tbuckley/cabot-search huggingface dataset:
Hypofractionated versus conventional fractionated postmastectomy radiotherapy for patients with high-risk breast cancer: a randomised, non-inferiority, open-label, phase 3 trial
Authors: Shu-Lian Wang, Hui Fang, Yong-Wen Song, Wei-Hu Wang, Chen Hu, Yue-Ping Liu, Jing Jin, Xin-Fan Liu, Zi-Hao Yu, Hua Ren, Ning Li, Ning-Ning Lu, Yu Tang, Yuan Tang, Shu-Nan Qi, Guang-Yi Sun, Ran Peng, Shuai Li, Bo Chen, Yong Yang, Ye-Xiong Li
Journal: The Lancet Oncology (2019)
Intraaortic Balloon Pump in Cardiogenic Shock Complicating Acute Myocardial Infarction
Authors: Holger Thiele, Uwe Zeymer, Nathalie Thelemann, Franz-Josef Neumann, Jörg Hausleiter, Mohamed Abdel-Wahab, Roza Meyer-Saraei, Georg Fuernau, Ingo Eitel, Rainer Hambrecht, Michael Böhm, Karl Werdan, Stephan B. Felix, Marcus Hennersdorf, Steffen Schneider, Taoufik Ouarrak, Steffen Desch, Suzanne de Waha-Thiele, Zehra Alkisoglu, Ferenc Follath, Sonja Frey, Johannes Haerting, Kurt Huber, Bernhard Maisch, Beate Messemer, Taoufik Ourrak, Gerhard Schuler, Karin Vonderschmitt, Karl Werdan
Journal: Circulation (2019)

Background: The role of intraaortic balloon counterpulsation (IABP) in cardiogenic shock is still a subject of intense debate despite the neutral results of the IABP-SHOCK II trial (Intraaortic Balloon Pump in Cardiogenic Shock II) with subsequent downgrading in international guidelines. So far, randomized data on the impact of IABP on long-term clinical outcomes in patients with cardiogenic shock complicating acute myocardial infarction are lacking. Furthermore, only limited evidence is available on general long-term outcomes of patients with cardiogenic shock treated by contemporary practice. Methods: The IABP-SHOCK II trial is a multicenter, randomized, open-label trial. Between 2009 and 2012, 600 patients with cardiogenic shock complicating acute myocardial infarction undergoing early revascularization were randomized to IABP versus control. Results: Long-term follow-up was performed 6.2 years (interquartile range 5.6–6.7) after initial randomization. Follow-up was completed for 591 of 600 patients (98.5%). Mortality was not different between the IABP and the control group (66.3% versus 67.0%; relative risk, 0.99; 95% CI, 0.88–1.11; P =0.98). There were also no differences in recurrent myocardial infarction, stroke, repeat revascularization, or rehospitalization for cardiac reasons (all P &gt;0.05). Survivors’ quality of life as assessed by the EuroQol 5D questionnaire and the New York Heart Association class did not differ between groups. Conclusions: IABP has no effect on all-cause mortality at 6-year long-term follow-up. Mortality is still very high, with two thirds of patients with cardiogenic shock dying despite contemporary treatment with revascularization therapy. Clinical Trial Registration: URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT00491036.
Favorable Outcome of Sequential HLA-Haploidentical Transplantation Using Ptcy As GvHD Prophylaxis in High Risk AML and MDS of the Elderly
Authors: Alessia Fraccaroli, Dusan Prevalsek, Sarah Elena Häbe, Veit Bücklein, Christoph Schulz, Heidrun Drolle, Susanne Fritsch, Georg Ledderose, Michael von Bergwelt, Wolfgang Hiddemann, Johanna Tischer
Journal: Blood (2018)
Abstract 17323: Microbubble-Mediated Sonothrombolysis for Treatment of Patients With Acute St-Segment Elevation Myocardial Infarction: Improvement in Recanalization Rate, Systolic Function and Microvascular Perfusion
Authors: Wilson Mathias, Jeane M Tsutsui, Miguel O Aguiar, Bruno Tavares, Jose Nicolau, Erica P Viana, Mucio T Oliveira, Alexandre Soeiro, Pedro Lemos, Bernardo Lopes, Joao Sbano, Roberto Kalil, Thomas Porter
Journal: Circulation (2017)

Background: Microbubble-mediated sonothrombolysis has been shown to improvevascular and microvascular thrombotic obstruction. Initial results in ST elevation myocardial infarction (STEMI) seem promising. Hypothesis: We hypothesized that early application of diagnostic ultrasound (DUS) high mechanical index (MI) during microbubble infusion would augment epicardial and microvascular flow when integrated with the emergent management of acute STEMI with percutaneous coronary intervention (PCI). Methods: 57 patients (44 males; 59±10 years) with STEMI underwent DUS and microbubbles (3% Definity®). Patients were randomized to either DUS with intermittent high MI impulses (1.2) when microbubbles were visualized within the risk area (therapy group, n=32) or low MI imaging (control group, n=25). The therapy group received sonothrombolysis prior and after PCI. Comparisons between groups were coronary recanalization rate at initial angiography, left ventricular ejection fraction (LVEF), wall motion score index (WMSI)...
Extracorporeal membrane oxygenation and surgical embolectomy for high-risk pulmonary embolism
Authors: Fabio Ius, Marius M. Hoeper, Christine Fegbeutel, Christian Kühn, Karen Olsson, Nurbol Koigeldiyev, Igor Tudorache, Gregor Warnecke, Jörg Optenhöfel, Jakob Ono Puntigam, Andreas Schäfer, Bernhard C. Meyer, Jan B. Hinrichs, Johann Bauersachs, Axel Haverich, Serghei Cebotari
Journal: European Respiratory Journal (2019)

<b>A treatment protocol for patients with high-risk pulmonary embolism, which avoids thrombolysis and establishes rapid haemodynamic stabilisation <i>via</i> v-a ECMO support followed by semi-elective surgical embolectomy, is associated with excellent outcomes.</b>http://ow.ly/rGNd30nBd22
<i>L</i>-Carnitine–Mediated Tumor Cell Protection and Poor Patient Survival Associated with OCTN2 Overexpression in Glioblastoma Multiforme
Authors: Matthias A. Fink, Heiko Paland, Susann Herzog, Markus Grube, Silke Vogelgesang, Kerstin Weitmann, Angela Bialke, Wolfgang Hoffmann, Bernhard H. Rauch, Henry W.S. Schroeder, Sandra Bien-Möller
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Apoptotic dysregulation, redox adaptive mechanisms, and resilience to hypoxia are major causes of glioblastoma (GBM) resistance to therapy. Commonly known as crucial factors in energy metabolism, OCTN2 (SLC22A5) and its substrate L-carnitine (LC) are increasingly recognized as actors in cytoprotection. This study provides a comprehensive expression and survival analysis of the OCTN2/LC system in GBM and clarifies the system's impact on GBM progression. Experimental Design: OCTN2 expression and LC content were measured in 121 resected human GBM specimens and 10 healthy brain samples and analyzed for prognostic significance. Depending on LC administration, the effects of hypoxic, metabolic, and cytotoxic stress on survival and migration of LN18 GBM cells were further studied in vitro. Finally, an orthotopic mouse model was employed to investigate inhibition of the OCTN2/LC system on in vivo GBM growth. Results: Compared with healthy brain, OCTN2 expression was increased in primary and even more so in recurrent GBM on mRNA and protein level. High OCTN2 expression was associated with a poor overall patient survival; the unadjusted HR for death was 2.7 (95% CI, 1.47–4.91; P &amp;lt; 0.001). LC administration to GBM cells increased their tolerance toward cytotoxicity, whereas siRNA-mediated OCTN2 silencing led to a loss of tumor cell viability. In line herewith, OCTN2/LC inhibition by meldonium resulted in reduced tumor growth in an orthotopic GBM mouse model. Conclusions: Our data indicate a potential role of the OCTN2/LC system in GBM progression and resistance to therapy, and suggests OCTN2 as a prognostic marker in patients with primary GBM.
Implementation, Practices, and Barriers to the 2017 Peanut Allergy Prevention Guidelines Among Pediatricians
Authors: Ruchi S. Gupta, Jialing Jiang, Alexandria Bozen, Jacqueline Johnson, Samuel J. Arbes, Susan Cooper, Jack W. Hu, Jennifer Martin, Jamie Reese, Lucy A. Bilaver, Matthew M. Davis, Alkis Togias
Journal: Journal of Allergy and Clinical Immunology (2019)
The crane technique: a novel traction method for use during rectal endoscopic submucosal dissection
Authors: Hiroya Sakaguchi, Takashi Toyonaga, Hidetoshi Kaku, Yoshiko Nakano, Shinwa Tanaka, Toshitatsu Takao, Yuzo Kodama
Journal: Endoscopy (2019)

In order to make it easier to access the submucosal layer during endoscopic submucosal dissection (ESD), various traction devices have been developed and used during colorectal ESD [1] [2]. We report a novel traction method, "the crane technique," which involves the use of the EndoTrac (Top Corporation, Tokyo, Japan) [3], for rectal ESD.
<i>Fto</i> Deficiency Reduces Anxiety- and Depression-Like Behaviors in Mice via Alterations in Gut Microbiota
Authors: Lijuan Sun, Lanjing Ma, Haohao Zhang, Ying Cao, Chenchen Wang, Nannan Hou, Niu Huang, Karen M. von Deneen, Changhai Zhao, Yupeng Shi, Yan Pan, Meixia Wang, Gang Ji, Yongzhan Nie
Journal: Theranostics (2019)

Depression and obesity have high concurrence within individuals, which may be explained by sharing the same risk factors, including disruption of the intestinal microbiota.However, evidence that delineated the causal connections is extremely scarce.Methods: Mice lacking fat mass-and obesity-associated gene (Fto) were generated.Fto-deficient and wild-type control mice were subjected to novel conditions with or without chronic unpredictable mild stress (CUMS) for 6 weeks.Some mice were treated with antibiotics via their drinking water for 6 weeks in order to deplete their microbiota.Behavioral tests were performed to evaluate anxiety-and depression-like behaviors.16S rRNA amplicon and metagenomic sequencing were employed to analyse fecal microbiota.Plasma levels of inflammatory cytokines and lipopolysaccharides (LPS) were also compared.Results: Deletion of Fto led to lower body weight and decreased anxiety-and depression-like behaviors, Fto+/-mice were also less susceptible to stress stimulation, highlighting the essential role of Fto in pathogenesis of depression.With regard to gut microbiota, Fto deficiency mice harbored specific bacterial signature of suppressing inflammation, characterized with higher abundance of Lactobacillus, lower Porphyromonadaceae and Helicobacter.Critically, behavioral alterations of Fto +/-mice are mediated by shift in gut microbiota, as such changes can be partially attenuated using antibiotics.Exposure to CUMS increased serum IL-6 level while Fto deficiency reduced its level, which may be explained by a lower LPS concentration.Conclusion: Together, our findings uncover the roles of Fto on depression and provide insights into microbiota-related biological mechanisms underlying the association between obesity and depression.
Abstract 19536: Weight Loss in Obese Patients May Abrogate the Tendency to Develop Cardiac Allograft Vasculopathy During the First-Year After Heart Transplant
Authors: Richard Cheng, Sadia Dimbil, Ryan Levine, Babak Azarbal, Jignesh Patel, Michelle Kittleson, Lawrence Czer, Jon A Kobashigawa
Journal: Circulation (2017)

Introduction: Cardiac allograft vasculopathy is associated with both immunological factors (i.e. pro-inflammatory cytokines and HLA antibodies) and non-immunologic factors related to the heart transplant patient, including diabetes, hyperlipidemia, hypertension, and obesity. We sought to investigate whether body mass index (BMI) is associated with the development of CAV and whether changes in BMI results in a different outcome. Methods: Between 2007 and 2012 we assessed 424 heart transplant patients from our single center. We stratified our population into the following groups: no obesity at HTx which persisted to 12-months post-transplant (n=342), obesity at transplant which persisted to 12-months post-transplant (n=48), and obesity at HTx to normal BMI at 12-months post-transplant (n=8). BMI ≥ 30 was indicative of obesity. We evaluated the demographics of all groups, including the proportion of patients with diabetes and hypertension. The endpoint of this study was 1-year freedom from cardiac allograft ...
Prognostic immune markers for recurrence and survival in locally advanced esophageal adenocarcinoma.
Authors: Laila Babar, Ali Hussainy Zaidi, Ashten N. Omstead, Ping Zheng, Ronan Joseph Kelly, Blair Anderson Jobe
Journal: Journal of Clinical Oncology (2019)

50 Background: Treatment options and risk stratification for esophageal adenocarcinomas (EAC) primarily rely on clinical and pathological criteria, such as tumor stage and pathological response (PR) evaluation. However, with immunotherapy showing hints of activity in EAC there is an emerging need to develop new predictive biomarkers that will not only identify high-risk patients but also unlock novel therapeutic strategies. The aim of this study was to evaluate if LAG3, TIM3, IDO and CXCL9 gene expression along with pathological classifiers correlate with recurrence and/or death in EAC. Methods: Clinical and histopathology data on 49 resectable EAC patients was captured. Mean age at diagnosis was 64.2 years with a median follow up of 21.2 months. Laser capture microdissection followed by qRT-PCR was performed on pretreatment FFPE samples to quantify LAG3, TIM3, IDO and CXCL9 gene levels. Statistical tools established individual biomarker cutoffs and these were correlated with clinical outcomes. Results: For disease free survival, a best fit Cox model was generated consisting of PR (HR=9.54, 95% CI = 2.13 ~ 42.62, p = .003), LAG3 (HR = 2.86, 95% CI = 1.03 ~ 7.94, p = .044), and CXCL9 (HR = 0.40, 95% CI = 0.16 ~ 0.99, p = .049). Moreover, the classification performance of the 3 predictor Cox model was deemed superior to PR alone; P = 0.0001 (Likelihood Ratio Test (LRT)) indicated strong significance in predictability with the recurrence model. For overall survival, a best fit Cox model was generated consisting of TIM3 (HR = 4.43, 95% CI= 1.70 ~ 11.5, p = .002) PR (HR = 3.09, 95% CI= 1.00 ~ 9.56, p = .051) and IDO (HR = 0.31, 95% CI = 0.11 ~ 0.82, p = .019). Likewise, the classification performance of the 3 predictor Cox model was deemed superior to PR alone; P = 0.0004 (LRT) indicated strong significance in predictability with the survival model. Conclusions: LAG3, TIM3, IDO and CXCL9 expression in conjunction with PR to neoadjuvant therapy provide superior tools to predict recurrence and death in locally advanced EAC patients. Additionally, given the paucity of treatment options for esophageal cancer we must check for these markers early on in the disease course to better risk stratify patients and provide newer targets for novel treatments.
The 1-Hour Esophageal String Test: A Non-Endoscopic Minimally Invasive Test to Accurately Detect Disease Activity in Eosinophilic Esophagitis
Authors: Steven J. Ackerman, Amir F. Kagalwalla, Ikuo Hirano, Nirmala Gonsalves, Paul Menard-Katcher, Sandeep Gupta, Joshua B. Wechsler, Milica M. Grozdanovic, Zhaoxing Pan, Joanne C. Masterson, Jian Du, Robert J. Fantus, Sergei I. Ochkur, Faria Ahmed, Kelley E. Capocelli, Hector Melin-Aldana, Juliet Hammer, Allison Dubner, Katie Amsden, Kaitlin Keeley, Maureen Sulkowski, Angelika Zalewski, Fred (Dan) Atkins, Glenn T. Furuta
Journal: Journal of Allergy and Clinical Immunology (2019)
Using circulating tumor DNA (ctDNA) to predict surgical outcome and postoperative recurrence following neoadjuvant chemoradiation (CRT) for borderline resectable/locally advanced rectal cancer (LARC).
Authors: Susan G.R. McDuff, Karin Hardiman, Aparna Raj Parikh, Peter Ulintz, Mehlika Hazar-Rethinam, Hui Zheng, Emily Van Seventer, Isobel Fetter, Brandon Nadres, David P. Ryan, Colin D. Weekes, Jeffrey W. Clark, James C. Cusack, Lipika Goyal, Andrew X. Zhu, Jennifer Yon-Li Wo, Lawrence Scott Blaszkowsky, Jill N. Allen, Ryan Bruce Corcoran, Theodore S. Hong
Journal: Journal of Clinical Oncology (2019)

562 Background: This study was designed to assess the capability of perioperative ctDNA analysis to predict surgical outcome and recurrence following neoadjuvant CRT for LARC. Methods: Thirty-one patients (pts) with newly diagnosed LARC ( n = 29) or locally recurrent (non-metastatic) rectal cancer ( n= 3) were treated between 7/2013 - 7/2017. Pts received long-course neoadjuvant CRT prior to surgical resection: 50.4 Gy/28 fractions. Serum ctDNA was typically measured at baseline, weekly during CRT, pre-operatively, and post-operatively. Next-generation sequencing was used to identify mutations in the primary tumor, and mutation-specific droplet digital PCR was used to detect mutation fraction in ctDNA. Results: The median age of the cohort was 53 years (IQR 46.5-65.3 y). The overall R0-node negative (R0-NN) resection rate was 66.7%. The rate of R0-NN resection was significantly higher among pts with undetectable preoperative ctDNA ( n = 17, 88%) compared to pts with a detectable preoperative ctDNA ( n = 10, 30%, Fisher’s exact p = 0.036). The overall pathologic complete response (pCR) rate was 18.5%. The pCR rate among pts with undetectable preoperative ctDNA was 23.5% vs 10% among pts with detectable preoperative ctDNA ( ns). For patients with a positive assay at baseline and weekly draws available, those who went on to have an R0NN resection were observed to exhibit ctDNA clearance by the second week of chemoradiation. Recurrence free survival (RFS) was calculated for the subset ( n= 22) who were able to undergo surgery and had post-operative ctDNA available. Pts with detectable postoperative ctDNA experienced poorer RFS than those with undetectable ctDNA, HR 8.0, p &lt; 0.001. Conclusions: Undetectable preoperative ctDNA is associated with R0-NN surgical outcome, and detectable postoperative ctDNA is associated with worse RFS in a cohort of pts treated with neoadjuvant CRT for LARC. Validation is ongoing in a larger cohort of 39 pts.
Effect of Adding Docetaxel to Androgen-Deprivation Therapy in Patients With High-Risk Prostate Cancer With Rising Prostate-Specific Antigen Levels After Primary Local Therapy
Authors: Stéphane Oudard, Igor Latorzeff, Armelle Caty, Laurent Miglianico, Emmanuel Sevin, Anne Claire Hardy-Bessard, Remy Delva, Frédéric Rolland, Loic Mouret, Franck Priou, Philippe Beuzeboc, Gwenaelle Gravis, Claude Linassier, Philippe Gomez, Eric Voog, Xavier Muracciole, Christine Abraham, Eugeniu Banu, Jean-Marc Ferrero, Alain Ravaud, Ivan Krakowski, Jean-Léon Lagrange, Gaël Deplanque, David Zylberait, Laurence Bozec, Nadine Houede, Stéphane Culine, Reza Elaidi
Journal: JAMA Oncology (2019)

Androgen-deprivation therapy (ADT) plus docetaxel is the standard of care in hormone-naive metastatic prostate cancer but is of uncertain benefit in a nonmetastatic, high-risk prostate cancer setting.To assess the benefit of ADT plus docetaxel in patients presenting with rising prostate-specific antigen (PSA) levels after primary local therapy and high-risk factors but no evidence of metastatic disease.This open-label, phase 3, randomized superiority trial comparing ADT plus docetaxel vs ADT alone enrolled patients from 28 centers in France between June 4, 2003, and September 25, 2007; final follow-up was conducted April 12, 2017, and analysis was performed May 2 to July 31, 2017. Patients had undergone primary local therapy for prostate cancer, were experiencing rising PSA levels, and were considered to be at high risk of metastatic disease. Stratification was by prior local therapy and PSA-level doubling time (≤6 vs >6 months), and intention-to-treat analysis was used.Patients were randomly assigned to receive ADT (1 year) plus docetaxel, 70 mg/m2 (every 3 weeks [6 cycles]), or ADT alone (1 year).The primary outcome was PSA progression-free survival (PSA-PFS). Secondary end points were PSA response, radiologic PFS, overall survival, safety, and quality of life.Overall, 254 patients were randomized (1:1) to the trial; median age, 64 years in the ADT plus docetaxel arm, 66 years in the ADT alone arm. At a median follow-up of 30.0 months, the median PSA-PFS was 20.3 (95% CI, 19.0-21.6) months in the ADT plus docetaxel arm vs 19.3 (95% CI, 18.2-20.8) months in the ADT alone arm (hazard ratio [HR], 0.85; 95% CI, 0.62-1.16; P = .31). At a median follow-up of 10.5 years, there was no significant between-arm difference in radiologic PFS (HR, 1.03; 95% CI, 0.74-1.43; P = .88). Overall survival data were not mature. The most common grade 3 or 4 hematologic toxic effects in the ADT plus docetaxel arm were neutropenia (60 of 125 patients [48.0%]), febrile neutropenia (10 [8.0%]), and thrombocytopenia (4 [3.0%]). There was no significant between-arm difference in overall quality of life.Compared with ADT alone, combined ADT plus docetaxel therapy with curative intent did not significantly improve PSA-PFS in patients with high-risk prostate cancer and rising PSA levels and no evidence of metastatic disease.French Health Products Safety Agency identifier: 030591; ClinicalTrials.gov identifier: NCT00764166.
Bias against female doctors won’t end until evidence based interventions are mandatory
Authors: Jane Feinmann
Journal: BMJ (2019)

Systemic interventions such as mandatory checklists and other “bias busting” strategies are needed to end ingrained discrimination against female doctors, according to a review of current “ineffectual” diversity and inclusion policies in healthcare organisations.

The review by management and innovation scientists at the University of Toronto and published in the Lancet ,1 says that despite considerable investment in inclusion policies, women doctors continue to face “everyday experiences of sexism.” These include exposure to sexist jokes, sexual harassment, weaker references letters, a lower income, and a decreased likelihood of being addressed using one’s professional title, say the researchers, who drew on …
KMT2E-Mediated Epigenetic Reprogramming Promotes the Sensitivity to All-Trans Retinoic Acid and Increases the Granulocytic Differentiation in AML Cells
Authors: Luciana Yamamoto Almeida, Isabel Weinhäuser, Diego Antonio Pereira-Martins, Josiane Lilian Schiavinato, Patrícia Vianna Bonini Palma, Camila Bonaldo, Cleide Lucia Silva, Juliana Oliveira Poltronieri, Larissa Cândido, Antonio R. Lucena-Araujo, Eduardo Magalhães Rego
Journal: Blood (2018)