tbuckley/cabot-search huggingface dataset:
Prognostic factors of recurrence of colorectal cancers with microsatellite instability after curative resection: An AGEO retrospective multicenter study.
Authors: David Tougeron, Gaelle Sickersen, Thierry Lecomte, Aziz Zaanan, Gaetan Des Guetz, Cedric Lecaille, Aurelie Ferru, Estelle Cauchin, David Sefrioui, Romain Coriat, Thomas Aparicio, Pascal Artru, Isabelle Trouilloud, Tamara Matysiak-Budnik, Julien Taïeb, Pierre Michel, Jean Marc Tourani, Pierre Levillain, Christine Silvain, Lucie Karayan-Tapon
Journal: Journal of Clinical Oncology (2013)

3536 Background: Microsatellite instability (MSI) phenotype is found in approximately 12% of colorectal cancers (CRC). MSI CRC is associated with a low recurrence rate and 5-fluorouracil chemoresistance in adjuvant setting. Clinical and pathological prognostic factors of recurrence are well-identified after surgery of CRC but not in the subgroup of MSI CRC. Methods: This multicenter retrospective study included patients with stage I, II and III MSI CRC. The following prognostic factors were studied: age, sex, perforation, occlusion, tumor location, tumor differentiation, T4 stage, lymph node invasion, VELIPI criteria (vascular emboli, lymphatic invasion and perinervous invasion), BRAF mutation and adjuvant chemotherapy. Disease-free survival (DFS) was calculated using the Kaplan-Meier method. Prognostic factors of DFS were analyzed in multivariate analysis using Cox model. Results: A total of 294 MSI CRC patients were analyzed, including 10%, 49% and 41% stage I, II and III, respectively. Mean age was 67.2 ± 16.0 years. Occlusion was observed in 10% of cases. VELIPI criteria were found in 39%, including 26% with vascular emboli. BRAF mutation was detected in 27% of cases. All in all, 40% of patients received adjuvant chemotherapy, predominantly stage III (74%). Mean follow-up was 39.2 ± 33.2 months. The disease recurrence rate was 3%, 8% and 21% in stage I, II and III patients, respectively. The 3-year DFS rate was 85%. In univariate analysis, age, occlusion, lymph node invasion, T4 stage, vascular emboli and perinervous invasion were associated with decreased DFS (p&lt;0.05). In multivariate analysis, only occlusion (RR=3.0; 95% CI 1.2-7.7, p=0.02) and vascular emboli (RR=4.5; 95% CI 1.6-12.7, p&lt;0.01) were associated with decreased DFS. Recurrence rates for MSI CRC with and without vascular emboli were respectively, 22% versus 5% for stage II and 33% versus 15% for stage III. Conclusions: Occlusion and vascular emboli were independently associated with recurrence of MSI CRC but not lymph node invasion. We advocate vascular emboli analysis in routine clinical practice to facilitate adjuvant chemotherapy decision-making in MSI CRC.
Golgi Acidification by NHE7 Regulates Cytosolic pH Homeostasis in Pancreatic Cancer Cells
Authors: Koen M.O. Galenkamp, Paulina Sosicka, Michael Jung, M. Victoria Recouvreux, Yijuan Zhang, Matthew R. Moldenhauer, Giovanni Brandi, Hudson H. Freeze, Cosimo Commisso
Journal: Cancer Discovery (2020)

Abstract abstract Cancer cells reprogram their metabolism to meet elevated energy demands and favor glycolysis for energy production. This boost in glycolytic flux supports proliferation, but also generates acid in the form of hydrogen ions that must be eliminated from the cytoplasm to maintain the alkaline intracellular pH (pHi) associated with transformation. To cope with acid production, tumor cells employ ion transport systems, including the family of sodium–hydrogen exchangers (NHE). Here, we identify NHE7 as a novel regulator of pHi in pancreatic ductal adenocarcinoma (PDAC). We determine that NHE7 suppression causes alkalinization of the Golgi, leading to a buildup of cytosolic acid that diminishes tumor cell fitness mainly through the dysregulation of actin. Importantly, NHE7 knockdown in vivo leads to the abrogation of tumor growth. These results identify Golgi acidification as a mechanism to control pHi and point to the regulation of pHi as a possible therapeutic vulnerability in PDAC. Significance: NHE7 regulates cytosolic pH through Golgi acidification, which points to the Golgi as a “proton sink” for metabolic acid. Disruption of cytosolic pH homeostasis via NHE7 suppression compromises PDAC cell viability and tumor growth. See related commentary by Ward and DeNicola, p. 768. This article is highlighted in the In This Issue feature, p. 747
GENDER DIFFERENCES IN COMORBIDITIES AND OUTCOMES AFTER ORTHOTROPIC HEART TRANSPLANTATION: A NATIONWIDE ANALYSIS
Authors: Srinidhi J. Meera, Deepak Kumar Pasupula, Anusha Ganapati Bhat, Sudeep K. Siddappa Malleshappa, Srilakshmi Vallabhaneni, Jamshid Shirani
Journal: Journal of the American College of Cardiology (2020)
Association of injury related hospital admissions with commuting by bicycle in the UK: prospective population based study
Authors: Claire Welsh, Carlos A Celis-Morales, Frederick Ho, Donald M Lyall, Daniel Mackay, Lyn Ferguson, Naveed Sattar, Stuart R Gray, Jason M R Gill, Jill P Pell, Paul Welsh
Journal: BMJ (2020)

Abstract Objective To determine whether bicycle commuting is associated with risk of injury. Design Prospective population based study. Setting UK Biobank. Participants 230 390 commuters (52.1% women; mean age 52.4 years) recruited from 22 sites across the UK compared by mode of transport used (walking, cycling, mixed mode versus non-active (car or public transport)) to commute to and from work on a typical day. Main outcome measure First incident admission to hospital for injury. Results 5704 (2.5%) participants reported cycling as their main form of commuter transport. Median follow-up was 8.9 years (interquartile range 8.2-9.5 years), and overall 10 241 (4.4%) participants experienced an injury. Injuries occurred in 397 (7.0%) of the commuters who cycled and 7698 (4.3%) of the commuters who used a non-active mode of transport. After adjustment for major confounding sociodemographic, health, and lifestyle factors, cycling to work was associated with a higher risk of injury compared with commuting by a non-active mode (hazard ratio 1.45, 95% confidence interval 1.30 to 1.61). Similar trends were observed for commuters who used mixed mode cycling. Walking to work was not associated with a higher risk of injury. Longer cycling distances during commuting were associated with a higher risk of injury, but commute distance was not associated with injury in non-active commuters. Cycle commuting was also associated with a higher number of injuries when the external cause was a transport related incident (incident rate ratio 3.42, 95% confidence interval 3.00 to 3.90). Commuters who cycled to work had a lower risk of cardiovascular disease, cancer, and death than those who did not. If the associations are causal, an estimated 1000 participants changing their mode of commuting to include cycling for 10 years would result in 26 additional admissions to hospital for a first injury (of which three would require a hospital stay of a week or longer), 15 fewer first cancer diagnoses, four fewer cardiovascular disease events, and three fewer deaths. Conclusion Compared with non-active commuting to work, commuting by cycling was associated with a higher risk of hospital admission for a first injury and higher risk of transport related incidents specifically. These risks should be viewed in context of the health benefits of active commuting and underscore the need for a safer infrastructure for cycling in the UK.
Findings of lung ultrasonography of novel corona virus pneumonia during the 2019–2020 epidemic
Authors: Qian-Yi Peng, Xiao-Ting Wang, Li-Na Zhang
Journal: Intensive Care Medicine (2020)

have been 77,269 officially reported confirmed cases of 2019 novel corona virus (SARS-CoV-2) infection in China.As lung abnormalities may develop before clinical manifestations and nucleic acid detection, experts have recommended early chest computerized tomography (CT) for screening suspected patients [1].The high contagiousness of SARS-CoV-2 and the risk of transporting unstable patients with hypoxemia and hemodynamic failure make chest CT a limited option for the patient with suspected or established COVID-19.Lung ultrasonography gives the results that are similar to chest CT and superior to standard chest radiography for evaluation of pneumonia and/ or adult respiratory distress syndrome (ARDS) with the added advantage of ease of use at point of care, repeatability, absence of radiation exposure, and low cost [2].In this report, we summarize our early experience with lung ultrasonography for evaluation of SARS-CoV-2 infection in China with the intent of alerting frontline intensivists to the utility of lung ultrasonography for management of COVID-19. Ultrasonographic features of nCoV pneumoniaWe performed lung ultrasonography on 20 patients with COVID-19 using a 12-zone method [3].
The impact of diabetes on HCC.
Authors: Suzanne Graef, Sarah Berhane, Mabel Joey Teng, Anna Skowronska, Philip James Johnson
Journal: Journal of Clinical Oncology (2013)

4029 Background: The incidence of hepatocellular carcinoma (HCC) in the UK has increased by 40% over the last 20 years, with a corresponding increase in mortality rate. The rising incidence of obesity and type II diabetes are believed to be contributing factors due to the association with non-alcoholic fatty liver and steatohepatitis. We aimed to examine if diabetes was as an independent risk factor for the development of HCC and to assess the impact of diabetes on overall survival (OS). Methods: Data from 724 patients with HCC and a control group comprising 340 patients with chronic liver disease were collected prospectively between 2007 and 2012. The odds ratio (OR) for HCC in diabetic versus non-diabetic patients was calculated. Univariate and multivariate analysis was performed using logistic regression. Cox proportional hazards analysis was used to estimate hazard ratio (HR) for death for HCC patients, with and without diabetes and for the impact of variation in diabetic treatments. Results: The prevalence of diabetes was 39% within the HCC population and 10.3% within the chronic liver disease group. Univariate analysis demonstrated increased risk of HCC associated with age, sex, diabetes, haemochromatosis, cirrhosis, alcohol abuse and Child’s score. In patients with diabetes OR for HCC was 5.74 (CI 3.9-8.3; p&lt;0.001). Age, sex, cirrhosis, Child’s score, diabetes and diabetes treatment with insulin, retained significance as independent risk factors in multivariate analysis. There was no survival difference for HCC patients with and without diabetes. In diabetic patients with HCC, treatment of diabetes with metformin, compared against other diabetic treatment options, was associated with a significantly longer OS (31 versus 24 months, p = 0.016; HR 0.74, p = 0.027). Conclusions: This study has demonstrated that diabetes is an independent risk factor for the development of HCC in a high risk population and that treatment with insulin appears to confer further independent risk. Diabetes has no effect on survival following the development of HCC but treatment of diabetes with metformin is associated with prolonged survival. In considering the optimal treatment for diabetes in chronic liver disease the beneficial effects of metformin on OS, if HCC develops, should be taken into account.
Prognostic factors for overall survival in non-Hodgkin lymphomas: Nonlinear effect of continuous covariates.
Authors: Claudio J. Flores, Luis Augusto Casanova
Journal: Journal of Clinical Oncology (2013)

e19538 Background: To evaluate prognostic factors in patients with primary non-Hodgkin lymphomas (NHL). Methods: We retrospectively analyzed prognostic factors (PFs) for overall survival (OS) in 2160 patients (pts) with NHL treated at INEN between 1990-2002. PFs were determinate according to Cox model with P-splines. Results: The median age was 54 years (range 14 - 96) and 51% were male. The majority of the pts had good performance status (73%, WHO 0-1). The Ann Arbor stage was I-II in 51%, III-IV in 49% and B symptoms were present in 38% of the pts. The hemoglobin (Hb) was low in 48%. Leukocytes (WBC), lymphocytes and LDH were elevated in 17.7%, 7.7% and 60% of pts, respectively. Of all patients, 709 (32.8 %) pts had died. The median follow-up was 12.6 months, with a median survival of 61.8 months and the survival rate at 5 and 10 years of 51.2 % and 41.7 % respectively. PFs identified were: age, sex, zubrod, clinical stage, Hb, leukocytes, lymphocytes and LDH. The following table shows the p-value and hazard ratio (HR). The effect of continuous covariates in the log(HR) is non-linear. The cutoff points of highest (HR &gt;1) match the clinically defined ones, which are: age &gt;60yrs, Hb&lt;12g/dl and LDH &gt;240UI/L. Both leukocytes and lymphocytes have two higher risk breakpoints: leukocytes &gt;3x10 3 and &gt;10x10 3 , lymphocytes &lt;20% and &gt;60%. Conclusions: PFs for OS in our group of pts were similar to other reports in NHL. Age, Hb, leukocytes, and lymphocytes are relevant to OS, which showed a nonlinear effect in the log (HR). [Table: see text]
Second-line pemetrexed (P) for the treatment of hormone refractory prostate cancer (HRPC): A Hoosier Oncology Group phase II study—Preliminary analysis
Authors: N. M. Hahn, C. Whalen, C. J. Sweeney
Journal: Journal of Clinical Oncology (2006)

4644 Background: We evaluated the efficacy and toxicity of pemetrexed in men with HRPC who had progressed on one prior taxane chemotherapy regimen. Methods: Patients with HRPC received P 500 mg/m 2 IV d1 q21d cycle with B12 and folate supplementation until progression or dose-limiting toxicity. The primary outcome measure was PSA response rate (PSAr) defined as a &gt; 50% decline from baseline PSA that was confirmed at least four weeks later. Pts were required to have documented PSA progression prior. If no metastatic disease, a PSA &gt; 20 ng/dL was required. A two-stage Simon phase II design with early stopping rules is being utilized with a PSA response rate of 20% deemed to be clinically relevant. Results: Patient characteristics: To date, 21 of the planned 42 patients have been treated with a median age of 67 years (53–79), median baseline PSA 97.8 (0.7–754.3), and median Karnofsky performance status of 90 (70–100). Treatment Cycles: A total of 83 treatment cycles have been administered with a median of 3 cycles per patient (0–12). Toxicity: 6 of 21 (28.6%) patients experienced a total of 17 grade 3 events. Treatment related grade 3 events included thrombocytopenia (1), anemia (2), mucositis (1), rash (1), and fatigue (1). 3 of 21 (14.3%) patients experienced a total of 8 grade 4 events. Treatment related grade 4 events included neutropenia (2), thrombocytopenia (3), anemia (1), and neutropenic fever (1). Response: Best response observed included 4 PSAr (19.0%, 95% CI 2.2–35.8%), 8 stable disease (SD) (38.1%, 95% CI 17.3–58.8%) and 9 progressive disease (PD) (42.9%, 95% CI 21.7–64.1%). PSAr were maintained at 5, 12+, 5+, and 3+ weeks with sustained SD seen at 15, 12, 15, 21+, 18+, and 12+ weeks. Survival data is immature at this time. Conclusion: This preliminary analysis reveals that pemetrexed has met criteria to move into the second stage of the study and has an acceptable toxicity profile in this patient population. [Table: see text]
Chemotherapy (CT) for advanced biliary tract cancers (BTC): A retrospective analysis from UT Southwestern Medical Center (UTSW) and Parkland Hospital (PH).
Authors: Mohammed Abdul Ahad Athar, Sirisha Karri, Yull Edwin Arriaga, Udit N. Verma
Journal: Journal of Clinical Oncology (2013)

e15200 Background: CT is the main treatment option for patients (pts) with advanced BTC. There is limited randomized data to guide treatment selection. Based on phase 3 data, gemcitabine (G)/cisplatin (C) is an acceptable 1 st line CT, but 5-FU based regimens are also used. We reviewed data from our institution to elucidate treatment preferences and responses. Methods: This is a retrospective analysis of pts treated at UTSW and PH from Jan 2008 to Dec 2011. Patient lists were obtained from the tumor registry at each hospital from Jan 2008 to Dec 2011. Results: 60 pts had inoperable or metastatic disease. 26/60 pts did not receive CT due to poor functional status. 34/60 pts received 1 st -line CT- 26 cholangiocarcinoma, 7 gall bladder cancer, 1 ampullary cancer. 10/34 pts were not evaluated for treatment response due to lack of follow-up. Of the remaining 24 pts, 12 received 2 nd line CT. In combined analysis of 1 st and 2 nd line CT in pts with adequate clinic follow-up, G alone (n=10) or in combination (with C n=9, C+ Cetuximab (CX) n=1, Oxaliplatin n=5, Capecitabine (CAP) n=1, Docetaxel n=1) was the most frequently used CT. 2 pts received CAP with radiation. 6 pts received 5-FU based regimen (FOLFOX n=1, FOLFOX/CX n=1, FOLFIRI n=1, FOLFIRI/CX n=1, FOLFIRI/panitumumab n=2). In 1 st line, best response (BR)—partial response (PR) 4 pts, stable disease (SD) 14 pts, progressive disease (PD) 6 pts. Response duration range (RDR) in 1 st line was 2-22 months (m). In 2 nd line, BR—PR 1 pt, SD 7 pts, PD 2 pts. RDR in 2 nd line was 2-10 m. Of the 4 pts who received CT combined with an EGFR inhibitor (EGFRI), 2 had SD, 2 had PR; RDR 3-10 m. Disease control (DC) rate (PR+SD) from 1 st line CT 53%, 2 nd line CT 67%. All 4 pts who received EGFRI in combination with CT showed evidence of DC. Conclusions: CT is effective in BTC with benefit seen in the majority of treated pts. 43% of pts were unable to receive CT which underscores the poor outlook in this malignancy. Interestingly we noted that even in our small subgroup who received EGFRI based combination CT, there was clinical benefit even in 2 nd line CT. There is some published data to support this finding. EGFRI based CT should be further studied in this population.
COMPARISON OF TRANSFEMORAL VERSUS TRANSRADIAL SECONDARY ACCESS IN TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Lucia Junquera Vega, Marina Urena, Azeem Latib, Antonio J. Muñoz-García, Luis Nombela-Franco, Benjamin Faurie, Gabriela Veiga Fernandez, Alberto Alperi Garcia, Vicente Serra, Ander Regueiro, Quentin Fisher, Dominique Himbert, Antonio Mangieri, Antonio Colombo, Erika Muñoz Garcia, Rafael Vera Urquiza, Pilar Jimenez-Quevedo, Jose de la Torre Hernandez, Isaac Pascual, Bruno Garcia del Blanco, Manel Sabate, Siamak Mohammadi, Afonso Freitas-Ferraz, Leonardo Guimaraes, Josep Rodes-Cabau
Journal: Journal of the American College of Cardiology (2020)
Re: Owsley et al.: Commentary: Cautionary remarks on linking cognitive impairment to glaucoma and age-related macular degeneration (Ophthalmology. 2020;127:667)
Authors: Ellen Freeman, Mélanie Varin, Marie-Jeanne Kergoat, Sylvie Belleville, Gisele Li, Marie-Hélène Roy-Gagnon, Solmaz Moghadaszadeh, Jacqueline Rousseau
Journal: Ophthalmology (2020)
EFFECT OF TREATMENT WITH DAPAGLIFLOZIN ACCORDING TO BASELINE SYSTOLIC BLOOD PRESSURE IN PATIENTS WITH HFREF: AN ANALYSIS OF THE DAPA-HF TRIAL
Authors: John McMurray, Michael Boehm, Matteo Serenelli, Silvio E. Inzucchi, Pardeep Jhund, Lars Kober, Mikhail Kosiborod, Anna Maria Langkilde, Felipe Martinez, Olof Bengtsson, Piotr Ponikowski, Marc Sabatine, Mikaela Sjoestrand, Scott D. Solomon
Journal: Journal of the American College of Cardiology (2020)
Association of Silent Myocardial Infarction With Major Cardiovascular Events in Diabetes: The ACCORD Trial
Authors: Matthew J. Singleton, Charles A. German, Alain G. Bertoni, Walter T. Ambrosius, Prashant D. Bhave, Elsayed Z. Soliman, Joseph Yeboah
Journal: Diabetes Care (2020)

The epidemic of diabetes continues to grow, with recent prevalence estimates of 12% among U.S. adults. Though type 2 diabetes is associated with a two- to fourfold heightened risk of cardiovascular disease, this risk is heterogeneously distributed (1). Thus, markers of cardiovascular risk beyond traditional risk factors are needed. Prior efforts to incorporate novel blood biomarkers in risk prediction have found only modest additive value in risk discrimination, despite significant economic cost (2,3). The routine 12-lead electrocardiogram (ECG) may represent a cost-effective measure to refine atherosclerotic cardiovascular disease (ASCVD) risk. Silent myocardial infarction (SMI) is more common among those with diabetes due to impaired nociception. The risk of ASCVD among those with prior SMI and diabetes has not been adequately studied.

We used patient-level data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study and the ACCORDION follow-up study to assess the additive utility of SMI for discrimination of risk. For this analysis, eligible participants were free of prevalent cardiovascular disease (defined as history of myocardial infarction, stroke, coronary revascularization, carotid or peripheral revascularization, or positive stress test) at study enrollment and had adequate baseline ECG data. SMI was defined as the presence of a …
Pan-cancer diagnostic consensus through searching archival histopathology images using artificial intelligence
Authors: Shivam Kalra, H. R. Tizhoosh, Sultaan Shah, Charles Choi, Savvas Damaskinos, Amir Safarpoor, Sobhan Shafiei, Morteza Babaie, Phedias Diamandis, Clinton J. V. Campbell, Liron Pantanowitz
Journal: npj Digital Medicine (2020)

The emergence of digital pathology has opened new horizons for histopathology. Artificial intelligence (AI) algorithms are able to operate on digitized slides to assist pathologists with different tasks. Whereas AI-involving classification and segmentation methods have obvious benefits for image analysis, image search represents a fundamental shift in computational pathology. Matching the pathology of new patients with already diagnosed and curated cases offers pathologists a new approach to improve diagnostic accuracy through visual inspection of similar cases and computational majority vote for consensus building. In this study, we report the results from searching the largest public repository (The Cancer Genome Atlas, TCGA) of whole-slide images from almost 11,000 patients. We successfully indexed and searched almost 30,000 high-resolution digitized slides constituting 16 terabytes of data comprised of 20 million 1000 × 1000 pixels image patches. The TCGA image database covers 25 anatomic sites and contains 32 cancer subtypes. High-performance storage and GPU power were employed for experimentation. The results were assessed with conservative "majority voting" to build consensus for subtype diagnosis through vertical search and demonstrated high accuracy values for both frozen section slides (e.g., bladder urothelial carcinoma 93%, kidney renal clear cell carcinoma 97%, and ovarian serous cystadenocarcinoma 99%) and permanent histopathology slides (e.g., prostate adenocarcinoma 98%, skin cutaneous melanoma 99%, and thymoma 100%). The key finding of this validation study was that computational consensus appears to be possible for rendering diagnoses if a sufficiently large number of searchable cases are available for each cancer subtype.
MENTAL STRESS-INDUCED MYOCARDIAL ISCHEMIA AS A MARKER FOR ADVERSE CARDIOVASCULAR EVENTS AFTER MI
Authors: Zakaria Almuwaqqat, Bruno Lima, An Young, Samaah Sullivan, Amit J. Shah, Muhammad Hammadah, Mariana Garcia, Oleksiy Levantsevych, Lisa Elon, Ernest Garcia, Doug Bremner, Paolo Raggi, Tene Lewis, Arshed A. Quyyumi, Viola Vaccarino
Journal: Journal of the American College of Cardiology (2020)