tbuckley/cabot-search huggingface dataset:
Fast time estimation to predict levels of anxiety in cancer patients.
Authors: Ivan Tonev, Nikolay Vladimirov Conev, Spartak Stoyanov Valev, Teodorika Panayotova, Teodora Karanikolova, Ivan Donev
Journal: Journal of Clinical Oncology (2019)

e23162 Background: Our study explored the potential relationship between the time estimation and the level of anxiety in cancer patients prior to starting chemotherapy. Methods: Time estimation was assessed in 90 chemonaïve patients with solid tumors by evaluating each subject’s prospective estimation of how fast one minute passed compared to the actual time. The median value (37 sec) of time estimation was used to stratify the patients into two categories of fast and slow time estimation. We used generalized anxiety disorder (GAD-7) as a screening tool for detecting levels of anxiety. Scores ≥10 we considered as clinically significant. Results: Patients with clinically significant levels of anxiety were 23 (25.5%). The pattern of the time estimation distributions significantly changed according to the reported levels of GAD-7 scales. Scores ≥10 correlated with fast time estimation and gender. Patients who scores ≥10 estimated time significantly faster than the rest (27.3±9.2 vs 43.4±17.3; p &lt; 0.001). ROC analysis revealed that at the optimal cutoff value of time estimation, clinically significant levels of anxiety can be discriminated with an AUC = 0.78 (95% CI: 0.68-0.87, p &lt; 0.001) and with a sensitivity of 78.3% and a specificity of 65.2%. Moreover, in a multivariate logistic regression model, fast time estimation was an independent predictor of clinically significant levels of anxiety (OR 7.07; 95% CI 2.2-22.8; p = 0.001). Conclusions: Time estimation is a novel potent indicator for moderate and severe levels of anxiety in cancer patients. This test is an easily performed, time-saving and nonintrusive ultrashort screening tool for clinically significant levels of anxiety.
Radiolabeled Oligonucleotides Targeting the RNA Subunit of Telomerase Inhibit Telomerase and Induce DNA Damage in Telomerase-Positive Cancer Cells
Authors: Mark R. Jackson, Bas M. Bavelaar, Philip A. Waghorn, Martin R. Gill, Afaf H. El-Sagheer, Tom Brown, Madalena Tarsounas, Katherine A. Vallis
Journal: Cancer Research (2019)

Telomerase is expressed in the majority (>85%) of tumors, but has restricted expression in normal tissues. Long-term telomerase inhibition in malignant cells results in progressive telomere shortening and reduction in cell proliferation. Here we report the synthesis and characterization of radiolabeled oligonucleotides that target the RNA subunit of telomerase, hTR, simultaneously inhibiting enzymatic activity and delivering radiation intracellularly. Oligonucleotides complementary (Match) and noncomplementary (Scramble or Mismatch) to hTR were conjugated to diethylenetriaminepentaacetic dianhydride (DTPA), allowing radiolabeling with the Auger electron-emitting radionuclide indium-111 (
Assessing community physician ability to identify and manage immune-mediated adverse events (imAEs) through online continuing medical education (CME).
Authors: Lori Keys Pender, Richard Caracio
Journal: Journal of Clinical Oncology (2019)

78 Background: Immune checkpoint inhibitors (ICIs) produce a wide variety of imAEs that differ dramatically from chemotherapy adverse events. This study assessed whether online CME activities improve the knowledge, competence, and confidence of community physicians across disciplines in guideline management of imAEs in patients receiving ICI therapy. Methods: Data from a series of online, CME-certified, educational activities consisting of case-based video discussion between expert faculty were analyzed to determine the efficacy of education among oncologists and other specialists regarding imAE recognition, management, and referral. Three multiple-choice knowledge/competence questions and 1 confidence question were presented to learners before and immediately after each activity. A pre-/post-assessment study design was used. Chi-square tests assessed educational effect for each activity. The activities launched online in March 2018. Data were collected through July 15, 2018. Results: Over 18,000 community physicians completed the assessment questions and were included in the study. Results are summarized by discipline in the table. Conclusions: This study demonstrates the success of online, case-based video discussions on improving knowledge, competence, and confidence of community-based specialists related to diagnosis and management of imAEs among patients who are receiving ICI-based therapy. [Table: see text]
B lymphocytes directly contribute to tissue fibrosis in patients with IgG4-related disease
Authors: Emanuel Della-Torre, Elena Rigamonti, Cory Perugino, Simona Baghai-Sain, Na Sun, Naoki Kaneko, Takashi Maehara, Lucrezia Rovati, Maurilio Ponzoni, Raffaella Milani, Marco Lanzillotta, Vinay Mahajan, Hamid Mattoo, Ivan Molineris, Vikram Deshpande, John H. Stone, Massimo Falconi, Angelo A. Manfredi, Shiv Pillai
Journal: Journal of Allergy and Clinical Immunology (2019)
Abstract 14816: Radial Viscoelastic Behavior of Myocardium is Not Affected by Aging
Authors: Jan Mangual, Daniela Föll, Bernd Jung, Gianni Pedrizzetti, Arash Kheradvar
Journal: Circulation (2011)

BACKGROUND: Aging has considerable impacts on myocardial function. Previous research based on MRI tissue phase mapping (TPM) suggests that aging may significantly influence regional myocardial moti...
Bortezomib, lenalidomide, and dexamethasone (VRd) ± daratumumab (DARA) in patients (pts) with newly diagnosed multiple myeloma (NDMM) for whom transplant is not planned as initial therapy: A multicenter, randomized, phase III study (CEPHEUS).
Authors: Sonja Zweegman, Saad Zafar Usmani, Katherine Chastain, Jodi Carey, Karen Ren, Elena Smith, Maria Krevvata, Jianping Wang, Jessica Vermeulen, Thierry Facon
Journal: Journal of Clinical Oncology (2019)

TPS8056 Background: DARA is a human, anti-CD38 IgGκ monoclonal antibody that significantly reduced the risk of progression/death with a manageable safety profile across several phase 3 studies in relapsed/refractory MM and NDMM. DARA + VRd (D-VRd) demonstrated efficacy and tolerability in the safety run-in cohort of the ongoing phase 2 GRIFFIN study that included transplant-eligible NDMM pts. To determine whether D-VRd demonstrates efficacy and tolerability in NDMM pts for whom transplant is not intended as initial therapy, the phase 3 CEPHEUS study will evaluate the efficacy and safety of D-VRd vs VRd alone in this pt population. Methods: This is an ongoing multicenter, open-label, randomized phase 3 study of D-VRd vs VRd alone in pts with NDMM for whom transplant is not intended as initial therapy. Approximately 360 pts will be stratified by ISS stage and age/transplant eligibility (age &lt; 70 years and transplant-ineligible, or age &lt; 70 years and refusal to transplant, or age ≥70 years) and will be randomized in a 1:1 ratio. All pts will receive eight 21-day cycles of VRd (V: 1.3 mg/m 2 SC Days 1, 4, 8, 11; R: 25 mg PO Days 1-14; d: 20 mg PO/IV Days 1, 2, 4, 5, 8, 9, 11, 12), followed by 28-day cycles of Rd (R: 25 mg PO Days 1-21; d: 40 mg PO/IV Days 1, 8, 15, 22) until progressive disease (PD). Patients in the DARA group will also receive subcutaneous DARA (1,800 mg co-formulated with recombinant human hyaluronidase PH20 [rHuPH20; Halozyme]) weekly in Cycles 1-2, every 3 weeks in Cycles 3-8, and every 4 weeks in Cycles 9+ until PD. All pts will receive preinfusion medications. Minimal residual disease (MRD)-negative rate at 10 –5 sensitivity threshold by NGS is the primary endpoint. MRD will be evaluated at suspected complete response or better. Secondary endpoints include progression-free survival (PFS), MRD-negative rate at 1-year, durable MRD negativity, overall response rate, time to and duration of response, PFS on next line of therapy, overall survival, clinical efficacy in high-risk molecular subgroups, health-related quality of life, pharmacokinetics, immunogenicity, and safety. Clinical trial information: NCT03652064.
<i>Salmonella typhimurium</i> A1-R targets chemoresistant stem-like human pancreatic cancer cells.
Authors: Yukihiko Hiroshima, Ming Zhao, Yong Zhang, Ali Maawy, Mohamed K. Hassanein, Atsushi Suetsugu, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Robert M. Hoffman
Journal: Journal of Clinical Oncology (2013)

e22011 Background: Salmonella typhimurium A1-R can selectively target tumors. XPA1 human pancreatic cancer cells are dimorphic (spindle and round shape); the spindle-shaped cancer cells have stem-like properties (J Cell Biochem 112, 3549-3554, 2011). Methods: Serial dilution was performed to obtain clones of both cellular morphologies. To determine chemosensitivity, in vitro IC 50 values were obtained for both types of XPA1 cells for (1) Cisplatin (CDDP); (2) 5-fluorouracil (5-FU); (3) Gemcitabine (GEM); and (4) S. typhimurium A1-R. The efficacy of these drugs was also determined for both types of XPA1 cells in vivo. Results: IC 50 values of spindle-shaped and round XPA1 cells, respectively, were 2.65 ± 0.22 μg/ml and 1.43 ± 0.36 μg/ml for CDDP (p = 0.012); 2.44 ± 0.25 μg/ml and 1.48 ± 0.19 μg/ml for 5-FU (p = 0.007); 3.17 ± 0.15 ng/ml and 2.70 ± 0.29 ng/ml for GEM (p = 0.133); and (19.7 ± 1.46) x 10 8 cfu/ml and (17.8 ± 9.78) × 10 8 cfu /ml for S. typhimurium A1-R (p = 0.771). In vivo, 5-FU and A1-R significantly reduced the tumor weight of round cells (5-FU; p = 0.028; S. typhimurium A1-R; p = 0.011). However, only S. typhimurium A1-R significantly reduced the tumor weight of spindle-shaped cells (p = 0.012). Conclusions: The spindle-shaped stem-like XPA1 cells were thus chemo-resistant but sensitive to S. typhimurium A1-R, suggesting S. typhimurium A1-R could be a promising therapy for chemo-resistant human pancreatic cancer stem-like cells.
Annals Consult Guys - New Left Bundle Branch Block: Should This Block Surgery?
Authors: Geno J. Merli, Howard H. Weitz
Journal: Annals of Internal Medicine (2019)

Web Exclusives16 July 2019Annals Consult Guys - New Left Bundle Branch Block: Should This Block Surgery?FREEGeno J. Merli, MD, Howard H. Weitz, MDGeno J. Merli, MDThomas Jefferson University, Philadelphia, Pennsylvania (G.J.M., H.H.W.)Search for more papers by this author, Howard H. Weitz, MDThomas Jefferson University, Philadelphia, Pennsylvania (G.J.M., H.H.W.)Search for more papers by this authorAuthor, Article and Disclosure Informationhttps://doi.org/10.7326/W18-0046 CME/MOC SectionsSupplemental MaterialAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Annals Consult Guys brings a new perspective to the art and science of medicine with lively discussion and analysis of real-world cases and situations. They address medically relevant topics—whether they be poignant, thought-provoking, or just plain entertaining.For more videos from and information on Annals Consult Guys, visit go.annals.org/ConsultGuys. Comments0 CommentsSign In to Submit A Comment Author, Article and Disclosure InformationAffiliations: Thomas Jefferson University, Philadelphia, Pennsylvania (G.J.M., H.H.W.)Disclosures: Geno J. Merli, MD, reports the following: Research grants/contracts: Bristol-Myers Squibb. Howard H. Weitz, MD, reports that he has no financial relationships or interests to disclose.Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Catharine B. Stack, PhD, MS, Deputy Editor, Statistics, reports that she has stock holdings in Pfizer, Johnson & Johnson, and Colgate-Palmolive. Christina C. Wee, MD, MPH, Deputy Editor, reports employment with Beth Israel Deaconess Medical Center. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Yu-Xiao Yang, MD, MSCE, Deputy Editor, reports that he has no financial relationships or interest to disclose. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByCorrection: Annals Consult Guys - Preventing Coronary Disease in Rheumatoid Arthritis: Do Guidelines Apply? 16 July 2019Volume 171, Issue 2Page: CG1KeywordsDiagnostic techniquesSurgeryResearch reporting guidelinesDisclosureResearch grants ePublished: 16 July 2019 Issue Published: 16 July 2019 CopyrightCopyright © 2019 by American College of Physicians. All Rights Reserved.Loading ...
Suppressed immune microenvironment and repertoire in brain metastases from patients with resected non-small-cell lung cancer
Authors: Y. Kudo, C. Haymaker, J. Zhang, A. Reuben, D.Y. Duose, J. Fujimoto, S. Roy-Chowdhuri, L.M. Solis Soto, H. Dejima, E.R. Parra, B. Mino, R. Abraham, N. Ikeda, A. Vaporcyan, D. Gibbons, J. Zhang, F.F. Lang, R. Luthra, J.J. Lee, C. Moran, J.T. Huse, H. Kadara, I.I. Wistuba
Journal: Annals of Oncology (2019)
Neoantigen Synthetic Peptide Vaccine for Multiple Myeloma Elicits T Cell Immunity in a Pre-Clinical Model
Authors: Selma Bekri, Mohamed Uduman, Diana Gruenstein, Anna Huo-Chang Mei, Kaity Tung, Reunet Rodney-Sandy, Bjarne Bogen, Jennifer Buell, Robert Stein, Kaitlin Doherty, Mark Findeis, Benjamin Morin, Bishnu Joshi, Antoine Tanne, John Castle, Daniel Levey, Hearn Jay Cho
Journal: Blood (2017)
Association of Serum Albumin With Apnea in Infants With Bronchiolitis
Authors: Jonathan M. Mansbach, Ruth J. Geller, Kohei Hasegawa, Janice A. Espinola, Michelle D. Stevenson, Ashley F. Sullivan, Carlos A. Camargo
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Apnea is a rare, life-threatening complication of bronchiolitis, the leading cause of infant hospitalization in the United States. Currently, no objective method exists for identifying which infants will become apneic. <h3>Objective</h3> To investigate whether serum albumin levels are associated with apnea in infants with severe bronchiolitis. <h3>Design, Setting, and Participants</h3> A secondary data analysis of the 35th Multicenter Airway Research Collaboration, an ongoing multicenter cohort study of infants hospitalized for bronchiolitis, was conducted from December 11, 2018, to May 30, 2019. Seventeen hospitals across the United States enrolled infants (n = 1016) during 3 consecutive bronchiolitis seasons (November 1 to April 30) between 2011 and 2014. Infants with heart-lung disease or a gestational age less than 32 weeks were excluded. <h3>Exposures</h3> Serum albumin level was categorized as low (&lt;3.8 g/dL) or normal (≥3.8 g/dL). <h3>Main Outcomes and Measures</h3> Apnea during the hospitalization. <h3>Results</h3> Of the 1016 infants hospitalized for bronchiolitis, the median (interquartile range [IQR]) age was 3 (2-6) months, 610 (60.0%) were male, and 186 (18.3%) were born preterm (32-37 weeks' gestation). Among the 25 infants (2.5%) with apnea while hospitalized, the median (IQR) serum albumin level was 3.5 (3.1-3.6) g/dL, and 22 (88.0%) had low serum albumin levels. The prevalence of apnea was 5.7% among all infants with low albumin levels, compared with 0.5% prevalence in infants with normal serum albumin levels. In unadjusted analyses, apnea was associated with younger age, preterm birth, weight-for-age<i>z</i>score, and low albumin (odds ratio [OR], 12.69; 95% CI, 3.23-49.82). After adjustment for age, preterm birth, and weight-for-age<i>z</i>score, low serum albumin levels remained statistically significantly associated with apnea (OR, 4.42; 95% CI, 1.21-16.18). <h3>Conclusions and Relevance</h3> Low serum albumin levels appeared to be associated with increased risk of apnea after adjustment for known apnea risk factors. This finding provides a path to potentially identifying apnea, a life-threatening complication of bronchiolitis.
Tight control for Crohn’s disease with adalimumab-based treatment is cost-effective: an economic assessment of the CALM trial
Authors: Remo Panaccione, Jean-Frederic Colombel, Simon P L Travis, Peter Bossuyt, Filip Baert, Tomáš Vaňásek, Ahmet Danalıoğlu, Gottfried Novacek, Alessandro Armuzzi, Walter Reinisch, Scott Johnson, Marric Buessing, Ezequiel Neimark, Joel Petersson, Wan-Ju Lee, Geert R D’Haens
Journal: Gut (2019)

Objective To evaluate the cost-effectiveness of an inflammatory biomarker and clinical symptom directed tight control strategy (TC) compared with symptom-based clinical management (CM) in patients with Crohn’s disease (CD) naïve to immunosuppressants and biologics using a UK public payer perspective. Design A regression model estimated weekly CD Activity Index (CDAI)-based transition matrices (remission: CDAI &lt;150, moderate: CDAI ≥150 to &lt;300, severe: CDAI ≥300 to &lt;450, very severe: CDAI ≥450) based on the Effect of Tight Control Management on Crohn’s Disease (CALM) trial. A regression predicted hospitalisations. Health utilities and costs were applied to health states. Work productivity was monetised and included in sensitivity analyses. Remission rate, CD-related hospitalisations, adalimumab injections, other direct medical costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) were calculated. Results Over 48 weeks, TC was associated with a higher clinical remission (CDAI &lt;150) rate (58.2% vs 46.8%), fewer CD-related hospitalisations (0.124 vs 0.297 events per patient) and more injections of adalimumab (40 mg sc) (mean 31.0 vs 24.7) than CM. TC was associated with 0.032 higher QALYs and £593 higher total medical costs. The ICER was £18 656 per QALY. The ICER was cost-effective in 57.9% of simulations. TC became dominant, meaning less costly but more effective, when work productivity was included. Conclusion A TC strategy as used in the CALM trial is cost-effective compared with CM. Incorporating costs related to work productivity increases the economic value of TC. Cross-national inferences from this analysis should be made with caution given differences in healthcare systems. Trial registration number NCT01235689 ; Results.
Venom immunotherapy in patients with clonal mast cell disorders: IgG4 correlates with protection
Authors: Jesper Jarkvist, Clara Salehi, Cem Akin, Theo Gülen
Journal: Allergy (2019)

Abstract Background Patients with clonal mast cell disorders (cMCD), systemic mastocytosis (SM) and monoclonal mast cell activation syndrome (MMAS), represent an increased risk for Hymenoptera venom anaphylaxis (HVA). Lifelong venom immunotherapy (VIT) is recommended; however, its efficacy and safety are controversial. Hence, we sought to evaluate the efficacy and safety of VIT in HVA patients with cMCD. Methods A retrospective study was conducted among 46 patients with Vespula venom allergy who had experienced severe HVA, 32 cMCD (22 with SM and 10 with MMAS) and 14 controls. There were no differences between cMCD patients and controls in age (58 vs 66) and duration of VIT (47 vs 48 months), respectively. Results During VIT, 11 (34%) cMCD patients experienced adverse reactions (ARs) (7% in controls), including 1 anaphylaxis. There were 23 re‐stings in 17 (53%) patients during VIT. Of episodes, four (17%) presented with anaphylaxis, 14 (60%) presented with local reaction, and five (23%) were asymptomatic. In 11 episodes (48%), the patient did not take epinephrine, of these 8 (73%) presented with local reaction, and 3 (27%) were asymptomatic. Patient‐based protection from anaphylaxis was 76% (4/17) in cMCD vs. 100% in controls during VIT. The venom‐specific IgG4 concentrations increased during VIT ( P &lt; .001) although tryptase and IgE were unaltered. Conclusion Both safety and efficacy of VIT in cMCD patients were slightly reduced than controls. Severe ARs were rare. The elevated IgG4 levels may be a biomarker for efficacy of VIT in cMCD patients, as it correlates with protection from re‐stings.
Non-small cell lung cancer (NSCLC) case study examining whether results in a randomized control arm are replicated by a synthetic control arm (SCA).
Authors: Ruthie Davi, Mark Chandler, Barbara Elashoff, Andrea Stern Ferris, Andrew Howland, David Lee, Antara Majumdar, Mark Stewart, Larry Strianese, Elizabeth Stuart, Xiang Yin, Antoine Yver
Journal: Journal of Clinical Oncology (2019)

9108 Background: The FDA’s accelerated approval (AA) pathway provides conditional approval for an investigational product (IP) after positive effect on a surrogate endpoint has been provided, allowing patients earlier access to the therapy. Confirmation of a positive effect on the clinical endpoint after conditional approval is required and usually includes a randomized trial. However, such a trial is challenged by availability of the IP outside the trial. Recruitment becomes more difficult, and patients assigned to control are more likely to drop-out and use the non-assigned IP, which may bias the observed treatment effect. In AA settings we propose a SCA composed of patient level data from previous clinical trials to augment or replace the randomized control. Validity of this approach in one case study is assessed by examining if a SCA can replicate the outcomes of a target randomized control (TRC) from a recent NSCLC trial. Methods: The patients for the NSCLC SCA were required to have satisfied the key eligibility criteria of the target trial and were further selected using a propensity score-based approach to balance the baseline characteristics in the SCA and TRC. All patient selections were made without knowledge of patient outcomes. Results: The results show comparable balance in observed baseline characteristics of the SCA and TRC was achieved. Overall survival (OS) in TRC was replicated by SCA. The Kaplan Meier curves for OS in the SCA and TRC visually overlap. In addition, the log rank test (p = 0.65) and hazard ratio of 1.04 (95% CI: (0.88, 1.23)) were not statistically significant. Conclusions: If the SCA had been in place of the randomized control in this study, conclusions about the treatment effect would have been the same. While this may not hold when it is not possible to balance the groups on all confounders, this suggests that in some settings, SCA could augment or replace the randomized control in future trials easing recruitment, retention, and crossover challenges without compromising the understanding of the treatment effect. Future work should examine in what settings SCA is appropriate and consider the implications of potential unobserved confounders.
Transbronchial cryobiopsy for diffuse parenchymal lung disease: 30- and 90-day mortality
Authors: Jasleen Pannu, Lance J. Roller, Fabien Maldonado, Robert J. Lentz, Heidi Chen, Otis B. Rickman
Journal: European Respiratory Journal (2019)

<b>This study suggests 30- and 90-day mortality after transbronchial cryobiopsy is higher than reported, confirming concerns raised about safety in advanced diffuse lung disease. Keen attention towards patient selection and procedural planning is warranted.</b>http://bit.ly/2ySoZNq