tbuckley/cabot-search huggingface dataset:
Lack of efficacy of adjuvant lapatinib in HER2-negative breast cancer (HER2–ve BC): Analysis of patients in the TEACH trial.
Authors: Yanin Chavarri Guerra, Arlene Chan, Dianne M. Finkelstein, Valorie F. Chan, Vernon J. Harvey, Keun Seok Lee, Minish Mahendra Jain, Katarina Petrakova, Vinod Raina, Binghe Xu, Henry Gomez, Erica Rappold, Tomomi Kaneko, Yingjie Huang, Paul E. Goss
Journal: Journal of Clinical Oncology (2013)

628 Background: Benefit from trastuzumab (T) in patients (pts) with HER2–ve tumors by central laboratory FISH testing was shown in an exploratory analysis of the NSABP B-31trial and confirmed by levels of expression of HER2 mRNA. DNA sequencing studies demonstrate that undetected HER2 mutations may drive tumor growth. It is hypothesized that pts with BC deemed as HER2–ve based on amplification may still benefit from anti-HER2 therapy. We undertook an exploratory analysis of disease free survival (DFS) in pts in TEACH whose tumors were HER2–ve or borderline by central FISH testing. Methods: TEACH, a randomized, double-blind, placebo (P)-controlled trial in 33 countries, evaluated lapatinib (L) in reducing relapse risk in T-naive pts pretreated with chemotherapy for HER2+ BC. L showed a hazard ratio (HR) for DFS compared with P of 0.83 (95% confidence interval [CI] 0.70-1.00); P=.053 in the ITT population (n=3147) and in pts with HER2+ BC by central FISH [HR: 0.82 (0.67-1.00); P=.04]. We conducted an exploratory analysis of DFS in pts with borderline or HER2–ve tumors by central FISH. Estimated DFS times were calculated using a stratified log-rank test. HR was estimated by a stratified Cox regression model. Results: 657 pts (21%) did not have centrally confirmed HER2+ BC (L: 341 and P: 316) in the ITT population: 425 had negative (HER2:CEP-17 ratio &lt;1.8) or borderline (≥1.8–&lt;2.0) FISH testing (L: 218 and P: 207), 216 were unevaluable due to insufficient tissue or sample failed to hybridize (L: 114 and P: 102) and 16 were not centrally tested. In the 425 pts with centrally confirmed HER2–ve or borderline FISH results with 27 events in L and 34 in P, the HR for DFS in L compared with P was 0.94 (0.56-1.57). The percentage of pts with DFS at 4 yrs was 85.0% (79.5%-90.4%) in L and 81% (75.1%-87.1%) in P. Conclusions: Although L showed efficacy in pts with centrally confirmed HER2+ BC in the TEACH trial, our analysis did not show benefit in pts whose tumors were HER2–ve or borderline by central FISH. The TEACH trial shows once again that quality control of HER2 testing is crucial and central laboratory testing should be considered for non-specialized centers worldwide. Clinical trial information: NCT00374322.
Prospective MRI score to predict negative EULAR response in patients with rheumatoid arthritis (RA) before therapy-escalation to a biological therapy
Authors: Philipp Sewerin, Stefan Vordenbaeumen, Ralph Brinks, Benedikt Ostendorf
Journal: Annals of the Rheumatic Diseases (2017)

Prospective MRI score to predict negative EULAR response in patients with rheumatoid arthritis (RA) before therapy-escalation to a biological therapy Dear EditorWe read with great interest the article by Baker et al 1 who showed that early MRI measures independently predict erosive progression on X-ray and MRI after 1 and 2 years in therapynaive patients with rheumatoid arthritis (RA) from the randomised-controlled GO-BEFORE trial.Due to these findings, we re-evaluated MRI data from the German REMISSION-PLUS Cohort 2 3 at our centre to verify if a MRI score may predict negative response in patients with RA before therapy-escalation to a biological therapy.MRI was performed in 257 patients before therapy-escalation (T0) and after 12 months (T1) and analysed by using the Outcome Measures in Rheumatology (OMERACT) rheumatoid arthritis MRI score (RAMRIS).In addition, clinical and laboratory parameters (Disease Activity Score 28 (DAS-28) and C-reactive protein (CRP)) were collected for each visit.Logistic regression combining clinical and MRI parameters was performed resulting in a combination of the patients' age and the RAMRIS-T0 performing best for prediction of non-response.Bootstrapping with 5000 resamples was performed to estimate the accuracy of the model.Of the patients included, 29 were escalated to a biological therapy (20 women, median age 57 years (IQR 46-65), 95% anti-tumour necrosis factor (TNF)-alpha therapy).Poor responders (n=5) and responders (n=24) had a mean RAMRIS-T0 score of 14.4 and 52.0, respectively (Wilcoxon test p<0.01).High RAMRIS score showed a trend towards a protective effect against non-response (OR 0.90 per RAMRIS point, 95% CI 0.79 to 1.03, p=0.12).The strength of the association was stable after adjusting for age, CRP, anti citrullinated peptide antibodies (ACPA)/rheumatoid factor and DAS-28 at baseline.The median area under the curve in the bootstrap analysis was 88.9% with 95% CI 84.0% to 92.8%.Thus, while Baker et al clearly demonstrated that a high inflammatory activity on MRI (ie, RAMRIS) is associated with
Perspectives on Care for the Elderly in China—Reply
Authors: XinQi Dong
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
포스터발표 : 컨벤션홀 특설 발표장 ; 유전자 비1형 만성 C형간염에서 페그인터페론과 리바비린 병합요법의 치료 효과
Authors: 김연주, 박선영, 김형일, 김성균, 이석, 윤경원, 조성범, 이완식, 박창환, 김현수, 최성규, 유종선
Journal: Clinical and Molecular Hepatology (2008)
Assessment of Pancreas Safety in the Development Program of Once-Weekly GLP-1 Receptor Agonist Dulaglutide
Authors: Michael A. Nauck, Jean-Louis Frossard, Jamie S. Barkin, Greg Anglin, Ingrid E. Hensley, Kristine D. Harper, Zvonko Milicevic
Journal: Diabetes Care (2017)

To assess the risk of acute pancreatitis during treatment with glucagon-like peptide 1 receptor agonist dulaglutide, placebo, and active comparators across phase 2/3 dulaglutide trials.A total of 6,005 patients with type 2 diabetes participated (dulaglutide group N = 4,006 [dose range 0.1-3.0 mg]; active comparator group [metformin, sitagliptin, exenatide twice daily, insulin glargine] N = 1,541; placebo group N = 703; 245 placebo-treated patients subsequently received dulaglutide or sitagliptin and were also included in these groups) for up to 104 weeks. The following events were adjudicated: investigator-reported pancreatitis, adverse events (AEs) of severe or serious abdominal pain of unknown etiology, and confirmed asymptomatic increases in pancreatic enzymes ≥3× the upper limit of normal range.Overall, 203 events from 151 patients underwent adjudication (dulaglutide group n = 108; comparator group including placebo n = 43). Acute pancreatitis was confirmed by adjudication in seven patients (dulaglutide n = 3, placebo n = 1, sitagliptin n = 3). Exposure-adjusted incidence rates were as follows: dulaglutide group 0.85 patients/1,000 patient-years, placebo group 3.52 patients/1,000 patient-years, sitagliptin group 4.71 patients/1,000 patient-years. No events of pancreatitis were confirmed by adjudication in patients treated with exenatide twice daily, metformin, or glargine. Increases in median values of lipase and pancreatic amylase within the normal range were observed with all treatments except glargine. These changes were not associated with AEs.The exposure-adjusted incidence rate of acute pancreatitis in dulaglutide-treated patients was similar to the rates with placebo, with few reported cases during the entire program.
Bone Marrow Stromal Cells Protect Both FLT3-ITD and FLT3-WT Primary AML Cells from the Anti-Leukemic Activity of the FLT3 Inhibitor AC220
Authors: Cedric Dos Santos, Georges Habineza Ndikuyeze, Michael Nisssan, Chenghui Zhou, Xiaochuan Shan, Alexander E. Perl, Martin P. Carroll, Gwenn Danet-Desnoyers
Journal: Blood (2014)
Consultants vote against automatic ballot on new contract
Authors: Abi Rimmer
Journal: BMJ (2017)

Consultants have voted against automatically holding a collective ballot of consultants and senior trainees on a new contract.

Instead, consultants could decide individually whether they wish to accept the new contract or remain on the existing consultant contract. Likewise, senior trainees, once they became consultants, could choose between the 2003 consultant contract and the new contract.

At the BMA’s consultants’ conference in London on Tuesday 28 February, delegates voted against a motion calling on the association’s Consultants Committee to neither approve nor accept any new contract “without balloting appropriate branches of the BMA membership.”

In his opening speech to the conference, Keith Brent, chair of the committee, said, “A scenario has arisen whereby the best possible terms for both present and …
Asymmetric subgenome selection and cis-regulatory divergence during cotton domestication
Authors: Maojun Wang, Lili Tu, Min Lin, Zhongxu Lin, Pengcheng Wang, Qingyong Yang, Zhengxiu Ye, Chao Shen, Jianying Li, Lin Zhang, Xiaolin Zhou, Xinhui Nie, Zhonghua Li, Kai Guo, Yizan Ma, Cong Huang, Shuangxia Jin, Longfu Zhu, Xiyan Yang, Ling Min, Daojun Yuan, Qinghua Zhang, Keith Lindsey, Xianlong Zhang
Journal: Nature Genetics (2017)
Paediatric hearing loss
Authors: Hannah Nieto, James Dearden, Stacey Dale, Jayesh Doshi
Journal: BMJ (2017)

#### What you need to know

A 3 year old child attends with his mother, who is worried about his hearing. Staff at the child’s nursery say he doesn’t always respond immediately, and his mother is concerned that he is not talking as much as other children.

Paediatric hearing loss is a common problem; diagnosis and appropriate intervention are central to the child’s development. It is estimated that one in five children of around 2 years will have been affected by glue ear and eight in 10 will have been affected once or more by the age of 10.1

### History

The observations of parents or professionals are key; explore inattentiveness at home, nursery, or school, and increased television volume, delayed language skills, and speech impediment. Symptoms will vary with severity and the age of the child.

Ask about

#### Box 1: Neonatal hearing screening programme

A well baby (where there is no need for special care, or <48 hours special care) undergoes an automated otoacoustic emissions test. If this is not “passed” after two attempts, then the baby has an automated auditory brainstem response test.

Babies in neonatal intensive care or at risk have …
Down-Regulation of MicroRNA-143 and -145 in Childhood B-Lineage Acute Lymphoblastic Leukemia at Initial Diagnosis and in Relapse but up-Regulated When in Remission
Authors: Yung-Li Yang, Shiann-Tarng Jou, Shu-Wha Lin, Dong-Tsamn Lin, Chung-Yi Hu, Sheng-Kai Chang, Ching-Tzu Yen, Rong-Jing Chiou, Kai-Hsin Lin, Meng-Yao Lu, Hsiu-Hao Chang, Shu-Rung Lin
Journal: Blood (2008)
Prevalence of type I sensitization to alpha‐gal in forest service employees and hunters
Authors: J. Fischer, E. Lupberger, J. Hebsaker, G. Blumenstock, E. Aichinger, A. S. Yazdi, D. Reick, R. Oehme, T. Biedermann
Journal: Allergy (2017)

Abstract Background The production of IgE molecules specific to the carbohydrate galactose‐α‐1,3‐galactose (alpha‐gal) is known to induce delayed anaphylaxis against mammalian meat. Tick bites constitute the primary sensitization source, as ticks transfer alpha‐gal in their saliva to a host during a bite. The reported prevalence of alpha‐gal‐specific IgE (alpha‐gal‐ sIgE ) positivity varies between different populations from diverse geographic regions. Objective To investigate the prevalence of alpha‐gal‐ sIgE positivity in a population of forest service employees who are highly exposed to ticks in comparison with a residential population and a historic sample. Methods A cross‐sectional study evaluating 300 forest service employees and hunters from southwest Germany was performed. Alpha‐gal‐ sIgE levels were assessed by Immuno CAP assay. The prevalence of alpha‐gal‐ sIgE ‐positive individuals was compared with a matched cohort composed of a residential population and blood samples from forest service employees collected 15 years ago. Results In the study population, the prevalence of alpha‐gal‐ sIgE ‐positive (≥0.10 kU A /L) individuals was 35.0%, whereas the prevalence of individuals with alpha‐gal‐ sIgE levels ≥0.35 kU A /L was 19.3%. Alpha‐gal‐ sIgE positivity was associated with total IgE levels and recent tick bites. Mammalian meat‐induced delayed anaphylaxis was found in 8.6% of the participants with alpha‐gal‐ sIgE levels ≥0.35 kU A /L. For forest service employees and hunters, the odds ratio for alpha‐gal‐ sIgE positivity was 2.48 compared to the residential population. The prevalence of alpha‐gal‐ sIgE positivity in the current and historic cohort was comparable. Conclusion Forest service employees and hunters compose a population with a high prevalence of alpha‐gal‐ sIgE positivity and carry a considerable risk of red meat allergy.
Abstract OT3-03-02: Maximising recruitment and retention of patients into UK-ANZ POSNOC trial
Authors: A Goyal, RE Coleman, D Dodwell, L Fallowfield, VA Jenkins, B Mann, MW Reed
Journal: Cancer Research (2017)

Abstract The success of a clinical trial is often dependant on whether recruitment targets can be met in the required time frame. Surgeons want to gather robust evidence but may experience considerable discomfort in relation to their clinical instincts and concerns about patient eligibility and safety. The ongoing POSNOC study design is pragmatic to maximise recruitment. A patient information DVD is used as an adjunct to patient information leaflet. The protocol allows for either axillary radiotherapy or axillary node clearance. Here we report recruitment and retention of participants into POSNOC, the associated barriers and challenges, and various strategies employed to overcome these barriers. A total of 368 participants were recruited till May 2016. A total of 90%(331) of participants were recruited via non intra-operative pathway, and 10%(37) from intra-operative pathway. The most common known reasons for non-participation of eligible women were - woman wanting axillary treatment and clinician/MDT deciding woman needs axillary treatment. The mean randomisation yield from screening was 30% (range 6 to 100%). The highest recruiting sites were Derby, Manchester, Oxford, Belfast and Bristol. The screening logs identified barriers as: fewer than estimated eligible women, clinicians not offering trial to all eligible patients and patient acceptability. To reach recruitment targets in a timely fashion, a multifaceted approach is being employed. a) Protocol amendments to widen the inclusion criteria, b) 250 patients to be recruited by Australia and New Zealand sites, c) additional 50 sites to be opened in the UK, d) encourage OSNA centres to follow the non intra-operative pathway, e) communication workshops, f) POSNOC poster in breast units to raise awareness, g) questionnaire survey - sites to identify local issues and their perceptions about recruitment, h) social media - POSNOC WhatsApp group i) newsletters and briefings, j) competitions, k) tips to maximise recruitment document that includes a template script of one way to introduce the study l) regional telephone conferences for research nurses, m) investigator meeting. The success of these strategies remains to be assessed and shall be reported separately. Citation Format: Goyal A, Coleman RE, Dodwell D, Fallowfield L, Jenkins VA, Mann B, Reed MW, POSNOC Trial Management Group. Maximising recruitment and retention of patients into UK-ANZ POSNOC trial [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT3-03-02.
Discovery of STAT5b Mutations and Small Subclones of STAT3 Mutations in Large Granular Lymphocytic (LGL) Leukemia
Authors: Hanna L M Rajala, Samuli Eldfors, Heikki Kuusanmäki, Emma I Andersson, Arjan J van Adrichem, Sonja Lagström, Thomas Olson, Andres Jerez, Michael J. Clemente, Dan Zhang, Andy Awwad, Markus Pihlman, Pekka Ellonen, Olli Kallioniemi, Krister Wennerberg, Kimmo Porkka, Jaroslaw P. Maciejewski, Thomas P. Loughran, Caroline A Heckman, Satu Mustjoki
Journal: Blood (2012)
A pedunculated nasal nodule
Authors: Magnus Lynch, Faisal Ali, Raj Mallipeddi
Journal: BMJ (2017)

A 92 year old man presented to his primary care doctor complaining of a lesion on his right nostril (fig 1⇓). The lesion had been present for 10 or more years, however recently it had increased in size. His only history was of chronic renal impairment. Examination revealed a 10 mm pink, pearlescent, pedunculated nodule with telangiectasia arising from the right nasal ala.



Fig 1  A pearlescent nodule with telangiectasia arising from the right nasal ala



### 1. What is the most likely diagnosis?

#### Short answer

Basal cell carcinoma.

#### Discussion

The lesion is a pearly nodule with telangiectasia arising from the right nasal ala. The clinical appearances are characteristic of basal cell carcinoma, which is the most common cutaneous malignancy.1 The main risk factor is ultraviolet light exposure; other risk factors include having fair skin, exposure to radiation, and various genetic syndromes including naevoid basal cell carcinoma (Gorlin) syndrome and xeroderma pigmentosum. A history of slow …
F<scp>ifty</scp> Y<scp>ears of</scp> R<scp>esearch in</scp> ARDS.Insight into Acute Respiratory Distress Syndrome. From Models to Patients
Authors: John G. Laffey, Brian P. Kavanagh
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Clinicians who treat patients with acute respiratory distress syndrome (ARDS) use information and guidance from a wide array of sources, ranging from laboratory experiments, clinical data, health services research, intuition, to personal experience. Each of these sources of information brings unique methodology and information, but each is inherently limited. Because ARDS is a syndrome (and not a disease), the clinician or scientist must take additional care when applying knowledge to individual patients among a group, because patients often do not have identical lung pathophysiology. However, an overwhelming body of knowledge has accumulated in the field from multiple sources. In this review, we describe the nature of some of these sources as they relate to ARDS and review examples of when they have succeeded (and sometimes failed) in shaping practice or advancing knowledge about ARDS.
TCR Diversity Is a Predictive Marker for Donor Lymphocyte Infusion Response
Authors: Christian Schultze-Florey, Solaiman Raha, Sarina Ravens, Leonie Kuhlmann, Melanie Drenker, Linda Oberdörfer, Anke Breithaupt, Elke Dammann, Lothar Hambach, Michael Stadler, Michael Heuser, Felicitas Thol, Reinhold Foerster, Arnold Ganser, Immo Prinz, Christian Koenecke
Journal: Blood (2016)
Abstract IA16: Patient-derived xenograft models in glioblastoma
Authors: Joan Seoane
Journal: Clinical Cancer Research (2016)

Abstract One the most important challenges in the treatment of cancer is its evolving genomic intratumor heterogeneity. Tumors are composed of assortments of cells with subclonal genomic alterations that evolve following Darwinian selection. Glioblastoma (GBM) is a prototypical heterogeneous tumor and still little is known about how intratumor heterogeneity influences the progression of GBM and, most importantly, determines the response to treatments and tumor relapse. The study of the spatial and temporal genomic architecture of GBM is essential to understand the biology and improve the treatment of this dismal disease. Through the study of primary and relapsed tumors and patient-derived xenograft models (PDX) of GBM, we are studying the genomic subclones emerging after treatment since these subclones might be enriched in genomic alterations that confer a selective advantage and resistance to treatment. Putative genomic alterations involved in tumor resistance to treatment are further studied and validated through PDX models. Citation Format: Joan Seoane. Patient-derived xenograft models in glioblastoma. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr IA16.
Efficacy and safety of cancer vaccine with 4-fold gene-modified allogeneic tumor cells: Results of the phase I/II ASET study in patients with advanced renal cell carcinoma.
Authors: Steffen Weikert, Viktor Grünwald, Ingo GH Schmidt-Wolf, Stefan Hauser, Kerstin Kapp, Manuel Schmidt, Matthias Schroff, Ekaterina Weith, Marina Tschaika, Burghardt Wittig
Journal: Journal of Clinical Oncology (2012)

4636 Background: MGN1601 was tested in the first-in-man phase I-II clinical study in patients with advanced renal cell carcinoma (RCC) who failed several previous therapy lines and had no further standard therapy available. MGN1601 consists of two active pharmaceutical ingredients in fixed combination: fourfold gene-modified allogeneic tumor cells expressing IL-7, GM-CSF, CD80 and CD154 through MIDGE vectors and a TLR-9 agonist, the immunomodulator dSLIM. Methods: The ASET study is a multicentric, single-arm phase I-II clinical trial. Clinical response was evaluated using CT scans (RECIST 1.1 or immune related Response Criteria, irRC). Efficacy data were evaluated in terms of PFS and OS for the intended to treat and the treated per protocol (TPP) populations, clinical parameters and quality of life. Immune response was determined using DTH to MGN1601, LTT assay, frequency and activation of blood cells, and mRNA, chemokine and cytotoxic T cells analysis as well as tumor tissue evaluation. Results: Nine of 19 included patients completed the TPP, the others discontinued the study earlier due to PD. Median PFS in the TPP group was 12 wks (3 months) and OS (not reached yet) 46 wks (11 months). Three patients achieved disease control (1 PR, 2 SD) after 12 wks. Two patients are continuing treatment in the extension phase and are progression free since 37 and 46 wks, respectively. Re-evaluation of tumor response data using irRC revealed 1 additional patient with a delayed tumor response 4 wks after treatment stop. Herewith, 4 out of 9 TPP patients (45%) achieved disease control. Of 7 patients receiving targeted therapy upon stop of study treatment, 4 had substantial objective responses, providing evidence that the study drug is able to render their tumors more vulnerable to subsequent therapies. Immune analysis showed trends towards increases of T-, NKT-cell and pDC frequencies and other immune parameters in those patients with clinical responses, indicating anti-tumor immunity of study treatment. Conclusions: The therapeutic cancer vaccine MGN1601 shows promising efficacy in late stage mRCC patients. Results warrant further clinical studies with MGN1601.