tbuckley/cabot-search huggingface dataset:
Malaria drugs left ineffective by spread of multidrug resistant parasites in southeast Asia
Authors: Elisabeth Mahase
Journal: BMJ (2019)

Multidrug resistant forms of the most lethal species of malaria causing parasite Plasmodium falciparum have evolved even higher levels of resistance to antimalarial drugs and spread rapidly since 2015 in regions of Cambodia, Laos, Thailand, and Vietnam.

The findings come from two new studies12 published in Lancet Infectious Diseases , which found the spread of the multidrug resistant parasites have caused high treatment failure rates to a widely used frontline malaria drug combination—dihydroartemisinin-piperaquine (DHA-PPQ).

Researchers are now calling for the use of DHA-PPQ to be abandoned in the affected countries, as well as an accelerated malaria elimination programme to prevent the resistant malaria spreading further and causing a global health emergency.

Antimalarial treatments mainly involve artemisinin combination therapies (ACTs) that …
Abstract 13741: Clinical Value of the Detection of Autoantibodies Against β1, β2 and α1 Adrenergic Receptors in Patients With Heart Failure
Authors: Dongyan Hou, Yanhong Liang, Lin Zhang
Journal: Circulation (2015)

Background: Metoprolol and carvedilol are the β-blockers most often used in the management of patients with heart failure (HF), and the choice of drug is still unclear. Autoantibodies against β1, β2 and α1 adrenergic receptors (anti-β1-AR, anti-β2-AR and anti-α1-AR) participate in the pathology of HF. The purpose of the current study is to determine anti-β1-AR, anti-β2-AR and anti-α1-AR may be association with carvedilol treatment in HF patients. Methods: Synthetic β1, β2 and α1 adrenoreceptors peptides served as the target antigen. ELISA was used to screen the sera of 267 HF patients, which were divided into different groups based on their autoantibodies reactively. Echocardiography was performed between carvedilol therapy. Results: Final analysis covered 137 patients, including 65 patients with three autoantibodies and 72 negative. The frequency and geometric mean titer of anti-β1-AR, anti-β2-AR and anti-α1-AR were significantly lower in the positive group after 6 months of carvedilol (all P&lt;0.01, from 100% to 57%, 50%, 49% and from 1:118, 1:138, 1:130 to 1:72, 1:61,1:67 respectively). Of these, 28 patients showed no autoantibodies. Both groups showed improvement left ventricular remodeling and function by carvedilol in combination with standard treatment regime for six months (all P&lt;0.01). However, the 68 patients with three antibodies improved more obviously than 72 negative patients (P&lt;0.01). Conclusion: Carvedilol treatment significantly decreased the frequency and geometric mean titer in patients with three autoantibodies, even to complete ablation, and with more improvement in cardiac function and remodeling. Three autoantibodies may be useful biomarker of over-activation of the sympathetic nerves system for clinical medication.
CD19-Chimeric Antigen Receptor (CAR) Engineered Natural Killer (NK) Cell Therapy: Novel Off the Shelf Immunotherapy in CD20 Resistant B-Cell Non-Hodgkin Lymphoma (NHL) Cell Lines, Primary NHL Cells, and a Human Lymphoma Xenograft Model
Authors: Sneha Purvey, Ravi Dashnamoorthy, Afshin Beheshti, Andreas Klein, Laurent Boissel, Saheli Sarkar, Tali Konry, Andrew M Evens
Journal: Blood (2017)
A case report of clonal EBV-like memory CD4+ T cell activation in fatal checkpoint inhibitor-induced encephalitis
Authors: Douglas B. Johnson, Wyatt J. McDonnell, Paula I. Gonzalez-Ericsson, Rami N. Al-Rohil, Bret C. Mobley, Joe-Elie Salem, Daniel Y. Wang, Violeta Sanchez, Yu Wang, Cody A. Chastain, Kristi Barker, Yan Liang, Sarah Warren, Joseph M. Beechem, Alexander M. Menzies, Martin Tio, Georgina V. Long, Justine V. Cohen, Amanda C. Guidon, Méabh O’Hare, Sunandana Chandra, Akansha Chowdhary, Bénédicte Lebrun-Vignes, Simone M. Goldinger, Elisabeth J. Rushing, Elizabeth I. Buchbinder, Simon A. Mallal, Chanjuan Shi, Yaomin Xu, Javid J. Moslehi, Melinda E. Sanders, Jeffrey A. Sosman, Justin M. Balko
Journal: Nature Medicine (2019)
Prophylactic cranial irradiation after reaching complete response, partial response, or stable disease in non-small cell lung cancer patients treated with epidermal growth factor receptor tyrosine kinase inhibitors (ProACT).
Authors: Amanda Tufman, Claus Belka, Heike Kuenzel, Rudolf M. Huber
Journal: Journal of Clinical Oncology (2012)

TPS7617 Background: Patients with non-small cell lung cancer (NSCLC) who respond to treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) seem to be at increased risk of central nervous system relapse, and may benefit from prophylactic cranial irradiation (PCI) more than other NSCLC patients. Methods: This study investigates the safety and efficacy of combining PCI with EGFR TKIs in stage IV NSCLC. Patients with stage IV NSCLC, no evidence of brain metastases, and an indication for first or later line therapy with an EGFR TKI will be enrolled. Those with complete response (CR), partial response (PR), or stable disease (SD) following 6 weeks of therapy and no evidence of brain metastases on MRI will be treated with PCI. Neurocognitive function, depression indices, quality of life, symptoms, and ability to function independantly will be assessed at baseline, before PCI, and at 6 week and then 3 month intervals following PCI. MRI will be repeated 6 weeks following PCI and at 3 month intervals, and serum markers of blood brain barrier permeability (neuron-specific enolase (NSE), protein S100 beta) will be assessed at all visits. Safety data will be formally reviewed after the first 10 patients. The primary endpoint for efficacy is overall survival. Secondary endpoints include progression free survival, site of progression, quality of life and neurological disability. Planed subgroup analyses based on mutation status, line of treatment with TKIs, comorbidity, precise histology and molecular biology will be carried out.
Totally laparoscopic pancreaticoduodenectomy: Learning curve.
Authors: Igor Khatkov, Viktor Tsvirkun, Roman Izrailov, Pavel Tiutiunnik
Journal: Journal of Clinical Oncology (2012)

e14717 Background: Laparoscopic pancreaticoduodenectomy (LPDE) has become increasingly popular in the world and now is considered to be a technically feasible and safe procedure for patients with tumors of the head of the pancreas and the periampullare area. At the same time, according to the literature data, a lot of surgeons stop performing totally laparoscopic pancreaticoduodenectomy (TLPDE) after 5 – 15 procedures because of the difficulties of learning curve. Aim of thew study: to evaluate the learning curve of totally laparoscopic pancreaticoduodenectomy. Methods: The data of 43 patients who were planed for LPDE during 5 year were analyzed. All the procedures were performed by one surgical team. 35 patients underwent totally laparoscopic pancreaticoduodenectomy (TLPDE). For 8 patients the procedures were palliative or converted. Patients were divided in three groups. Group A, B and C – 12;12;11 patients respectively. Operative time, intraoperative blood loss and the level of postoperative morbidity were examined. Results: Among the 43 patients, 35 patients underwent TLPDE. The conversion rate was in the group A - 33% (4 patients), group B – 33%(4 patients) and group C – no conversions. Mean operative time of TLPDE for the group A was - 542min; group B – 542min and group C less than 360min, minimally - 280). Mean blood loss was for group A - 683ml, group B – 612ml and group C 250ml. Total level of all kinds of postoperative morbidity was: group A - 66,5%, group B – 65,5% and group C – 36,0%. Postoperative mortality was: group A - 8,3%(one of the patients died from insufficiency of the pancreatojejenostomy, another – because of acute heart failure without any surgical complications); group B – 0% and group C - 0%. Conclusions: The results of TLPDE become significantly better after 25 procedures. The most difficult and potentially dangerous for intra and postoperative complications were: dissection along superior mesenteric and portal vein and suturing of pancreaticojejuno anastomosis. Performing TLPDE by the same team, including nurses, is a very important factor for quick learning curve and safety.
New Tests to Assess Lung Function
Authors: Peter T. Macklem, Norman L. Jones
Journal: New England Journal of Medicine (1975)

THE aim of these two papers is to describe briefly the use of exercise testing in patients with respiratory problems. In the first, the background will be covered as an introduction to the available methods; a description of the normal response will set the scene for the second, in which the value of exercise testing in assessment of pulmonary disease will be described.*Why Study Exercise?Dynamic exercise employing large muscle groups is accompanied by increases in metabolic oxygen consumption and carbon dioxide production. The increases in metabolic demand lead to stresses on all the mechanisms taking part in oxygen . . .
Efficacy and safety of IBI305 compared with bevacizumab in advanced non-squamous NSCLC patients as first-line treatment in a randomized, double-blind, phase III study.
Authors: Li Zhang, Bin Wu, Linian Huang, Meiqi Shi, Yunpeng Liu, Yanqiu Zhao, Lijun Wang, Shun Lu, Gongyan Chen, Baolan Li, Conghua Xie, Jian Fang, Nong Yang, Yiping Zhang, Jiuwei Cui, Yong Song, Cuiying Zhang, Xiaodong Mei, Bangwei Cao, Lan Yang
Journal: Journal of Clinical Oncology (2019)

9095 Background: IBI305 is a recombinant humanized anti-VEGF monoclonal antibody, a biosimilar candidate to bevacizumab in analytical and functional comparisons. Pharmacokinetic similarity has been demonstrated in healthy males. Here we present primary efficacy and safety results from a phase 3 comparative study in non-small cell lung cancer (NSCLC). Methods: In this double-blind, active-controlled study, subjects with advanced non-squamous NSCLC on first-line treatment with carboplatin and paclitaxel were randomized (1:1) to IBI305 or bevacizumab (15 mg/kg IV Q3W). After six cycles, patients were on maintenance treatment with IBI305 or bevacizumab (7.5 mg/kg IV Q3W) till progression. Clinical equivalence of the primary endpoint, confirmed objective response rate (ORR) was evaluated by comparing the 2-sided 90% confidence interval (CI) of the risk ratio (RR) between study arms with the prespecified margin (0.75, 1.33). Results: A total of 450 subjects were randomized (IBI305: n = 224; bevacizumab: n = 226). Baseline characteristics were well balanced between treatment arms. ORR evaluated by Independent Radiological Review Committee (IRRC) in full analysis set (FAS) was 44.3% (98/221) for IBI305 and 46.4% (102/220) for bevacizumab; the RR for ORR was 0.95 (90% CI: 0.803, 1.135). Sensitive analysis result on RRs of ORR in Intention to Treat (ITT) population (IBI305: n = 224; bevacizumab: n = 226) and other analysis set were consistent and all within the prespecified equivalence margin. The medium PFS were 8.4 months for IBI305 and 8.3 months for bevacizumab and duration of response (DOR) was also similar in both arms. Treatment-emergent adverse events (TEAEs) were well balanced between treatment arms and consistent with the known adverse event profile of bevacizumab. Patients developing binding antibodies were 0.5% in the IBI305 arm vs 0% in the bevacizumab arm; no subject tested positive for neutralizing antibodies. Conclusions: This is the first released phase 3 clinical study with maintenance treatment for bevacizumab biosimilar in NSCLC patients till now. The comparative study met its predefined primary endpoint that the RR for confirmed ORR was within the prespecified equivalence margin. There was no significant difference between the two arms in safety profile and immunogenicity. Clinical trial information: NCT02954172.
Abstract 18660: CVSN Best Abstract Award: Genome-wide Candidates Unique to Females With Coronary Artery Disease Significantly Predict Mortality Risk
Authors: Jennifer R Dungan, Xue Qin, Melissa Hurdle, Carol Haynes, Elizabeth Burns, Damian Craig, Simon G Gregory, Elizabeth R Hauser, Svati H Shah, William E Kraus
Journal: Circulation (2015)

Introduction: Women are disproportionately affected by coronary artery disease (CAD). Among major factors such as age and anatomical differences, biologic contributions are purported; yet, little is understood about the underlying genomic architecture that may contribute to female-specific disparities. We explored whether genome-wide variants could predict survival in females with clinically-appreciable CAD, unique to that of male cases. Methods: A sex-stratified genome-wide association analysis was conducted for survivorship in Caucasian patients with CAD in a discovery cohort ( N =1,099; 589 females) and a replication cohort ( N = 404; 198 females), selected from a cardiovascular biorepository consisting of sequential patients referred for cardiac catheterization. CAD cases were defined as having a CAD index &gt;32 (at least one vessel CAD) and indication for catheterization was concern for ischemic heart disease. GWAS genotyping was done using the Illumina Omni Quad v1.0 GWAS chip with stringent QC metrics. Sex-stratified, Cox multivariable regression models for each SNP (additive), adjusted for age and four Eigenstrat-defined principal components, were constructed (R statistical package), with models censored on time from cardiac catheterization to all-cause mortality/last follow-up (med 5.2 yrs). Results: Fourteen SNPs met nominal significance (p&lt;10 -5 ) for increased hazards of all-cause mortality in women; none of these SNPs or genes were even nominally significant at p&lt;0.05 in male cases. Three top SNPs were biologically relevant: rs17591646 ( SLC9A9 ; HR 6.2, 95%CI 2.9-13.3, p discovery =3.2x10 -6 , p replication =0.68, p male =0.87); rs12145981 ( NEK2/LPGAT1 ; HR 3.3, 95%CI 2.0-5.6, p d =4.2x10 -6 , p r =0.05, p m =0.92); and rs7217169 ( RAP1GAP2 ; HR 4.1, 95%CI 2.3-7.5, p d =4.3x10 -6 , p r =0.02, p m =0.44), as they are involved in endosome recycling ( SLC9A9 ), cardiolipin synthesis ( LPGAT1 ), and regulating dense granule secretion from platelets at endothelial damage sites ( RAP1GAP2 ). Conclusions: We present preliminary evidence of genome-wide candidates that appear to uniquely predict mortality risk in women with CAD. Further investigation of genomic variation may help improve understanding of sex differences in CAD disparities.
Prognostic implications of co-occurring dermatologic and gastrointestinal toxicity from immune checkpoint inhibition therapy for advanced malignancies: A retrospective cohort study
Authors: Gabriel E. Molina, Ian M. Allen, Michael S. Hughes, Leyre Zubiri, Hang Lee, Meghan J. Mooradian, Kerry L. Reynolds, Michael Dougan, Steven T. Chen
Journal: Journal of the American Academy of Dermatology (2019)
Adhesive Small-Bowel Obstruction—Surgery for All?—Reply
Authors: Ramy Behman, Avery B. Nathens, Paul Karanicolas
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
Recurrent/metastatic salivary gland malignancies (RMSGM): Final report of 60 cases treated with cisplatin plus vinorelbine (DDP+VNB).
Authors: Fulvia Pedani, Mario Airoldi, Massimiliano Garzaro, Luca Raimondo, Simona Carnio, Gianluca Fora, Carlo Giordano, Giancarlo Pecorari
Journal: Journal of Clinical Oncology (2012)

5548 Background: RMSGM are not amenable to the usual treatment with surgery and post-operative radiotherapy. The role of chemotherapy (CT) for RMSGM is palliative only. VNB showed moderate activity in our experience (Bull Cancer 85:892;1998) and in a randomized phase II trial we had demonstrated that the DDP+VNB combination had a better outcome than VNB alone (Cancer 91:541; 2001). In this abstract we report the final results of this combination in 60 cases. Methods: From April 2001 to February 2009 , 60 cases with RMSGM were enrolled. All patients received the following regimen: DDP 80 mg/sm d.1 + VNB 25 mg/sm d. 1,8 every 3 weeks. The study foresees a maximum of 6 cycles. Results: Patients characteristics were as follows: 35 males (58%) and 25 females (42%).; median age: 56 yrs (range 20-68); median ECOG PS: 1 (0-2); histology: adenocarcinoma 15 (25%), adenoid cystic ca. 34 (57%), others 11 (18%); site of disease: local 30 (50%) , mts +/- local 30 (50%). Forty-two pts received DDP+VNB as first line CT (70%) while 18 pts (30%) had the combination as second-line CT (30%). After a median of 5 cycles of first line DDP+VNB responses were: 3 CR (7%), 10 PR (24%), 14 NC (33%) and 15 PD (36%). After a median of 4 cycles of second line CT responses were: 0 CR; 1 PR (5%), 6 NC (33%) 11 PD (62%). Median survival: 10 months (3-29) for first line CT ; 4 months (1-12) for second line CT. G3-4 toxicity: neutropenia (20%), anemia (12%), nausea/vomiting (12%) , peripheral toxicity (3%). Conclusions: DDP+VNB is an effective first line CT in RMSGM ; second line CT has a low palliative activity. Toxicity seems acceptable. This regimen could be suitable for an integration with new biologic target agents.
Abortion set to be decriminalised in Northern Ireland after historic Lords vote
Authors: Ingrid Torjesen
Journal: BMJ (2019)

The House of Lords has voted overwhelmingly to decriminalise abortion in Northern Ireland in the absence of a functioning Northern Ireland Executive.1

In an historic vote last night, the house backed last week’s decision by MPs that abortion in Northern Ireland should be decriminalised unless Stormont returns by October.

Peers voted 182 to 37 to pass the changes in a free vote.

Both the Royal College of Obstetricians and Gynaecologists (RCOG) and …
Overcoming EZH2 Inhibitor Resistance by Taxane in PTEN-Mutated Cancer
Authors: Linlin Ma, Yuqian Yan, Yang Bai, Yinhui Yang, Yunqian Pan, Xiaokun Gang, R. Jeffrey Karnes, Jun Zhang, Qiubo Lv, Qiang Wu, Haojie Huang
Journal: Theranostics (2019)

Rationale: The Polycomb group (PcG) protein EZH2 is implicated in cancer progression due to its frequent overexpression in many cancer types and therefore is a promising therapeutic target. Forkhead box transcription factor-1 (FOXO1) is a tumor suppressor that is often transcriptionally downregulated in human cancers such as prostate cancer although the underlying regulatory mechanisms remain elusive. Methods: Analysis of EZH2 ChIP-seq and ChIP-on-chip data in various cell types was performed. ChIP-qPCR, RT-qPCR, and western blot analyses were conducted to determine the mechanism by which EZH2 represses FOXO1 expression. Immunohistochemistry was employed to assess the correlation between EZH2 and FOXO1 protein expression in prostate cancer patient specimens. In vitro MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) and animal experiments were performed to determine the anti-cancer efficacy of EZH2 inhibitor alone or in combination of docetaxel, a chemotherapy agent of the taxane family, and dependency of the efficacy on FOXO1 expression. Results: We demonstrated that EZH2 binds to the FOXO1 gene promoter. EZH2 represses FOXO1 gene expression at the transcriptional level. EZH2 protein level inversely correlated with FOXO1 protein expression in prostate cancer patient specimens. This repression requires the methyltransferase activity and the functional PRC2 complex. While effectively inducing loss of viability of PTEN-positive 22Rv1 prostate cancer cells, EZH2 inhibitor failed to inhibit growth of PTEN-negative C4-2 prostate cancer cells. Co-treatment with docetaxel overcame EZH2 inhibitor resistance in PTEN-negative cancer cells in vitro and in mice. This effect was largely mediated by docetaxel-induced nuclear localization and activation of FOXO1. Conclusions: This study identifies FOXO1 as a bona fide repression target of EZH2 and an essential mediator of EZH2 inhibition-induced cell death. Our findings suggest that EZH2 repression of FOXO1 can be targeted by EZH2 inhibitor as a monotherapy for PTEN-proficient cancers or in combination with taxane for treatment of cancers with PTEN mutation or deletion.
Abstract 20326: Atypical Symptom Presentation is the Strongest Predictor for Prolonged Care-Seeking Delay in Patients With Acute Myocardial Infarction
Authors: Polly W. C. Li
Journal: Circulation (2016)

Introduction: This study aimed to determine the predictors of prehospital delay in care seeking among the Chinese patients with acute myocardial infarction (AMI). Methods: This multicenter cross-se...
Final results of a phase I trial of chemotherapy combination with docetaxel, cisplatin, and S-1 (TPS) in patients with locally advanced or recurrent metastatic head and neck cancer (HNC)
Authors: M. Tahara, K. Araki, N. Kiyota, S. Okano, N. Fuse, K. Minashi, T. Yoshino, T. Doi, H. Minami, A. Ohtsu
Journal: Journal of Clinical Oncology (2009)

6021 Background: An oral fluoropyrimidine, S-1, has shown high efficacy against head and neck cancer (HNC), with a response rate of 34%. We investigated the maximum tolerated dose (MTD) of combination therapy with docetaxel, cisplatin and S-1 (TPS) in patients (pts) with locally advanced or recurrent/metastatic HNC. Methods: Eligibility criteria were histologically proven HNC, PS 0–1, age ≤75 years, adequate organ function, and no prior chemotherapy. Treatment consisted of 1-hour infusion of docetaxel at escalating doses of 50, 60 and 70 mg/m2, 2-hour infusion of cisplatin at 70 mg/m2/day on day 1, and S-1 twice daily on days 1–14 at escalating doses of 40, 60, and 80 mg/m2/day. This regimen was repeated every 3 or 4 weeks. Pts with locally advanced HNC received concurrent chemoradiotherapy after completion of 3 cycles of TPS. Results: Forty pts were enrolled, consisting of 33 males and 7 females with a median age of 50 years (range 22–74 years). Twenty-nine cases were locally advanced cancer and 11 were metastatic cancer. 116 cycles (median = 3, range 1–6) were administered in 6 dose levels. Grade 3 or 4 hematological toxicities were neutropenia (59%), febrile neutropenia (13%), and anemia (8%), whereas no grade 3 or 4 thrombocytopenia was seen. Two dose-limiting toxicities (DLTs) were observed at dose level 5 (TPS: 70/70/80 mg/m2/day every 3 weeks), namely one grade 3 infection and one grade 3 hyperbilirubinemia, establishing this as the MTD. Of 12 pts treated at dose level 6 (TPS: 70/70/60 mg/m2/day every 3 weeks), three DLTs were seen, namely one grade 3 diarrhea, one grade 3 ALT/AST and one grade 2 creatinine elevation. Of a total of 40 pts, 6 achieved a complete response and 22 a partial response according to RECIST, giving an overall response rate of 70%. Conclusions: The TPS combination was well tolerated. The recommended phase II dose was determined to be TPS at 70/70/60 mg/m2/day every 3 weeks. Antitumor activity was highly promising, and warrants further investigation. No significant financial relationships to disclose.