tbuckley/cabot-search huggingface dataset:
Evaluating safety and efficacy of immune checkpoint inhibitors (ICI) in elderly patients (pts) for advanced cancer treatment: A retrospective study
Authors: S.J. Brixius, F. Meiss, D. von Bubnoff, R. Zeiser, C.F. Waller, J. Duyster, J. Rawluk
Journal: Annals of Oncology (2018)

Background: Older pts with cancer require special consideration with respect to cancer treatment due to multiple comorbidities and an altered immune status. However, older pts are often under-represented in clinical trials, so information about the use of ICIs in elderly pts is marginal. Methods: We retrospectively identified cancer pts aged over 70 yrs treated with any ICI between 04/2012 and 04/2018. Tumor entities, laboratory parameters, steroid use, adverse events (AE) as well as survival and therapy data were compared. Results: 176 pts were included (120 M, 56 F), the median age was 75 yrs (range 70-89) with 89 pts aged 75 or younger (%) and 87 pts over 75 (%). 38 pts (22%) had ECOG 0, 100 pts (57%) had ECOG 1, 23 pts had ECOG 2-3 (13%), in 15 pts (8%) data was not available. 175 pts (99%) had preexisting medical problems. Assessed by the Cumulative Illness Rating Scale for Geriatrics (CIRS-G), 100 pts (57%) had severe comorbidities in at least one, 43 pts (24%) in at least two organ systems. 76 pts (43%) had no severe comorbidities. 89 pts (51%) had malignant melanoma, 62 (35%) non-small cell lung cancer and 8 (5%) renal-cell carcinoma. 155 pts (93%) were in a metastasized stage. 81 pts (46%) received pembrolizumab, 72 (41%) nivolumab, 35 (20%) ipilimumab, 3 (2%) atezolizumab, 1 (0.6%) durvalumab and azacitidin and 6 pts (3%) were treated with a combination of anti-PD(L)1- and anti-CTLA4-antibodies. 19pts (11%) received various consecutive ICIs. An average immunotherapy consisted of 10.2 doses (range 1-52 doses) and took 6.5 months (range 1 day – 3.9 yrs). 152 pts (86%) had AEs. 59 (34%) had severe AEs (CTCAE grad 3-4) and 63 pts (36%) required systemic corticosteroids due to AEs. We observed common described immune related AEs in 82 pts (47%). Therapy discontinuations due to AEs were in 35 pts (20%), in 23 pts (13%) the ICI was definitely stopped. We note a disease control rate (DCR) of 60% (21pts CR; 60pts PR, 67 pts SD) in the follow-up CT scans. The median survival under ICI was 11.8 months (range 5 days – 4.6 yrs). Conclusions: Our data encourage that the use of ICI in elderly is beneficial even though AEs are commonly reported and potentially harmful. Legal entity responsible for the study: Department of Hematology, Oncology and Stem Cell Transplantation, Freiburg University Medical Center, Freiburg, Germany. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Abstract 18611: JMJD2B Regulates Endothelial to Mesenchymal Cell Transition
Authors: Simone-Franziska Glaser, Jes-Niels Boeckel, David John, Claudia Döring, Sebastian Cremer, Stefanie Dimmeler
Journal: Circulation (2016)

Introduction: Endothelial to mesenchymal transition (EndMT) is a variation of epithelial to mesenchymal transition (EMT). The process of EndMT comprises the transition of an endothelial cell (EC) t...
Combined Targeting of Bcl-2 and XPO1 Overcomes Acquired Resistance to Tyrosine Kinase Inhibitors in the FLT3-ITD/TKD Double Mutant AML
Authors: Yoko Tabe, Kotoko Yamatani, Haeun Yang, Kaori Saito, Yuko Murakami-Tonami, Koya Suzuki, Weiguo Zhang, Sonoko Kinjo, Kazuho Ikeo, Masaki Hosoya, Kaoru Mogushi, Shigeo Yamaguchi, Hironori Harada, Takashi Miida, Neil Shah, Marina Y. Konopleva, Yoshihide Hayashizaki, Michael Andreeff
Journal: Blood (2018)
Abstract P015: Objectively Measured Step Counts Was Independently Associated With Higher Cognition in Apparently Healthy Japanese Men
Authors: Takeshi Shibukawa, Akira Fujiyoshi, Katsuyuki Miura, Naoko Miyagawa, Yoshino Saito, Maryam Zaid, Takashi Hisamatsu, Takayoshi Ohkubo, Hisatomi Arima, Ikuo Tooyama, Hirotsugu Ueshima
Journal: Circulation (2018)

Introduction: A positive association between physical activity and cognition has been reported. However, very few pertinent studies have evaluated physical activity by objective measures. Hypothesis: In a community-based sample of non-demented men, objectively measured step count was positively associated with higher cognitive function. Methods: The Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA) randomly recruited community-dwelling apparently healthy men aged 40-79 years from Shiga, Japan, and measured their step counts over 7 consecutive days using a pedometer (DIGI-Walker, DW-200) at baseline (2006-08). Among 853 mem who returned for follow-up (2010-12), we assessed their cognition using Cognitive Abilities Screening Instrument (CASI) score. The score can range from 0 to 100, and higher score indicates better cognition. We restricted our analyses to those with a valid 7-day average step count at baseline and who remained free of stroke (N=678). We calculated crude and adjusted mean CASI score according to quartile of average step count using linear regression models. All adjusting covariates used in models were asssessed at baseline including age, educational attainment, smoking, and drinking. Results: The mean [standard deviation] of age and unadjusted score were 63.8 [9.1] years and 90.8 [5.8]. Mean CASI score was higher in higher quartile of average step: 90.2, 90.4, 90.6, and 91.8 from the lowest to the highest quartile of average step ( P for trend =0.004) in a model adjusted for age and education. Further adjustment for smoking, drinking and other cardiovascular risk factors resulted in similar pattern of association (Table 1). Conclusions: Apparently healthy Japanese men with greater 7-day average step count at baseline measured with pedometer was associated with a small but significantly higher CASI score than those with fewer step count. The finding is consistent with the hypothesis that physical activity is protective for cognition in non-demented individuals.
Culture-free genotyping of Neisseria gonorrhoeae revealed distinct strains at different anatomical sites in a quarter of patients, the Netherlands, 2012 to 2016
Authors: Brian MJW van der Veer, Petra FG Wolffs, Christian JPA Hoebe, Nicole HTM Dukers-Muijrers, Lieke B van Alphen
Journal: Eurosurveillance (2018)

BackgroundGenotyping of Neisseria gonorrhoeae (NG) is essential for surveillance to monitor NG transmission and dissemination of resistant strains. Current genotyping methods rely on bacterial culture which frequently fails.AimOur aim was to develop a culture-free genotyping method that is compatible with the widely used N. gonorrhoeae multi-antigen sequence typing (NG-MAST) database, which facilitates genotyping of NG detected at separate anatomical sites in individual patients.MethodsSpecific primers for both PCR targets porB and tbpB were designed and technically validated by assessing the analytical sensitivity, cross-reactivity with 32 non-gonoccocal Neisseria species, and concordance with NG-MAST. Clinical application was assessed on 205 paired samples from concurrent NG infections at different anatomical sites of 98 patients (81 men who have sex with men and 17 women) visiting our sexually transmitted infections clinic.ResultsTyping could be consistently performed on samples with a PCR quantification cycle (Cq) value <35. Furthermore, the method showed no cross-reactivity and was concordant with NG-MAST. Culture-free NG-MAST improved the typing rate from 62% (59/95) for cultured samples to 94% (89/95) compared with culture-dependent NG-MAST. Paired samples of 80 of 98 patients were genotyped, revealing distinct NG strains in separate anatomical sites in 25% (20/80) of the patients.ConclusionsThis NG-specific genotyping method can improve NG surveillance as it facilitates genotyping of non-culturable and extra-genital samples. Furthermore, 25% of patients were infected with multiple NG strains, which is missed in current culture-dependent surveillance. Including non-culturable and concurrent NG infections in surveillance informs actions on dissemination of multidrug-resistant NG strains.
Abstract 13657: Induced Hypothermia Improves a Novel Array of Metabolic Outcomes After Mouse Hemorrhagic Shock
Authors: Jing Li, Huashan Wang, Chunpei Lee, James Costakis, Xiangdong Zhu, Terry L Vanden Hoek
Journal: Circulation (2015)

Introduction: Hemorrhagic shock results in myocardial dysfunction which involves impaired aerobic metabolism leading to energy depletion (ATP and NAD) and lactate production. Prior studies demonstrated that hypothermia (TH) protects heart against HS injury and is associated with decreased metabolic activity and energy demand. We hypothesized that TH protection is result of preservation of energy substrates in tissues via reduced release into blood. Methods: Mice underwent arterial bleed (2.25 ml/100 g over 10 min) and were randomized to normothermia (NT, 37 ± 0.5 °C) and hypothermia (TH, 33 ± 0.5 °C) groups. MAP was then maintained at 35 ± 5 mmHg for 90 min. Resuscitation was initiated by reinfusion of shed blood plus L-lactate Ringer’s solution. TH was induced at 30 min of shock and maintained for 2 h. Hearts were collected at Sham, shock 5, 15, 30 and 90 min (S5, S15, S30 and S90 respectively), and the end of resuscitation (R180). Tissue and blood ATP, NAD, the inflammatory markers PBEF and tissue sorbitol were measured. Tissue content of ATP, NAD and the NAD synthesizing enzyme nicotinamide phosphoribosyltransferase (Nampt) were also measured. Results: Compared to NT, TH improved survival (33% vs. 83%, p &lt; 0.5). In the NT group, ATP, NAD and Nampt were released into blood during shock with resuscitation, with significant attenuation by TH. In contrast, tissue levels of ATP and NAD were significantly higher than blood and were reduced during shock, with restoration to baseline levels in mice that survived to R180. Tissue sorbitol concentrations were increased during shock, were reduced by hypothermia and returned to baseline levels at R180 in mice that survived. Conclusions: Hemorrhagic shock resulted in rapid depletion of ATP and NAD, an effect attenuated by TH, as measured by increased release from muscle tissue into blood. This work identifies a novel array of metabolic markers potentially important to hemorrhagic shock outcome.
For Nobel Peace Prize Winner Dr Denis Mukwege, His Patients Motivate and Inspire
Authors: Rita Rubin
Journal: JAMA (2018)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Mechanisms and Management of Asthma Exacerbations
Authors: J. Michael Ramsahai, Philip M. Hansbro, Peter A. B. Wark
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Acute asthma remains an important medical emergency, the most frequent cause of acute admissions in children and a major source of morbidity for adults with asthma. In all ages with asthma, the presence of exacerbations is an important defining characteristic of asthma severity. In this review, we assess the epidemiology of acute asthma, the triggers of acute exacerbations, and the mechanisms that underlie these exacerbations. We also assess current treatments that prevent exacerbations, with an emphasis on the role of type 2 airway inflammation in the context of acute exacerbations and the novel treatments that effectively target this. Finally we review current management strategies of the exacerbations themselves.
Association of Noninfectious Pneumonia With Ustekinumab Use
Authors: Allen Brinker, Carmen Cheng, Vicky Chan
Journal: JAMA Dermatology (2018)

The US Food and Drug Administration (FDA) conducts ongoing public health safety surveillance for drug and therapeutic biologic products. Identifying cases of acute and subacute noninfectious pneumonia supports the public health mission of the FDA.To identify and analyze postmarketing cases of noninfectious pneumonia associated with ustekinumab use.This retrospective analysis of postmarketing (spontaneous) case reports reviewed the FDA Adverse Event Reporting System (FAERS) and the PubMed databases from September 25, 2009, through November 20, 2017. Twelve cases of new-onset acute and subacute noninfectious pneumonia were identified after general marketing of ustekinumab. Cases were excluded if the time to symptom onset was more than 2 years from ustekinumab initiation and if an alternative origin for the noninfectious pneumonia (other than drug-induced) was reported.Cases of noninfectious pneumonia associated with ustekinumab use were analyzed for baseline and demographic information, reason for ustekinumab use, symptoms, time to onset, dose sequence, laboratory and diagnostic information, and clinical outcome.Of the 12 cases, 8 were identified from the FAERS database and 4 from PubMed. The 12 cases (7 men [58%] and 5 women [42%], with a median [range] age of 63 [27-80] years) included 7 interstitial pneumonia (58%), 3 eosinophilic pneumonia (25%), 1 organizing pneumonia (8%), and 1 hypersensitivity pneumonitis (8%) diagnoses. All 12 cases reported a serious outcome, including 7 hospitalizations (58%) and 1 respiratory failure requiring mechanical ventilation (8%). No outcome of death was reported. All 12 cases were supportive of a temporal association; specifically, in 9 cases (75%), the pulmonary symptoms appeared after 1 to 3 doses of ustekinumab. In addition, 7 cases (58%) of positive dechallenge were reported, including 1 case of a positive rechallenge.The postmarketing cases suggest an association between noninfectious pneumonia and use of ustekinumab; these findings have led to the addition of a new warning for ustekinumab users regarding the risk of developing noninfectious pneumonia.
Artificial intelligence may not recognise the nuances of general practice
Authors: Keith Hopcroft
Journal: BMJ (2018)

I agree with Rampton and Spinas’s view that the doctor-patient relationship is so central to medicine—especially primary care—that artificial intelligence (AI) will not make doctors obsolete.1 Their arguments could be strengthened, though, particularly when viewed from the perspective of general practice.

Any practising GP soon realises that patients are often less bothered by …
Identifying the anti-inflammatory response to lipid lowering therapy: a position paper from the working group on atherosclerosis and vascular biology of the European Society of Cardiology
Authors: José Tuñón, Lina Badimón, Marie-Luce Bochaton-Piallat, Bertrand Cariou, Mat J Daemen, Jesus Egido, Paul C Evans, Imo E Hoefer, Daniel F J Ketelhuth, Esther Lutgens, Christian M Matter, Claudia Monaco, Sabine Steffens, Erik Stroes, Cécile Vindis, Christian Weber, Magnus Bäck
Journal: Cardiovascular Research (2018)

Dysregulated lipid metabolism induces an inflammatory and immune response leading to atherosclerosis. Conversely, inflammation may alter lipid metabolism. Recent treatment strategies in secondary prevention of atherosclerosis support beneficial effects of both anti-inflammatory and lipid-lowering therapies beyond current targets. There is a controversy about the possibility that anti-inflammatory effects of lipid-lowering therapy may be either independent or not of a decrease in low-density lipoprotein cholesterol. In this Position Paper, we critically interpret and integrate the results obtained in both experimental and clinical studies on anti-inflammatory actions of lipid-lowering therapy and the mechanisms involved. We highlight that: (i) besides decreasing cholesterol through different mechanisms, most lipid-lowering therapies share anti-inflammatory and immunomodulatory properties, and the anti-inflammatory response to lipid-lowering may be relevant to predict the effect of treatment, (ii) using surrogates for both lipid metabolism and inflammation as biomarkers or vascular inflammation imaging in future studies may contribute to a better understanding of the relative importance of different mechanisms of action, and (iii) comparative studies of further lipid lowering, anti-inflammation and a combination of both are crucial to identify effects that are specific or shared for each treatment strategy.
Long Term Follow-up of a Phase 2 Study Examining Intratumoral G100 Alone and in Combination with Pembrolizumab in Patients with Follicular Lymphoma
Authors: Christopher R Flowers, Carlos Panizo, Iris Isufi, Alex F. Herrera, Craig Okada, Elizabeth H. Cull, Bela Kis, Jorge M. Chaves, Nancy L. Bartlett, Weiyun Ai, Luis de la Cruz-Merino, Locke J. Bryan, Roch Houot, Kim Linton, Javier Briones, Ian Chau, Gottfried R. von Keudell, Hailing Lu, Frank J Hsu, Ahmad S Halwani
Journal: Blood (2018)
Comparison of Induction Strategies and Responses for Acute Myeloid Leukemia Patients after Resistance to Hypomethylating Agents for Antecedent Myeloid Malignancy
Authors: Chetasi Talati, Aaron D Goldberg, Amanda Przespolewski, Onyee Chan, Najla Al Ali, Christopher Famulare, David A Sallman, Eric Padron, Andrew Kuykendall, Alan F. List, Jeffrey E. Lancet, Eunice S. Wang, Martin S. Tallman, Rami S. Komrokji, Kendra L. Sweet
Journal: Blood (2018)
The Link between the Multiverse of Immune Microenvironments in Metastases and the Survival of Colorectal Cancer Patients
Authors: Marc Van den Eynde, Bernhard Mlecnik, Gabriela Bindea, Tessa Fredriksen, Sarah E. Church, Lucie Lafontaine, Nacilla Haicheur, Florence Marliot, Mihaela Angelova, Angela Vasaturo, Daniela Bruni, Anne Jouret-Mourin, Pamela Baldin, Nicolas Huyghe, Karin Haustermans, Annelies Debucquoy, Eric Van Cutsem, Jean-Francois Gigot, Catherine Hubert, Alex Kartheuser, Christophe Remue, Daniel Léonard, Viia Valge-Archer, Franck Pagès, Jean-Pascal Machiels, Jérôme Galon
Journal: Cancer Cell (2018)
Alpha‐Fetoprotein Decrease from &gt; 1,000 to &lt; 500 ng/mL in Patients with Hepatocellular Carcinoma Leads to Improved Posttransplant Outcomes
Authors: Neil Mehta, Jennifer L. Dodge, John P. Roberts, Ryutaro Hirose, Francis Y. Yao
Journal: Hepatology (2018)

High alpha‐fetoprotein (AFP) &gt; 1,000 ng/mL is associated with poor outcomes after liver transplantation (LT) for hepatocellular carcinoma (HCC). A new national policy has been implemented for AFP &gt; 1,000 ng/mL requiring a decrease to &lt; 500 ng/mL before LT, but there is a paucity of data on the optimal AFP threshold before LT. We aimed to evaluate the effects of a reduction in AFP from &gt; 1,000 ng/mL to different AFP thresholds before LT on survival and HCC recurrence after LT using the United Network for Organ Sharing database. We identified 407 patients who underwent transplant between January 2005 and September 2015 and who had AFP &gt; 1,000 ng/mL at least once before LT. The last AFP measurement before LT was &gt; 1,000 ng/mL in 72.0%, decreased from &gt; 1,000 to 101‐499 ng/mL in 9.6%, and decreased to ≤ 100 ng/mL in 14.3%. Local‐regional therapy was not performed in 45.4% of patients with AFP &gt; 1,000 ng/mL at LT versus 12.8% of those with AFP of 101‐499 ng/mL and 10.3% of those with AFP ≤ 100 ng/mL at LT ( P &lt; 0.001). Kaplan‐Meier 5‐year post‐LT survival for those with AFP &gt; 1,000 ng/mL at LT was 48.8% versus 67.0% for those with a decrease in AFP to 101‐499 ng/mL ( P &lt; 0.001) and 88.4% for those with AFP ≤ 100 ng/mL at LT ( P &lt; 0.001). HCC recurrence probability at 5 years was 35.0% for patients with AFP &gt; 1,000 ng/mL versus 13.3% for patients with AFP of 101‐499 ng/mL and 7.2% for patients with AFP ≤ 100 ng/mL at LT ( P &lt; 0.001). In multivariable analysis, a decrease in the AFP to 101‐499 ng/mL was associated with a &gt; 2‐fold reduction in posttransplant mortality ( P = 0.01) and a nearly 3‐fold reduction in HCC recurrence ( P = 0.02) compared with AFP &gt; 1,000 ng/mL at LT. Conclusion : Our results demonstrated significantly improved post‐LT outcomes when restricting LT to patients with a reduction in AFP from &gt; 1,000 to &lt; 500 ng/mL, validating the recently implemented national policy.
Natural Killer–Derived Exosomal miR-186 Inhibits Neuroblastoma Growth and Immune Escape Mechanisms
Authors: Paolo Neviani, Petra M. Wise, Mariam Murtadha, Cathy W. Liu, Chun-Hua Wu, Ambrose Y. Jong, Robert C. Seeger, Muller Fabbri
Journal: Cancer Research (2018)

Abstract In neuroblastoma, the interplay between immune cells of the tumor microenvironment and cancer cells contributes to immune escape mechanisms and drug resistance. In this study, we show that natural killer (NK) cell–derived exosomes carrying the tumor suppressor microRNA (miR)-186 exhibit cytotoxicity against MYCN-amplified neuroblastoma cell lines. The cytotoxic potential of these exosomes was partly dependent upon expression of miR-186. miR-186 was downregulated in high-risk neuroblastoma patients, and its low expression represented a poor prognostic factor that directly correlated with NK activation markers (i.e., NKG2D and DNAM-1). Expression of MYCN, AURKA, TGFBR1, and TGFBR2 was directly inhibited by miR-186. Targeted delivery of miR-186 to MYCN-amplified neuroblastoma or NK cells resulted in inhibition of neuroblastoma tumorigenic potential and prevented the TGFβ1-dependent inhibition of NK cells. Altogether, these data support the investigation of a miR-186–containing nanoparticle formulation to prevent tumor growth and TGFβ1-dependent immune escape in high-risk neuroblastoma patients as well as the inclusion of ex vivo–derived NK exosomes as a potential therapeutic option alongside NK cell–based immunotherapy. Significance: These findings highlight the therapeutic potential of NK cell–derived exosomes containing the tumor suppressor miR-186 that inhibits growth, spreading, and TGFβ-dependent immune escape mechanisms in neuroblastoma.
Macrophage-Derived IL1β and TNFα Regulate Arginine Metabolism in Neuroblastoma
Authors: Livingstone Fultang, Laura D. Gamble, Luciana Gneo, Andrea M. Berry, Sharon A. Egan, Fenna De Bie, Orli Yogev, Georgina L. Eden, Sarah Booth, Samantha Brownhill, Ashley Vardon, Carmel M. McConville, Paul N. Cheng, Murray D. Norris, Heather C. Etchevers, Jayne Murray, David S. Ziegler, Louis Chesler, Ronny Schmidt, Susan A. Burchill, Michelle Haber, Carmela De Santo, Francis Mussai
Journal: Cancer Research (2018)

Neuroblastoma is the most common childhood solid tumor, yet the prognosis for high-risk disease remains poor. We demonstrate here that arginase 2 (ARG2) drives neuroblastoma cell proliferation via regulation of arginine metabolism. Targeting arginine metabolism, either by blocking cationic amino acid transporter 1 (CAT-1)-dependent arginine uptake