tbuckley/cabot-search huggingface dataset:
Serum REG4 protein in pancreatic cancer as a tumor marker: A prospective study
Authors: A. Sawaki, R. Takayama, N. Mizuno, M. Tajika, N. Hoki, Z. E. Sayed, K. Matsuo, H. Nakagawa, Y. Nakamura, K. Yamao
Journal: Journal of Clinical Oncology (2007)

15063 Background: Pancreatic cancer (PC) shows the worst mortality rate in common malignancies, with 5-year survival rate of 4%. The only way to cure the disease is surgical resection of early stage PC. Establishment of a screening strategy to detect early stage PC is eagerly expected. REG4, a member of the regenerating islet-derived (REG) family, are secreted proteins that play a role in tissue regeneration and inflammation in digestive organs. We reported overexpression of REG4 in PC cells and serum, and preliminary data of the serum REG4 level of pancreatic disease patients including PC patients. We conducted a prospective study to evaluate the role of serum REG4 in PC. Methods: The series included 57 patients diagnosed pathologically as PC between November 2004 and December 2005. Serum REG4 was quantified by standard sandwich ELISA (Enzyme Linked Immunosorbent Assay) using original kit (MBL116: provided by Medical and Biological Laboratories Co., LTD, Japan) before treatment. The upper limit of the test was set at 3.52ng/ml and was based on studies of serum from 48 healthy control subjects. Results: With a specificity of 100%, the diagnostic sensitivity and accuracy were 63.2% and 80.0%, respectively. The ROC (receiver operating characteristic) analysis showed that area under the curve was 0.91. REG4 levels were a significant differences between PC and control (p&lt;0.001), between each T stage and control (T1,T2, T3 or T4 v control), and between each TMN stage and control (stage 1, stage 2, stage 3 or stage 4 v control), but were not a statistical significance with T stage (T1 v T2 v T3 v T4), M stage (M0 v M1) or TNM stage (stage 1 v stage 2 v stage 3 v stage 4) in PC patients. The diagnostic sensitivity of carcinoembryonic antigen (CEA&gt;5.0ng/ml) and carbohydrate antigen19–9 (CA19–9&gt;50U/ml) was 56.5% and 68.4%, respectively. No significant correlation was demonstrated between REG4 and CA19–9 (coefficient of correlation [rs]=0.45). Conclusions: This study shows the potential of serum REG4 as a screening test for PC, especially for early PC. REG4 is considered to be a more useful marker in combination with CA19- 9. No significant financial relationships to disclose.
The long-acting C5 inhibitor, Ravulizumab, is effective and safe in adult patients with atypical hemolytic uremic syndrome naïve to complement inhibitor treatment
Authors: Eric Rondeau, Marie Scully, Gema Ariceta, Tom Barbour, Spero Cataland, Nils Heyne, Yoshitaka Miyakawa, Stephan Ortiz, Eugene Swenson, Marc Vallee, Sung-Soo Yoon, David Kavanagh, Hermann Haller, Sunil Babu, Nilufer Broeders, Nicole Lietar, Fiona Brown, Philip Campbell, Paramit Chowdhury, Theo Kasimatis, Lino Cirami, Leonardo Caroti, Guilia Antognoli, Yahsou Delmas, Vladimir Dobronravov, Anja Gaeckler, Cyril Garrouste, Gregory Greenwood, Siân Griffin, Chiu-Ching Huang, I-Ru Chen, Susan Huang, Jin Seok Kim, Gaetano La Manna, Giorgia Comai, Maria Cappuccilli, Moglie Le Quintrec, Guillaume Jeantet, Iino Fumie, Yosu Luque, Jan Menne, Johan Morelle, Eric Goffin, Anja Muhlfeld, Shashi Nagaraj, Gowthami Arepally, Doyeun Oh, Masayoshi Okumi, Manuel Praga Terente, Elena Gutierréz, Paola Rodriguez, Francois Provot, Ulf Schönermarck, Michael Fischereder, Natalia Ramos Terrada, Barbara Seitz-Polski, Guillaume Favre, Sonia Boyer-Suavet, Maria Vinogradova, Tatiana Kirsanova, Edwin K.S. Wong
Journal: Kidney International (2020)

Ravulizumab is a long-acting C5 inhibitor engineered from eculizumab with increased elimination half-life, allowing an extended dosing interval from two to eight weeks. Here we evaluate the efficacy and safety of ravulizumab in adults with atypical hemolytic uremic syndrome presenting with thrombotic microangiopathy. In this global, phase 3, single arm study in complement inhibitor-naïve adults (18 years and older) who fulfilled diagnostic criteria for atypical hemolytic uremic syndrome, enrolled patients received ravulizumab through a 26-week initial evaluation period. The primary endpoint was complete thrombotic microangiopathy response defined as normalization of platelet count and lactate dehydrogenase and 25% or more improvement in serum creatinine. Secondary endpoints included changes in hematologic variables and renal function. Safety was also evaluated. Ravulizumab treatment resulted in an immediate, complete, and sustained C5 inhibition in all patients. Complete thrombotic microangiopathy response was achieved in 53.6% of patients. Normalization of platelet count, lactate dehydrogenase and 25% or more improvement in serum creatinine was achieved in 83.9%, 76.8% and 58.9% of patients, respectively. Improvement in estimated glomerular filtration rate by one or more stage was achieved in 68.1% of patients by day 183. No unexpected adverse events were reported across a safety analysis set of 58 patients. Four deaths occurred (three within one month of study initiation, including one in a patient excluded based on eligibility criteria after the first dose) with none considered treatment-related by the study investigator. Thus, treatment with ravulizumab once every eight weeks resulted in rapidly improved hematologic and renal endpoints with no unexpected adverse events in adults with atypical hemolytic uremic syndrome.
A phase I study of bortezomib in combination with 5FU/LV plus oxaliplatin in patients (pts) with advanced colorectal cancer (CRC): EORTC 16029
Authors: D. A. Lacombe, F. Caponigro, A. Anthoney, J. Bauer, A. Govaerts, A. Milano, S. Marréaud, C. Twelves
Journal: Journal of Clinical Oncology (2007)

4090 Background: Bortezomib is a potent and reversible inhibitor of the ubiquitin-mediated proteasome pathway, whose inhibition results in the stabilization of p53, p21 Cip1 , p27 Kip1 , Bax, in cell-cycle dysregulation and, finally, apoptosis. A phase I study of the combination of 5FU/LV and bortezomib has shown a significant stable disease rate in advanced CRC (Iqbal, ASCO 2004). Methods: In this phase I study bortezomib was given as an IV push over 3 to 5 seconds on days 1, 8 and 15 in combination with standard FOLFOX-4 every 28 days in chemo-naïve pts with advanced CRC. Bortezomib starting dose level was 1.3 mg/m 2 . A 3+3 study design was utilized at predefined dose levels (DL). Dose-limiting-toxicity (DLT) was assessed during cycle 1. Exploratory pharmacogenetics research was conducted. Results: 15 pts were treated and 46 cycles given. At DL2 (1.6 mg/m 2 ), 2/4 pts experienced a DLT: G3 febrile neutropenia causing treatment delay and bortezomib dose reduction in 1pt and one bortezomib dose skipped due to persistent G2 peripheral neuropathy and myalgia in 1pt. At DL1 (1.3 mg/m 2 ), 2/6 pts had a DLT. Both pts experienced a G3 neutropenia on day 15, which prevented treatment from being given as scheduled. DL-1 (1 mg/m 2 ) was therefore investigated and no DLT was observed among 5 pts. The most frequently reported toxicities in cycle 1 were γGT (64%), nausea, fatigue and sensory neuropathy (53%), pain (33%), diarrhea and fever (27%), vomiting (20%), anorexia, dyspnea and mucositis (13%) and neutropenia 29% (G2,3). 12 pts are currently evaluable for response; 6 had a partial response, 3 stable disease and 3 disease progression. Conclusion: The toxicity profile of this combination is predictable and early evidence of clinical activity has been observed. The recommended bortezomib dose for further investigation within this regimen is 1 mg/m 2 . No significant financial relationships to disclose.
Secondary causes of cancer-related anorexia: Recognition in daily practice by a novel checklist, a pilot study
Authors: A. G. Omlin, F. Strasser
Journal: Journal of Clinical Oncology (2007)

9058 Background: Secondary - potentially reversible - causes of cancer-related anorexia, a common and devastating complication of advanced cancer, remain poorly recognised in daily practice. To explore the frequency of SecAn and evaluate the practice- guiding-potential (PGP) of a novel clinical assessment checklist (CL-SecAn). Methods: The 11 item CL-SecAn is based on literature review and multiprofessional clinical expert opinions. Patients rate the answers to the questions “I feel anorectic because of [i.e. stomatitis]” by an 1–4 categorical scale (no, little, moderate, a lot). Consecutive patients of an interdisciplinary palliative-oncological outpatient “nutrition &amp; fatigue” clinic (NF-clinic) and of a multicenter cross-sectional advanced cancer pain study completed the CL-SecAn. Charts of the NF-clinic were retrospectively reviewed for onset or change of therapeutic interventions (Tx-SecAn) focused on identified causes of SecAn. Patients with (rating 3 or 4) or without (1 or 2) one of the 11 SecAn causes were compared to estimate PGP. In addition, matched (age, sex, tumor, cachexia) “regular” out-patients are compared to NF-clinic patients for Tx-SecAn. Results: SecAn was present (defined as =3/4) in 63 of 113 (56%) patients (53 NF-clinic, 60 study; f:m 45:68; age 64 [median, range 25, 88]; 30% gastrointestinal, 20% lung, 13% prostate, 10% urogenital, and 17% other cancer, 10% lymphoma). SecAn causes were: stomatitis 4%, dysgeusia 19%, dysphagia 8%, epigastric pain 9%, abdominal pain 14%, constipation19%, diarrhea 5%, defecation after a meal 2%, pain 12%, dyspnoea 3% and fatigue 13%. In 36 (32%) patients more than one cause was present. Tx-SecAn for dysgeusia was applied in 7 of 15 patients (46%) with and 3 of 38 (8%) without Sec-An Dysgeusia. For constipation, Tx-SecAn was modified in 70% with and 27% without Sec-An constipation. The other 9 Sec-An were analysed accordingly. The case-control study is currently ongoing. Conclusions: SecAn causes seem to be common in advanced cancer patients. The CL-SecAn carries a Practice-Guiding-Potential, at least for some of the 11 SecAn causes, its potential might be underrecognized in frequently treated syndromes, such as constipation. Future research will investigate further the impact of CL-SecAn. No significant financial relationships to disclose.
Endoscopic ultrasonography-guided deployment of embolization coils and cyanoacrylate injection in gastric varices versus coiling alone: a randomized trial
Authors: Carlos Robles-Medranda, Roberto Oleas, Manuel Valero, Miguel Puga-Tejada, Jorge Baquerizo-Burgos, Jesenia Ospina, Hannah Pitanga-Lukashok
Journal: Endoscopy (2020)

Abstract Background Gastric variceal bleeding is a life-threating condition with challenging management. We aimed to compare the efficacy and safety of endoscopic ultrasonography (EUS)-guided coil embolization and cyanoacrylate injection versus EUS-guided coil embolization alone in the management of gastric varices. Methods A single-center, parallel-randomized controlled trial involving 60 participants with gastric varices (GOV II and IGV I) who were randomly allocated to EUS-guided coil embolization and cyanoacrylate injection (n = 30) or EUS-guided coil embolization alone (n = 30). The primary end points were the technical and clinical success rates of both procedures. The secondary end points were the reappearance of gastric varices during follow-up, along with rebleeding, the need for reintervention, and complication and survival rates. Results The technical success rate was 100 % in both groups. Immediate disappearance of varices was observed in 86.7 % of patients treated with coils and cyanoacrylate, versus 13.3 % of patients treated with coils alone (P &lt; 0.001). Median survival time was 16.4 months with coils and cyanoacrylate versus 14.2 months with coils alone (P = 0.90). Rebleeding occurred in 3.3 % of patients treated with combined treatment and 20 % of those treated with coils alone (P = 0.04). With combined treatment, 83.3 % of patients were free from reintervention versus 60 % with coils alone (hazard ratio 0.27; 95 % confidence interval 0.095 – 0.797; P = 0.01). Conclusions EUS-guided coil embolization with cyanoacrylate injection achieved excellent clinical success, with lower rates of rebleeding and reintervention than coil treatment alone. Multicenter studies are required to define the most appropriate technique for gastric variceal obliteration.
Change in Reporting of USMLE Step 1 Scores and Potential Implications for International Medical Graduates
Authors: Aakash Desai, Aparna Hegde, Devika Das
Journal: JAMA (2020)

This Viewpoint reviews the roles international medical graduates (IMGs) play in US health care systems and discusses the potential challenges that the announced 2022 change in USMLE Step 1 examination scoring from a 3-digit score to a pass/fail designation will pose for this workforce segment.
Abstract MP08: Targeted Healthy Food Incentives Influence Grocery Purchase Quality and Purchase of Targeted Foods: Results From the Randomized Controlled Crossover Smart Cart Study
Authors: Maya K Vadiveloo, Haley W Parker, Xintong Guan, Stephen Atlas, Elie Perraud, Ashley Buchanan, Anne N Thorndike
Journal: Circulation (2020)

Introduction: Incentives can increase healthy food purchases, but less is known about whether they improve dietary quality. The Smart Cart Study evaluated whether healthful food incentives based on customer preferences and purchase history increased grocery purchase quality and the proportion of spending on targeted foods. Hypothesis: Targeted incentives will increase grocery purchase quality as measured by the Grocery Purchase Quality Index- 2016 (GPQI) and percent spending on targeted healthful foods. Methods: Adults (n=224) who shopped at an independent supermarket for ≥50% of their groceries, participated in the store’s loyalty program, and completed study questionnaires were enrolled in summer 2018. All participants received a 5% loyalty card discount. The intervention group received targeted weekly coupons (~$10 value) with brief education to improve purchase quality for 13-weeks. A computerized study algorithm allocated targeted healthy food coupons to participants’ loyalty cards by using purchase history, dietary preferences, and diet quality. The control group received weekly brief education and occasional generic coupons. After a brief washout, the groups crossed over. GPQI-16 scores (range 0-75) were calculated from cumulative food purchasing data by comparing actual to recommended spending within 11 food groups, with higher scores reflecting higher purchase quality; % spending on targeted vs. all foods was also compared. Paired t-tests examined differences between groups. Results: Participants with extreme spending (i.e. top/bottom 1%) were excluded, leaving an analytic sample of 207 mostly white adults (95%), with mean age of 56 and 50% with household incomes ≥100K. The Table shows changes in GPQI-16 scores and % spending in the first 13-week intervention period, followed by the cross-over intervention period. Conclusions: Results from this pilot trial suggest that targeted healthy supermarket incentives are feasible and are promising tools to help improve diet quality and health.
Abstract P379: Features to Increase Primary Care Provider Referrals to Intensive Behavioral Counseling for Cardiovascular Disease Prevention
Authors: John D Omura, Kathleen B Watson, Fleetwood V Loustalot, Janet E Fulton, Susan A Carlson
Journal: Circulation (2020)

Background: The US Preventive Services Task Force recommends adults with certain cardiovascular disease (CVD) risk factors be offered or referred to intensive behavioral counseling to promote a healthful diet and physical activity for CVD prevention. However, only 1 in 12 primary care providers (PCPs) currently follow this recommendation. This study assessed system and programmatic features PCPs reported would increase their likelihood of referring patients at risk for CVD to intensive behavioral counseling and whether this varied by the percentage of at-risk patients with whom they discuss physical activity. Methods: DocStyles 2018, a web-based panel survey of PCPs, assessed the percentage of at-risk patients with whom PCPs discuss physical activity and the degree to which select features would increase their likelihood of referring to intensive behavioral counseling. Results: Overall, 60.8% of PCPs discussed physical activity with most of their at-risk patients; 21.8% did so with many and 17.4% with few or some. The proportion of PCPs identifying features as increasing their likelihood of referring to intensive behavioral counseling by a great extent ranged from 24.1% for an automated referral in electronic health records, 35.3% for patient progress reports, 41.5% for the program being accredited or evidence-based, to 67.2% for the program having no cost to the patient (Table). These proportions increased for each feature as the percentage of at-risk patients with whom they discuss physical activity increased. Conclusion: PCPs identified programmatic features (i.e. being accredited and of no cost) as having the greatest influence on their likelihood of referring patients at risk for CVD to intensive behavioral counseling, although this varied by the percentage of at-risk patients with whom they discuss physical activity. Findings suggest that the effectiveness of strategies to improve behavioral counseling referrals by PCPs may depend on their current physical activity counseling practices.
Randomized prospective phase II trial of two schedules of sorafenib daily and interferon-α2a (IFN) in metastatic renal cell carcinoma (RAPSODY): GOIRC Study 0681
Authors: S. Bracarda, C. Porta, C. Boni, A. Santoro, F. Artioli, C. Di Bartolomeo, A. Contu, D. Gasparro, V. De Angelis, C. Caserta
Journal: Journal of Clinical Oncology (2007)

5100 Background: Sorafenib is an oral multi-kinase inhibitor with a demonstrated efficacy in MRCC (Eisen, ASCO 2006). IFN is a pleiotropic molecule with an antiangiogenic activity probably dose and schedule-dependent (Folkman, 1992). Aim of this study was to evaluate the activity and safety of sorafenib combined with IFN in two different schedules. Methods: Eligible patients had metastatic renal cell carcinoma (MRCC) with a clear cell component = 50%, previous nephrectomy, ECOG Performance Status 0–2, no cerebral metastases or previous treatment, measurable disease; any Motzer’s score was allowed. Patients received oral sorafenib 400mg BID continuously plus sc IFN, 9 MU three times a week (arm-A) or 3 MU five times a week (arm-B), started 7 days after sorafenib to increase compliance. Planned sample size of this single-stage study was 100 cases to be enrolled over 18 months. Primary end points: Progression Free Survival (PFS) in the two arms and safety; secondary end-points: overall response (intention-to treat analysis) and overall survival. Results: Between January 2006 and January 2007 all the expected cases were enrolled into the study (median age 63 years, range 34–82; male/female: 71/29). Of 63 patients for whom a post baseline assessment was available (31 in arm A and 32 in arm B), 16 achieved a partial response (25.4%: 29% in arm A, 95% CI 13.2–44.9 and 22% in arm B, 95% CI 7.6–36.2), 26 had a stable disease (41.3%: 29% in arm A and 53% in arm B) and 21 progressed (33.3%: 42% in arm A and 25% in arm B). Due to the short follow-up period PFS data are not yet available. The most common grade 3/4 toxicities affecting more than 5% of the pts were equally distributed between arms except for fatigue and skin rash (respectively 19% and 8%, only arm A): hypophosphatemia (43%), hand-foot syndrome (22%), anorexia, stomatitis, hyperamylasemia (11% each), diarrhea (8%) and hyperlipasemia (5%). Conclusions: With an overall response rate of 25.4% and a tumor control rate (partial response + stable disease) of 66.7% (58.1% in arm A, 95% CI 40.7–75.5 and 75.0% in arm B, 95% CI 60.0–90.0; p = ns) sorafenib plus IFN can be considered a promising regimen in MRCC. Further investigations of the active and safe low-dose IFN combination arm are warranted. [Table: see text]
Abstract 31: Higher Levels of Light Intensity Physical Activity and Lower Sedentary Time are Associated With a Lower Risk of All-cause Mortality in Older Adults: The Framingham Heart Study
Authors: Joowon Lee, Nicole L Spartano, Ramachandran S Vasan, Vanessa Xanthakis
Journal: Circulation (2020)

Introduction: Habitual physical activity (PA) and less sedentary behavior have been associated with a lower risk of mortality in middle-aged adults. However, little is known about the associations of objectively-assessed PA of varying levels and sedentary time with mortality in community-dwelling older adults. Hypothesis: We hypothesized that higher overall PA and less sedentary time will be associated with a lower risk of all-cause mortality in older adults. Methods: We evaluated 1,262 Framingham Offspring Study participants (mean age 69 yrs, 54% women) with accelerometry-derived PA data (wear time ≥10 hours/day for at least 4 days using an Actical device) at their ninth examination (2011-2014). Multivariable Cox proportional hazards regression models were used to relate PA and sedentary time (separate model for each) with all-cause mortality adjusting for potential confounders. In sensitivity analysis to mitigate the potential impact of frailty on the associations evaluated, we excluded those with frailty at baseline. Results: Overall, 67 participants died during a median follow-up of 4.8 years (25 th -75 th percentiles: 4.3 - 5.3 [years]). Higher total PA, light intensity PA (LIPA), adherence to PA guidelines, and lower sedentary time were associated with a lower risk of all-cause mortality ( Table ). The results remained statistically significant even after excluding those with frailty. Higher LIPA and lower sedentary time were associated with a lower risk of all-cause mortality regardless of MVPA in both models including all participants and excluding those with frailty. Conclusions: In our investigation of a moderate-size sample of community-dwelling older adults, we confirmed that being physically active substantially lowered mortality risk. Additionally, our findings suggest that reducing sedentary time and increasing LIPA (regardless of MVPA) may be sufficient to reduce mortality risk in older adults. Additional studies of larger multi-ethnic samples of older adults are warranted to confirm our findings.