tbuckley/cabot-search huggingface dataset:
Phase II study of modified FOLFIRINOX for chemotherapy-naïve patients with metastatic pancreatic cancer.
Authors: Makoto Ueno, Masato Ozaka, Hiroshi Ishii, Tosiya Sato, Masafumi Ikeda, Kazuhiro Uesugi, Naohiro Sata, Kouichirou Miyashita, Nobumasa Mizuno, Kunihiro Tsuji, Takuji Okusaka, Junji Furuse
Journal: Journal of Clinical Oncology (2016)

4111 Background: FOLFIRINOX is considered one of the standard chemotherapy regimens for chemotherapy-naïve pts. with MPC, but carries an unfavorable adverse event (AE) profile, especially in Japanese Phase II study of full dose FOLFIRINOX, the incidence of grade 3 or more neutropenia and febrile neutropenia was 77.8% and 22.2% respectively. Objective: The purpose of this study was to evaluate the efficacy and safety of modified FOLFIRINOX regimen: intravenous oxaliplatin 85 mg/m2, irinotecan 150 mg/m2, 5-FU infusion 2,400 mg/m2over 46 h, no bolus 5-FU. Methods: This study was an open-label, multicenter, single-arm phase II study. The primary endpoint was overall survival and the incidence of grade 3 or more neutropenia. All patients did not receive prophylactic pegfilgrastim. Results: Sixty-nine pts. were enrolled from 39 institutions in Japan. Median age was 62.6 years (range 42.4 - 74.2). All pts. had no prior treatment and had distant metastatic lesions. 68.1% of the pts. had a PS 0, the primary site of the tumor was the head of the pancreas in 44.9% of pts., 20.3% of pts. had a biliary stent, and 5.8% of pts. experienced recurrence after resection. The UGT1A1 genotype was wild type in 79.7%, heterozygous (*1/*6, *1/*28) in 20.3%. Median overall survival was 11.2 months (95% confidence interval [CI], 9.0-) and the 1-year survival proportion was 0.481. Median progression-free survival was 5.5 months (95% CI, 4.1-6.7). The response rate was 37.7% (95% CI, 26.3-50.2) and disease control rate was 78.3% (95% CI, 66.7–87.3). The incidence of grade 3 or more neutropenia was 47.8%. Other major grade 3 or more toxicities were febrile neutropenia (8.7%), thrombocytopenia (2.9%), anemia (4.3%), anorexia (15.9%), diarrhea (10.1%), nausea (8.7%), cholangitis (5.8%) and peripheral sensory neuropathy (5.8%). Serious adverse events occurred in 6 pts. (8.7%). All AE proportions were less than those in the previous Japanese full dose Phase II study. One patient died due to interstitial pneumonia related to a treatment. Conclusions: This is the first prospective study of modified FOLFIRINOX in Asia. Modified FOLFIRINOX of this study has an improved safety profile with maintained efficacy in MPC without prophylactic pegfilgrastim. Clinical trial information: UMIN000013301.
Up-regulated LINC01234 promotes non-small-cell lung cancer cell metastasis by activating VAV3 and repressing BTG2 expression
Authors: Zhenyao Chen, Xin Chen, Binbin Lu, Yu Gu, Qinnan Chen, Tianyao Lei, Fengqi Nie, Jingyao Gu, Jiali Huang, Chenchen Wei, Ming Sun, Zhaoxia Wang
Journal: Journal of Hematology & Oncology (2020)

Abstract Background Long noncoding RNAs (lncRNAs) are known to regulate tumorigenesis and cancer progression, but their contributions to non-small-cell lung cancer (NSCLC) metastasis remain poorly understood. Our previous and other studies have revealed the involvement of upregulated LINC01234 in regulating gastric cancer and colon cancer cells proliferation, and we aimed to investigate whether LINC01234 overexpression also contribute to cancer cells metastasis in this study. Methods We collect the NSCLC tissues and adjacent non-tumor tissues and analyzed expression levels of LINC01234 by quantitative reverse-transcription PCR. LINC01234 were knocked down by using siRNAs or shRNAs, and overexpressed by transfection with overexpression vector; RNA levels of miRNA were downregulated or upregulated with inhibitors or mimics. Transwell assays were used to evaluate cell migration and invasive ability; in vivo metastasis experiments were performed to investigate the effect of LINC01234 on NSCLC cells metastasis. Luciferase reporter, RIP, and ChIP assays were used to determine the regulation of LINC01234 on its targets. Results LINC01234 expression is increased in NSCLC tissues, and its upregulation is associated with metastasis and shorter survival in NSCLC. Downregulation of LINC01234 impairs cell migration and invasion in vitro, and inhibits cells metastasis in vivo by acting as a competing endogenous RNA for the miR-340-5p and miR-27b-3p. LINC01234 also interacts with the RNA-binding proteins LSD1 and EZH2, leading to histone modification and transcriptional repression of the anti-proliferative genes BTG2. Conclusions Taken together, our findings identify two oncogenic regulatory axes in NSCLC centering on LINC01234: one involving miR-340-5p/miR-27b-3p in the cytoplasm and the second involving EZH2, LSD1, and BTG2 in the nucleus. Our study indicates that these genes may be targeted to reduce or prevent NSCLC metastasis.
Oligopeptide-modified poly(beta-amino ester)s-coated AdNuPARmE1A: Boosting the efficacy of intravenously administered therapeutic adenoviruses
Authors: Pau Brugada-Vilà, Anna Cascante, Miguel Ángel Lázaro, Cristina Castells-Sala, Cristina Fornaguera, Maria Rovira-Rigau, Lorenzo Albertazzi, Salvador Borros, Cristina Fillat
Journal: Theranostics (2020)

Oncolytic adenoviruses are used as agents for the treatment of cancer.However, their potential is limited due to the high seroprevalence of anti-adenovirus neutralizing antibodies (nAbs) within the population and the rapid liver sequestration when systemically administered.To overcome these challenges, we explored using nanoparticle formulation to boost the efficacy of systemic oncolytic adenovirus administration.Methods: Adenovirus were conjugated with PEGylated oligopeptide-modified poly(β-amino ester)s (OM-pBAEs).The resulting coated viral formulation was characterized in terms of surface charge, size, aggregation state and morphology and tested for anti-adenovirus nAbs evasion and activity in cancer cells.In vivo pharmacokinetics, biodistribution, tumor targeting, and immunogenicity studies were performed.The antitumor efficacy of the oncolytic adenovirus AdNuPARmE1A coated with OM-pBAEs (SAG101) in the presence of nAbs was evaluated in pancreatic ductal adenocarcinoma (PDAC) mouse models.Toxicity of the coated formulation was analyzed in vivo in immunocompetent mice.Results: OM-pBAEs conjugated to adenovirus and generated discrete nanoparticles with a neutral charge and an optimal size.The polymeric coating with the reporter AdGFPLuc (CPEG) showed enhanced transduction and evasion of antibody neutralization in vitro.Moreover, systemic intravenous administration of the formulation showed improved blood circulation and reduced liver sequestration, substantially avoiding activation of nAb production.OM-pBAEs coating of the oncolytic adenovirus AdNuPARmE1A (SAG101) improved its oncolytic activity in vitro and enhanced antitumor efficacy in PDAC mouse models.The coated formulation protected virions from neutralization by nAbs, as antitumor efficacy was preserved in their presence but was completely lost in mice that received the non-formulated AdNuPARmE1A.Finally, coated-AdNuPARmE1A showed reduced toxicity when high doses of the formulation were administered. Conclusions:The developed technology represents a promising improvement for future clinical cancer therapy using oncolytic adenoviruses.
Outpatient Management of Chronic Asthma in 2020
Authors: Julia W. Tripple, Bill T. Ameredes, William J. Calhoun
Journal: JAMA (2020)

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
False-positive Aspergillus galactomannan immunoassays associated with intravenous human immunoglobulin administration
Authors: W.-D. Liu, S.-W. Lin, M.-C. Shih, C.-L. Su, Y.-W. Wang, S.-C. Lin, Y.-F. Lee, H.-H. Huang, W.-C. Chou, U.-I. Wu, Y.-C. Chen, S.-C. Chang
Journal: Clinical Microbiology and Infection (2020)
Abstract 11244: Pulse Deficit as a New, Innovative, Non-Invasive Measure to Risk-Stratify Atrial Fibrillation Patients
Authors: Ya-El Mandel Portnoy, Lynne D Richardson
Journal: Circulation (2018)

Introduction: Atrial Fibrillation (AFib) is the most common cardiac arrhythmia, affecting millions globally and will affect 12 million patients by 2030 nationwide. The cost associated with AFib in ...
Association of Surgical Jacket and Bouffant Use With Surgical Site Infection Risk
Authors: Bradley W. Wills, Walter R. Smith, Alexandra M. Arguello, Gerald McGwin, Elie S. Ghanem, Brent A. Ponce
Journal: JAMA Surgery (2020)

<h3>Importance</h3> Surgical site infections (SSIs) are associated with increased morbidity and mortality. Various measures have been enacted decrease the occurrence of SSIs involving the regulation of the attire worn by the operating room staff, at times without sufficient peer-reviewed literature to support their implementation. <h3>Objective</h3> To evaluate whether the combination of mandated surgical jackets and bouffants in the operating room is associated with the risk of surgical site infection. <h3>Design, Setting, and Participants</h3> A retrospective cohort study of 34 042 inpatient surgical encounters at a large academic tertiary care hospital was performed. Three periods between January 2017 and October 2018 were compared, corresponding with implementation of surgical jackets and the subsequent mandate of surgical jackets plus bouffant head covers. All inpatient surgical cases were included from University of Alabama at Birmingham University Hospital, a single-center, large academic tertiary care hospital. The study comprised a consecutive sample of all inpatient surgical cases over a 22-month period. <h3>Exposures</h3> No surgical jackets or bouffants mandated (8 months), surgical jackets mandated (6 months), both surgical jackets and bouffants mandated (8 months). <h3>Main Outcomes and Measures</h3> The primary study outcome was SSIs, which were collected from institutional infection control monthly summary reports, according to the National Healthcare Safety Network definitions for superficial incisional, deep incisional, and organ/space SSIs. Secondary outcomes included wound dehiscence, postoperative sepsis, death, and cost of interventions. <h3>Results</h3> A total of 34 042 inpatient surgical encounters cases were included in the analysis over the 22-month study period. Of the total patients, 16 380 were women (48%) and 17 638 were men (52%). There was no significant difference in the risk of SSI (1.01% vs 0.99% vs 0.83%;<i>P</i> = .28), mortality (1.83% vs 2.05% vs 1.92%;<i>P</i> = .54), postoperative sepsis (6.60% vs 6.24% vs 6.54%;<i>P</i> = .54), or wound dehiscence (1.07% vs 0.84% vs 1.06%;<i>P</i> = .20) between the 3 groups. Receipts from the first 6 months of the 2018/2019 fiscal year provided an estimated expenditure of more than $300 000 annually on surgical jackets. Bouffants were found to be less expensive than surgical skull caps. <h3>Conclusions and Relevance</h3> The results of this study suggest that surgical jackets and bouffants are neither beneficial nor cost-effective in preventing SSIs. Institutions should evaluate their own data to determine whether recommendations by outside governing organizations are beneficial and cost-effective.
Associations between metabolites and pancreatic cancer risk in a large prospective epidemiological study
Authors: Rachael Stolzenberg-Solomon, Andriy Derkach, Steven Moore, Stephanie J Weinstein, Demetrius Albanes, Joshua Sampson
Journal: Gut (2020)

To assess whether prediagnostic metabolites were associated with incident pancreatic ductal adenocarcinoma (PDAC) in a prospective cohort study.We conducted an untargeted analysis of 554 known metabolites measured in prediagnostic serum (up to 24 years) to determine their association with incident PDAC in a nested case-control study of male smokers (372 matched case-control sets) and an independent nested case-control study that included women and non-smokers (107 matched sets). Metabolites were measured using Orbitrap Elite or Q-Exactive high-resolution/accurate mass spectrometers. Controls were matched to cases by age, sex, race, date of blood draw, and follow-up time. We used conditional logistic regression adjusted for age to calculate ORs and 95% CIs for a 1 SD increase in log-metabolite level separately in each cohort and combined the two ORs using a fixed-effects meta-analysis.Thirty-one metabolites were significantly associated with PDAC at a false discovery rate <0.05 with 12 metabolites below the Bonferroni-corrected threshold (p<9.04×10-5). Similar associations were observed in both cohorts. The dipeptides glycylvaline, aspartylphenylalanine, pyroglutamylglycine, phenylalanylphenylalanine, phenylalanylleucine and tryptophylglutamate and amino acids aspartate and glutamate were positively while the dipeptides tyrosylglutamine and α-glutamyltyrosine, fibrinogen cleavage peptide DSGEGDFXAEGGGVR and glutathione-related amino acid cysteine-glutathione disulfide were inversely associated with PDAC after Bonferroni correction. Five top metabolites demonstrated significant time-varying associations (p<0.023) with the strongest associations observed 10-15 years after participants' blood collection and attenuated thereafter.Our results suggest that prediagnostic metabolites related to subclinical disease, γ-glutamyl cycle metabolism and adiposity/insulin resistance are associated with PDAC.
Prospective CMR Survey in Children With Thalassemia Major
Authors: Alessia Pepe, Antonella Meloni, Aldo Filosa, Laura Pistoia, Zelia Borsellino, Domenico Giuseppe D’Ascola, Roberto Lisi, Maria Caterina Putti, Massimo Allò, Maria Rita Gamberini, Antonella Quarta, Carmelo Fidone, Tommaso Casini, Gennaro Restaino, Massimo Midiri, Maurizio Mangione, Vincenzo Positano, Maddalena Casale
Journal: JACC. Cardiovascular imaging (2020)
Impact of Glucose Level on Micro- and Macrovascular Disease in the General Population: A Mendelian Randomization Study
Authors: Frida Emanuelsson, Sarah Marott, Anne Tybjærg-Hansen, Børge G. Nordestgaard, Marianne Benn
Journal: Diabetes Care (2020)

OBJECTIVE To evaluate whether high glucose levels in the normoglycemic range and higher have a causal genetic effect on risk of retinopathy, neuropathy, nephropathy, chronic kidney disease (CKD), peripheral arterial disease (PAD), and myocardial infarction (MI; positive control) in the general population. RESEARCH DESIGN AND METHODS This study applied observational and one-sample Mendelian randomization (MR) analyses to individual-level data from 117,193 Danish individuals, and validation by two-sample MR analyses on summary-level data from 133,010 individuals from the Meta-Analyses of Glucose and Insulin-Related Traits Consortium (MAGIC), 117,165 from the CKDGen Consortium, and 452,264 from the UK Biobank. RESULTS Observationally, glucose levels in the normoglycemic range and higher were associated with high risks of retinopathy, neuropathy, diabetic nephropathy, PAD, and MI (all P for trend &amp;lt;0.001). In genetic causal analyses, the risk ratio for a 1 mmol/L higher glucose level was 2.01 (95% CI 1.18–3.41) for retinopathy, 2.15 (1.38–3.35) for neuropathy, 1.58 (1.04–2.40) for diabetic nephropathy, 0.97 (0.84–1.12) for estimated glomerular filtration rate (eGFR) &amp;lt;60 mL/min/1.73 m2, 1.19 (0.90–1.58) for PAD, and 1.49 (1.02–2.17) for MI. Summary-level data from the MAGIC, the CKDGen Consortium, and the UK Biobank gave a genetic risk ratio of 4.55 (95% CI 2.26–9.15) for retinopathy, 1.48 (0.83–2.66) for peripheral neuropathy, 0.98 (0.94–1.01) for eGFR &amp;lt;60 mL/min/1.73 m2, and 1.23 (0.57–2.67) for PAD per 1 mmol/L higher glucose level. CONCLUSIONS Glucose levels in the normoglycemic range and higher were prospectively associated with a high risk of retinopathy, neuropathy, diabetic nephropathy, eGFR &amp;lt;60 mL/min/1.73 m2, PAD, and MI. These associations were confirmed in genetic causal analyses for retinopathy, neuropathy, diabetic nephropathy, and MI, but they could not be confirmed for PAD and seemed to be refuted for eGFR &amp;lt;60 mL/min/1.73 m2.
Engineered immunogen binding to alum adjuvant enhances humoral immunity
Authors: Tyson J. Moyer, Yu Kato, Wuhbet Abraham, Jason Y. H. Chang, Daniel W. Kulp, Nicki Watson, Hannah L. Turner, Sergey Menis, Robert K. Abbott, Jinal N. Bhiman, Mariane B. Melo, Hayley A. Simon, Sara Herrera-De la Mata, Shu Liang, Gregory Seumois, Yash Agarwal, Na Li, Dennis R. Burton, Andrew B. Ward, William R. Schief, Shane Crotty, Darrell J. Irvine
Journal: Nature Medicine (2020)
Competing interests: GMC rejects calls to establish central register for doctors
Authors: Gareth Iacobucci
Journal: BMJ (2020)

The UK General Medical Council has rejected calls for it to set up a central register of doctors’ declared interests, saying that it lacked the legal power to enforce such a move and arguing that conflicts were much better managed at a local level.

However, the GMC said that it supported moves by some NHS trusts to establish publicly available registers on which doctors must declare their interests and added that it would be willing to discuss how to roll these out more widely and extend them to GPs.

Last month 11 senior doctors wrote to the GMC’s chair, Clare Marx, urging the regulator to establish a central register to improve transparency.1 …
Potential therapeutic targets for lung repair during human<i>ex vivo</i>lung perfusion
Authors: Aaron Wong, Ricardo Zamel, Jonathan Yeung, Gary D. Bader, Claudia C. Dos Santos, Xiaohui Bai, Yubo Wang, Shaf Keshavjee, Mingyao Liu
Journal: European Respiratory Journal (2020)

Introduction The ex vivo lung perfusion (EVLP) technique has been developed to assess the function of marginal donor lungs and has significantly increased donor lung utilisation. EVLP has also been explored as a platform for donor lung repair through injury-specific treatments such as antibiotics or fibrinolytics. We hypothesised that actively expressed pathways shared between transplantation and EVLP may reveal common mechanisms of injury and potential therapeutic targets for lung repair prior to transplantation. Materials and methods Retrospective transcriptomics analyses were performed with peripheral tissue biopsies from “donation after brain death” lungs, with 46 pre-/post-transplant pairs and 49 pre-/post-EVLP pairs. Pathway analysis was used to identify and compare the responses of donor lungs to transplantation and to EVLP. Results 22 pathways were enriched predominantly in transplantation, including upregulation of lymphocyte activation and cell death and downregulation of metabolism. Eight pathways were enriched predominantly in EVLP, including downregulation of leukocyte functions and upregulation of vascular processes. 27 pathways were commonly enriched, including activation of innate inflammation, cell death, heat stress and downregulation of metabolism and protein synthesis. Of the inflammatory clusters, Toll-like receptor/innate immune signal transduction adaptor signalling had the greatest number of nodes and was central to inflammation. These mechanisms have been previously speculated as major mechanisms of acute lung injury in animal models. Conclusion EVLP and transplantation share common molecular features of injury including innate inflammation and cell death. Blocking these pathways during EVLP may allow for lung repair prior to transplantation.
Abstract P1-10-21: PD-L1 expression of tumor infiltrating immune cells has potential as a biomarker in triple-negative breast cancers
Authors: Yurina Harada, Makoto Kubo, Hitomi Mori, Masaya Kai, Mai Yamada, Kanako Kurata, Hitomi Kawaji, Kazuhisa Kaneshiro, Saori Hayashi, Akiko Shimazaki, Takafumi Morisaki, Rin Yamaguchi, Nobuyuki Arima, Reiki Nishimura, Masayuki Okido, Masafumi Nakamura
Journal: Cancer Research (2020)

Abstract [background] In general, TNBC has a high distant metastasis rate and is highly aggressive. Despite good response to chemotherapy, it has a poorer prognosis compared to other subtypes. There is a need to develop new treatments for the selection of appropriate treatments. At present, treatments using an immune check point blockade are attracting attention, and the evaluations as biomarkers of and, PD-1 / PD-L1 expression on immune cells for therapeutic effects and prognosis in TNBC are controversial. In order to select patients with TNBC for who immunotherapy is likely to be effective, new biomarkers need to be explored. [Purpose] Our aim is to investigate the possibility as a biomarker of PD-L1 expression on immune cells(PD-L1/IC) in TNBC. We also assess the relationship among PD-L1/IC, PD-L1 expression on tumor cells(PD-L1/TC) and TIL. [Methods] This study included 248 patients with primary TNBC who underwent resection without neoadjuvant chemotherapy at Kyushu University Hospital(Fukuoka, Japan) and related hospitals between January 2004 and December 2014. [Results] PD-L1/IC was positive in 129 cases (52.0%) of 248 TNBCs. Although there was no significant difference in RFS and OS between the positive and negative groups, PD-L1/IC-positive and TIL-High group showed the best prognosis, considering the combination whether PD-L1/IC was positive or negative, and TIL was high or low. PD-L1/IC was significantly correlated with PD-L1/TC(p&amp;lt;0.001). In addition, there was a significant correlation between TIL rate and PD-L1/IC(p&amp;lt;0.001). Moreover, PD-L1/IC-positive group showed stronger therapeutic effects of anthracycline both in OS and RFS, compared with the PD-L1/IC-negative group. [Conclusion] In TNBC, the relationship between PD-L1/IC and prognosis is still not clear, but in IMpassion130 trial, PD-L1/IC is a predictive marker for the effect of Atezolizumab. PD-L1/IC has potential as an immune biomarker in TNBCs. This study also found that PD-L1/IC was related to the therapeutic effect of anthracycline. PD-L1/IC may be a predictive marker of the efficacy of various treatments. Citation Format: Yurina Harada, Makoto Kubo, Hitomi Mori, Masaya Kai, Mai Yamada, Kanako Kurata, Hitomi Kawaji, Kazuhisa Kaneshiro, Saori Hayashi, Akiko Shimazaki, Takafumi Morisaki, Rin Yamaguchi, Nobuyuki Arima, Reiki Nishimura, Masayuki Okido, Masafumi Nakamura. PD-L1 expression of tumor infiltrating immune cells has potential as a biomarker in triple-negative breast cancers [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-10-21.