.4) in those able to carry out normal activity (PS1) compared to 78.7% (95% CI, 76.7‐80.5) in those completely reliant on care (PS5). For HCC patients, these estimates were 89.9% (95% CI, 85.4‐93.2) and 83.1% (95% CI, 61.0‐93.3), respectively. Reduction in survival in non‐HCC patients with poorer PS was in the first 90 days after transplant, with no major effect observed between 90 days and 1 year. Adjustment for donor and recipient characteristics did not change the findings. Comparing era, post‐LT mortality improved for HCC (adjusted HR, 0.55; 95% CI, 0.40‐0.74) and non‐HCC recipients (0.48; 95% CI, 0.42‐0.55), but this did not differ according to PS score ( P = 0.39 and 0.61, respectively). Conclusions Impact on mortality of the recipient’s pretransplant PS is principally limited to the first 3 months after LT. Over time, mortality has improved for both HCC and non‐HCC recipients and across the full range of PS.
Comparison of Diagnostic Utility of Fluciclovine PET/CT Versus Pelvic Multiparametric MRI for Prostate Cancer in the Pelvis in the Setting of Rising PSA After Initial Treatment
Authors: Bo Chen, Tharakeswara K. Bathala, Guofang Xu, Ajalaya Teyateeti, Brian F. Chapin, Chad Tang, Shi-Ming Tu, Homer A. Macapinlac, Yang Lu
Journal: Clinical Nuclear Medicine (2020)

The aim of this study was to investigate the imaging diagnostic performance of F-fluciclovine PET/CT and pelvic multiparametric MRI (mpMRI) for prostate cancer in the setting of rising PSA after initial treatment, with a focus on detection of recurrent and metastatic prostate cancer in the pelvis.Patients with prostate cancer who had fluciclovine PET and pelvic mpMRI between October 2017 and October 2018 in our center were retrospectively reviewed. Patients were included if they had fluciclovine PET/CT and mpMRI within a 3-month interval. Patients were excluded if they had separate concurrent cancer or if the PSA were more than 2-fold difference with an absolute difference more than 1 ng/mL between the 2 image studies. For each eligible patient, we compared all abnormal lesions identified on either scan. The findings were verified by pathology or other imaging techniques within minimal 10-month clinical follow-up.A total of 129 patients with 129 paired tests were included in this study. Fluciclovine PET/CT and pelvic MRI had a high degree of concordance (121/129, 93.8%). The sensitivity, specificity, positive predictive value, and negative predictive value for fluciclovine PET/CT and mpMRI were 96.6%, 94.3%, 93.4%, and 97%, and 91.5%, 95.7%, 94.7%, and 93%, respectively. There were no statistical significant differences in diagnostic performance between the 2 imaging tests. Among the 8/129 discordant cases, although fluciclovine PET/CT provided definitive diagnosis when mpMRI was equivocal due to paramagnetic artifacts from fiducial markers and detected normal-sized regional lymph nodes, mpMRI detected subcentimeter periurethral recurrence and clarified physiological urinary artifacts that was not appreciated on fluciclovine PET/CT.Our single-center study demonstrated that fluciclovine PET/CT has similar diagnostic performance with pelvic mpMRI in detecting recurrent/metastatic prostate disease in the pelvis in the setting of rising PSA after initial treatment. Moreover, fluciclovine PET/CT and mpMRI have different implications in different clinical scenario; each test has its own limitation and pitfalls, but can be complementary to each other.
Yeshi Dhonden: personal physician to the 14th Dalai Lama
Authors: Rebecca Wallersteiner
Journal: BMJ (2020)

Credit: The Tibetan Herbal Clinic, India

Yeshi Dhonden, the foremost Tibetan doctor in the world, has died from respiratory failure at his residence in Dharamsala, northern India, surrounded by his family.

He was born in Namrao village, in Tibet, into a farming family. He entered monastic life when he was 6 years old and took novice vows as a Buddhist monk two years later. When he was 11, he joined the Chakpori Institute of Tibetan Medicine, where he studied for nine years and displayed impressive skills during the study of the four tantra. One of his teachers was his uncle, the famous Tibetan doctor and teacher Khenrab Norbu. At 20, Dhonden was recognised as the best in his class. He passed his exams with distinction and was made an honorary doctor of the 14th Dalai Lama. From 1951 onwards, he practised medicine in Tibet in his native region, where he became renowned for his skill as a physician after he managed an influenza epidemic. He became the foremost expert in Sowa-Rigpa, the Tibetan herbal medicinal system that combines the ancient healing systems of India and China, practised for thousands of years in Tibet. In 1959 he chose to accompany the Dalai Lama into exile in India, when he fled the Chinese invasion of Tibet.

In 1961, when the Dalai Lama re-established the Men-Tsee-Khang, the Tibetan Medical and Astro-Science Institute, …
MVAC vs Platinum – Gemcitabine (PG) in a Risk-Adapted Policy of Adjuvant Chemotherapy (ACT) after Radical Cystectomy (C) in Patients with Invasive Bladder Carcinoma (IBC)
Authors: J.A. Arranz Arija, R. Mondejar Solis, M.P. López Martí, P. Sabin Domínguez, M.C. Lopez Lopez, G. Tapia Rico, B. Moya Ortega, D. Urosa Velasco, E. López Juarez, R. González Beca
Journal: Annals of Oncology (2012)
Abstract 15058: Resuscitative Endovascular Balloon Occlusion of the Aorta versus Aortic Cross Clamping Among Patients With Critical Trauma: A Nationwide Cohort Study in Japan
Authors: Toshikazu Abe, Masatoshi Uchida, Isao Nagata, Daizo Saitoh, Nanako Tamiya
Journal: Circulation (2016)

Introduction:  Measures of aortic occlusion for resuscitation in patients with severe torso trauma remain controversial.   Hypothesis:  Resuscitative endovascular balloon occlusion of the aorta (REBOA) may be an alternative method to resuscitative aortic cross-clamping (ACC) among patients with critical trauma.   Methods:  This study was a retrospective cohort study between 2004 and 2013 from a nationwide trauma registry in Japan (Japan Trauma Data Bank). Participant’s criteria were adult patients who underwent REBOA or ACC. We excluded patients with cardiopulmonary arrest at prehospital or an AIS score of 6. Their characteristics, interventions, and outcomes were analyzed to compare REBOA and ACC. The primary outcome was in-hospital mortality. Logistic regression analysis was performed to compare the outcomes between REBOA and ACC adjusting severity. One to one propensity score matching was also performed to compare them.   Results:  903 of the 159,157 trauma patients were eligible based on the selection criteria. Overall, 405/607 patients (67%) who had REBOA died compared to 210/233 patients (90%) who had ACC. Patients with REBOA had higher RTS (mean±SD; 5.2±2.0 vs. 4.2±2.2; P   Conclusions:  Patients who underwent aortic occlusion had a high mortality. REBOA may be one of favorable alternative methods to resuscitative ACC for severe torso trauma although some indication bias could still remain. Further studies needed to elucidate optimal indications.
Blood Pressure Thresholds and Neurologic Outcomes After Endovascular Therapy for Acute Ischemic Stroke
Authors: Mads Rasmussen, Silvia Schönenberger, Pia Löwhagen Hendèn, Jan B. Valentin, Ulrick S. Espelund, Leif H. Sørensen, Niels Juul, Lorenz Uhlmann, Søren P. Johnsen, Alexandros Rentzos, Julian Bösel, Claus Z. Simonsen
Journal: JAMA Neurology (2020)

<h3>Importance</h3> The optimal blood pressure targets during endovascular therapy (EVT) for acute ischemic stroke (AIS) are unknown. <h3>Objective</h3> To study whether procedural blood pressure parameters, including specific blood pressure thresholds, are associated with neurologic outcomes after EVT. <h3>Design, Setting, and Participants</h3> This retrospective cohort study included adults with anterior-circulation AIS who were enrolled in randomized clinical trials assessing anesthetic strategy for EVT between February 2014 and February 2017. The trials had comparable blood pressure protocols, and patients were followed up for 90 days. A total of 3630 patients were initially approached, and 3265 patients were excluded. <h3>Exposure</h3> Endovascular therapy. <h3>Main Outcomes and Measures</h3> The primary efficacy variable was functional outcome as defined by the modified Rankin Scale (mRS) score at 90 days. Associations of blood pressure parameters and time less than and greater than mean arterial blood pressure (MABP) thresholds with outcome were analyzed. <h3>Results</h3> Of the 365 patients included in the analysis, the mean (SD) age was 71.4 (13.0) years, 163 were women (44.6%), and the median National Institutes of Health Stroke Scale score was 17 (interquartile range [IQR], 14-21). For the entire cohort, 182 (49.9%) received general anesthesia and 183 (50.1%) received procedural sedation. A cumulated period of minimum 10 minutes with less than 70 mm Hg MABP (adjusted OR, 1.51; 95% CI, 1.02-2.22) and a continuous episode of minimum 20 minutes with less than 70 mm Hg MABP (adjusted OR, 2.30; 95% CI, 1.11-4.75) were associated with a shift toward higher 90-day mRS scores, corresponding to a number needed to harm of 10 and 4, respectively. A cumulated period of minimum 45 minutes with greater than 90 mm Hg MABP (adjusted OR, 1.49; 95% CI, 1.11-2.02) and a continuous episode of minimum 115 minutes with greater than 90 mm Hg MABP (adjusted OR, 1.89; 95% CI, 1.01-3.54) were associated with a shift toward higher 90-day mRS scores, corresponding to a number needed to harm of 10 and 6, respectively. <h3>Conclusions and Relevance</h3> Critical MABP thresholds and durations for poor outcome were found to be MABP less than 70 mm Hg for more than 10 minutes and MABP greater than 90 mm Hg for more than 45 minutes, both durations with a number needed to harm of 10 patients. Mean arterial blood pressure may be a modifiable therapeutic target to prevent or reduce poor functional outcome after EVT.
<i>CDKN1B</i> Deletions are Associated with Metastasis in African American Men with Clinically Localized, Surgically Treated Prostate Cancer
Authors: Farzana A. Faisal, Sanjana Murali, Harsimar Kaur, Thiago Vidotto, Liana B. Guedes, Daniela Correia Salles, Vishal Kothari, Jeffrey J. Tosoian, Sumin Han, Daniel H. Hovelson, Kevin Hu, Daniel E. Spratt, Alexander S. Baras, Scott A. Tomlins, Edward M. Schaeffer, Tamara L. Lotan
Journal: Clinical Cancer Research (2020)

Abstract Purpose: The potential biological determinants of aggressive prostate cancer in African American (AA) men are unknown. Here we characterize prostate cancer genomic alterations in the largest cohort to date of AA men with clinical follow-up for metastasis, with the aim to elucidate the key molecular drivers associated with poor prognosis in this population. Experimental Design: Targeted sequencing was retrospectively performed on 205 prostate tumors from AA men treated with radical prostatectomy (RP) to examine somatic genomic alterations and percent of the genome with copy-number alterations (PGA). Cox proportional hazards analyses assessed the association of genomic alterations with risk of metastasis. Results: At RP, 71% (145/205) of patients had grade group ≥3 disease, and 49% (99/202) were non–organ confined. The median PGA was 3.7% (IQR = 0.9%–9.4%) and differed by pathologic grade (P &amp;lt; 0.001) and stage (P = 0.02). Median follow-up was 5 years. AA men with the highest quartile of PGA had increased risks of metastasis (multivariable: HR = 13.45; 95% CI, 2.55–70.86; P = 0.002). The most common somatic mutations were SPOP (11.2%), FOXA1 (8.3%), and TP53 (3.9%). The most common loci altered at the copy number level were CDKN1B (6.3%), CHD1 (4.4%), and PTEN (3.4%). TP53 mutations and deep deletions in CDKN1B were associated with increased risks of metastasis on multivariable analyses (TP53: HR = 9.5; 95% CI, 2.2–40.6; P = 0.002; CDKN1B: HR = 6.7; 95% CI, 1.3–35.2; P = 0.026). Conclusions: Overall, PGA, somatic TP53 mutations, and a novel finding of deep deletions in CDKN1B were associated with poor prognosis in AA men. These findings require confirmation in additional AA cohorts.