tbuckley/cabot-search huggingface dataset:
A phase I/IIa study of icotinib hydrochloride, a novel oral EGFR-TKI, to evaluate its safety, tolerance, and preliminary efficacy in advanced NSCLC patients in China.
Authors: Q. Zhao, J. Zhou, J. Shentu, N. Xu, F. Tan
Journal: Journal of Clinical Oncology (2010)

7574 Background: To assess the safety, tolerance and efficacy of icotinib hydrochloride (BPI-2009H), a new selective EGFR TKI in Chinese patients (pts) with advanced NSCLC after failure of prior platinum-based chemotherapy. Methods: Sixty advanced NSCLC pts with PS 0/1 were enrolled in the open-label, single-center, phase I/IIa study during Dec 2007 to Jun 2009. Oral icotinib was administered once per 8 hours (Q8H) for a 28- continuous day cycle until disease progression or intolerable toxicity. Enrollment required age ≥ 18 and ≤ 70 yrs, ECOG performance status 0-1 and adequate organ functions. Tumor response was assessed according to RECIST. Progressive free survival (PFS) was calculated and a Cox regression model was used to identify factors that potentially affect PFS and DCR. Results: Adverse events (AEs) were generally mild (grade 1 and 2) and reversible. The most frequent AEs were rash (56.9%), diarrhea (15.5%), Dose-limiting toxicity (DLT) didn't occur even in the dosage group of 750 mg per day (250 mg Tid) ,thus the maximum-tolerated dose (MTD) was not reached yet. Among the 60 pts enrolled, 58 pts were eligible for clinical response assessment. The objective tumor response rate (ORR) and disease control rate (DCR) were 24.1% and 79.3%,and median PFS was 16 weeks (95%CI 9.3-22.8). Preliminary 1-year survival rate was 60% (30/50). PFS multivariate Cox regression analysis indicated that smoking, skin AE are key influencing factors. DCR multivariate logistic regression analysis indicated rash became the only significant influencing factor. PK analysis showed steady-state concentration exposured to icotinib 125 mg Q8H was obviously higher than it exposured to icotinib 100 mg Q8H. The T1/2 was around 6 hours and Tmax was around 2 hours in all six different dose levels. Conclusions: Oral icotinib was generally well tolerated, with manageable and reversible AEs, and showed positive clinical antitumor activities in patients with advanced NSCLC. No MTD was defined yet in this study. Updated results and OS of all pts will be presented. A head to head, double blinded, multicenter phase III study of icotinib to gefitinib is currently undergoing in China. No significant financial relationships to disclose.
Weekly cetuximab and paclitaxel combination in metastatic/recurrent squamous cell cancer carcinoma of the head and neck (SCCHN): Clinical experience of a single institution
Authors: I. Diaz de Corcuera, C. Serrano, J. Pérez, I. Quispe, M. Arguis, E. Muñoz, S. Benavente, P. Martínez, M. Parera, J. M. del Campo
Journal: Journal of Clinical Oncology (2009)

e17043 Background: Results of a recent phase III randomized study with cetuximab and platin-5FU chemotherapy support its use in recurrent/metastatic SCCHN. However, many patients (pts) are not able to be treated with platin combinations. Paclitaxel (P) and cetuximab (C) have shown an encouraging activity in a similar patients subset. We review the data of the patients treated with this schedule in our centre. Methods: From our database, we conducted a retrospective study of 20 patients with recurrent SCCHN who did not meet criteria for platin therapy and were treated with weekly P (80 mg/m2) and C (initially 400 mg/m2 followed by 250 mg/m2) until progression or intolerable toxicity. We have collected data regarding previous treatments, response rate (RR), progression free survival (PFS), overall survival (OS) and toxicity. Results: From January 2007 to November 2008, 20 patients were included (18 male, 2 female) with a median age of 63 (50–81). Oral cavity (35%) and oropharynx (25%) were the most frequent locations. Most of the pts (13/20) had been treated with previous chemotherapy combinations (range 1–3 lines). All pts were evaluable for response and toxicity. Overall RR was 45% (1CR, 8 PR) and 35% of the pts (7/10) had SD. Response in radiated areas were 35% (6/17). With a median follow up of 10 months the median PFS and OS were 6.5 and 7 months respectively. Main related toxicities (Gr 2/3) were acne-like rash (30%), asthenia (15%), anemia (10%), and mucositis (10%). Conclusions: Our analysis confirms that weekly paclitaxel-cetuximab is an effective and safety combination in metastatic/recurrent SCCHN. Treatment is very well tolerated and could be a good alternative to platin-based chemotherapy in unfit patients for this therapy. No significant financial relationships to disclose.
Diagnosis and treatment of depression
Journal: American Journal of Psychiatry (1989)

Depression has become one of the world's four major disabling diseases.In Beijing and Shanghai,the prevalence of depressive disorder were 2.5% and 1.7%,respectively.This article explains the depression risk factors,clinical symptoms,self-recognition,and analyzes the reasons for the low recognition rate.Also new type antidepressants,physical therapy,and psychotherapy for depression are recommended.
Gastroesophageal reflux disease and Barrett’s esophagus
Authors: M. Bittinger, H. Messmann
Journal: Endoscopy (2007)

Once again, the past year has seen the publication of numerous new papers in the fields of gastroesophageal reflux disease (GERD) and Barrett’s esophagus. From these papers we want to focus on six relevant studies that reflect the most interesting topics in the field.
Tumor-Infiltrating Lymphocytes, Crohn’s-Like Lymphoid Reaction, and Survival From Colorectal Cancer
Authors: Laura S. Rozek, Stephanie L. Schmit, Joel K. Greenson, Lynn P. Tomsho, Hedy S. Rennert, Gad Rennert, Stephen B. Gruber
Journal: JNCI Journal of the National Cancer Institute (2016)

Background: While clinical outcomes from colorectal cancer (CRC) are influenced by stage at diagnosis and treatment, mounting evidence suggests that an enhanced lymphocytic reaction to a tumor may also be an informative prognostic indicator. Methods: The roles of intratumoral T lymphocyte infiltration (TIL), peritumoral Crohn's-like lymphoid reaction (CLR), microsatellite instability (MSI), and clinicopathological characteristics in survival from CRC were examined using 2369 incident CRCs from a population-based case-control study in northern Israel. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC-specific and all-cause mortality in multivariable models adjusted for age, sex, ethnicity, grade, stage, and MSI. All statistical tests were two-sided. Results: Tumors with TIL/high-powered field (HPF) of 2 or greater were associated with a statistically significant increase in CRC-specific (P < .001) and overall survival (P < .001) compared with tumors with TIL/HPF of less than 2. Similarly, tumors with a prominent CLR experienced better CRC-specific (P < .001) and overall survival (P < .001) as compared with those with no response. High TILs (HR = 0.76, 95% CI = 0.64 to 0.89, P < .001) and a prominent CLR (HR = 0.71, 95% CI = 0.62 to 0.80, P < .001), but not MSI, were associated with a statistically significant reduction in all-cause mortality after adjustment for established prognostic factors. Conclusions: TILs and CLR are both prognostic indicators for CRC after adjusting for traditional prognostic indicators.
Efficacy and Safety Of Temsirolimus In Patients With Relapsed Or Refractory Mantle Cell Lymphoma: Results From The Spanish Experience
Authors: Adolfo de la Fuente, Gloria González, Iciar García-Carbonero, Javier García-Frade, Javier Munárriz, David Aguiar, Beatriz Cuevas, María Victoria Cuevas, Rafael Aporta, Abelardo Bárez, Marta Callejas, Adolfo Murias, Albert Altés, Antonio Salar, Blanca Sanchez-Gonzalez, Carlos Grande, Jose A. Garcia-Marco, Ángeles López, Marina Morán, Andrea Viqueira, Javier Briones
Journal: Blood (2013)
Enhancing insulin oral absorption by using mucoadhesive nanoparticles loaded with LMWP-linked insulin conjugates
Authors: Jianyong Sheng, Huining He, Limei Han, Jing Qin, Sunhui Chen, Ge Ru, Ruixiang Li, Pei Yang, Jianxin Wang, Victor C. Yang
Journal: Journal of Controlled Release (2016)
Use of systems biology to decipher host–pathogen interaction networks and predict biomarkers
Authors: A. Dix, S. Vlaic, R. Guthke, J. Linde
Journal: Clinical Microbiology and Infection (2016)

In systems biology, researchers aim to understand complex biological systems as a whole, which is often achieved by mathematical modelling and the analyses of high-throughput data. In this review, we give an overview of medical applications of systems biology approaches with special focus on host-pathogen interactions. After introducing general ideas of systems biology, we focus on (1) the detection of putative biomarkers for improved diagnosis and support of therapeutic decisions, (2) network modelling for the identification of regulatory interactions between cellular molecules to reveal putative drug targets and (3) module discovery for the detection of phenotype-specific modules in molecular interaction networks. Biomarker detection applies supervised machine learning methods utilizing high-throughput data (e.g. single nucleotide polymorphism (SNP) detection, RNA-seq, proteomics) and clinical data. We demonstrate structural analysis of molecular networks, especially by identification of disease modules as a novel strategy, and discuss possible applications to host-pathogen interactions. Pioneering work was done to predict molecular host-pathogen interactions networks based on dual RNA-seq data. However, currently this network modelling is restricted to a small number of genes. With increasing number and quality of databases and data repositories, the prediction of large-scale networks will also be feasible that can used for multidimensional diagnosis and decision support for prevention and therapy of diseases. Finally, we outline further perspective issues such as support of personalized medicine with high-throughput data and generation of multiscale host-pathogen interaction models.
Effect of Noninvasive Ventilation Delivered by Helmet vs Face Mask on the Rate of Endotracheal Intubation in Patients With Acute Respiratory Distress Syndrome
Authors: Bhakti K. Patel, Krysta S. Wolfe, Anne S. Pohlman, Jesse B. Hall, John P. Kress
Journal: JAMA (2016)

<h3>Importance</h3> Noninvasive ventilation (NIV) with a face mask is relatively ineffective at preventing endotracheal intubation in patients with acute respiratory distress syndrome (ARDS). Delivery of NIV with a helmet may be a superior strategy for these patients. <h3>Objective</h3> To determine whether NIV delivered by helmet improves intubation rate among patients with ARDS. <h3>Design, Setting, and Participants</h3> Single-center randomized clinical trial of 83 patients with ARDS requiring NIV delivered by face mask for at least 8 hours while in the medical intensive care unit at the University of Chicago between October 3, 2012, through September 21, 2015. <h3>Interventions</h3> Patients were randomly assigned to continue face mask NIV or switch to a helmet for NIV support for a planned enrollment of 206 patients (103 patients per group). The helmet is a transparent hood that covers the entire head of the patient and has a rubber collar neck seal. Early trial termination resulted in 44 patients randomized to the helmet group and 39 to the face mask group. <h3>Main Outcomes and Measures</h3> The primary outcome was the proportion of patients who required endotracheal intubation. Secondary outcomes included 28-day invasive ventilator–free days (ie, days alive without mechanical ventilation), duration of ICU and hospital length of stay, and hospital and 90-day mortality. <h3>Results</h3> Eighty-three patients (45% women; median age, 59 years; median Acute Physiology and Chronic Health Evaluation [APACHE] II score, 26) were included in the analysis after the trial was stopped early based on predefined criteria for efficacy. The intubation rate was 61.5% (n = 24) for the face mask group and 18.2% (n = 8) for the helmet group (absolute difference, −43.3%; 95% CI, −62.4% to −24.3%;<i>P</i> &lt; .001). The number of ventilator-free days was significantly higher in the helmet group (28 vs 12.5,<i>P</i> &lt; .001). At 90 days, 15 patients (34.1%) in the helmet group died compared with 22 patients (56.4%) in the face mask group (absolute difference, −22.3%; 95% CI, −43.3 to −1.4;<i>P</i> = .02). Adverse events included 3 interface-related skin ulcers for each group (ie, 7.6% in the face mask group had nose ulcers and 6.8% in the helmet group had neck ulcers). <h3>Conclusions and Relevance</h3> Among patients with ARDS, treatment with helmet NIV resulted in a significant reduction of intubation rates. There was also a statistically significant reduction in 90-day mortality with helmet NIV. Multicenter studies are needed to replicate these findings. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT01680783
β- and γ-Human Papillomavirus Types and Smoking in Head and Neck Cancer—Reply
Authors: Ilir Agalliu, Tao Wang, Robert D. Burk
Journal: JAMA Oncology (2016)

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Treatment of Attention-Deficit/Hyperactivity Disorder in Adolescents
Authors: Eugenia Chan, Jason M. Fogler, Paul G. Hammerness
Journal: JAMA (2016)

Although attention-deficit/hyperactivity disorder (ADHD) is highly prevalent in adolescents and often persists into adulthood, most studies about treatment were performed in children. Less is known about ADHD treatment in adolescents.To review the evidence for pharmacological and psychosocial treatment of ADHD in adolescents.The databases of CINAHL Plus, MEDLINE, PsycINFO, ERIC, and the Cochrane Database of Systematic Reviews were searched for articles published between January 1, 1999, and January 31, 2016, on ADHD treatment in adolescents. Additional studies were identified by hand-searching reference lists of retrieved articles. Study quality was rated using McMaster University Effective Public Health Practice Project criteria. The evidence level for treatment recommendations was based on Oxford Centre for Evidence-Based Medicine criteria.Sixteen randomized clinical trials and 1 meta-analysis, involving 2668 participants, of pharmacological and psychosocial treatments for ADHD in adolescents aged 12 years to 18 years were included. Evidence of efficacy was stronger for the extended-release methylphenidate and amphetamine class stimulant medications (level 1B based on Oxford Centre for Evidence-Based Medicine criteria) and atomoxetine than for the extended-release α2-adrenergic agonists guanfacine or clonidine (no studies). For the primary efficacy measure of total symptom score on the ADHD Rating Scale (score range, 0 [least symptomatic] to 54 [most symptomatic]), both stimulant and nonstimulant medications led to clinically significant reductions of 14.93 to 24.60 absolute points. The psychosocial treatments combining behavioral, cognitive behavioral, and skills training techniques demonstrated small- to medium-sized improvements (range for mean SD difference in Cohen d, 0.30-0.69) for parent-rated ADHD symptoms, co-occurring emotional or behavioral symptoms, and interpersonal functioning. Psychosocial treatments were associated with more robust (Cohen d range, 0.51-5.15) improvements in academic and organizational skills, such as homework completion and planner use.Evidence supports the use of extended-release methylphenidate and amphetamine formulations, atomoxetine, and extended-release guanfacine to improve symptoms of ADHD in adolescents. Psychosocial treatments incorporating behavior contingency management, motivational enhancement, and academic, organizational, and social skills training techniques were associated with inconsistent effects on ADHD symptoms and greater benefit for academic and organizational skills. Additional treatment studies in adolescents, including combined pharmacological and psychosocial treatments, are needed.
Impact of NCCN distress thermometer screening at new patient oncology visits in a large community cancer institute.
Authors: Shanthi Sivendran, Patti Roda, Kristen De la Torre, Kristina Braine Newport
Journal: Journal of Clinical Oncology (2014)

226 Background: Psychosocial distress can impact a patient’s quality of life and potentially impact timely and effective cancer management. The National Comprehensive Cancer Network (NCCN) developed a distress thermometer that includes a ten point scale of distress and checklist of psychosocial issues. In this analysis we compare rates of referrals to our support services prior to and post implementation of this tool in our community oncology practice. Methods: Data one year prior to and post implementation of the NCCN distress thermometer was retrospectively reviewed. The tool was implemented in July 2013 and administered to the patients by our clinical staff at the patient’s first visit. Based on this tool, the clinical staff offered referrals to social work, chaplaincy, nutrition, or financial counseling. Re-education on administration of this tool occurred in January 2014. In this study we compare support service referrals pre and post NCCN distress screening implementation and staff education. Results: From July 2012 to June 2013, 829 referrals were made to support services. Specifically, 39% of these referrals were to social work, 19% to chaplaincy, and 38% to nutrition. From July 2013 to May 2014, 1434 referrals were made to support services. Specifically, 37% of these referrals were to social work, 10% to chaplaincy, 20% to nutrition, and 34% to financial counseling. Referrals to social work were most impacted by implementation of the NCCN distress screening with a median increase from 26.5 (range 14-45) to 45 (range 32-68). Referrals to other support services were not impacted. Referrals to financial counseling were most impacted by the re-education process with a median increase from 38 (range 28-42) to 53 (range 42-58). Conclusions: Implementation of the NCCN distress thermometer allowed better identification of patients for social work and financial counseling interventions. This tool was less effective at increasing referrals to nutrition and chaplaincy. The need for these services may be better captured during the treatment period. Future investigation into this may include application of the distress tool during subsequent patient visits.
Characterization of pediatric Philadelphia-negative B-cell precursor acute lymphoblastic leukemia with kinase fusions in Japan
Authors: T Imamura, N Kiyokawa, M Kato, C Imai, Y Okamoto, M Yano, K Ohki, Y Yamashita, Y Kodama, A Saito, M Mori, S Ishimaru, T Deguchi, Y Hashii, Y Shimomura, T Hori, K Kato, H Goto, C Ogawa, K Koh, T Taki, A Manabe, A Sato, A Kikuta, S Adachi, K Horibe, A Ohara, A Watanabe, Y Kawano, E Ishii, H Shimada
Journal: Blood Cancer Journal (2016)

Recent studies revealed that a substantial proportion of patients with high-risk B-cell precursor acute lymphoblastic leukemia (BCP-ALL) harbor fusions involving tyrosine kinase and cytokine receptors, such as ABL1, PDGFRB, JAK2 and CRLF2, which are targeted by tyrosine kinase inhibitors (TKIs). In the present study, transcriptome analysis or multiplex reverse transcriptase-PCR analysis of 373 BCP-ALL patients without recurrent genetic abnormalities identified 29 patients with kinase fusions. Clinically, male predominance (male/female: 22/7), older age at onset (mean age at onset: 8.8 years) and a high white blood cell count at diagnosis (mean: 94 200/μl) reflected the predominance of National Cancer Institute high-risk (NCI-HR) patients (NCI-standard risk/HR: 8/21). Genetic analysis identified three patients with ABL1 rearrangements, eight with PDGFRB rearrangements, two with JAK2 rearrangements, three with IgH-EPOR and one with NCOR1-LYN. Of the 14 patients with CRLF2 rearrangements, two harbored IgH-EPOR and PDGFRB rearrangements. IKZF1 deletion was present in 16 of the 22 patients. The 5-year event-free and overall survival rates were 48.6±9.7% and 73.5±8.6%, respectively. The outcome was not satisfactory without sophisticated minimal residual disease-based stratification. Furthermore, the efficacy of TKIs combined with conventional chemotherapy without allogeneic hematopoietic stem cell transplantation in this cohort should be determined.
Safety of prolonged Doxil administration in recurrent gynecologic cancers
Authors: F. Muggia, E. Kim, A. Downey, K. McCaffrey, R. Green, M. F. Ho, D. Mirchandani, J. Sorich, H. Hochster, A. Hamilton
Journal: Journal of Clinical Oncology (2004)

5055 Background: Liposomal doxorubicin (Doxil [D]) has activity in ovarian (OC), tubal (TC), and endometrial (EC) cancers. Since 2nd responses in OC are shorter than the 1st and always followed by relapse, patients achieving maximal response after D-containing doublets or monotherapy, were then continued on D. Methods: 18 patients (after platinum-based induction: 14OC, 2TC, 1EC; or after radiation: 1EC) were treated with D + carboplatin (3), topotecan (9) or taxane (1) doublet trials, or D alone (5). Treatment consisted of D 30–40 mg/m2 given every 4–6 weeks (adjusted to skin tolerance); routine cardiac status (MUGA, ECHO) follow-up was obtained at cumulative doses > 300 mg/m2; duration of treatment and its tolerance are analyzed. Results: 5 continue in complete response (4 OC, 1EC) with D as 2nd line to cumulative doses of 750+, 750+, 760+, 1515+ mg/m2 for 4OC & 390+ mg/m2 for 1EC; time on monotherapy maintenance lasting 22+, 24+, 25+, 57+ & 11+ m vs 34, 13, 8, 7, & 5 m, respectively, for 1st unmaintained interval. In 13, D was given after partial response (8OC, 1EC, 2TC) or in stable disease (2OC), after ≥ 2nd line for median 710 mg/m2 (range 405-1435+) for median 19 m, range (0-37+ m); their preceding treatment-free interval median 7 m, (0–31 m). Confirmed drops in ejection fraction (EF) did not occur during D. An event of shock, neutropenia, and 23% EF occurred 10 m after last D in a patient toxic from oral topotecan; prior EF on D was normal. Ten on continued maintenance have had no changes in EF, alopecia, or bone marrow suppression, –eight have stopped D for progression. Conclusion: Neither clinical cardiac toxicity nor cumulative myelosuppression has been noted on D maintenance; it may lengthen progression-free survival in relapsed OC. Supported by The Chemotherapy Foundation and the Lynne Cohen for Ovarian Cancer Research Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ortho Biotec Ortho Biotech
Alcohol intake increases the risk of HCC in hepatitis C virus-related compensated cirrhosis: A prospective study
Authors: Hélène Vandenbulcke, Christophe Moreno, Isabelle Colle, Jean-François Knebel, Sven Francque, Thomas Sersté, Christophe George, Chantal de Galocsy, Wim Laleman, Jean Delwaide, Hans Orlent, Luc Lasser, Eric Trépo, Hans Van Vlierberghe, Peter Michielsen, Marc van Gossum, Marie de Vos, Astrid Marot, Christopher Doerig, Jean Henrion, Pierre Deltenre
Journal: Journal of Hepatology (2016)