tbuckley/cabot-search huggingface dataset:
Immune activation by DNA damage predicts response to chemotherapy and survival in oesophageal adenocarcinoma
Authors: Richard C Turkington, Laura A Knight, Jaine K Blayney, Maria Secrier, Rosalie Douglas, Eileen E Parkes, Eilis K Sutton, Leanne Stevenson, Damian McManus, Sophia Halliday, Andrena M McCavigan, Gemma E Logan, Steven M Walker, Christopher J Steele, Juliane Perner, Jan Bornschein, Shona MacRae, Ahmad Miremadi, Eamon McCarron, Stephen McQuaid, Kenneth Arthur, Jacqueline A James, Martin M Eatock, Robert O’Neill, Fergus Noble, Timothy J Underwood, D Paul Harkin, Manuel Salto-Tellez, Rebecca C Fitzgerald, Richard D Kennedy
Journal: Gut (2019)

Objective Current strategies to guide selection of neoadjuvant therapy in oesophageal adenocarcinoma (OAC) are inadequate. We assessed the ability of a DNA damage immune response (DDIR) assay to predict response following neoadjuvant chemotherapy in OAC. Design Transcriptional profiling of 273 formalin-fixed paraffin-embedded prechemotherapy endoscopic OAC biopsies was performed. All patients were treated with platinum-based neoadjuvant chemotherapy and resection between 2003 and 2014 at four centres in the Oesophageal Cancer Clinical and Molecular Stratification consortium. CD8 and programmed death ligand 1 (PD-L1) immunohistochemical staining was assessed in matched resection specimens from 126 cases. Kaplan-Meier and Cox proportional hazards regression analysis were applied according to DDIR status for recurrence-free survival (RFS) and overall survival (OS). Results A total of 66 OAC samples (24%) were DDIR positive with the remaining 207 samples (76%) being DDIR negative. DDIR assay positivity was associated with improved RFS (HR: 0.61; 95% CI 0.38 to 0.98; p=0.042) and OS (HR: 0.52; 95% CI 0.31 to 0.88; p=0.015) following multivariate analysis. DDIR-positive patients had a higher pathological response rate (p=0.033), lower nodal burden (p=0.026) and reduced circumferential margin involvement (p=0.007). No difference in OS was observed according to DDIR status in an independent surgery-alone dataset. DDIR-positive OAC tumours were also associated with the presence of CD8+ lymphocytes (intratumoural: p&lt;0.001; stromal: p=0.026) as well as PD-L1 expression (intratumoural: p=0.047; stromal: p=0.025). Conclusion The DDIR assay is strongly predictive of benefit from DNA-damaging neoadjuvant chemotherapy followed by surgical resection and is associated with a proinflammatory microenvironment in OAC.
Full Study Report of Andexanet Alfa for Bleeding Associated with Factor Xa Inhibitors
Authors: Stuart J. Connolly, Mark Crowther, John W. Eikelboom, C. Michael Gibson, John T. Curnutte, John H. Lawrence, Patrick Yue, Michele D. Bronson, Genmin Lu, Pamela B. Conley, Peter Verhamme, Jeannot Schmidt, Saskia Middeldorp, Alexander T. Cohen, Jan Beyer-Westendorf, Pierre Albaladejo, Jose Lopez-Sendon, Andrew M. Demchuk, Daniel J. Pallin, Mauricio Concha, Shelly Goodman, Janet Leeds, Sonia Souza, Deborah M. Siegal, Elena Zotova, Brandi Meeks, Sadia Ahmad, Juliet Nakamya, Truman J. Milling
Journal: New England Journal of Medicine (2019)

Andexanet alfa is a modified recombinant inactive form of human factor Xa developed for reversal of factor Xa inhibitors.We evaluated 352 patients who had acute major bleeding within 18 hours after administration of a factor Xa inhibitor. The patients received a bolus of andexanet, followed by a 2-hour infusion. The coprimary outcomes were the percent change in anti-factor Xa activity after andexanet treatment and the percentage of patients with excellent or good hemostatic efficacy at 12 hours after the end of the infusion, with hemostatic efficacy adjudicated on the basis of prespecified criteria. Efficacy was assessed in the subgroup of patients with confirmed major bleeding and baseline anti-factor Xa activity of at least 75 ng per milliliter (or ≥0.25 IU per milliliter for those receiving enoxaparin).Patients had a mean age of 77 years, and most had substantial cardiovascular disease. Bleeding was predominantly intracranial (in 227 patients [64%]) or gastrointestinal (in 90 patients [26%]). In patients who had received apixaban, the median anti-factor Xa activity decreased from 149.7 ng per milliliter at baseline to 11.1 ng per milliliter after the andexanet bolus (92% reduction; 95% confidence interval [CI], 91 to 93); in patients who had received rivaroxaban, the median value decreased from 211.8 ng per milliliter to 14.2 ng per milliliter (92% reduction; 95% CI, 88 to 94). Excellent or good hemostasis occurred in 204 of 249 patients (82%) who could be evaluated. Within 30 days, death occurred in 49 patients (14%) and a thrombotic event in 34 (10%). Reduction in anti-factor Xa activity was not predictive of hemostatic efficacy overall but was modestly predictive in patients with intracranial hemorrhage.In patients with acute major bleeding associated with the use of a factor Xa inhibitor, treatment with andexanet markedly reduced anti-factor Xa activity, and 82% of patients had excellent or good hemostatic efficacy at 12 hours, as adjudicated according to prespecified criteria. (Funded by Portola Pharmaceuticals; ANNEXA-4 ClinicalTrials.gov number, NCT02329327.).
Interferon-induced guanylate-binding proteins: Guardians of host defense in health and disease
Authors: Kyle Tretina, Eui-Soon Park, Agnieszka Maminska, John D. MacMicking
Journal: The Journal of Experimental Medicine (2019)

Guanylate-binding proteins (GBPs) have recently emerged as central orchestrators of immunity to infection, inflammation, and neoplastic diseases. Within numerous host cell types, these IFN-induced GTPases assemble into large nanomachines that execute distinct host defense activities against a wide variety of microbial pathogens. In addition, GBPs customize inflammasome responses to bacterial infection and sepsis, where they act as critical rheostats to amplify innate immunity and regulate tissue damage. Similar functions are becoming evident for metabolic inflammatory syndromes and cancer, further underscoring the importance of GBPs within infectious as well as altered homeostatic settings. A better understanding of the basic biology of these IFN-induced GTPases could thus benefit clinical approaches to a wide spectrum of important human diseases.
Neurocritical Care Outcomes, Research, and Technology
Authors: Katharina Maria Busl, Thomas P. Bleck, Panayiotis N. Varelas
Journal: JAMA Neurology (2019)

Neurocritical care has grown into an organized specialty that may have consequences for patient care, outcomes, research, and neurointensive care (neuroICU) technology.Neurocritical care improves care and outcomes of the patients who are neurocritically ill, and neuroICUs positively affect the financial state of health care systems. The development of neurocritical care as a recognized subspecialty has fostered multidisciplinary research, neuromonitoring, and neurocritical care information technology, with advances and innovations in practice and progress.Neurocritical care has become an important part of health systems and an established subspecialty of neurology. Understanding its structure, scope of practice, consequences for care, and research are important.
Predicting Survival in Patients Undergoing Resection for Locally Recurrent Retroperitoneal Sarcoma: A Study and Novel Nomogram from TARPSWG
Authors: Chandrajit P. Raut, Dario Callegaro, Rosalba Miceli, Francesco Barretta, Piotr Rutkowski, Jean-Yves Blay, Guy Lahat, Dirk C. Strauss, Ricardo Gonzalez, Nita Ahuja, Giovanni Grignani, Vittorio Quagliuolo, Eberhard Stoeckle, Antonino De Paoli, Venu G. Pillarisetty, Carolyn Nessim, Carol J. Swallow, Sanjay Bagaria, Robert Canter, John Mullen, Hans J. Gelderblom, Elisabetta Pennacchioli, Frits van Coevorden, Kenneth Cardona, Marco Fiore, Mark Fairweather, Alessandro Gronchi
Journal: Clinical Cancer Research (2019)

Abstract Purpose: The role of surgery for first relapse locally recurrent retroperitoneal sarcoma (RPS-LR1) is uncertain. We report outcomes of the largest RPS-LR1 series and propose a new prognostic nomogram. Experimental Design: Patients with consecutive RPS-LR1 without distant metastases who underwent resection at 22 centers (2002–2011) were included. Endpoints were disease-free and overall survival (DFS, OS) and crude-cumulative-incidence (CCI) of local/distant recurrence from second surgery. Nomograms predicting DFS and OS from second surgery were developed and validated (calibration plots); discrimination was assessed (Harrell C index). Results: Of 684 patients identified, full prognostic variable data were available for 602. Initial surgery for primary RPS was performed at our institutions in 188 patients (31%) and elsewhere in 414 (69%). At a median follow-up of 119 months [Interquartile range (IQR), 80–169] from initial surgery and 75 months (IQR 50–105) from second surgery, 6-year DFS and OS were 19.2% [95% confidence interval (CI), 16.0–23.0%] and 54.1% (95% CI, 49.8–58.8%), respectively. Recurrence patterns and survival probability were histology-specific, with liposarcoma subtypes having the highest 6-year CCI of second local recurrence (LR, 60.2%–70.9%) and leiomyosarcoma (LMS) having higher 6-year CCI of distant metastasis (DM, 36.3%). Nomograms included age at second surgery, multifocality, grade, completeness of second surgery, histology, chemotherapy/radiotherapy at first surgery, and number of organs resected at first surgery. OS and DFS nomograms showed good calibration and discriminative ability (C index 0.70 and 0.67, respectively). Conclusions: We developed nomograms to predict DFS and OS for patients undergoing RPS-LR1 resection. Nomograms provide individualized, disease-relevant estimations of survival for RPS-LR1 patients and assist in clinical decisions.
A randomized phase III trial of S-1/oxaliplatin (SOX) versus UFT/leucovorin as adjuvant chemotherapy for high-risk stage III colon cancer: The ACTS-CC 02 trial.
Authors: Takao Takahashi, Eiji Sunami, Tetsuya Kusumoto, Mitsuyoshi Ota, Yoshiyuki Sakamoto, Naohiro Tomita, Atsuyuki Maeda, Jin Tejima, Michio Okabe, Chihiro Tanaka, Junichiro Yamauchi, Michio Itabashi, Kenjiro Kotake, Keiichi Takahashi, Hideo Baba, Narikazu Boku, Keisuke Aiba, Megumi Ishiguro, Satoshi Morita, Kenichi Sugihara
Journal: Journal of Clinical Oncology (2019)

484 Background: The ACTS-CC 02 trial was designed to verify the superiority of postoperative adjuvant chemotherapy with S-1/oxaliplatin (SOX) over UFT/leucovorin (LV), one of the standard oral fluoropyrimidine regimens in Japan, in terms of disease-free survival (DFS) in patients (pts) with high-risk stage III colon cancer (any T, N2, or positive nodes around the origin of the feeding arteries). The results of the safety analysis have been reported previously (Clin Colorectal Cancer, 2018). We now present the 3-year DFS results as the primary endpoint. Methods: Pts who underwent curative resection for pathologically confirmed high-risk stage III colon cancer were randomly assigned to receive either UFT/LV (300–600 mg/day of UFT according to body surface area [BSA] and 75 mg/day of LV on days 1-28, every 35 days, 5 courses) or SOX (100 mg/m 2 of oxaliplatin on day 1 and 80–120 mg/day of S-1 according to BSA on days 1-14, every 21 days, 8 courses). The primary endpoint was DFS. Results: From April 2010 through October 2014, a total of 966 pts were enrolled at 260 institutions. The full analysis set, excluding pts who withdrew informed consent before protocol treatment, comprised 478 and 477 pts in the UFT/LV group and SOX group, respectively. The median age was 65.0 years. The ECOG PS was 0 in 94.0%, and the disease stage was IIIA/IIIB/IIIC in 1.3%/50.2%/48.6%. The 3-year DFS rate was 60.6% in the UFT/LV group and 62.7% in the SOX group (HR: 0.90; 95% CI: 0.74-1.09; p = 0.28); the superiority of SOX was not demonstrated. In stage IIIB, the 3-year DFS rate was 69.3% and 68.5% in the UFT/LV group and SOX group, respectively (HR: 1.01; 95% CI: 0.74-1.37; p = 0.95). In Stage IIIC, the 3-year DFS rate was 50.6% and 55.8% in the UFT/LV group and SOX group, respectively (HR: 0.82, 95% CI: 0.63-1.06; p = 0.12). Notably, in the N2b subgroup, the 3-year DFS rate was 46.0% and 54.7% in the UFT/LV group and SOX group, respectively (HR: 0.76, 95% CI: 0.55-1.05; p = 0.10). Conclusions: SOX was not shown to be superior to UFT/LV in pts with high-risk stage III colon cancer. However, the oxaliplatin-based regimen was suggested to be more effective in advanced disease, such as stage IIIC and N2b. Clinical trial information: JapicCTI-101073.
A Phase 1 Clinical Trial of Personalized Adoptive Cellular Therapy Targeting Myelodysplastic Syndrome (MDS) Stem Cell Neoantigens (PACTN)
Authors: Valentina Ferrari, Tiffany N Tanaka, Alison Tarke, Hanna Fields, Luca Ferrari, Alex Ni, Franco Ferrari, John Warner, Theresa Jochelson, Rafael Bejar, Antonella Vitiello, Thomas A Lane
Journal: Blood (2018)
Abstract 10449: Pre-Infarction Angina and Short-term Outcomes in Non St Segment Elevation Myocardial Infarction: Data From the Rico Survey.
Authors: Aurélie Gudjoncik, Luc Lorgis, Laurent Mock, Philippe Buffet, Carole Richard, Luc Janin-Manificat, Jean Claude Beer, Luc Rochette, Yves Cottin, Marianne Zeller
Journal: Circulation (2010)

Background: The presence of preinfarction angina (PIA) has been shown to confer cardioprotection after ST segment elevation myocardial infarction (MI). However, the impact of PIA in non ST segment elevation (NSTEMI) remains to be determined. Methods: From the obseRvatoire des Infarctus de Cote d'Or (RICO) survey, 1789 consecutive patients admitted in ICU with a first NSTEMI were included. Patients who experienced chest pain, chest discomfort or left arm and jaw pain  1) and 30-day mortality were also collected. Results: Among the 1789 patients included, 564 (26%) patients presented PIA. Baseline clinical characteristics and GRACE risk score were similar for the 2 groups. However, PIA was associated with a lower CRP on admission (5.1(2.0–12.0) vs. 6.0(2.4–19.1) ...
Rapid Emergency Medical Services Response Saves Lives of Persons Injured in Motor Vehicle Crashes
Authors: Marie Crandall
Journal: JAMA Surgery (2019)

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Recurrence pattern and outcomes in T4 colon cancer: A single institution analysis.
Authors: David Macari, Samer Kawak, Lilian Hanna, Daniel Ezekwudo, John Khoury, Harry Wasvary, Ishmael A. Jaiyesimi
Journal: Journal of Clinical Oncology (2019)

706 Background: Patients with T4 colon adenocarcinoma have an increased risk of peritoneal recurrence due to direct seeding malignant cells. It has been theorized that adjuvant chemotherapy may not sterilize the peritoneal surface due to inadequate intraperitoneal concentration. We seek to further define the metastatic pattern, predictors of recurrence, and efficacy of adjuvant treatment in T4 colon cancer. Methods: We reviewed records of 181 adults [median age 71 (22-97)] with T4 N0-3 colon adenocarcinoma at Beaumont Hospital, Michigan from May 2005 –Nov 2015. Baseline factors and data on follow up, metastasis, and survival were collected and analyzed. Results: Overall recurrence rates for N0, N1, and N2 were 27/85 (32%), 17/50 (34%), and 29/46 (63%) (p = 0.001). Locoregional recurrence (LR) rates for N0, N1, and N2 were 21/85 (24.7%), 14/50 (28%), and 21/46 (45.7%) (p = 0.014). Multivariate analysis for distant recurrence was significant only for positive nodes with hazard ratio (HR) 3.3, 95% confidence interval (CI) 1.1-9.9. Multivariate analysis for increased risk of LR was significant for the following variables: perforation (HR 2.7, 95% CI 1.2 – 6.2), lymphovascular invasion (HR 2.7, 95% CI 1.1 – 6.7), positive nodes (HR 2.8, 95% CI 1.2 – 6.9), and positive margins (HR 5.0, 95% CI 2.1 – 12.1). Adjuvant chemotherapy did not decrease risk of LR (HR 0.6, 95% CI 0.3-1.2) or distant recurrence (HR 0.9, 95% CI 0.3-2.8). Multivariate analysis for overall survival revealed the following to be associated with increased risk of mortality: signet ring (HR 2.5, 95% CI 1.2-5.8), positive nodes (HR 2.3, 95% CI 1.2-4.4), positive margin (HR 2.8, 95% CI 1.4-5.8). Adjuvant chemotherapy was not associated with improved survival (HR 0.8, 95% CI 0.4-1.7). Recurrence was strongly associated with colon cancer-specific death with a p &lt; 0.001. Conclusions: Adjuvant chemotherapy is standard of care for most T4 colon cancer patients, however, this data suggests there is no improvement in survival or other significant outcomes. We have identified several risk factors which predict increased risk of LR. This data suggests LR is frequent and not affected by systemic chemotherapy. Prospective trials are needed to reduce the substantial risk of LR in T4 colon cancer.
Posttranscriptional modulation of TERC by PAPD5 inhibition rescues hematopoietic development in dyskeratosis congenita
Authors: Wilson Chun Fok, Siddharth Shukla, Alexandre Teixeira Vessoni, Kirsten Ann Brenner, Roy Parker, Christopher M. Sturgeon, Luis Francisco Zirnberger Batista
Journal: Blood (2019)
High dietary fat intake induces a microbiota signature that promotes food allergy
Authors: Maryam Hussain, Germán Bonilla-Rosso, Cheong K.C. Kwong Chung, Lukas Bäriswyl, Maria Pena Rodriguez, Brian S. Kim, Philipp Engel, Mario Noti
Journal: Journal of Allergy and Clinical Immunology (2019)
Liquid biopsy for optimizing the rechallenge of cetuximab in metastatic colorectal cancer: Additional study of E-Rechallenge Trial.
Authors: Yoshihito Ohhara, Eiji Shinozaki, Hiroshi Osawa, Masato Nakamura, Yoshiaki Shindo, Manabu Shiozawa, Hiroyuki Uetake, Hiroshi Matsumoto, Norio Ureshino, Hironaga Satake, Takaaki Kobayashi, Takeshi Suto, Shiro Kitano, Yasuo Ohashi, Kohei Uemura, Kensei Yamaguchi
Journal: Journal of Clinical Oncology (2019)

585 Background: Several previous reports indicated that cetuximab (Cmab) rechallenge may be efficacious in some patients for whom Cmab was previously effective. Liquid biopsy can detect the some emerging mutations for resistance with Cmab. Considering the plasticity and elasticity of sensitive clone, we assumed we could identify the patients with benefit from Cmab rechallenge by liquid biopsy. This current study investigates the predictability of efficacy for Cmab rechallenge by liquid biopsy in the E-Rechallenge Trial. Methods: The E-Rechallenge Trial is a multicenter phase II study in mCRC patients who have become refractory to fluoropyrimidines, L-OHP, CPT-11, Cmab, and bevacizumab, and in whom previous treatment with Cmab was effective in any earlier line (achieving CR, PR, or SD that persisted for ≥ 6 months). The other main eligibility criteria are; RAS wild type, measurable disease, aEFI ≥ 16 weeks between the last dose of Cmab during previous treatment and the start of Cmab rechallenge. Protocol treatment is the combination of weekly Cmab with biweekly CPT-11. Additional research of ctDNA was conducted optionally. Baseline plasma samples were analyzed for KRAS, NRAS, BRAF and EGFR S492R mutations using digital PCR (LBx probe, RIKEN GENESIS). A cut-off of the mutation allele frequency was &gt; 0.1%. Results: Between Dec. 2014 and Oct. 2017, 33 patients were enrolled. The primary endpoint; the rates of PR/SD/PD were PR 15.6%/SD 40.6%/PD 43.8%. Twenty-four of 33 patients participated in the additional research. In the additional cohort, the rates of PR/SD/PD were PR 12.5%/SD 50.0%/PD 37.5%. The mutations were detected at the baseline of Cmab rechallenge as followings; KRAS exon 2 29.2%, exon 3,4 33.3%, BRAF V600E 12.5%, EGFR S492R 12.5%. In wild type of these genes the PR and SD rate increased to 25% and 50%, respectively. Conclusions: Cmab rechallenge showed some activity in the salvage setting, in patients for whom Cmab was previously effective. KRAS, BRAF, and EGFR S492R screening by liquid biopsy may contribute to identify patients with benefit from Cmab rechallenge. The additional data of ctDNA may be provided in the conference. Clinical trial information: UMIN 000016439.
Failure to Cite Related Studies and Report Complete Information on Patients and Tissue Samples
Authors: Jiejie Xu
Journal: JAMA Surgery (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Single-dose CRISPR–Cas9 therapy extends lifespan of mice with Hutchinson–Gilford progeria syndrome
Authors: Ergin Beyret, Hsin-Kai Liao, Mako Yamamoto, Reyna Hernandez-Benitez, Yunpeng Fu, Galina Erikson, Pradeep Reddy, Juan Carlos Izpisua Belmonte
Journal: Nature Medicine (2019)
Specific IgG4 to milk proteins during oral immunotherapy for milk allergy: relationship to eosinophilic esophagitis
Authors: Claudia Leiko Yonekura Anagusko, Juliana Mendonca, Mariele Morandin Lopes, Pablo Torres, Catherine Sonaly Ferreira Martins, Fabio M. Castro, Jeffrey M. Wilson, Ariana C. Yang, Thomas A.E. Platts-Mills
Journal: Journal of Allergy and Clinical Immunology (2019)