tbuckley/cabot-search huggingface dataset:
An analysis of methodologic quality in survey research reported in the <i>Journal of Clinical Oncology</i>.
Authors: Carrie M Tamarelli, David D. Howell
Journal: Journal of Clinical Oncology (2013)

6616 Background: Survey research (SR) has been increasing as a percentage of published manuscripts in medical journals. SR plays an important role in studies of quality of life and patient preferences in treatment. Appropriate quality of methodology in SR is critical both to assure reliability and validity of survey results as well as to derive sound generalizations for larger populations from the subsets surveyed. Surveys that have deficient methodological criteria may suffer from significant flaws. A complete description and discussion of quality survey methodology, analysis, and results is essential for a thorough understanding and evaluation of published SR. Methods: Between January 2006 and December 2010, 227 articles in JCO were identified to have either “survey” or “questionnaire” in either the title or abstract. The most recent 52 consecutive articles fulfilling criteria from that time period were reviewed for reporting of survey methodology. A modification of Bennett et al.’s checklist for reporting SR was used for this analysis (Bennett C., et al. Reporting guidelines for survey research: An analysis of published guidance and reporting practices. PLoS Med 8(8): e1001069, 2011.). 35 metrics were used to analyze each survey. These metrics were grouped in the following categories: 1) title and abstract, 2) introduction, 3) methods (research tool, sample selection, survey administration and analysis), 4) results, 5) discussion, and 6) ethical quality indicators. Results: Of the 52 survey articles reviewed, the top quartile reported greater than 72% of the analyzed metrics. Half of the articles contained 63% or more of the desired metrics, and half of the articles had between 42% and 62% of the desired metrics. Some metrics were usually reported, such as ethics board review (reported in 85% of articles), but others were not consistently reported, such as calculation or justification of sample size (neither were reported in 71% of articles). Conclusions: A substantial number of articles reviewed reporting on survey research in JCO did not report critical components of survey methodology. More rigorous quality recommendations should be offered to guide authors in the report of survey research results.
DEVELOPING A BIOMARKER-BASED PREDICTIVE MODEL OF POSTOPERATIVE OUTCOMES IN CHILDREN: PRE-OPERATIVE NT-PROBNP IS INDEPENDENTLY ASSOCIATED WITH ARRHYTHMIA AND THROMBOSES AFTER CONGENITAL HEART SURGERY
Authors: Jeffrey Weiner, Andrea Lambert, David Bichell, Brett Mettler, Karla Christian, Kimberly Crum, Sarita Madell, Andrew Smith, Sara Van Driest, Thomas J. Wang, Prince J. Kannankeril
Journal: Journal of the American College of Cardiology (2020)
Annals for Hospitalists Inpatient Notes - Hospital Wards
Authors: Joel D. Howell
Journal: Annals of Internal Medicine (2020)

Web Exclusives17 March 2020Annals for Hospitalists Inpatient Notes - Hospital WardsJoel D. Howell, MD, PhDJoel D. Howell, MD, PhDUniversity of Michigan, Ann Arbor, Michigan (J.D.H.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M20-0268 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Nineteenth-century U.S. physicians who sought postgraduate training lived in the hospital, which often looked like a house, hence the term “house officer.” They saw their patients in a ward, a large room with 20 to 40 beds lined up on either side. Yet today, with the exception of specialized locations, such as intensive care units, we usually see patients in much smaller, 1- to 2-bed rooms.What happened? Why don't we have wards anymore? What difference does it make? To answer these questions, we need to consider the changing character of the U.S. hospital.Until the early 20th century, hospitals ...References1. Rosenberg CE. The Care of Strangers: The Rise of America's Hospital System. New York: Basic Books; 1987. Google Scholar2. Adams A. Medicine by Design: The Architect and the Modern Hospital, 1893-1943. Minneapolis, MN: Univ Minnesota Pr; 2008. Google Scholar3. Howell JD. Technology in the Hospital: Transforming Patient Care in the Early Twentieth Century. Baltimore: Johns Hopkins Univ Pr; 1995. Google Scholar4. Emerson C. The American hospital field. In: Aikens CA, eds. Hospital Management. Philadelphia: WB Saunders; 1911:18-9. Google Scholar5. Stevens R. In Sickness and in Wealth: American Hospitals in the Twentieth Century. New York: Basic Books; 1999. Google Scholar Author, Article, and Disclosure InformationAffiliations: University of Michigan, Ann Arbor, Michigan (J.D.H.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M20-0268.Corresponding Author: Joel D. Howell, MD, PhD, University of Michigan, North Campus Research Complex, 2800 Plymouth Road, Ann Arbor, MI 48109-2800; e-mail, [email protected]edu. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoAnnals for Hospitalists - 17 March 2020 David H. Wesorick and Vineet Chopra Metrics 17 March 2020Volume 172, Issue 6Page: HO2-HO3KeywordsHealth economicsHospital medicineInpatientsLength of stayLibrariesNursesPatientsResidencySmellSurgery ePublished: 17 March 2020 Issue Published: 17 March 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
GATA6 Expression Distinguishes Classical and Basal-like Subtypes in Advanced Pancreatic Cancer
Authors: Grainne M. O’Kane, Barbara T. Grünwald, Gun-Ho Jang, Mehdi Masoomian, Sarah Picardo, Robert C. Grant, Robert E. Denroche, Amy Zhang, Yifan Wang, Jessica K. Miller, Bernard Lam, Paul M. Krzyzanowski, Ilinca M. Lungu, John M.S. Bartlett, Melanie Peralta, Foram Vyas, Rama Khokha, James Biagi, Dianne Chadwick, Stephanie Ramotar, Shawn Hutchinson, Anna Dodd, Julie M. Wilson, Faiyaz Notta, George Zogopoulos, Steven Gallinger, Jennifer J. Knox, Sandra E. Fischer
Journal: Clinical Cancer Research (2020)

Abstract Purpose: To determine the impact of basal-like and classical subtypes in advanced pancreatic ductal adenocarcinoma (PDAC) and to explore GATA6 expression as a surrogate biomarker. Experimental Design: Within the COMPASS trial, patients proceeding to chemotherapy for advanced PDAC undergo tumor biopsy for RNA-sequencing (RNA-seq). Overall response rate (ORR) and overall survival (OS) were stratified by subtypes and according to chemotherapy received. Correlation of GATA6 with the subtypes using gene expression profiling, in situ hybridization (ISH) was explored. Results: Between December 2015 and May 2019, 195 patients (95%) had enough tissue for RNA-seq; 39 (20%) were classified as basal-like and 156 (80%) as classical. RECIST response data were available for 157 patients; 29 basal-like and 128 classical where the ORR was 10% versus 33%, respectively (P = 0.02). In patients with basal-like tumors treated with modified FOLFIRINOX (n = 22), the progression rate was 60% compared with 15% in classical PDAC (P = 0.0002). Median OS in the intention-to-treat population (n = 195) was 9.3 months for classical versus 5.9 months for basal-like PDAC (HR, 0.47; 95% confidence interval, 0.32–0.69; P = 0.0001). GATA6 expression by RNA-seq highly correlated with the classifier (P &amp;lt; 0.001) and ISH predicted the subtypes with sensitivity of 89% and specificity of 83%. In a multivariate analysis, GATA6 expression was prognostic (P = 0.02). In exploratory analyses, basal-like tumors, could be identified by keratin 5, were more hypoxic and enriched for a T-cell–inflamed gene expression signature. Conclusions: The basal-like subtype is chemoresistant and can be distinguished from classical PDAC by GATA6 expression. See related commentary by Collisson, p. 4715
TICAGRELOR VERSUS PRASUGREL IN PATIENTS WITH ACUTE CORONARY SYNDROME: AN INSIGHT FROM A NETWORK META-ANALYSIS
Authors: Mohammed Osman, Sudarshan Balla, Babikir Kheiri, Peter Farjo, Yasir Abdul Ghaffar, Amanda Jo Shigle, Kinjan Patel, Firas Zahr, Mohamad Alkhouli
Journal: Journal of the American College of Cardiology (2020)
Antiandrogen modulation of prostate-specific membrane antigen (PSMA): Dynamics and synergy with PSMA-targeted therapy.
Authors: Vincent A. DiPippo, Wells W. Magargal, Sameer M. Moorji, Jose D. Murga, William C. Olson
Journal: Journal of Clinical Oncology (2013)

e16007 Background: Recent approvals of four new prostate cancer (PCa) drugs and a growing number of pipeline agents have created opportunities for designing rational drug combinations. Potent antiandrogens such as enzalutamide and abiraterone affect expression of a host of androgen-regulated molecules, including those that represent targets for therapy. One such target is PSMA, a well-characterized cell-surface antigen abundant on prostate cancer cells. PSMA ADC is a PSMA-targeted antibody-drug conjugate currently in phase II clinical testing, comprised of a fully human IgG1 mAb conjugated to vcMMAE (valine-citrulline monomethylauristatin E). Here we examined the kinetics and reversibility of PSMA induction by potent antiandrogens and their associated effects on the preclinical activity of PSMA ADC. Methods: Androgen-dependent and -independent PCa cell lines with varying basal levels of PSMA expression were cultured for up to one month in the presence of enzalutamide or abiraterone, followed by drug washout. Cells were tested for PSMA expression over time and for susceptibility to cytotoxicity by PSMA ADC. Potential drug synergy or antagonism was evaluated using the combination index method. Results: Enzalutamide (1 mM) increased PSMA expression by approximately 2.5-fold in LNCaP (androgen-dependent) and C4-2 (androgen-independent) cells, with maximal expression observed after approximately 4 weeks’ culture. PSMA expression returned to basal levels within days following removal of enzalutamide from the culture. Enzalutamide and PSMA ADC exhibited synergistic antitumor activity in LNCaP and C4-2 cells (P &lt; 0.05). Similar results were observed for abiraterone in C4-2 cells. Less induction of PSMA expression by antiandrogens and modest effects on cytotoxicity were observed using 22Rv1 cells, an androgen-independent cell line with low basal expression of PSMA. Conclusions: Enzalutamide and abiraterone significantly and reversibly augmented PSMA expression and potentiated the activity of PSMA ADC in PCa cell lines in vitro. The findings support clinical exploration of regimens that combine potent antiandrogens and PSMA-targeted therapies.
Rationale and Design of the Aspirin Dosing—A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness (ADAPTABLE) Trial
Authors: Guillaume Marquis-Gravel, Matthew T. Roe, Holly R. Robertson, Robert A. Harrington, Michael J. Pencina, Lisa G. Berdan, Bradley G. Hammill, Madelaine Faulkner, Daniel Muñoz, Gregg C. Fonarow, Brahmajee K. Nallamothu, Dan J. Fintel, Daniel E. Ford, Li Zhou, Sarah E. Daugherty, Elizabeth Nauman, Jennifer Kraschnewski, Faraz S. Ahmad, Catherine P. Benziger, Kevin Haynes, J. Greg Merritt, Thomas Metkus, Sunil Kripalani, Kamal Gupta, Raj C. Shah, James C. McClay, Richard N. Re, Carol Geary, Brent C. Lampert, Steven M. Bradley, Sandeep K. Jain, Hani Seifein, Jeff Whittle, Véronique L. Roger, Mark B. Effron, Giselle Alvarado, Ythan H. Goldberg, Jeffrey L. VanWormer, Saket Girotra, Peter Farrehi, Kathleen M. McTigue, Russell Rothman, Adrian F. Hernandez, W. Schuyler Jones
Journal: JAMA Cardiology (2020)

<h3>Importance</h3> Determining the right dosage of aspirin for the secondary prevention treatment of atherosclerotic cardiovascular disease (ASCVD) remains an unanswered and critical question. <h3>Objective</h3> To report the rationale and design for a randomized clinical trial to determine the optimal dosage of aspirin to be used for secondary prevention of ASCVD, using an innovative research method. <h3>Design, Setting, and Participants</h3> This pragmatic, open-label, patient-centered, randomized clinical trial is being conducted in 15 000 patients within the National Patient-Centered Clinical Research Network (PCORnet), a distributed research network of partners including clinical research networks, health plan research networks, and patient-powered research networks across the United States. Patients with established ASCVD treated in routine clinical practice within the network are eligible. Patient recruitment began in April 2016. Enrollment was completed in June 2019. Final follow-up is expected to be completed by June 2020. <h3>Interventions</h3> Participants are randomized on a web platform in a 1:1 fashion to either 81 mg or 325 mg of aspirin daily. <h3>Main Outcomes and Measures</h3> The primary efficacy end point is the composite of all-cause mortality, hospitalization for nonfatal myocardial infarction, or hospitalization for a nonfatal stroke. The primary safety end point is hospitalization for major bleeding associated with a blood-product transfusion. End points are captured through regular queries of the health systems’ common data model within the structure of PCORnet’s distributed data environment. <h3>Conclusions and Relevance</h3> As a pragmatic study and the first interventional trial conducted within the PCORnet electronic data infrastructure, this trial is testing several unique and innovative operational approaches that have the potential to disrupt and transform the conduct of future patient-centered randomized clinical trials by evaluating treatments integrated in clinical practice while at the same time determining the optimal dosage of aspirin for secondary prevention of ASCVD. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT02697916
Comparing the efficacies of neoadjuvant non-cisplatin-based and cisplatin-based chemotherapies in obtaining pathologic complete remissions in muscle-invasive bladder cancer.
Authors: Praveen Sivakumaran, Vishal Navnitray Ranpura, David John Perry
Journal: Journal of Clinical Oncology (2013)

e15577 Background: Muscle-invasive bladder cancer (MIBC) is an aggressive disease and cisplatin-based neoadjvuant chemotherapy is standard therapy. Because of renal insufficiency, many patients are unfit to receive cisplatin and, instead receive carboplatin-based chemotherapy. The efficacy of carboplatin-based chemotherapy has not been studied in this setting. We performed a study comparing the efficacies of neoadjuvant carboplatin-containing and cisplatin-containing chemotherapies in achieving pathologic complete responses (pCR) in MIBC. Overall survival (OS) was also calculated. Methods: Medical records for all patients who underwent cystectomy at MedStar Washington Hospital Center between January 1, 2002 and December 31, 2011 were reviewed to determine which neoadjuvant chemotherapy was given and whether a pCR was reached at the time of cystectomy. OS was also calculated. Results: 232 patients qualified for study. 13 received neoadjuvant cisplatin-based treatment (Group 1) and 12 received neoadjuvant carboplatin-based treatment (Group 2). pCR rates were 53.8% and 41.7% in Groups 1 and 2, respectively. 5-year OS for Groups 1 and 2 were 69% and 75%, respectively. Conclusions: Given the limitations of this small retrospective analysis, carboplatin-based neoadjuvant chemotherapy prior to cystectomy for MIBC appears to be comparable in efficacy to cisplatin-based neoadjuvant chemotherapy.
Abstract 17930: Association Between Changes in the Intrathoracic Impedance as Measured by the Optivol Fluid Index in Patients With Heart Failure and Episodes of Ventricular Arrhythmias
Authors: Mohammed Osman, Azza Ahmed, Hussam Alzubi, Mustafa Hassan, Ghassan Bachuwa, Carlos F Rios-Bedoya
Journal: Circulation (2017)

Introduction: Ventricular arrhythmias are independently related to the mortality risk in patients with heart failure. The wide availability of implantable cardioverter defibrillators (ICD) and Card...
A STITCH IN TIME SAVES NINE: PROMPT SURGICAL REPAIR OF AORTIC ROOT RUPTURE DURING TRANS-CATHETER AORTIC VALVE REPLACEMENT
Authors: Tanushree Agrawal, Apurva Patel, Isaac Tea, Marvin Atkins, Nadeen Nader Faza, Neal S. Kleiman, Stephen Henry Little
Journal: Journal of the American College of Cardiology (2020)
AN OVERLOOKED CAUSE OF MYOCARDIAL INFARCTION WITH NORMAL CORONARY ARTERIES PRESENTING AS SUDDEN CARDIAC DEATH AND STRESS CARDIOMYOPATHY IN YOUNG FEMALES
Authors: Krishna Patel, Femina S. Patel, Annapoorna Singh, David Skolnick, Arthur McGhie, Ibrahim Saeed, Anna Grodzinsky, John Saxon
Journal: Journal of the American College of Cardiology (2020)
Intestinal HIF-2 to protect against radiation-induced gastrointestinal syndrome.
Authors: Cullen M Taniguchi, Colleen Wu, Todd Atwood, Peter Maxim, Amato Giaccia
Journal: Journal of Clinical Oncology (2012)

10629 Background: Gastrointestinal (GI) toxicity accounts for significant morbidity during systemic chemotherapy or abdominopelvic radiation therapy. Unfortunately, there are no effective preventative treatments. Hypoxic signaling through hypoxia-inducible factor-1 (HIF-1) and -2 (HIF-2) is critical for intestinal homeostasis during inflammatory challenges and was posited to play a role in radioprotection. Methods: We stabilized both HIF-1 and HIF-2 pharmacologically with the prolyl hydroxylase inhibitor DMOG and with transgenic mice. Male C57/Bl6 mice eight weeks of age were pretreated with saline or 8mg DMOG 16hrs and 4hrs prior to being irradiated with a single fraction of 20Gy to the abdomen using a modified TLI jig that shields the upper body of the mouse to reduce hematopoietic toxicity. After XRT, the mice got daily doses of saline or DMOG for 5 days. Results: Mice treated with DMOG had a 1.5-fold enrichment of crypt regeneration in the colon as determined by microcolony assay (13.3±3.4 vs 21.2±1.7 crypts/section, saline vs DMOG, n=10/group, p=0.005). Death from GI radiotoxicity can result from compromised epithelial integrity. We tested epithelial and barrier function by gavaging irradiated mice with FITC-dextran, which undetectable in the blood unless the GI epithelia is compromised. Treatment with DMOG decreased FITC-dextran uptake by 4-fold over controls (52.6±14.7 vs 12.4±3.4 mcg/ml, n=6/group, p=0.02). These physiologic improvements translated to improved overall survival with DMOG treatment after being exposed to 20Gy of abdominal radiation (p=0.03). To determine if the radioprotective effect of DMOG was specific to HIF-1 or HIF-2, we overexpressed stabilized HIF1 or HIF2 in the intestinal epithelia using a lox-stop-lox (LSL) system and Villin-Cre. The overexpression of HIF1 had no effect on survival (p=0.22), while mice with intestinal-specific HIF2-overexpression had significantly improved survival after receiving 20Gy of abdominal radiation (p=0.001). Conclusions: Activation of HIF-2 is sufficient to protect mice from lethal doses of abdominal radiation may provide a novel class of treatments to protect the GI epithelium from the deleterious side effects of chemotherapy and radiation.
Sphincter preserving surgery after preoperative treatment for ultra-low rectal carcinoma. A French multicenter prospective trial: GRECCAR 1
Authors: P. Rouanet, M. Rivoire, B. Lelong, E. Rullier, F. Dravet, L. Mineur, L. Vanseymortier, M. Pocard, J. Faucheron, S. Gourgou, B. Saint Aubert
Journal: Journal of Clinical Oncology (2006)

3527 Background: GRECCAR 1 is a phase III randomised multicenter trial which compared two preoperative treatments for low rectal carcinoma which should be classicaly treated by abdominoperineal resection (Eligibility: distance between the tumor [T] and the levator ani [LA] less than 2 cm). Methods: Between 2001 and 2005, 207 patients with rectal adenocarcinomas were included in 13 French centers. The average distance between the tumor and the levator ani was 0.8 cm. 72% of the tumors were classified T3 with 60% of N1 on pre treatment endorectal ultrasonography. The mean lenght of the tumors was 5 cm on colonoscopy. Preoperative treatment randomisation was made between high dose radiation (HDR: 45 + 18 Gy: 106 patients) and radio-chemotherapy (RTCT: 45 Gy + 5FU continuous infusion: 101 patients). All surgeons performed homogeous technique for intersphincteric resection. Results: Conservative rate was 83% (HDR) and 86% (RTCT) (p: 0.64) with 84% (140/168) of intersphincteric resection. Conservative rate did not differ according to the distance T-LA: 0 cm: 84% / 1–2 cm: 84% and 3 cm: 91%. No post operative mortality was noticed with a 15% post operative morbidity rate, same in the two arms. Sterilized specimen rate was respectively 7% and 12.5% (p: 0.29), the mean inferior safety margin and radial margin was 1 cm and 4 mm, same in the two groups as the 90% R0 resection rate. On specimen, nodal involvement rate was 5.6% for pT0–1, 29% for pT2 and 56% for pT3–4. No difference was seen for down-staging between the two groups (p: 0.59). With a 22 months follow up, we noticed 92% rate of stoma closure in the conservative group. Seven patients had a local recurrence and 25 metastases with 12 patient’s death. Conclusions: GRECCAR 1 is the first prospective randomized trial which shows an 85% rate of sphincter conservative surgery due to down staging induced by preoperative tretament. No significant difference was seen between HDR and RTCT with a trend for more morbidity in the first group. Intersphincteric resection is a safe technical procedure in order to preserv the striated sphincter with sufficient lateral and inferior margins. No significant financial relationships to disclose.
Mutations in the RNA Splicing Factor SF3B1 Promote Tumorigenesis through MYC Stabilization
Authors: Zhaoqi Liu, Akihide Yoshimi, Jiguang Wang, Hana Cho, Stanley Chun-Wei Lee, Michelle Ki, Lillian Bitner, Timothy Chu, Harshal Shah, Bo Liu, Anthony R. Mato, Peter Ruvolo, Giulia Fabbri, Laura Pasqualucci, Omar Abdel-Wahab, Raul Rabadan
Journal: Cancer Discovery (2020)

Abstract Although mutations in the gene encoding the RNA splicing factor SF3B1 are frequent in multiple cancers, their functional effects and therapeutic dependencies are poorly understood. Here, we characterize 98 tumors and 12 isogenic cell lines harboring SF3B1 hotspot mutations, identifying hundreds of cryptic 3′ splice sites common and specific to different cancer types. Regulatory network analysis revealed that the most common SF3B1 mutation activates MYC via effects conserved across human and mouse cells. SF3B1 mutations promote decay of transcripts encoding the protein phosphatase 2A (PP2A) subunit PPP2R5A, increasing MYC S62 and BCL2 S70 phosphorylation which, in turn, promotes MYC protein stability and impair apoptosis, respectively. Genetic PPP2R5A restoration or pharmacologic PP2A activation impaired SF3B1-mutant tumorigenesis, elucidating a therapeutic approach to aberrant splicing by mutant SF3B1. Significance: Here, we identify that mutations in SF3B1, the most commonly mutated splicing factor gene across cancers, alter splicing of a specific subunit of the PP2A serine/threonine phosphatase complex to confer post-translational MYC and BCL2 activation, which is therapeutically intervenable using an FDA-approved drug. See related commentary by O'Connor and Narla, p. 765. This article is highlighted in the In This Issue feature, p. 747
Abstract 17552: Beat to Beat Control of Sinus Rate by Sympathetic Nerve Activity in Normal Anesthetized Dogs
Authors: Yufan Yang, Yuan Yuan, Peng-Sheng Chen, Thomas H Everett
Journal: Circulation (2017)

Introduction: The coupling between local nerve activity and electrical activation at the sinoatrial node (SAN) remains unclear. Hypothesis: We hypothesized that there is beat-to-beat coupling betwe...