tbuckley/cabot-search huggingface dataset:
Epidemiology and characteristics of patients (pts) with hepatocellular carcinoma (HCC) and care in the United States.
Authors: Yunes Doleh, Huifen Wang, Ping Sun, Binbing Yu, Iksha Herr
Journal: Journal of Clinical Oncology (2019)

231 Background: The incidence of liver and intrahepatic bile duct cancer, with HCC accounting for 72.7%, has doubled from 1992 to 2014 in the U.S. This study examined the latest epidemiology of HCC by analyzing 2 large U.S. databases. Methods: IBM MarketScan (IBM-MS) and Surveillance, Epidemiology, and End Results-National Program of Cancer Registries (SEER-NPCR) databases were analyzed separately. Pts (aged ≥ 18 years) with HCC as the primary cancer were identified from the IBM-MS database, who were covered by employer-provided commercial or Medicare Supplemental insurance. A new HCC diagnosis (Dx) was defined as the first HCC Dx using ICD-9/10 codes within the study period (Jan 2012-Sep 2017) and no other HCC Dx in the prior 12 months. Comorbidities, performance status, distribution of pts, and treatments received were described. In SEER-NPCR (Jan 2010-Dec 2014), a nationally representative patient sample was analyzed to describe the incidence and mortality of pts with HCC. Results: A total of 8,150 and 119,927 pts were identified in IBM-MS and SEER-NPCR, respectively. Pts were predominately male in both databases. The HCC incidence rates among the IBM-MS cohort were 5.9, 5.5, 4.9, and 4.7 per 100,000 person-years from 2013 to 2016, respectively. The downward trend in the HCC incidence rate post-2013 for this population coincided with the drop in HCC incidence rate from 2013 to 2014 in SEER-NPCR. Amongst the IBM-MS cohort, 6%, 36%, and 59% of pts had hepatitis B, hepatitis C, and cirrhosis at Dx, respectively. Most pts (88%) were considered having good performance status at Dx. Embolization and chemo/targeted therapies were the most common treatments received by pts irrespective of the disease stage (31% and 12%, respectively) and pts with de novo metastatic HCC (19% and 18%, respectively). About 44% of the HCC Dx occurred at hospital outpatient settings; 31% at inpatient settings and 23% at physician offices. Conclusions: This study identifies the recent epidemiologic changes in pts with HCC and characterizes their comorbidities in a commercially-insured and a U.S. representative population. These epidemiologic data may be important considerations for U.S. payers making coverage policies for pts with HCC.
Pre-Operative Grade of Decompressing Systemic Venous Collaterals, But Not Jugular Venous Pressure, Predicts Short- and Medium-Term Outcome After Completion of the Total Cavopulmonary Connection
Authors: Marina L. Hughes, Michael Broadhead, Angus McEwan, Oliver Tann, Sylvia Krupickova, Vivek Muthurangu
Journal: JACC. Cardiovascular imaging (2019)
Genomic Contextualism: Shifting the Rhetoric of Genetic Exceptionalism
Authors: Nanibaa' A. Garrison, Kyle B. Brothers, Aaron J. Goldenberg, John A. Lynch
Journal: The American Journal of Bioethics (2019)

As genomic science has evolved, so have policy and practice debates about how to describe and evaluate the ways in which genomic information is treated for individuals, institutions, and society. The term genetic exceptionalism, describing the concept that genetic information is special or unique, and specifically different from other kinds of medical information, has been utilized widely, but often counterproductively in these debates. We offer genomic contextualism as a new term to frame the characteristics of genomic science in the debates. Using stasis theory to draw out the important connection between definitional issues and resulting policies, we argue that the framework of genomic contextualism is better suited to evaluating genomics and its policy-relevant features to arrive at more productive discussion and resolve policy debates.
Guanylate cyclase C (GUCY2C) as a preventative and therapeutic target in colorectal cancers (CRCs) arising through divergent genomic pathways.
Authors: Babar Bashir, Dante Merlino, Jeffrey Rappaport, Esteban D Gnass, Juan Palazzo, Yeng Fing, Eric R Fearon, Adam Snook, Scott A Waldman
Journal: Journal of Clinical Oncology (2019)

595 Background: CRCs arise through distinct mutations, including in APC pathway leading to tubular adenomas (TAs); in BRAF, with epigenetic silencing of CDX2, leading to serrated adenomas (SAs); and in the DNA mismatch repair machinery driving microsatellite instability (MSI). The APC pathway involves loss of the hormone guanylin, silencing the tumor suppressing receptor GUCY2C. Indeed, oral hormone replacement is an emerging strategy to reactivate GUCY2C and prevent CRC. Moreover, retained expression by tumors arising from TAs has established GUCY2C as a therapeutic target to prevent and treat metastatic CRC. Here, we defined the potential role of the guanylin-GUCY2C axis, and its suitability as a target, in tumors arising through the SA and MSI pathways. Methods: We compared guanylin-GUCY2C protein and mRNA expression between human TAs (n = 18), SAs (n = 15), MSI tumors (n = 7) and their matched normal adjacent tissue. Genetic mouse models of serrated and MSI tumors were used to confirm findings and elucidate mechanisms. Results: Guanylin hormone was eliminated in TAs, SAs and MSI tumors compared to their normal adjacent tissues. In contrast to the hormone, the tumor suppressing receptor GUCY2C was retained in TAs and MSI tumors. Surprisingly, GUCY2C expression was nearly eliminated in SAs reflecting loss of the transcription factor CDX2. Changes in the guanylin-GUCY2C axis in human SAs and MSI tumors were precisely recapitulated in genetic mouse models. Conclusions: Guanylin is universally lost at the earliest stages of transformation in tumors arising through divergent genomic mechanisms suggesting its utility as a biomarker of CRC initiation. These data reveal the possibility of guanylin loss silencing GUCY2C in the pathophysiology of, and oral hormone replacement to restore GUCY2C signaling to prevent, MSI tumors. Also, they highlight the potential for targeting GUCY2C to prevent and treat metastases arising from TAs and MSI tumors. In contrast, loss of GUCY2C excludes patients with SAs as candidates for GUCY2C-based prevention and therapy.
Abstract 14160: Correlation Between Regional Cerebral Oxygen Saturation (rSO2) and Arterial Blood Gas (ABG) During Cardiopulmonary Resuscitation
Authors: Goro Tajima, Tadahiko Shiozaki, Yoshihito Ogawa, Tomoya Hirose, Nobuto Mori, Tomohiro Ueki, Hiroo Izumino, Shuhei Yamano, Tomohito Hirao, Takamitsu Inokuma, Kazunori Yamashita, Osamu Tasaki
Journal: Circulation (2016)

Introduction: It is not fully understood yet how we assess regional cerebral oxygen saturation (rSO2) in the patients under cardiopulmonary resuscitation (CPR). We aimed to clarify the correlation ...
Prognostic Biomarkers Converge on a Germinal Centre Dark Zone Phenotype As a Determinant of Adverse Outcome in Follicular Lymphoma Patients Treated with Rituximab and Chemotherapy
Authors: Anjali Silva, Clementine Sarkozy, Tracy Lackraj, Anja Mottok, Vindi Jurinovic, Laurie H Sehn, Oliver Weigert, Christian Steidl, Robert Kridel
Journal: Blood (2018)
Association of Surgical Intervention for Adhesive Small-Bowel Obstruction With the Risk of Recurrence
Authors: Ramy Behman, Avery B. Nathens, Stephanie Mason, James P. Byrne, Nicole Look Hong, Petros Pechlivanoglou, Paul Karanicolas
Journal: JAMA Surgery (2019)

Adhesive small-bowel obstruction (aSBO) is a potentially chronic, recurring surgical illness. Although guidelines suggest trials of nonoperative management, the long-term association of this approach with recurrence is poorly understood.To compare the incidence of recurrence of aSBO in patients undergoing operative management at their first admission compared with nonoperative management.This longitudinal, propensity-matched, retrospective cohort study used health administrative data for the province of Ontario, Canada, for patients treated from April 1, 2005, through March 31, 2014. The study population included adults aged 18 to 80 years who were admitted for their first episode of aSBO. Patients with nonadhesive causes of SBO were excluded. A total of 27 904 patients were included and matched 1:1 by their propensity to undergo surgery. Factors used to calculate propensity included patient age, sex, comorbidity burden, socioeconomic status, and rurality of home residence. Data were analyzed from September 10, 2017, through October 4, 2018.Operative vs nonoperative management for aSBO.The primary outcome was the rate of recurrence of aSBO among those with operative vs nonoperative management. Time-to-event analyses were used to estimate hazard ratios of recurrence while accounting for the competing risk of death.Of 27 904 patients admitted with their first episode of aSBO, 6186 (22.2%) underwent operative management. Mean (SD) patient age was 61.2 (13.6) years, and 51.1% (14 228 of 27 904) were female. Patients undergoing operative management were younger (mean [SD] age, 60.2 [14.3] vs 61.5 [13.4] years) with fewer comorbidities (low burden, 382 [6.2%] vs 912 [4.2%]). After matching, those with operative management had a lower risk of recurrence (13.0% vs 21.3%; hazard ratio, 0.62; 95% CI, 0.56-0.68; P < .001). The 5-year probability of experiencing another recurrence increased with each episode until surgical intervention, at which point the risk of subsequent recurrence decreased by approximately 50%.According to this study, operative management of the first episode of aSBO is associated with significantly reduced risk of recurrence. Guidelines advocating trials of nonoperative management for aSBO may assume that surgery increases the risk of recurrence putatively through the formation of additional adhesions. The long-term risk of recurrence of aSBO should be considered in the management of this patient population.
Response to: ‘Risk of severe infection following rituximab and the efficacy of antimicrobial prophylaxis’ by Wallace <i>et al</i>
Authors: Andreas Kronbichler, Julia Kerschbaum
Journal: Annals of the Rheumatic Diseases (2019)

We thank Dr Wallace et al for their response to our recently published article ‘Trimethoprim–sulfamethoxazole prophylaxis prevents severe/life-threatening infections following rituximab in antineutrophil cytoplasm antibody-associated vasculitis’, highlighting some methodological limitations of our study.1 2 

One of the limitations mentioned by Wallace and colleagues is the inclusion of incident and prevalent cases and since only 15 out of 192 patients were incident cases, generalisability of our findings for this subset of patients may not be possible. We agree that the use of immunosuppression prior to initiation of rituximab likely confers a risk to develop infectious complications after rituximab administration. Cyclophosphamide was used to control disease in 62 patients the year before rituximab was initiated. Among these, 53 patients had no severe infection (median cyclophosphamide exposure 7 g, range 0.66–45 g), while 9 patients receiving cyclophosphamide the index year before had a severe infection following rituximab (median cyclophosphamide exposure 4.8 g, range 0.8–10 g). While this argues against an immediate impact of cyclophosphamide before rituximab on the risk of severe infections (53/143 with no severe infection against 9/49 with infection received …
Pulmonary Arterial Hypertension in ALK Receptor Tyrosine Kinase–Positive Lung Cancer Patient: Adverse Event or Disease Spread?
Authors: Fabrizio Tabbò, Alessandro D’Aveni, Daniele Tota, Daniele Pignataro, Paolo Bironzo, Simona Carnio, Susanna Cappia, Giancarlo Cortese, Luisella Righi, Silvia Novello
Journal: Journal of Thoracic Oncology (2019)
Abstract 19296: Clinical Accuracy of Physical Exam in Decompensated Heart Failure Patients Admitted to the Cardiac Care Unit
Authors: Nikhil Narang, Nimit J Desai, Jayant Raikhelkar, Nitasha Sarswat, Sirtaz Adatya, Gene H Kim, Gabriel T Sayer, Nir Uriel
Journal: Circulation (2017)

Background: Pulmonary artery catheter (PAC) guided therapy failed to demonstrate superiority when compared to clinical assessment in patients with decompensated heart failure (DHF). This study aims...
Diagnosis and Management of Kawasaki Disease
Authors: Tina Sosa, Laura Brower, Allison Divanovic
Journal: JAMA Pediatrics (2019)

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Re: Radiofrequency-induced Thermo-chemotherapy Effect Versus a Second Course of Bacillus Calmette-Guérin or Institutional Standard in Patients with Recurrence of Non-muscle-invasive Bladder Cancer Following Induction or Maintenance Bacillus Calmette-Guérin Therapy (HYMN): A Phase III, Open-label, Randomised Controlled Trial
Authors: Piotr Radziszewski, Sławomir Poletajew
Journal: European Urology (2019)
Characteristics and Outcomes of Patients With Metastatic KRAS-Mutant Lung Adenocarcinomas: The Lung Cancer Mutation Consortium Experience
Authors: Badi El Osta, Madhusmita Behera, Sungjin Kim, Lynne D. Berry, Gabriel Sica, Rathi N. Pillai, Taofeek K. Owonikoko, Mark G. Kris, Bruce E. Johnson, David J. Kwiatkowski, Lynette M. Sholl, Dara L. Aisner, Paul A. Bunn, Fadlo R. Khuri, Suresh S. Ramalingam
Journal: Journal of Thoracic Oncology (2019)
Sorafenib versus hepatic arterial infusion chemotherapy in patients with advanced hepatocellular carcinoma: A Japanese multi-center large cohort study.
Authors: Sadahisa Ogasawara, Kazuomi Ueshima, Masafumi Ikeda, Yutaka Yasui, Takeshi Terashima, Tatsuya Yamashita, Shuntaro Obi, Shinpei Sato, Hiroshi Aikata, Takumi Ohmura, Hidekatsu Kuroda, Takamasa Ohki, Kengo Nagashima, Masayuki Kurosaki, Kazuaki Chayama, Shuichi Kaneko, Namiki Izumi, Naoya Kato, Masatoshi Kudo, Masao Omata
Journal: Journal of Clinical Oncology (2019)

323 Background: Sorafenib, approved in Japan in 2009, is the first systemic therapy demonstrated to significantly improve overall survival (OS) in patients with advanced hepatocellular carcinoma (HCC). In Japan, hepatic arterial infusion chemotherapy (HAIC), which directly delivers high concentrations of cytotoxic agents to liver tumors, has been offered to patients with advanced HCC since before sorafenib was approved. HAIC is particularly used in patients without extrahepatic metastases (EHM). This study aimed to compare the outcomes of patients with advanced HCC who received HAIC and sorafenib. Methods: Consecutive patients with advanced HCC who received sorafenib or HAIC as the first-line systemic therapy were enrolled from 10 Japanese centers. The statistical analysis plan included pre-defined propensity score matching method and risk factors. All statistical analyses were performed by an independent biostatistician. Results: Between June 2009 and May 2016, 2006 patients were enrolled (sorafenib: 1465 patients, HAIC: 541 patients). The mean OS of patients with macrovascular invasion (MVI) and without EHM was significant longer in the HAIC group compared with the sorafenib group. After propensity score matching, there were 172 patients in each cohort. The OS was 9.1 months for the sorafenib group and 10.1 months for the HAIC group (hazard ratio [HR]: 0.668 [95% CI: 0.475–0.935], P = 0.018). There was no significant difference in OS between patients without both MVI and EHM. After propensity score matching, there were 76 patients in each cohort. The OS was 15.4 months for the sorafenib group and 12.2 months for the HAIC group (hazard ratio [HR]: 1.227 [95% CI: 0.699–2.155], P = 0.475). Conclusions: HAIC might be a potential initial treatment for patients with advanced HCC with MVI (without EHM). Currently, several new drugs appear clinically beneficial for patients with advanced HCC. Although this study only focused on sorafenib as the chemo-agent, additional studies should be conducted to confirm the benefits associated with HAIC in a limited population of patients with advanced HCC.
How cold is too cold? Establishing the minimum water temperature limits for marathon swim racing
Authors: Jane Saycell, Mitch Lomax, Heather Massey, Mike Tipton
Journal: British Journal of Sports Medicine (2019)

To provide a rationale for minimum water temperature rules for elite and subelite marathon swim racing and highlight factors that make individuals vulnerable to excessive cooling during open water swimming.12 lean competitive swimmers swam for up to 2 hours, three times in different water temperatures between 14°C and 20°C, wearing standard swimming costumes and hats. Rectal temperature (Tre), oxygen consumption, perception of cold and performance were measured.In 16°C, half the swimmers did not complete a 2-hour swim; four became (or were predicted to become) hypothermic within 2 hours. In 18°C, three-quarters completed the swim; three became (or were predicted to become) hypothermic. In 20°C, one swimmer was predicted to become hypothermic in under 2 hours. The mean linear rate of fall of Tre was greater in 16°C (-1.57°C/hour) than 18°C (-1.07°C/hour) (p=0.03). There was no change in swimming performance during the swims or between conditions. Most of the cooling rate could be explained by metabolic heat production and morphology for both 16°C (R2=0.94, p<0.01) and 18°C (R2=0.82, p<0.01) conditions. No relationship was observed between Tre and perception of thermal sensation (r=0.25, p=0.13), and there was a weak correlation between Tre and thermal comfort (r=0.32, p=0.04).We recommend that 16°C and 18°C water are too cold for elite marathon swim racing. FédérationInternationale de Natation rules were changed in 2017 to make wetsuits compulsory below 18°C and optional below 20°C.
Spaceflight-Associated Brain White Matter Microstructural Changes and Intracranial Fluid Redistribution
Authors: Jessica K. Lee, Vincent Koppelmans, Roy F. Riascos, Khader M. Hasan, Ofer Pasternak, Ajitkumar P. Mulavara, Jacob J. Bloomberg, Rachael D. Seidler
Journal: JAMA Neurology (2019)

<h3>Importance</h3> Spaceflight results in transient balance declines and brain morphologic changes; to our knowledge, the effect on brain white matter as measured by diffusion magnetic resonance imaging (dMRI), after correcting for extracellular fluid shifts, has not been examined. <h3>Objective</h3> To map spaceflight-induced intracranial extracellular free water (FW) shifts and to evaluate changes in brain white matter diffusion measures in astronauts. <h3>Design, Setting and Participants</h3> We performed retrospective, longitudinal analyses on dMRI data collected between 2010 and 2015. Of the 26 astronauts’ dMRI scans released by the National Aeronautics and Space Administration Lifetime Surveillance of Astronaut Health, 15 had both preflight and postflight dMRI scans and were included in the final analyses. Data were analyzed between 2015 and 2018. <h3>Interventions or Exposures</h3> Seven astronauts completed a space shuttle mission (≤30 days) and 8 completed a long-duration International Space Station mission (≤200 days). <h3>Main Outcomes and Measures</h3> The dMRI scans were acquired for clinical monitoring; in this retrospective analysis, we analyzed brain FW and white matter diffusion metrics corrected for FW. We also obtained scores from computerized dynamic posturography tests of balance to assess brain-behavior associations. <h3>Results</h3> Of the 15 astronauts included, the median (SD) age was 47.2 (1.5) years; 12 were men, and 3 were women. We found a significant, widespread increase in FW volume in the frontal, temporal, and occipital lobes from before spaceflight to after spaceflight. There was also a significant decrease in FW in the posterior aspect of the vertex. All FW changes were significant and ranged from approximately 2.5% to 4.0% across brain regions. We observed white matter changes in the right superior and inferior longitudinal fasciculi, the corticospinal tract, and cerebellar peduncles. All white matter changes were significant and ranged from approximately 0.75% to 1.25%. Spaceflight mission duration was associated with cerebellar white matter change, and white matter changes in the superior longitudinal fasciculus were associated with the balance changes seen in the astronauts from before spaceflight to after spaceflight. <h3>Conclusions and Relevance</h3> Free water redistribution with spaceflight likely reflects headward fluid shifts occurring in microgravity as well as an upward shift of the brain within the skull. White matter changes were of a greater magnitude than those typically seen during the same period with healthy aging. Future, prospective assessments are required to better understand the recovery time and behavioral consequences of these brain changes.
MSI-GC-01: Individual patient data (IPD) meta-analysis of microsatellite instability (MSI) and gastric cancer (GC) from four randomized clinical trials (RCTs).
Authors: Filippo Pietrantonio, Alessandra Raimondi, Yoon Young Choi, WonKi Kang, Ruth E. Langley, Young Woo Kim, Kyoung-Mee Kim, Matthew Guy Nankivell, Federica Perrone, Myeong-Cherl Kook, Ji Yeong An, Heike I. Grabsch, Federica Morano, Jae-Ho Cheong, Sung Hoon Noh, Jeeyun Lee, David Cunningham, Maria Di Bartolomeo, Giovanni Fucà, Elizabeth Catherine Smyth
Journal: Journal of Clinical Oncology (2019)

66 Background: In CLASSIC and MAGIC, MSI was a good prognostic factor, and adjuvant/perioperative chemotherapy had null/detrimental effect. Given the low prevalence of MSI in GCs and its association with other good prognostic variables, larger datasets are needed to draw more robust evidences on its specific prognostic/predictive impact. Methods: This was a multinational IPD meta-analysis of resectable GC pts enrolled in MAGIC, CLASSIC, ARTIST, ITACA-S. Data on pts’ demographics (age, sex, and race), primary site (stomach versus junctional), histotype (intestinal vs. other), T/N stage (7 th TNM), treatment received (multimodal therapy vs. surgery alone) and MSI were pooled. Univariable and multivariable associations with disease-free survival (DFS)/overall survival (OS) were assessed. The predictive role of MSI according to treatment received was assessed overall and in the 2 RCTs with a surgery alone arm (MAGIC+CLASSIC). Results: We pooled 1,552 pts with available MSI status: 121 (7,8%) were MSI, 572 Caucasian/980 Asian. In MSI versus MSS subgroups, 5-y DFS was 71.8% (95% CI: 63.8-80.7%) versus 52.3% (49.6-55.0%) (HR = 0.50, 95% CI 0.35-0.72; p &lt; 0.001); 5-y OS 77.4% (69.9-85.8%) versus 59.2% (56.6-62.0%) (HR = 0.50, 95% CI 0.34-0-74; p &lt; 0.001). In multivariable analyses, MSI was independently associated with DFS (HR = 0.48 [0.33-0.70]; p &lt; 0.001) and OS (HR = 0.48 [0.29-0.81]; p = 0.005), as T/N/race/treatment. Conclusions: In resectable primary GC, MSI is an independent good prognostic marker that should be adopted as stratification factor in future RCTs. Chemotherapy omission and/or immune checkpoint blockade should be prospectively investigated in MSI-high GCs according to the clinically-defined risk of relapse. [Table: see text]