tbuckley/cabot-search huggingface dataset:
Measles recognition during measles outbreak at a paediatric university hospital, Austria, January to February 2017
Authors: Benno Kohlmaier, Nina A Schweintzger, Werner Zenz
Journal: Eurosurveillance (2020)

Recognition of measles is crucial to prevent transmissions in the hospital settings. Little is known about the level of recognition of measles and possible causes of not recognising the disease by physicians in the post-vaccine era. We report on a measles outbreak in a paediatric hospital in Austria in January to February 2017 with strikingly high numbers of not recognised cases. The extent and course of the outbreak were assessed via retrospective case finding. Thirteen confirmed measles cases were identified, two with atypical clinical picture. Of eight cases with no known epidemiological link, only one was diagnosed immediately; four were recognised with delay and three only retrospectively. Eleven typical measles cases had four ‘unrecognised visits’ to the outpatient clinic and 28 on the ward. Two atypical cases had two ‘unrecognised visits’ to the outpatient clinic and 19 on the ward. Thirteen clinicians did not recognise typical measles (atypical cases not included). Twelve of 23 physicians involved had never encountered a patient with measles before. The direct and indirect costs related to the outbreak were calculated to be over EUR 80,000. Our findings suggest the need to establish regular training programmes about measles, including diagnostic pitfalls in paediatric hospitals.
Diagnostic bone marrow biopsy in patients with stage I EMZL treated with radiation therapy: needed or not?
Authors: Juan Pablo Alderuccio, Derek Isrow, Isildinha M. Reis, Sunil Girish Iyer, Jessica J. Meshman, Wei Zhao, Francisco Vega, Jennifer R. Chapman, Arnold M. Markoe, Izidore S. Lossos
Journal: Blood (2020)
Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Neuroendocrine Tumors: Results From the Phase II KEYNOTE-158 Study
Authors: Jonathan Strosberg, Nobumasa Mizuno, Toshihiko Doi, Enrique Grande, Jean-Pierre Delord, Ronnie Shapira-Frommer, Emily Bergsland, Manisha Shah, Marwan Fakih, Shunji Takahashi, Sarina A. Piha-Paul, Bert O'Neil, Sajeve Thomas, Martijn P. Lolkema, Menghui Chen, Nageatte Ibrahim, Kevin Norwood, Julien Hadoux
Journal: Clinical Cancer Research (2020)

Abstract Purpose: KEYNOTE-158 (ClinicalTrials.gov identifier: NCT02628067) investigated the efficacy and safety of pembrolizumab across multiple cancers. We present results from patients with previously treated advanced well-differentiated neuroendocrine tumors (NET). Patients and Methods: Pembrolizumab 200 mg was administered every 3 weeks for 2 years or until progression, intolerable toxicity, or physician/patient decision. Tumor imaging was performed every 9 weeks for the first year and then every 12 weeks. Endpoints included objective response rate (ORR) per RECIST v1.1 by independent central radiologic review (primary) and duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety (secondary). Results: A total of 107 patients with NETs of the lung, appendix, small intestine, colon, rectum, or pancreas were treated. Median age was 59.0 years (range, 29–80), 44.9% had ECOG performance status 1, 40.2% had received ≥3 prior therapies for advanced disease, and 15.9% had PD-L1–positive tumors (combined positive score ≥1). Median follow-up was 24.2 months (range, 0.6–33.4). ORR was 3.7% (95% CI, 1.0–9.3), with zero complete responses and four partial responses (three pancreatic and one rectal) all in patients with PD-L1–negative tumors. Median DOR was not reached, with one of four responses ongoing after ≥21 months follow-up. Median PFS was 4.1 months (95% CI, 3.5–5.4); the 6-month PFS rate was 39.3%. Median OS was 24.2 months (95% CI, 15.8–32.5). Treatment-related adverse events (AE) occurred in 75.7% of patients, 21.5% of whom had grade 3–5 AEs. Conclusions: Pembrolizumab monotherapy showed limited antitumor activity and manageable safety in patients with previously treated advanced well-differentiated NETs.
Local Intracerebral Immunomodulation Using Interleukin-Expressing Mesenchymal Stem Cells in Glioblastoma
Authors: Malte Mohme, Cecile L. Maire, Ulf Geumann, Simon Schliffke, Lasse Dührsen, Krystian Fita, Nuray Akyüz, Mascha Binder, Manfred Westphal, Christine Guenther, Katrin Lamszus, Felix G. Hermann, Nils Ole Schmidt
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Mesenchymal stem cells (MSCs) show an inherent brain tumor tropism that can be exploited for targeted delivery of therapeutic genes to invasive glioma. We assessed whether a motile MSC-based local immunomodulation is able to overcome the immunosuppressive glioblastoma microenvironment and to induce an antitumor immune response. Experimental Design: We genetically modified MSCs to coexpress high levels of IL12 and IL7 (MSCIL7/12, Apceth-301). Therapeutic efficacy was assessed in two immunocompetent orthotopic C57BL/6 glioma models using GL261 and CT2A. Immunomodulatory effects were assessed by multicolor flow cytometry to profile immune activation and exhaustion of tumor-infiltrating immune cells. Diversity of the tumor-specific immune response as analyzed using T-cell receptor sequencing. Results: Intratumoral administration of MSCIL7/12 induced significant tumor growth inhibition and remission of established intracranial tumors, as demonstrated by MR imaging. Notably, up to 50% of treated mice survived long-term. Rechallenging of survivors confirmed long-lasting tumor immunity. Local treatment with MSCIL7/12 was well tolerated and led to a significant inversion of the CD4+/CD8+ T-cell ratio with an intricate, predominantly CD8+ effector T-cell–mediated antitumor response. T-cell receptor sequencing demonstrated an increased diversity of TILs in MSCIL7/12-treated mice, indicating a broader tumor-specific immune response with subsequent oligoclonal specification during generation of long-term immunity. Conclusions: Local MSC-based immunomodulation is able to efficiently alter the immunosuppressive microenvironment in glioblastoma. The long-lasting therapeutic effects warrant a rapid clinical translation of this concept and have led to planning of a phase I/II study of apceth-301 in recurrent glioblastoma.
Effects of Bariatric Surgery in Early- and Adult-Onset Obesity in the Prospective Controlled Swedish Obese Subjects Study
Authors: Felipe M. Kristensson, Johanna C. Andersson-Assarsson, Per-Arne Svensson, Björn Carlsson, Markku Peltonen, Lena M.S. Carlsson
Journal: Diabetes Care (2020)

OBJECTIVE Bariatric surgery is an effective treatment for obesity, but it is unknown if outcomes differ between adults with early- versus adult-onset obesity. We investigated how obesity status at 20 years of age affects outcomes after bariatric surgery later in life. RESEARCH DESIGN AND METHODS The Swedish Obese Subjects study is a prospective matched study performed at 25 surgical departments and 480 primary health care centers. Participants aged 37–60 years with BMI ≥34 kg/m2 (men) or ≥38 kg/m2 (women) were recruited between 1987 and 2001; 2,007 participants received bariatric surgery and 2,040 usual care. Self-reported body weight at 20 years of age was used to stratify patients into subgroups with normal BMI (&amp;lt;25 kg/m2), overweight (BMI 25–29.9 kg/m2), or obesity (BMI ≥30 kg/m2). Body weight, energy intake, and type 2 diabetes status were examined over 10 years, and incidence of cardiovascular and microvascular disease was determined over up to 26 years using data from health registers. RESULTS There were small but statistically significant differences in reduction of body weight among the subgroups after bariatric surgery (interaction P = 0.032), with the largest reductions among those with obesity aged 20 years. Bariatric surgery increased type 2 diabetes remission (odds ratios 4.51, 4.90, and 5.58 in subgroups with normal BMI, overweight, or obesity at 20 years of age, respectively; interaction P = 0.951), reduced type 2 diabetes incidence (odds ratios 0.15, 0.13, and 0.15, respectively; interaction P = 0.972), and reduced microvascular complications independent of obesity status at 20 years of age (interaction P = 0.650). The association between bariatric surgery and cardiovascular disease was similar in the subgroups (interaction P = 0.674). Surgical complications were similar in the subgroups. CONCLUSIONS The treatment benefits of bariatric surgery in adults are similar regardless of obesity status at 20 years of age.
Advancing Safety and Equity Together
Authors: Karthik Sivashanker, Tejal K. Gandhi
Journal: New England Journal of Medicine (2020)

Interview with Dr. Karthik Sivashanker on leveraging models from patient-safety efforts to increase equity. (12:56)Download There are widespread inequities in health outcomes in the United States based on race, sex, language, and other factors. But there is no such thing as high-quality, safe care that is inequitable. Health systems can leverage patient-safety programs to advance equity.
Correction to: Expert statement on the ICU management of patients with thrombotic thrombocytopenic purpura
Authors: Elie Azoulay, Philippe R. Bauer, Eric Mariotte, Lene Russell, Paul Knoebl, Ignacio Martin-Loeches, Frédéric Pène, Kathryn Puxty, Pedro Povoa, Andreas Barratt-Due, Jose Garnacho-Montero, Julia Wendon, Laveena Munshi, Dominique Benoit, Michael von Bergwelt-Baildon, Marco Maggiorini, Paul Coppo, Spero Cataland, Agnès Veyradier, Andry Van de Louw
Journal: Intensive Care Medicine (2020)
U.S. Adults With Pain, a Group Increasingly Vulnerable to Nonmedical Cannabis Use and Cannabis Use Disorder: 2001–2002 and 2012–2013
Authors: Deborah S. Hasin, Dvora Shmulewitz, Magdalena Cerdá, Katherine M. Keyes, Mark Olfson, Aaron L. Sarvet, Melanie M. Wall
Journal: American Journal of Psychiatry (2020)

Given changes in U.S. marijuana laws, attitudes, and use patterns, individuals with pain may be an emerging group at risk for nonmedical cannabis use and cannabis use disorder. The authors examined differences in the prevalence of nonmedical cannabis use and cannabis use disorder among U.S. adults with and without pain, as well as whether these differences widened over time.Data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC, 2001-2002; N=43,093) and NESARC-III (2012-2013; N=36,309) were analyzed using logistic regression. Risk differences of past-year nonmedical cannabis use, frequent (at least three times a week) nonmedical use, and DSM-IV cannabis use disorder were estimated for groups with and without moderate to severe pain, and these risk differences were tested for change over time.Any nonmedical cannabis use was more prevalent in respondents with than without pain (2001-2002: 5.15% compared with 3.74%; 2012-2013: 12.42% compared with 9.02%), a risk difference significantly greater in the 2012-2013 data than in the 2001-2002 data. The prevalence of frequent nonmedical cannabis use did not differ by pain status in the 2001-2002 survey, but was significantly more prevalent in those with than without pain in the 2012-2013 survey (5.03% compared with 3.45%). Cannabis use disorder was more prevalent in respondents with than without pain (2001-2002: 1.77% compared with 1.35%; 2012-2013: 4.18% compared with 2.74%), a significantly greater risk difference in the data from 2012-2013 than from 2001-2002.The results suggest that adults with pain are a group increasingly vulnerable to adverse cannabis use outcomes, warranting clinical and public health attention to this risk. Psychiatrists and other health care providers treating patients with pain should monitor such patients for signs and symptoms of cannabis use disorder.
Oral fluoroquinolone was linked to mitral and aortic regurgitation compared with amoxicillin or azithromycin
Authors: Mike Fralick, Anne Holbrook
Journal: Annals of Internal Medicine (2020)

ACP Journal Club21 January 2020Oral fluoroquinolone was linked to mitral and aortic regurgitation compared with amoxicillin or azithromycinMike Fralick, MD, PhD, SM, Anne Holbrook, MD, PharmD, MScMike Fralick, MD, PhD, SMSinai Health System and University of Toronto, Toronto, Ontario, Canada (M.F.)Search for more papers by this author, Anne Holbrook, MD, PharmD, MScMcMaster University, Hamilton, Ontario, Canada (A.H.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJ202001210-010 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationEtminan M, Sodhi M, Ganjizadeh-Zavareh S, et al. Oral fluoroquinolones and risk of mitral and aortic regurgitation. J Am Coll Cardiol. 2019;74:1444-50. https://pubmed.ncbi.nlm.nih.gov/31514945Clinical Impact RatingsGIM/FP/GP: Cardiology: Infectious Disease: References1 Heidelbaugh JJ, Holmstrom H. The perils of prescribing fluoroquinolones. J Fam Pract. 2013;62:191-7. [PMID: 23570031] Google Scholar2 MacFadden DR, Ridgway JP, Robicsek A, Elligsen M, Daneman N. Predictive utility of prior positive urine cultures. Clin Infect Dis. 2014;59:1265-71. [PMID: 25048850] Google Scholar3 Rawla P, El Helou ML, Vellipuram AR. Fluoroquinolones and the risk of aortic aneurysm or aortic dissection: a systematic review and meta-analysis. Cardiovasc Hematol Agents Med Chem. 2019;17:3-10. [PMID: 30947680] Google Scholar Author, Article, and Disclosure InformationAffiliations: Sinai Health System and University of Toronto, Toronto, Ontario, Canada (M.F.)McMaster University, Hamilton, Ontario, Canada (A.H.)Disclosures: The commentators have disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M19-2922.This article was published at Annals.org on 7 January 2020. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 21 January 2020Volume 172, Issue 2Page: JC10KeywordsAdverse eventsAntibioticsAortic valveCardiovascular therapyDatabasesEscherichia coli infectionsPseudomonas infectionsStrokeTendonsValvular diseases ePublished: 21 January 2020 Issue Published: 21 January 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Dual-Functionalized MSCs that Express CX3CR1 and IL-25 Exhibit Enhanced Therapeutic Effects on Inflammatory Bowel Disease
Authors: Yong Fu, Junjun Ni, Jiahui Chen, Gailing Ma, Mingming Zhao, Shuaidong Zhu, Tongguo Shi, Jie Zhu, Zhen Huang, Junfeng Zhang, Jiangning Chen
Journal: Molecular Therapy (2020)

Mesenchymal stem cells (MSCs) have shown great promise in inflammatory bowel disease (IBD) treatment, owing to their immunosuppressive capabilities, but their therapeutic effectiveness is sometimes thwarted by their low efficiency in entering the inflamed colon and variable immunomodulatory ability in vivo. Here, we demonstrated a new methodology to manipulate MSCs to express CX3C chemokine receptor 1 (CX3CR1) and interleukin-25 (IL-25) to promote their delivery to the inflamed colon and enhance their immunosuppressive capability. Compared to MSCs without treatment, MSCs infected with a lentivirus (LV) encoding CX3CR1 and IL-25 (CX3CR1&IL-25-LV-MSCs) exhibited enhanced targeting to the inflamed colon and could further move into extravascular space of the colon tissues via trans-endothelial migration in dextran sodium sulfate (DSS)-challenged mice after MSC intravenous injection. The administration of the CX3CR1&IL-25-LV-MSCs achieved a better therapeutic effect than that of the untreated MSCs, as indicated by pathological indices and inflammatory markers. Antibody-blocking studies indicated that the enhanced therapeutic effects of dual-functionalized MSCs were dependent on CX3CR1 and IL-25 function. Overall, this strategy, which is based on enhancing the homing and immunosuppressive abilities of MSCs, represents a promising therapeutic approach that may be valuable in IBD therapy.
Combination of TMB and CNA Stratifies Prognostic and Predictive Responses to Immunotherapy Across Metastatic Cancer
Authors: Li Liu, Xue Bai, Jian Wang, Xin-Ran Tang, De-Hua Wu, Sha-Sha Du, Xiu-Ju Du, Yao-Wei Zhang, Hong-Bo Zhu, Yuan Fang, Ze-Qin Guo, Qin Zeng, Xue-Jun Guo, Zhu Liu, Zhong-Yi Dong
Journal: Clinical Cancer Research (2019)

Although tumor mutation burden (TMB) has been well known to predict the response to immune checkpoint inhibitors (ICI), lack of randomized clinical trial data has restricted its clinical application. This study aimed to explore the significance and feasibility of biomarker combination based on TMB and copy-number alteration (CNA) for the prognosis of each tumor and prediction for ICI therapy in metastatic pan-cancer milieu.Non-ICI-treated MSK pan-cancer cohort was used for prognosis analysis. Three independent immunotherapy cohorts, including non-small cell lung cancer (n = 240), skin cutaneous melanoma (n = 174), and mixed cancer (Dana-Farber, n = 98) patients from previous studies, were analyzed for efficacy of ICI therapy.TMB and CNA showed optimized combination for the prognosis of most metastatic cancer types, and patients with TMBlowCNAlow showed better survival. In the predictive analysis, both TMB and CNA were independent predictive factors for ICI therapy. Remarkably, when TMB and CNA were jointly analyzed, those with TMBhighCNAlow showed favorable responses to ICI therapy. Meanwhile, TMBhighCNAlow as a new biomarker showed better prediction for ICI efficacy compared with either TMB-high or CNA-low alone. Furthermore, analysis of the non-ICI-treated MSK pan-cancer cohort supported that the joint stratification of TMB and CNA can be used to categorize tumors into distinct sensitivity to ICI therapy across pan-tumors.The combination of TMB and CNA can jointly stratify multiple metastatic tumors into groups with different prognosis and heterogeneous clinical responses to ICI treatment. Patients with TMBhighCNAlow cancer can be an optimal subgroup for ICI therapy.
Long-gap peripheral nerve repair through sustained release of a neurotrophic factor in nonhuman primates
Authors: Neil B. Fadia, Jacqueline M. Bliley, Gabriella A. DiBernardo, Donald J. Crammond, Benjamin K. Schilling, Wesley N. Sivak, Alexander M. Spiess, Kia M. Washington, Matthias Waldner, Han-Tsung Liao, Isaac B. James, Danielle M. Minteer, Casey Tompkins-Rhoades, Adam R. Cottrill, Deok-Yeol Kim, Riccardo Schweizer, Debra A. Bourne, George E. Panagis, M. Asher Schusterman, Francesco M. Egro, Insiyah K. Campwala, Tyler Simpson, Douglas J. Weber, Trent Gause, Jack E. Brooker, Tvisha Josyula, Astrid A. Guevara, Alexander J. Repko, Christopher M. Mahoney, Kacey G. Marra
Journal: Science Translational Medicine (2020)

A polycaprolactone conduit containing growth factor–encapsulated microspheres repairs 5-cm median nerve defects in rhesus macaques.
A11 Blockade of Myeloid Suppressor Cells Overcomes the Anti-PD-1/PD-L1 Resistance in KRAS-Driven and LKB1-Deficient NSCLC
Authors: R. Li, R. Salehi-Rad, M. Momcilovic, R. Lim, S. Ong, Z. Huang, L. Tran, J. Zhe, M. Paul, M. Teitell, J. Minna, K. Krysan, D. Shackelford, B. Liu, S. Dubinett
Journal: Journal of Thoracic Oncology (2020)
Abstract 14620: Heart Failure-Related Deaths Through Early Adulthood Among Children Operated for Congenital Heart Disease
Authors: Lydia Wright, Matthew Oster, Courtney McCracken, William T Mahle, Lazaros Kochilas, Andreas P Kalogeropoulos
Journal: Circulation (2019)

Introduction: Congenital heart disease (CHD) is a major cause of heart failure (HF) in children and young adults, but the longitudinal risk of HF-related death or transplantation after congenital h...
International Brain Initiative: An Innovative Framework for Coordinated Global Brain Research Efforts
Authors: Amy Adams, Stephanie Albin, Katrin Amunts, Tasia Asakawa, Amy Bernard, Jan G. Bjaalie, Khaled Chakli, James O. Deshler, Yves De Koninck, Christoph J. Ebell, Gary Egan, Melina E. Hale, Michael Häusser, Sung-Jin Jeong, Judy Illes, Linda Lanyon, Pingping Li, Yan Li, Pierre Magistretti, Agnes McMahon, Caroline Montojo, Toshihisa Ohtsuka, Shigeo Okabe, Hideyuki Okano, Gang Pei, Alexandre Pouget, Jason Reindorp, Linda J. Richards, Karen S. Rommelfanger, Paul Sajda, Kimberly N. Scobie, Pann-Ghill Suh, Keiji Tanaka, Edda Thiels, Pedro A. Valdes-Sosa, Andrew E. Welchman, Samantha White, Gary Wilson, Rafael Yuste, Xu Zhang, Jialin Zheng
Journal: Neuron (2020)
A Phase I Dose-Finding Study of Vorinostat (V) Combined with Capecitabine (X) and Cisplatin (P) as First-Line Therapy in Patients with advanced Gastric Cancer
Authors: C. Yoo, M.H. Ryu, B. Ryoo, D.H. Koo, I. Park, Y. Kang
Journal: Annals of Oncology (2012)
The Importance of Coronary Artery Calcium Density
Authors: Michael H. Criqui, Nketi I. Forbang, Isac C. Thomas
Journal: JAMA Cardiology (2020)

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PI4KIIIβ is a therapeutic target in chromosome 1q–amplified lung adenocarcinoma
Authors: Xiaochao Tan, Priyam Banerjee, Edward A. Pham, Florentine U. N. Rutaganira, Kaustabh Basu, Neus Bota-Rabassedas, Hou-Fu Guo, Caitlin L. Grzeskowiak, Xin Liu, Jiang Yu, Lei Shi, David H. Peng, B. Leticia Rodriguez, Jiaqi Zhang, Veronica Zheng, Dzifa Y. Duose, Luisa M. Solis, Barbara Mino, Maria Gabriela Raso, Carmen Behrens, Ignacio I. Wistuba, Kenneth L. Scott, Mark Smith, Khanh Nguyen, Grace Lam, Ingrid Choong, Abhijit Mazumdar, Jamal L. Hill, Don L. Gibbons, Powel H. Brown, William K. Russell, Kevan Shokat, Chad J. Creighton, Jeffrey S. Glenn, Jonathan M. Kurie
Journal: Science Translational Medicine (2020)

This study identifies a molecular basis for malignant secretion and provides a rationale to test PI4KIIIβ antagonists as an intervention.