tbuckley/cabot-search huggingface dataset:
A phase 1 trial of JS001, a monoclonal antibody targeting programmed death-1 (PD-1) in patients with advanced or recurrent malignancies.
Authors: Sheng Yang, Jianliang Yang, Ying Han, Yan Qin, Xiaohong Han, Lihou Dong, Hui Feng, Haifeng Song, Yan Sun, Yuankai Shi
Journal: Journal of Clinical Oncology (2017)

e14581 Background: JS001, a humanized IgG4 anti-PD-1 antibody, showed potent anti-cancer activity in preclinical models. Notably, in vivo study suggests it promotes the proliferation of CD62L-CD45RA- effector memory cell effectively. A phase 1 dose escalation study was conducted to assess its safety, tolerability, pharmacokinetic (PK) profile and preliminary efficacy. Methods: This trial used a 3+3 design across 3 dose levels: 1, 3, 10 mg/kg/dose. At each level, two schedules were assessed: single dose and repeated doses every 2 weeks (up to 6 doses). JS-001 was administered as a 60-minute i.v. infusion. A dose limiting toxicity (DLT) was defined as a Grade≥3 drug-related adverse event (AE) occurring within 28 days of last dosing. Results: At the time of analysis, among 19 patients (pts) enrolled (single dose: 9 pts; multiple doses: 10 pts), no DLT was reported. Most treatment-related AEs were grade 1-2, including fever, diarrhea, rash, influenza-like symptoms, fatigue, mucositis, elevated transaminase and decreased lymphocyte count. One patient experienced grade 3 pneumonia. Although the cause of pneumonia is difficult to determine, and further assessment is ongoing, it resolved after prompt management. No treatment-related death occurred. The preliminary PK profile supports a biweekly schedule, and results in detail are under analyzing. 15 pts with evaluable lesions received response evaluation. Best responses were 1 CR (Hodgkin lymphoma, HL), 5 PR (HL: 3; soft tissue sarcoma, STS: 1; diffuse large B-cell lymphoma: 1) and 5 SD (non-small cell lung cancer: 3; head and neck cancer: 2), yielding a disease control rate of 11/15. Remarkably, a patient with STS achieved dramatic tumor shrinkage after a single injection of JS001. Biomarker analysis is in progress. Conclusions: JS001 is well tolerated and the preliminary efficacy results are promising. Updated data on the expansion cohorts at 3mg/kg and 10mg/kg will be presented. Clinical trial information: NCT02836834. Clinical trial information: NCT02836834.
An unusual gastric tumour with gastric outlet obstruction
Authors: I-Lin Frank Chen, Kai-Wen Liu, Tao-Qian Tang, Wen-Lun Wang
Journal: Gut (2017)

A 62-year-old male without significant medical history presented with intermittent epigastric pain and abdominal fullness for 2 months. He denied having bloody stool or weight loss. He visited the outpatient department, where the CT scan of abdomen was performed (figure 1). He then underwent oesophagogastroduodenoscopy (EGD), which revealed a subepithelial tumour at gastric antrum with obstruction of the pylorus (figure 2 and video in the online supplementary file 1). Endoscopic ultrasound sonography (EUS) was performed …
Serious incident investigations for cerebral palsy are “poor quality,” says watchdog
Authors: Gareth Iacobucci
Journal: BMJ (2017)

Patients and their families were involved in just 40% of investigations into whether negligent NHS care resulted in children being born with cerebral palsy between 2012 and 2016, a new analysis has found.

The report from NHS Resolution, formerly the NHS Litigation Authority, examined 50 cases of cerebral palsy or brain injury between 2012 and 2016 where a legal liability had been established.1 It estimated that the potential financial liability of these cases could surpass £390m (€440m; $530m), excluding defence costs and the wider healthcare costs to the NHS. Obstetric claims accounted for 10% of the 10 686 claims received under NHS Resolution’s indemnity schemes …
Nanomaterials in the Prevention, Diagnosis, and Treatment of <i>Mycobacterium Tuberculosis</i> Infections
Authors: Kaijin Xu, Zhen Chang Liang, Xin Ding, Haiyang Hu, Shaoqiong Liu, Martin Nurmik, Sheng Bi, Feishu Hu, Zhongkang Ji, Jingjing Ren, Shigui Yang, Yi Yan Yang, Lanjuan Li
Journal: Advanced Healthcare Materials (2017)

Abstract Despite the tremendous advancements that have been made in biomedical research, Mycobacterium tuberculosis (TB) still remains one of the top 10 causes of death worldwide, outpacing the Human Immunodeficiency Virus as a leading cause of death from an infectious disease. In the light of such significant disease burden, tremendous efforts have been made worldwide to stem this burgeoning spread of disease. The use of nanomaterials in TB management has increased in the past decade, particularly in the areas of early TB detection, prevention, and treatment. Nanomaterials have been proven to be efficacious in the rapid and accurate detection of TB pathogens. Novel nanocarriers have also shown tremendous promise in improving drug delivery, potentially enhancing drug concentrations in target organs while at the same time, reducing treatment frequency. In addition, the engineering of antigen nanocarriers represents an exciting front in TB research, potentially paving the way for the successful development of a new class of effective TB vaccines. This article discusses epidemiology and pathogenesis of TB infections, current TB therapeutics, advanced nanomaterials for anti‐TB drug delivery, and TB vaccines. In addition, challenges and future perspectives in developing safe and effective nanomaterials in TB diagnosis and therapy are also presented.
Humanizing the Treatment of Hyperactive Delirium in the Last Days of Life
Authors: Pratik P. Pandharipande, E. Wesley Ely
Journal: JAMA (2017)

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
5 x 5 Gy and consolidation chemotherapy vs long-course preoperative chemoradiation for locally advanced rectal cancer: An interim analysis of a randomized phase III study.
Authors: Jing Jin, Shixin Liu, Yuan Zhu, Wenling Wang, Xin Wang, Jun Wang, Gaofeng Li, Lin Fan, Kuan Zhang, Mei Shi, Yuan Tang, Haizeng Zhang, Yihebali Chi, Ai-Ping Zhou, Jing Huang, Hongmei Zhang, Liming Jiang, Jun Jiang, Shuangmei Zou, Ye-Xiong Li
Journal: Journal of Clinical Oncology (2017)

e15006 Background: To present an interim analysis of a phase III trial comparing short-course radiotherapy followed by chemotherapy with long-course chemoradiotherapy in locally advanced rectal cancer. Methods: Patients with distal or middle third, MRI diagnosed cT3-T4 or N+ rectal adenocarcinomas were randomized to either 5 x 5 Gy and 4 courses of CAPOX (experimental group) or 50 Gy delivered in 25 fractions given concurrently with capecitabine (control group). Total mesorectal excision (TME) in both groups was performed 6-8 weeks after neoadjuvant treatment. This is an interim analysis of acute toxicities for the first 127 patients who finished neoadjuvant therapy, as well as the pCR and surgical complications for the first 100 patients who received surgery. Results: From 08/30/2015 to 12/11/2016, 63 patients in experimental group and 64 in control group from 10 Chinese hospitals were analyzed. During preoperative treatment, any acute toxicities were 100% in both groups and grade III-IV 19.0% vs. 6.3% ( p= 0.03) in experimental group and control group, respectively. Full-dose completion rates of planned neoadjuvant treatment were 88.9% and 93.7% in each group ( p= 0.33), respectively. After median duration of 7 weeks and 9 weeks in experimental group and control group, TME was performed. Among the 100 patients who have finished surgery, 94.1% and 89.8% in experimental and control group had R0 resection ( p= 0.426), while 21.6% and 6.1% of them achieved pCR ( p= 0.026), respectively. There were 8 patients in experimental group diagnosed as clinical CR and refused to further radical surgery, while, none in control group ( p= 0.003). The incidences of surgical complications were similar between two groups (experimental 29.1% vs. control 26.5%; p= 0.748), with perineal healing delay as the main reason. Conclusions: The acute toxicity and surgical complication were acceptable and comparable in both groups, however, the people in experimental group showed a significantly clinical and pathological response. The short-course irradiation and consolidation chemotherapy maybe an alternative standard of care, though the final result is in prospect. Clinical trial information: NCT02533271.
Compulsivity Reveals a Novel Dissociation between Action and Confidence
Authors: Matilde M. Vaghi, Fabrice Luyckx, Akeem Sule, Naomi A. Fineberg, Trevor W. Robbins, Benedetto De Martino
Journal: Neuron (2017)

Confidence and actions are normally tightly interwoven-if I am sure that it is going to rain, I will take an umbrella-therefore, it is difficult to understand their interplay. Stimulated by the ego-dystonic nature of obsessive-compulsive disorder (OCD), where compulsive actions are recognized as disproportionate, we hypothesized that action and confidence might be independently updated during learning. Participants completed a predictive-inference task designed to identify how action and confidence evolve in response to surprising changes in the environment. While OCD patients (like controls) correctly updated their confidence according to changes in the environment, their actions (unlike those of controls) mostly disregarded this knowledge. Therefore, OCD patients develop an accurate, internal model of the environment but fail to use it to guide behavior. Results demonstrated a novel dissociation between confidence and action, suggesting a cognitive architecture whereby confidence estimates can accurately track the statistic of the environment independently from performance.
Impact of Age and Type of Underlying Disease on Long-Term Safety and Efficacy in Patients with Transfusional Hemosiderosis Treated with Deferasirox: Results from a 3-Year Non-Interventional Study (SENTINEL)
Authors: Mohsen Elalfy, Baba Inusa, David Beneitez, Blanca Xicoy, Maria Soledad Duran Nieto, Andreas Bruederle, Amin Azmon, Amal El-Beshlawy
Journal: Blood (2016)
Prevalence of Anemia 10 Years After Roux-en-Y Gastric Bypass in a Single Veterans Affairs Medical Center
Authors: Gao Linda Chen, Eric Kubat, Dan Eisenberg
Journal: JAMA Surgery (2017)

This database review evaluates the prevalence of anemia 10 years after Roux-en-Y gastric bypass and whether bariatric follow-up influences anemia rates in a population of veterans.
Comparison of the Molecular Spectrum of Lenalidomide-Treated Myelodysplastic Syndrome with and without Del(5q)
Authors: Vera Adema, Laura Palomo, Francisco Fuster-Tormo, Rocío Benito, Rocio Salgado, Esperanza Such, Olivier Kosmider, Maria Jose Larrayoz, Blanca Xicoy, Kamila Janusz, Paolo Maietta, Alexander Neef, Beatriz Arrizabalaga Amunchastegui, Michaela Fontenay, Paula Gomez-Marzo, Monica Del Rey, Mariam Ibáñez, Nuri Haro, Mar Mallo, Lurdes Zamora, Valeria Visconte, Jaroslaw P. Maciejewski, Pierre Fenaux, Jose Cervera, Maria Jose Calasanz, Jesús María Hernández-Rivas, Juan Cigudosa, Francesc Sole
Journal: Blood (2016)
Comparison of hospital costs in peripheral t-cell lymphoma patients treated with pralatrexate or romidepsin.
Authors: James W. Gilmore, Kathy Belk, Christopher W Craver, Michael McGuire
Journal: Journal of Clinical Oncology (2016)

e18280 Background: Peripheral T-Cell Lymphoma (PTCL) is a rare, aggressive form of non-hodgkin lymphoma. Initial treatment consists of conventional chemotherapy regimens; although novel therapies for relapsed/refractory patients are available there is a lack of information on real-world costs associated with these products. The objective of this study was to examine costs and healthcare resource use associated with two of these novel products, romidepsin and pralatrexate. Methods: A retrospective analysis examined costs in PTCL patients treated with pralatrexate- (n = 50) and romidepsin-based (n = 59) regimens in a nationally representative MedAssets hospital-based administrative claims dataset covering inpatient and outpatient services. Costs were collected during the time patients were considered to be on therapy and were standardized into cost per day. Between group differences were tested using analysis of variance and multivariable general linear regression Results: On average, pralatrexate patients had higher average total costs per day of therapy compared to romidepsin patients [$1,459 (SD: $1,502) vs $975 (SD: $759) p < 0.05]. Both treatment regimens had similar mean number of inpatient admissions (0.50 vs 0.46 p = 0.83) and length of stay (3.94 vs 3.31 days p = 0.68). Comparison of adverse events showed significantly higher rates of anemia (18.5% vs 6.3% p = 0.04) and infections (13% vs 3.1% p = 0.04) for pralatrexate patients compared to romidepsin. In a regression analysis, patients using pralatrexate based regimens had a 69% higher costs of $717 per day (IRR 1.69 p < 0.05) after controlling for differences in patient characteristics and lines of therapy Conclusions: Results of this analysis suggest that patients treated with pralatrexate have higher hospital related costs compared to patients treated with romidepsin, which appears to be driven in part by differences in adverse events. This analysis is limited in scope and does not consider patients treated by community oncologists not affiliated with hospitals. However, the finding of lower costs and fewer adverse events could be be considered as one part of healthcare resource allocation decisions.
Efficacy of Glecaprevir/Pibrentasvir for 8 or 12 Weeks in Patients With Hepatitis C Virus Genotype 2, 4, 5, or 6 Infection Without Cirrhosis
Authors: Tarik Asselah, Kris V. Kowdley, Neddie Zadeikis, Stanley Wang, Tarek Hassanein, Yves Horsmans, Massimo Colombo, Filipe Calinas, Humberto Aguilar, Victor de Ledinghen, Parvez S. Mantry, Christophe Hezode, Rui Tato Marinho, Kosh Agarwal, Frederik Nevens, Magdy Elkhashab, Jens Kort, Ran Liu, Teresa I. Ng, Preethi Krishnan, Chih-Wei Lin, Federico J. Mensa
Journal: Clinical Gastroenterology and Hepatology (2017)

Hepatitis C virus (HCV) has high genotypic diversity and global distribution. Agents that are effective against all major HCV genotypes, with shorter treatment duration, are needed to reduce disease burden. Glecaprevir (an NS3/4A protease inhibitor) and pibrentasvir (an NS5A inhibitor) have a high barrier to resistance and synergistic antiviral activity. We evaluated the safety and efficacy of 8 and 12 weeks' treatment with glecaprevir/pibrentasvir in patients with HCV genotype 2, 4, 5, or 6 infection without cirrhosis in 3 separate phase 3 trials.We performed 2 open label, single-arm studies (SURVEYOR-II, Part 4 and ENDURANCE-4) and a randomized, double-blind, placebo-controlled study (ENDURANCE-2). In the ENDURANCE-2 study, adult patients with untreated or previously treated HCV genotype 2 infection without cirrhosis were randomly assigned (2:1) to groups given once-daily oral glecaprevir/pibrentasvir (n = 202; 300 mg/120 mg) or placebo (n = 100) for 12 weeks. In the SURVEYOR-II, Part 4 and ENDURANCE-4 studies, adult patients with untreated or previously treated patients with HCV genotype 2, genotype 4, genotype 5, or genotype 6 infection, without cirrhosis, were given once-daily oral glecaprevir/pibrentasvir (n = 121 in ENDURANCE-4 and n = 145 in SURVEYOR-II) for 12 or 8 weeks, respectively. In all studies the primary endpoint was sustained virologic response at 12 weeks after treatment (SVR12) in the intention-to-treat population.Among patients receiving glecaprevir/pibrentasvir for 8 weeks, rates of SVR12 were 98% (95% CI, 94.1-99.3) in those infected with HCV genotype 2 and 93% (95% CI, 83.6-97.3) in those infected with HCV genotypes 4, 5, or 6. Among patients receiving glecaprevir/pibrentasvir for 12 weeks, rates of SVR12 were 99.5% (95% CI, 98.5-100) in those infected with HCV genotype 2 and 99% (95% CI, 97.6-100) in those infected with HCV genotype 4, 5, or 6. No virologic failures occurred in patients with HCV genotype 4, 5, or 6 infections. The frequency and severity of adverse events in patients receiving glecaprevir/pibrentasvir were similar to those of patients who received placebo.In 3 Phase 3 studies, 8 weeks' treatment with glecaprevir/pibrentasivr produced an SVR12 in at least 93% of patients with chronic HCV genotype 2, 4, 5, or 6 infection without cirrhosis, with virologic failure in less than 1%. The drug combination had a safety profile comparable to 12 week's treatment with glecaprevir/pibrentasvir. ClinicalTrials.gov numbers: NCT02640482 (ENDURANCE-2), NCT02636595 (ENDURANCE-4), and NCT02243293 (SURVEYOR-II).
Anti-metastatic effects of a TRAIL receptor agonist and interferon gamma in an orthotopic xenograft model of Ewing’s sarcoma
Authors: Melinda S. Merchant, Maria Romero, Fraia Melchionda, Maria Tsokos, Crystal L. Mackall
Journal: Cancer Research (2004)

4660  TRAIL receptor (TR) agonists selectively induce apoptosis in a variety of tumor cell types, including several pediatric solid tumors. We, and others, have previously shown that the majority of cell lines derived from Ewing’s Sarcoma Family of Tumors (ESFT) are sensitive to TR agonists in vitro. Of note, even chemoresistant ESFT cell lines were sensitive to TR agonists suggesting that TRAIL-based therapies may be successful in the treatment of high-risk ESFT patients. In order to test the efficacy of TRAIL in a model of high-risk ESFT, we developed an orthotopic xenograft by intramuscular injection of ESFT cells in SCID/bg mice that allows primary tumor development and subsequent bone, lung and abdominal metastases. Mice that received intraperitoneal injections of TR agonists (anti-TR2 mAb @5mg/kg/d or TRAIL/Apo2L @50mg/kg/d) following establishment of primary ESFT tumor had significantly decreased tumor growth or regression of disease. Based on the reported ability of IFNγ to sensitize TRAIL-resistant ESFT and neuroblastoma cell lines, human IFNγ (25000 IU/day) was added to the TR agonist treatment regimen in the xenograft model. Combination therapy was as effective as TR agonist alone at controlling primary tumor growth during treatment. Following cessation of therapy, tumor growth resumed in the majority of mice in both treatment arms and surgical removal was required when a volume of 1000mm3 was reached (day 27 [control or IFNγ only]; day 32 [TR agonist alone]; or day 38 [TR agonist + IFNγ]). No further treatment was administered and mice were followed for the development of metastatic disease. While TR agonists alone did not have a marked impact on incidence of metastases, combination therapy (TR agonist plus IFNγ) significantly decreased the incidence of metastatic disease and increased the overall survival to 60% at 5 months vs 0% in control and TR agonist groups. These data reveal both cytotoxic effects and anti-metastatic effects of anti-TR2 and IFNγ. These results are particularly intriguing because the effects of interferon are observed in the absence of an immune system and in murine tissues which can not respond to human IFNγ. Thus, the anti-metastatic activity of IFNγ are mediated by direct effects on the ESFT cells. We have begun to examine the expression of key mediators within the TRAIL pathway in vivo in order to determine the mechanisms by which IFNγ amplifies TRAIL-induced apoptosis in vivo and decreases the capacity of metastasis in ESFT cells.
Abstract 15296: Vernakalant Shows Superiority to Ibutilide in Recent-onset Atrial Fibrillation: A Randomized Controlled Trial at the Emergency Department
Authors: Alexander Simon, Jan Niederdöckl, Ekaterini Skyllouriotis, Nikola Schütz, Christoph Weiser, Harald Herkner, Anton N Laggner, Hans Domanovits, Alexander O Spiel
Journal: Circulation (2015)

Introduction: Ibutilide is a rapid-acting antiarrhythmic drug with worldwide use for conversion of recent-onset atrial fibrillation. Vernakalant is a novel drug, which is likewise used intravenously, with proven effectiveness and safety compared to placebo and amiodarone in randomized clinical trials. Hypothesis: We hypothesized that the time to sinus rhythm and the conversion rate within 90 minutes is different between vernakalant and ibutilide in patients with recent-onset atrial fibrillation. Methods: A randomized, controlled, open-label trial registered at clinicaltrials.gov (NCT01447862) was performed in one hundred patients with recent-onset atrial fibrillation treated at the emergency department of a tertiary care hospital. Patients received up to two short-infusions of vernakalant (n= 49; 3mg/kg, 2mg/kg) or ibutilide (n= 51; 1mg, 1mg) according to the manufacturer’s instructions. Clinical and laboratory variables, adverse events, conversion rates and time to conversion were recorded. Results: Time to conversion of AF to sinus rhythm was significantly shorter in the vernakalant group compared to the ibutilide group (median time: 10min vs. 26min, p=0.02), and likewise the conversion success within 90 minutes was significantly higher (69% vs. 43%, p=0.01) in the vernakalant group. In both groups no serious adverse events occurred. Conclusion: Vernakalant was significantly faster and more effective in converting recent-onset atrial fibrillation to sinus rhythm at the emergency department.
Abstract 18449: Mechanical Dispersion Improves Risk Stratification in Severe Aortic Stenosis Beyond Left Ventricular Ejection Fraction
Authors: Edgard A Prihadi, Melissa Leung, E M Vollema, Arnold Ng, Nina Ajmone Marsan, Jeroen J Bax, Victoria Delgado
Journal: Circulation (2016)

Background:  Left ventricular (LV) mechanical dispersion assessed with strain echocardiography reflects heterogeneity in systolic deformation and has been associated with ventricular arrhythmias and cardiac arrest in primary electrical and ischaemic heart disease. We hypothesized mechanical dispersion may predict occurrence of all-cause mortality in severe aortic stenosis (AS).   Methods:  424 patients (63.7 % men, 69±12 years) with severe AS (indexed aortic valve area 0.53±0.12 cm2/m2) were evaluated with transthoracic echocardiography. LV ejection fraction (LVEF) was calculated using biplane Simpson’s method. LV mechanical dispersion was calculated as standard deviation of time from Q wave on ECG to peak strain of 16 LV segments. Patients were followed for occurrence of all-cause mortality. Prognostic value of the 2 echocardiographic parameters was tested in different multivariable models.   Results:  During 82±47 months follow-up, surgical or transcatheter aortic valve replacement (AVR) was performed in 267 (63%) patients and 165 (39%) patients died. Non-survivors demonstrated worse LVEF and longer mechanical dispersion compared to survivors (LVEF 54±13% vs 58±9%, p   Conclusions:  Non-survivors with severe AS had a significantly higher LV mechanical dispersion and worse LVEF at baseline. In contrast to LVEF, LV mechanical dispersion was a significant prognostic parameter associated with all-cause mortality, indicating it may be an additional risk marker in patients with severe AS.