tbuckley/cabot-search huggingface dataset:
Hospital revisits within 30 days after discharge for medical conditions targeted by the Hospital Readmissions Reduction Program in the United States: national retrospective analysis
Authors: Rishi K Wadhera, Karen E Joynt Maddox, Dhruv S Kazi, Changyu Shen, Robert W Yeh
Journal: BMJ (2019)

Abstract Objective To determine any changes in total hospital revisits within 30 days of discharge after a hospital stay for medical conditions targeted by the Hospital Readmissions Reduction Program (HRRP). Design Retrospective cohort study. Setting Hospital stays among Medicare patients for heart failure, acute myocardial infarction, or pneumonia between 1 January 2012 and 1 October 2015. Participants Medicare fee-for-service patients aged 65 or over. Main outcomes Total hospital revisits within 30 days of discharge after hospital stays for medical conditions targeted by the HRRP, and by type of revisit: treat-and-discharge visit to an emergency department, observation stay (not leading to inpatient readmission), and inpatient readmission. Patient subgroups (age, sex, race) were also evaluated for each type of revisit. Results Our study cohort included 3 038 740 total index hospital stays from January 2012 to September 2015: 1 357 620 for heart failure, 634 795 for acute myocardial infarction, and 1 046 325 for pneumonia. Counting all revisits after discharge, the total number of hospital revisits per 100 patient discharges for target conditions increased across the study period (monthly increase 0.023 visits per 100 patient discharges (95% confidence interval 0.010 to 0.035)). This change was due to monthly increases in treat-and-discharge visits to an emergency department (0.023 (0.015 to 0.032) and observation stays (0.022 (0.020 to 0.025)), which were only partly offset by declines in readmissions (−0.023 (−0.035 to −0.012)). Increases in observation stay use were more pronounced among non-white patients than white patients. No significant change was seen in mortality within 30 days of discharge for target conditions (−0.0034 (−0.012 to 0.0054)). Conclusions In the United States, total hospital revisits within 30 days of discharge for conditions targeted by the HRRP increased across the study period. This increase was due to a rise in post-discharge emergency department visits and observation stays, which exceeded the decline in readmissions. Although reductions in readmissions have been attributed to improvements in discharge planning and care transitions, our findings suggest that these declines could instead be because hospitals and clinicians have intensified efforts to treat patients who return to a hospital within 30 days of discharge in emergency departments and as observation stays.
Development of a serum-based immunoassay for prostate cancer detection.
Authors: Christine Chavany, Steven S. Chen, Stephen R. Schramm, Rosaura P C Valle, Gunjan Malik, John O. Semmes, Moncef Jendoubi
Journal: Cancer Research (2006)

5290  Prostate cancer (PC) screening is currently based on evaluation of prostate specific antigen (PSA), however there is insufficient evidence to recommend that average-risk men undergo regular screening. PSA is more prostate specific than cancer specific, and elevated PSA can also be found in benign conditions of the prostate. Our aim is to develop improved non-invasive serum-based immunodiagnostic assays for PC detection and disease management. To this end, we have focused our efforts on: i) developing more sensitive and specific biomarkers for PC screening, and ii) developing biomarkers that allow discrimination between malignant and benign conditions of the prostate, including benign prostate hyperplasia (BPH). We have applied our proprietary technologies to discover and validate a panel of biomarkers using a multiplex screening platform known as Matrix Protein Array Technology (MPAT). The MPAT involves the screening of clinical samples with a large collection of 70,000 distinct polyclonal antibodies. Total proteome from normal, cancer, and benign serum samples was printed on a solid support, and reacted with individual antibodies. Antibody-sample reaction was detected by chemiluminescence, and computer analysis of a CCD-acquired image was applied to quantify each spot. Statistical analysis of the data points thus generated enabled the selection of a panel of biomarkers that are differentially expressed in early and advanced stage of PC versus normal controls, or in BPH versus PC samples and normal controls. Biomarkers were validated on a large number of samples, including 242 serum specimens comprising 73 T1/T2 (early stage PC), 69 T3/T4 (advanced stage PC), 50 BPH, and 50 normal controls, and sensitivity and specificity were determined from receiver operating curves (ROC) using statistical package GB-STAT (Dynamic microsystem). We found BPH specific biomarkers that were significantly elevated in BPH versus cancer and normal samples, and biomarkers that significantly discriminate cancer (early and late stage respectively) versus normal and benign. Sensitivity is ranging from 70-80% at 80% specificity. Biomarkers are being combined to optimize sensitivity. We are fully characterizing these biomarkers, and producing a large supply of monospecific antibodies to develop a serum-based immunodiagnostic assay for detection of BPH, early and advanced PC. These biomarkers may have application in early detection, and disease management of PC. A BPH specific diagnostic test would improve accurate PC detection, and reduce unnecessary biopsies.
AODTU-005 Risk of high grade dysplasia and submucosal invasion in different morphological sub-types of large colorectal neoplastic lesions resected at a uk tertiary referral unit
Authors: A Emmanuel, S Gulati, M Burt, B Hayee, A Haji
Journal: Gut (2017)

Introduction  Although it is recognised that the risk of invasive carcinoma in apparent benign colorectal lesions differs according to morphology, the incidence varies between studies and there is limited data from large western series to inform practice. The importance of appropriate resection techniques, including ESD, is increasingly recognised in western practice. It is therefore imperative that the risk of submucosal invasion is assessed accurately to prevent inappropriate attempts at resection. We determined the risk of submucosal invasion and high grade dysplasia (HGD) in different morphological sub-types of large colorectal lesions subjected to endoscopic resection.  Method  Colorectal lesions≥2 cm were included. Lesions were assessed with magnification chromoendoscopy. Data recorded included morphological type, degree of dysplasia and presence of submucosal invasion.  Results  435 colorectal lesions≥2 cm were resected. Mean lesion size was 55.2 mm (range 20 mm–160 mm). The frequency and incidence of HGD and invasive adenocarcinoma in different morphological sub-types are shown in Table 1. The incidence of HGD (8.6%) and invasive adenocarcinoma (1.2%) was very low in LST granular homogenous lesions (LST G H).  LST G MN =LST granular mixed nodular  LST NG =LST non-granular  ESD or hybrid ESD was used to resect 97 lesions. 53% had been subjected to previous failed attempts at resection or heavy manipulation prior to referral.  Of 29 invasive adenocarcinomas, 9 were deemed to be cured by endoscopic resection (superficial submucosal invasion with no adverse prognostic features). Of the remaining 20 patients, 10 were unfit for or refused surgical resection. 10 had surgery: 2 had residual tumour in the resection specimen, 5 had none and 3 had surgery at their referring institution. Only 3 patients (0.7%) with initial benign lesions developed adenocarcinoma in subsequent recurrent lesions – all were early cancers without nodal metastases at surgical resection.  Conclusion  In one of the largest European series reporting the incidence of invasive carcinoma in different morphological sub-types of colorectal neoplastic lesions, we confirm that LST granular homogeneous type lesions have a very low incidence of invasive carcinoma and that care should be taken in the choice of resection technique for other sub-types of LSTs which more frequently harbour malignancy. Accurate endoscopic assessment and classification to aid meticulous lesion selection is essential.  Disclosure of Interest  None Declared
Determination of microvessel density by real-time PCR in esophageal cancer: Correlation with histological methods, angiogenic growth factor expression and lymph node metastasis
Authors: S. Loges, H. Claussen, U. Reichelt, M. Bubenheim, A. Erbersdobler, P. Schurr, E. Yekebas, J. Izbicki, C. Bokemeyer, W. Fiedler
Journal: Journal of Clinical Oncology (2006)

10053 Background: Neoangiogenesis and lymphangiogenesis represent prognostic factors in human malignancies. Determination of microvessel density (MVD) by immunohistology is labor-intensive and subject to interobserver variability. We evaluated real time PCR to quantify MVD in primary tumor samples from patients with esophageal cancer. Methods: We performed real-time PCR analyzes of endothel-specific (VE-Cadherin, P1H12, VEGFR-2, tie-2), lymphendothel-specific (Prox, LYVE, VEGFR-3) antigens and of angiogenic growth factors (VEGF-A, VEGF-C, VEGF-D, Ang-1, Ang-2) in primary esophageal carcinoma tissue of 54 patients. These results were compared to MVD determined immunohistochemically by CD31 staining. Results: For validation, MNC samples spiked with HUVECs were analyzed by qPCR for VE-CAD and P1H12 yielding a linear correlation (r=0.99 and 0.96 respectively). Expression of endothelial markers was highly correlated in tumor samples, e.g. CD144 with CD146 τb=0.451, CD144 with VEGFR-2 τb =0.744 and CD144 with tie-2 τb=0.684 (p for all comparisons &lt; 0.0001). QPCR results were compared to MVD determination by CD31 staining in a subgroup of 33 patients. The highest association between both methods was found for CD144 (τb=0.258, p=0.0379) and VEGFR-2 (τb=0.222, p=0.0745) indicating that immunohistology and qPCR yield comparable results. MVD was significantly linked to the expression of VEGF-A, -C,-D and Ang1 and Ang2 (p for all comparisons &lt;0.0001). We analyzed expression of lymphendothelial cell antigens Prox, LYVE and VEGFR-3 for quantification of lymphatic vessels. A close association between the expression of different lymphendothelial factors was seen (LYVE with Prox τb=0.334, p=0.0021, LYVE with VEGFR-3 τb=0.450, p=0.0150). MVD and lymphvessel density was not linked. Lymph node metastases detected on surgical specimen were associated with MVD determined immunohistologically (p=0.003)or by qPCR (p=0.048) and to VEGF-C expression (p=0.04). Conclusions: QPCR analysis of CD144 and VEGFR2 represents a novel tool for quantification of MVD in tumor samples. Expression of VEGFR2 and VEGF-C is associated with lymph node metastasis in patients with esophageal carcinoma. No significant financial relationships to disclose.
Features and Outcome of Patients (Pts) with New Diagnosis of Acute Myeloid Leukemia (AML) with Monocytic Differentiation (AML-Mo) Following Standard Induction Therapy. Do We Need a Different Strategy?
Authors: James K. McCloskey, Samantha Depadova, Jamie L. Koprivnikar, Tracy Andrews, Marshall McKenna, Genique Stanislaus, Stuart L. Goldberg, Stefan Faderl
Journal: Blood (2016)
Extracorporeal Life Support for Adults With Respiratory Failure and Related Indications
Authors: Daniel Brodie, Arthur S. Slutsky, Alain Combes
Journal: JAMA (2019)

<h3>Importance</h3> The substantial growth over the last decade in the use of extracorporeal life support for adults with acute respiratory failure reveals an enthusiasm for the technology not always consistent with the evidence. However, recent high-quality data, primarily in patients with acute respiratory distress syndrome, have made extracorporeal life support more widely accepted in clinical practice. <h3>Observations</h3> Clinical trials of extracorporeal life support for acute respiratory failure in adults in the 1970s and 1990s failed to demonstrate benefit, reducing use of the intervention for decades and relegating it to a small number of centers. Nonetheless, technological improvements in extracorporeal support made it safer to use. Interest in extracorporeal life support increased with the confluence of 2 events in 2009: (1) the publication of a randomized clinical trial of extracorporeal life support for acute respiratory failure and (2) the use of extracorporeal life support in patients with severe acute respiratory distress syndrome during the influenza A(H1N1) pandemic. In 2018, a randomized clinical trial in patients with very severe acute respiratory distress syndrome demonstrated a seemingly large decrease in mortality from 46% to 35%, but this difference was not statistically significant. However, a Bayesian post hoc analysis of this trial and a subsequent meta-analysis together suggested that extracorporeal life support was beneficial for patients with very severe acute respiratory distress syndrome. As the evidence supporting the use of extracorporeal life support increases, its indications are expanding to being a bridge to lung transplantation and the management of patients with pulmonary vascular disease who have right-sided heart failure. Extracorporeal life support is now an acceptable form of organ support in clinical practice. <h3>Conclusions and Relevance</h3> The role of extracorporeal life support in the management of adults with acute respiratory failure is being redefined by advances in technology and increasing evidence of its effectiveness. Future developments in the field will result from technological advances, an increased understanding of the physiology and biology of extracorporeal support, and increased knowledge of how it might benefit the treatment of a variety of clinical conditions.
Visualizing Autophagic Flux during Endothelial Injury with a Pathway-Inspired Tandem-Reaction Based Fluorogenic Probe
Authors: Yu Lei, Wenming Ren, Cheng-Kun Wang, Rong-Rong Tao, Huai-Jiang Xiang, Li-Li Feng, Yin-Ping Gao, Quan Jiang, Xin Li, Youhong Hu, Feng Han
Journal: Theranostics (2019)

Autophagy is a dynamic and complicated catabolic process.Imaging autophagic flux can clearly advance knowledge of its pathophysiology significance.While the most common way autophagy is imaged relies on fluorescent protein-based probes, this method requires substantial genetic manipulation that severely restricts the application.Small fluorescent probes capable of tracking autophagic flux with good spatiotemporal resolution are highly demanable.Methods: In this study, we developed a small-molecule fluorogenic probe (AFG-1) that facilitates real-time imaging of autophagic flux in both intact cells and live mice.AFG-1 is inspired by the cascading nitrosative and acidic microenvironments evolving during autophagy.It operates over two sequential steps.In the first step, AFG-1 responds to the up-regulated peroxynitrite at the initiation of autophagy by its diphenylamino group being oxidatively dearylated to yield a daughter probe.In the second step, the daughter probe responds to the acidic autolysosomes at the late stage of autophagy by being protonated.Results: This pathway-dependent mechanism has been confirmed first by sequentially sensing ONOO -and acid in aqueous solution, and then by imaging autophagic flux in live cells.Furthermore, AFG-1 has been successfully applied to visualize autophagic flux in real-time in live mice following brain ischemic injury, justifying its robustness.Conclusion: Due to the specificity, easy operation, and the dynamic information yielded, AFG-1 should serve as a potential tool to explore the roles of autophagy under various pathological settings.
miR-19a-3p containing exosomes improve function of ischaemic myocardium upon shock wave therapy
Authors: Can Gollmann-Tepeköylü, Leo Pölzl, Michael Graber, Jakob Hirsch, Felix Nägele, Daniela Lobenwein, Michael W Hess, Michael J Blumer, Elke Kirchmair, Johannes Zipperle, Carina Hromada, Severin Mühleder, Hubert Hackl, Martin Hermann, Hemse Al Khamisi, Martin Förster, Michael Lichtenauer, Rainer Mittermayr, Patrick Paulus, Helga Fritsch, Nikolaos Bonaros, Rudolf Kirchmair, Joost P G Sluijter, Sean Davidson, Michael Grimm, Johannes Holfeld
Journal: Cardiovascular Research (2019)

As many current approaches for heart regeneration exert unfavourable side effects, the induction of endogenous repair mechanisms in ischaemic heart disease is of particular interest. Recently, exosomes carrying angiogenic miRNAs have been described to improve heart function. However, it remains challenging to stimulate specific release of reparative exosomes in ischaemic myocardium. In the present study, we sought to test the hypothesis that the physical stimulus of shock wave therapy (SWT) causes the release of exosomes. We aimed to substantiate the pro-angiogenic impact of the released factors, to identify the nature of their cargo, and to test their efficacy in vivo supporting regeneration and recovery after myocardial ischaemia.Mechanical stimulation of ischaemic muscle via SWT caused extracellular vesicle (EV) release from endothelial cells both in vitro and in vivo. Characterization of EVs via electron microscopy, nanoparticle tracking analysis and flow cytometry revealed specific exosome morphology and size with the presence of exosome markers CD9, CD81, and CD63. Exosomes exhibited angiogenic properties activating protein kinase b (Akt) and extracellular-signal regulated kinase (ERK) resulting in enhanced endothelial tube formation and proliferation. A miRNA array and transcriptome analysis via next-generation sequencing were performed to specify exosome content. miR-19a-3p was identified as responsible cargo, antimir-19a-3p antagonized angiogenic exosome effects. Exosomes and target miRNA were injected intramyocardially in mice after left anterior descending artery ligation. Exosomes resulted in improved vascularization, decreased myocardial fibrosis, and increased left ventricular ejection fraction as shown by transthoracic echocardiography.The mechanical stimulus of SWT causes release of angiogenic exosomes. miR-19a-3p is the vesicular cargo responsible for the observed effects. Released exosomes induce angiogenesis, decrease myocardial fibrosis, and improve left ventricular function after myocardial ischaemia. Exosome release via SWT could develop an innovative approach for the regeneration of ischaemic myocardium.
Optimizing Cardiac CT Protocols for Comprehensive Acquisition Prior to Percutaneous MV and TV Repair/Replacement
Authors: Todd C. Pulerwitz, Omar K. Khalique, Jay Leb, Rebecca T. Hahn, Tamim M. Nazif, Martin B. Leon, Isaac George, Torsten P. Vahl, Belinda D’Souza, Vinayak N. Bapat, Shifali Dumeer, Susheel K. Kodali, Andrew J. Einstein
Journal: JACC. Cardiovascular imaging (2019)
Clinical colorectal cancer (CRC) subsets in advanced disease: Patterns of metastatic spread to predict survival.
Authors: María Teresa Bourlon, Paulina Carpinteyro-Espin, Mauricio De Jesus Mora-Pineda, Armando Gamboa-Dominguez, Fidel David Huitzil-Melendez
Journal: Journal of Clinical Oncology (2013)

e14703 Background: Advanced CRC is a heterogeneous disease. Some patients exhibit diffuse metastatic spread while others show selective organ involvement. We aimed to investigate the frequency and survival implications of initial pattern of metastatic spread in a Mexican cohort. Methods: We retrospectively reviewed charts and radiologic images of patients with advanced CRC at our institution from 2004 to 2011. The initial pattern of spread was recorded. Categories depending on the predominant site of involvement were: 1) Locally advanced, 2) Hepatic, 3) Pulmonary, 4) Peritoneal or 5) Diffuse. Survival was estimated by the Kaplan Meier method and Log rank test used to determine survival differences among categories. Results: 179 patients with advanced CRC were identified. Median age was 60yo, 56% were male. Primary tumor location was 50.3% colon, 27.9% rectum, 17.9% recto-sigmoid and 3.4% had synchronous disease. 66% of patients had advanced disease at diagnosis and 34% were recurrent cases. Metastasis at diagnosis involved the liver in 105 (58.7%), peritoneum in 49 (27.4%), lung in 56 (31.3%) and non regional lymph nodes in 36 (20.1%) patients. Notably, 101 (56%) patients had a predominant site of metastatic involvement: locally advanced in 3 (1.7%), hepatic in 51 (28.5%), peritoneal in 21 (11.7%), pulmonary 21 (11.7%) while 78 patients (44%) had disseminated disease. Median overall survival was 15 months (n= 179) and differed according to predefined CRC subsets: 9, 13, 22, 23, and 52 months for peritoneal, disseminated, hepatic, locally advanced and pulmonary spread respectively p=.018 (significant after multivariate analysis). Other factors associated with better survival were female gender p=.040, absence of morbidity from primary tumor p=.27, resection of primary tumor p=.004, recurrent presentation p=.039, and access to 1 st line chemotherapy p=.00. Conclusions: Over 50% of patients exhibited selective metastatic spread. Clinically defined subsets correlate with better (pulmonary) or worse (peritoneal/disseminated) survival. This finding might have implications in patient selection for regional therapies and encourage research to find the molecular determinants of this biologic behavior.
CDK4 Regulates Lysosomal Function and mTORC1 Activation to Promote Cancer Cell Survival
Authors: Laia Martínez-Carreres, Julien Puyal, Lucía C. Leal-Esteban, Meritxell Orpinell, Judit Castillo-Armengol, Albert Giralt, Oleksandr Dergai, Catherine Moret, Valentin Barquissau, Anita Nasrallah, Angélique Pabois, Lianjun Zhang, Pedro Romero, Isabel C. Lopez-Mejia, Lluis Fajas
Journal: Cancer Research (2019)

Abstract Cyclin-dependent kinase 4 (CDK4) is well-known for its role in regulating the cell cycle, however, its role in cancer metabolism, especially mTOR signaling, is undefined. In this study, we established a connection between CDK4 and lysosomes, an emerging metabolic organelle crucial for mTORC1 activation. On the one hand, CDK4 phosphorylated the tumor suppressor folliculin (FLCN), regulating mTORC1 recruitment to the lysosomal surface in response to amino acids. On the other hand, CDK4 directly regulated lysosomal function and was essential for lysosomal degradation, ultimately regulating mTORC1 activity. Pharmacologic inhibition or genetic inactivation of CDK4, other than retaining FLCN at the lysosomal surface, led to the accumulation of undigested material inside lysosomes, which impaired the autophagic flux and induced cancer cell senescence in vitro and in xenograft models. Importantly, the use of CDK4 inhibitors in therapy is known to cause senescence but not cell death. To overcome this phenomenon and based on our findings, we increased the autophagic flux in cancer cells by using an AMPK activator in combination with a CDK4 inhibitor. The cotreatment induced autophagy (AMPK activation) and impaired lysosomal function (CDK4 inhibition), resulting in cell death and tumor regression. Altogether, we uncovered a previously unknown role for CDK4 in lysosomal biology and propose a novel therapeutic strategy to target cancer cells. Significance: These findings uncover a novel function of CDK4 in lysosomal biology, which promotes cancer progression by activating mTORC1; targeting this function offers a new therapeutic strategy for cancer treatment.
Mortality and Hospitalization Risk Following Oral Androgen Signaling Inhibitors Among Men with Advanced Prostate Cancer by Pre-existing Cardiovascular Comorbidities
Authors: Grace Lu-Yao, Nikita Nikita, Scott W. Keith, Ginah Nightingale, Krupa Gandhi, Sarah E. Hegarty, Timothy R. Rebbeck, Andrew Chapman, Philip W. Kantoff, Jennifer Cullen, Leonard Gomella, William Kevin Kelly
Journal: European Urology (2019)