tbuckley/cabot-search huggingface dataset:
Prognostic impact of human epidermal growth factor-2 (HER2) status on overall survival (OS) of advanced gastric cancer (AGC) patients (pts) treated with standard chemotherapy without trastuzumab as a first-line treatment: A Japanese multicenter collaborative retrospective study.
Authors: Tomohiro Nishina, Nozomu Fuse, Takeshi Kuwata, Shigenori Kadowaki, Eiji Shinozaki, Nozomu Machida, Satoshi Yuki, Akira Ooki, Shinya Kajiura, Takahiro Goji, Takeharu Yamanaka, Takahide Sasaki, Kohei Shitara, Yasutoshi Kuboki, Takayuki Yoshino, Atsushi Ochiai, Atsushi Ohtsu
Journal: Journal of Clinical Oncology (2013)

4075 Background: The prognostic impact of HER2 status on OS of AGC pts treated with standard chemotherapy without trastuzumab for first-line treatment remains controversial. This study investigated whether HER2 status is an independent prognostic factor for AGC pts. Methods: Formalin-fixed paraffin-embedded tumor samples from 293 eligible pts were examined for HER2 by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH). Eligible criteria included: 1) histologically confirmed gastric or gastroesophageal junction adenocarcinoma, 2) unresectable or recurrent cancer, 3) treated with S-1 plus cisplatin as first-line chemotherapy, 4) age: ≥20, 5) ECOG performance status score: 0-2 and 6) with archived tumor sample. HER2+ was defined as IHC 3+ or IHC 2+/FISH+. Results: Of 293 pts, 43 (15%) were HER2+. Baseline pt characteristics between HER2+ and HER2- pts were significantly different by histology (intestinal/diffuse, 65%/35% vs. 39%/61%; p=0.001), measurable disease by RECIST v1.0 (91% vs. 69%; p=0.003), No. of metastatic sites (≥2, 72% vs. 46%; p=0.003) and presence of liver metastasis (56% vs. 31%; p=0.003). After median follow-up time of 48.9 months with 270 (92%) death events, there was no significant difference in OS between HER2+ and HER2- pts (median, 11.7 vs. 13.7 months; hazard ratio [HR] 1.11, 95% CI 0.79–1.55; log rank p=0.550). After adjusting other prognostic factors with Cox hazard model, HER2+ was still not prognostic for OS (HR 0.890, 95% CI 0.627–1.262, p=0.513). Conclusions: HER2 status has no significant prognostic impact on OS of AGC pts treated with S-1 plus cisplatin without trastuzumab as a first-line treatment.
AFM11, a CD19/CD3 bispecific tandab, to facilitate T-cell-mediated killing of CD19+ cells.
Authors: Eugene Zhukovsky, Uwe Reusch, Carmen Burkhardt, Stefan Knackmuss, Ivica Fucek, Markus Eser, Fionnuala McAleese, Kristina Ellwanger, Melvyn Little
Journal: Journal of Clinical Oncology (2013)

3068 Background: CD19, due to broader expression on B cell subtypes, is an attractive alternative to CD20 as a target for treatment of B cell malignancies. T cells are potent tumor-killing effectors that cannot be recruited by full length antibodies, however TandAb technology harnesses their cytotoxic nature for oncology indications. The CD3 RECRUIT TandAb AFM11 enables T cells to potently and specifically kill CD19+ tumors and possesses advantageous PK properties enabling intravenous dosing. Methods: We constructed AFM11, a human bispecific tetravalent antibody with two binding sites for both CD3 and CD19. In vitro efficacy and safety were evaluated on CD19+ cell lines and primary tumors. In vivo efficacy was evaluated in a murine NOD/scid xenograft model reconstituted with human PBMC. Results: In vitro assays demonstrate higher potency and efficacy of target cell lysis by AFM11 relative to a bispecific tandem scFv. CD8+ T cells dominate early cytotoxicity (4 hrs) while after 24 hrs both CD4 + and CD8 + T cells equally contribute to tumor lysis with EC 50 of 0.5 – 5 pM; cytotoxicity is independent of cell CD19 density. AFM11 exhibits similar cytotoxicity at Effector:Target ratios from 5:1 to 1:5 and facilitates T cell serial killing of its targets. AFM11 activates T cells only in the presence of CD19+ cells. In PBMC cultures AFM11 induces CD69 and CD25 expression, T cell proliferation, and production of IFN-γ, TNF-α, IL-2, IL-6, and IL-10. Depletion of CD19 + cells from PBMC abrogates these effects, and indicates strict CD19 + target-dependent T cell activation. Thus, AFM11 should not elicit the devastating cytokine release observed when full length antibodies bind CD3. Cell lysis by AFM11 is restricted to CD19 + targets asCD19 - bystanders are not lysed in co-culture assays. Up to one week co-incubation with AFM11 does not inhibit T cell cytotoxicity and thus it does not induce anergy. In vivo AFM11 exhibits a dose-dependent growth inhibition of Raji tumors; a single dose of AFM11 exhibits similar efficacy as 5 daily injections. Conclusions: AFM11 is a highly efficacious novel drug candidate for the treatment of CD19+ malignancies with an advantageous safety profile and anticipated dosing regimen.
A Professional Standard for Informed Consent for Stem Cell Therapies
Authors: Jeremy Sugarman, Roger A. Barker, R. Alta Charo
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Health status in senior adult prostate cancer patients: Limits for active treatment and clinical trials inclusion
Authors: J. Droz, G. Albrand, A. Chaladaj, A. Fléchon, C. Terret
Journal: Journal of Clinical Oncology (2007)

15550 Background: Two-third of patients (pts) with prostate cancer are older than 70 years. Patients are likely to receive active treatments in the curative and palliative settings if they have good health status, moreover they are likely to be offered to participate to clinical trials. Health status evaluation is performed by Comprehensive Geriatric Assessement (CGA). Methods: We have prospectively performed a mini- CGA (Terret C, Expert Rev Anticancer Ther. 2004; 4 : 469–75.) in 69 patients with prostate cancer : 33% pts had localized disease, median age was 78.7 years (68–92). Mini-CGA was based on a careful clinical examination with analysis of physical function, nutritional status (MNA), functional domain (ADL, IADL), cognitive and emotional domains (MMSE, GDS), identification and grading of comorbid conditions (CIRS-G), and a medication review. Social and familial evaluations complete the procedure. Results: Dependancy: only 12% pts are fully independant for ADL and 11% for IADL; 20% pts experienced falls and 32% were at risk of fall. Cognitive functions and depression: 60% pts had normal cognitive funtions, 46% and 4% were moderately and deeply depressed respectively. Nutrition: 22% pts had severe weight loss, 23% were mal nourished and 41% at risk of denutrition. Comorbidities: median CISR-G score was 8 (3–12), 80% and 21% pts had at least one grade 3 and one grade 4 comorbidity respectively. The most frequent comorbidities were by decreasing order of incidence : psychologic, hematologic, endocrine and osteo-articular pathologies. Polymedication: median number of drugs taken by pts was 5 (0–14) and iatrogenicity was observed in 30% pts. A caregiver was identified in 83% pts and 16% pts were living alone. None of the pts were fully independant with no major comorbidity. Conclusions: Health status of prostate cancer patients older than 70 years must be evaluated with the objective to either tailor specific clinical trials or apply adapted standard treatments. Task forces of the International Society of Geriatric Oncology (SIOG) are on the process to establish specific guidelines for prostate cancer treatment in the senior adults and for selection of manageable CGA procedures. [Table: see text]
Functional dissection of the Sox9–Kcnj2 locus identifies nonessential and instructive roles of TAD architecture
Authors: Alexandra Despang, Robert Schöpflin, Martin Franke, Salaheddine Ali, Ivana Jerković, Christina Paliou, Wing-Lee Chan, Bernd Timmermann, Lars Wittler, Martin Vingron, Stefan Mundlos, Daniel M. Ibrahim
Journal: Nature Genetics (2019)
EGFR mutation testing, from bench to practice: A single Irish institute experience.
Authors: Hassan Shikhrakab, Cathal O'Brien, Nemer Osman, Kenneth John O'Byrne
Journal: Journal of Clinical Oncology (2013)

e19064 Background: Epidermal growth factor receptor (EGFR) gene mutations determine the treatment and prognosis in lung adenocarcinoma. Exon 19 and exon 21 (L858R) deletions represent the most common recognised mutations detected. To date, no figures regarding the prevalence of EGFR mutations in the Irish population have been published. Methods: The prevalence of EGFR mutations was retrospectively analysed for all patient samples tested since the introduction of EGFR testing routinely (Mar to Dec 2012) in a single Irish institute. The presence of 41 known treatment linked EGFR mutations in exons 18, 19, 20 and 21 of the EGFR gene was tested in 209 Irish patients. Resection, core biopsy or FNA samples were analysed using a commercially available CE-IVD marked multiplex real-time PCR assay. Samples were included from patients of curative and palliative treatment intent. Results: 30 out of 209 patients with lung adenocarcinoma tested had an EGFR mutation (13%, 95% CI 8.4-17.6%). Of the mutations detected relative frequency was as follows: exon 19 deletion 63.3% (n=19, 95% CI 46.1-80.6%), exon 21 (p.L858R) 16.7% (n=5, 95% CI 3.3-30.0%), exon 20 insertions 13.3% (n=4, 95% CI 1.2-25.5%) and exon 18 (p.G719X) and exon 20 (p.T790M) both at 3.3% (n=1, 95% CI 0-9.8%). Of those patients tested 51.2% were male (n=107) and 48.8% (n=102) female. The incidence of mutations was higher in females than in males; 63.3% of those with an EGFR mutation were female (n=19, 95% CI 46.1-80.6%). Reciprocally, the male percentage was 36.7% (n=11, 95% CI 19.4-53.9). The mean age at testing was 67 years. Complete smoking data was unavailable for this study. All samples tested were formalin fixed paraffin embedded tissue or cell preparations. Turn around time (TAT) for EGFR mutation processing substantially improved over ten month period, from over five weeks to less than four working days. Conclusions: This group of patients represent the largest cohort of patients tested for EGFR mutation in a single institute in Ireland in less than 12 months. The incidence of EGFR mutations in this patient population is comparable to current European estimates. The gender bias was notable amongst those tested, with female patients being nearly twice as likely to harbour an EGFR mutation.
Does the addition of COX-2 inhibitors alter the resistance to aromatase inhibitors?
Authors: C. Gemici, T. Salepci, N. Bese, E. Gocen, G. Yaprak, A. Mayadagli
Journal: Journal of Clinical Oncology (2007)

11511 Background: This study aimed to investigate whether the addition of COX-2 inhibitor to aromatase inhibitor alter the resistance to aromatase inhibitor, developed during first or second line hormonal treatment of estrogen (ER) and/or progesterone receptor (PR) positive metastatic breast cancer cases. Methods: ER and/or PR positive breast cancer patients with known high baseline CA 15–3 levels due to the tumor and receiving a first or second line (after first line tamoxifen) aromatase inhibitor due to soft tissue (lymphatic tissue, skin) or bone metastasis were evaluated in this study. A recurrent increase in CA 15–3 levels without tumor progression following an initial decrease in CA 15–3 levels was observed in 7 patients and this was considered as resistance to the aromatase inhibitor. For this reason, a COX- 2 inhibitor was added to either letrozole (5/7) or anastrozole (2/7) treatment. The aromatase inhibitor and COX-2 inhibitor combination (celecoxib 200 mg bid, 5/7 cases; rofecoxib 50 mg od, 2/7 cases) was used for 3 months. CA 15–3 levels and tumor response of these 7 cases was re- evaluated at the end of 3 months. Results: None of the seven cases had a decrease in CA 15–3 levels following the 3 months of aromatase inhibitor plus COX-2 inhibitor combination treatment, instead all cases had their levels increased. In addition, none of the 7 cases had clinical or radiological tumor response, all had tumor progression. Treatment was continued by either third line hormone treatment (4/7) or chemotherapy (3/7). Conclusions: COX-2 inhibitors are suggested to potentiate endocrine treatment since the overexpression of COX-2 contributes to the increased expression of aromatase in the breast tumor tissue. Thus, the combination of an aromatase inhibitor and a COX-2 inhibitor may be useful in the hormonal treatment of breast cancer. However, present study failed to demonstrate alteration of the developed aromatase resistance by the addition of a COX-2 inhibitor. No significant financial relationships to disclose.
Institutional Variation in Quality of Cardiovascular Implantable Electronic Device Implantation
Authors: Isuru Ranasinghe, Clementine Labrosciano, Dennis Horton, Anand Ganesan, Jeptha P. Curtis, Harlan M. Krumholz, Andrew McGavigan, Sadia Hossain, Tracy Air, Saranya Hariharaputhiran
Journal: Annals of Internal Medicine (2019)

Cardiovascular implantable electronic devices (CIEDs) are associated with procedure-related complications, yet little is known about variation in complication rates among institutions that may suggest disparities in care quality.To assess institutional variation in risk-standardized complication rates (RSCRs) for CIED.Cohort study.174 hospitals in Australia and New Zealand, 98 of which implanted at least 25 CIEDs during the study period.81 304 patients older than 18 years (mean, 74.7 years [SD, 12.4]; 37.9% female) who received a new CIED (65 711 permanent pacemakers [PPMs] and 15 593 implantable cardioverter-defibrillators [ICDs]) in 2010 to 2015.RSCRs and frequencies of major device-related complications during hospitalization or within 90 days of discharge.Of the cohort, 6664 patients (8.2%) had a major complication. Although complication rates were higher for ICDs than PPMs (10.04% vs. 7.76%), 76.5% of all complications were attributable to PPMs (5098 vs. 1566 for ICDs). Among hospitals that implanted at least 25 CIEDs, the median RSCR was 8.1%; however, rates varied from 5.3% to 14.3%, with 22 hospitals identified as having RSCRs that differed significantly from the national average. Similar variation was observed when RSCRs for PPM implantation (n = 96 hospitals) (median RSCR, 7.6% [range, 5.4% to 12.9%]) were considered separately from those for ICD placement (n = 68 hospitals) (median RSCR, 9.7% [range, 6.2% to 16.9%]) and persisted when only elective procedures were assessed (n = 88 hospitals) (median RSCR, 7.4% [range, 4.7% to 13.0%]).Possible unmeasured confounding from the use of administrative data.CIED complications are common and vary among hospitals, suggesting institutional variation in CIED care quality. Concerted clinical and policy interventions are needed to address CIED-related complications. These efforts should preferentially target PPMs, because most CIED complications are attributable to these devices.The Hospitals Contribution Fund Research Foundation.
Metastatic breast cancer: A regional audit of HER2 testing and trastuzumab access
Authors: P. Scullin, A. T. Drake, V. M. Coyle, J. J. McAleer
Journal: Journal of Clinical Oncology (2006)

6097 Background: Clinical trials have clearly established that patients receiving taxane-based chemotherapy for metastatic breast cancer (MBC) should be treated with trastuzumab if their tumour is shown to overexpress the human epidermal growth factor receptor 2 (HER2) receptor. This is based on median survival gains for patients with HER2 positive tumours treated with trastuzumab plus taxane chemotherapy compared to taxane alone. Methods: Patients commencing chemotherapy for MBC in Northern Ireland in 2004 were identified from pharmacy records. Their case notes were retrospectively reviewed to determine whether patients in routine clinical practice had HER2 testing and trastuzumab treatment if indicated. Results: One hundred and fifty six patients commenced chemotherapy, of whom 145(93%) had HER2 testing. In 69(44%) patients the HER2 result was already available at the time of this relapse. In the remaining 76(49%) patients the result became available in a median of 41.5 (range 0–368) days. Of those tested, 48 patients (33%) were HER2 positive (immuno-histochemistry 3+ or fluorescence in situ hybridization positive). Thirty eight of these patients were treated with trastuzumab, either as a single agent or in combination with chemotherapy. There were valid reasons for trastuzumab omission in 7 of 10 patients not given trastuzumab (4 given first line anthracycline-based regimen, 1 had cardiac dysfunction, 1 had extensive lung metastastes and 1 was unfit for treatment). The data were examined for variations in chemotherapy and trastuzumab use across the 4 health boards which comprise the region. The number of patients commencing chemotherapy ranged from 6.9 to 11.4 patients per 100,000 population indicating a significantly different utilisation (p&lt;0.001). Conclusions: In our region 145 of 156 patients who received chemotherapy for MBC were tested for overexpression of the HER2 receptor (93%). Of those patients who were eligible to receive trastuzumab 31 out of 34 (91%) received trastuzumab. There were inequalities in the region regarding chemotherapy for MBC and the time required to obtain a HER2 result averaged 41.5 days. Testing of HER2 status at time of original diagnosis would streamline management of metastatic disease. No significant financial relationships to disclose.
Sixty seconds on . . . fact checking
Authors: Abi Rimmer
Journal: BMJ (2019)

Kind of. It is a truth universally acknowledged that you shouldn’t believe everything you read on Facebook, and now, thanks to Full Fact, an independent fact checking charity, it’s, well, a fact.

The UK charity (fullfact.org) has published a report on the first six months of the third party fact checking programme it’s running for Facebook.1

The fact checkers are given a “queue” of content by Facebook (which they can add …
Risk of gout flares after vaccination: a prospective case cross-over study
Authors: Chio Yokose, Natalie McCormick, Clara Chen, Tuhina Neogi, Christine Chaisson, Robert Terkeltaub, David J Hunter, Yuqing Zhang, Hyon Choi
Journal: Annals of the Rheumatic Diseases (2019)

The recombinant zoster vaccine (RZV) containing a strong non-aluminium adjuvant is associated with increased risk of gout flares, presumably via NLRP3 inflammasome activation. We tested the possibility that other vaccines may also be associated with gout flares.We conducted an online case-crossover study of patients with gout to examine the association between vaccination and gout flares. We collected information through the Internet on exposures to potential risk factors, including vaccinations, during 2-day hazard periods prior to gout flare and 2-day control periods without a flare. Conditional logistic regression was used to adjust for covariates.There were 517 participants with gout (mean age 55 years, 79% male) who experienced gout flares during follow-up. There were 28 vaccinations during 990 hazard periods and 21 vaccinations during 1407 control periods. Vaccination was associated with twofold higher odds of gout flare (adjusted OR 1.99; 95% CI 1.01 to 3.89).Our findings suggest vaccines other than RZV are associated with increased odds of gout flares, potentially through a shared pathogenetic mechanism like NLRP3 inflammasome. However, the absolute magnitude of increased odds of gout flares with vaccinations remains small and must be interpreted within the context of the overwhelming benefits of vaccinations.
FRI0083 Elevated il-16 level is a non-genetic characteristic of patients with severe systemic lupus erythematosus
Authors: LR Lard, BO Roep, TW Huizinga
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> IL-16, origanilly named lymphocyte chemoattractant factor, is a cytokine which is mainly produced by CD8<sup>+</sup> T cells. Several reports have described that increased levels of IL-16 are in part responsible for T cell abnormalities in SLE patients. <h3>Objectives</h3> To investigate whether increased levels of IL-16 is a characteristic underlying susceptibility to SLE or is a characteristic of the disease itself. <h3>Methods</h3> Accumulated organ damage was measured with the SLICC/ACR Damage Index. Twenty-five severe (SLICC/ACR: 4.9 + 2.5) and ten non-severe (SLICC/ACR: 1.0 + 0.8) SLE patients were included in this study. Also 11 first degree relatives and 12 healthy volunteers were included in this study. Plasma IL-16 levels were measured by ELISA. <h3>Results</h3> No significant difference in the IL-16 levels of the first degree relatives of patients with SLE (38.3 + 11.1 pg/ml) were observed when compared to controls (31.2 + 10.1 pg/ml). In order to analyse characteristics of the SLE in relation to concentration of IL-16, IL-16 was measured in severe SLE patients (71.3 + 87.4 pg/ml; P = 0.025) compared to healthy controls. On the other hand, no significant differences were observed between the non-severe SLE patients (37.8 + 26.1 pg/ml) and controls. <h3>Conclusion</h3> No evidence for increased IL-16 levels in first degree relatives of the SLE patients was observed. IL-16 is enhanced in SLE patients with a severe disease, but not in patients with non-severe disease, thereby suggesting that IL-16 is associated with disease severity, and not with susceptibility for SLE.