tbuckley/cabot-search huggingface dataset:
Bone metastasis (BM) based on SEER registry versus Medicare claims among metastatic prostate cancer (PCa) patients (pts) in SEER-Medicare.
Authors: Ebere Onukwugha, C. Daniel Mullins, Candice Yong, Diane L. McNally, Brian S. Seal, Arif Hussain
Journal: Journal of Clinical Oncology (2012)

e15148 Background: There is questionable reliability of administrative claims data to identify BM, yet historically such claims were the only source for identifying BM in SEER-Medicare (SM). Starting in 2004, SEER provided tumor registry information on incident BM. We compared frequencies of BM using registry and claims data among men diagnosed with PCa. Methods: We analyzed pts aged 66 and older from the linked SM database. Pts with stage IV (M1) PCa diagnosed between 2004 and 2007 were followed until death or censoring. Identifying pts with BM using claims required at least one inpatient or outpatient claim with a diagnosis code of 198.5 within (i.e., +/-) 1 month of the SEER diagnosis month (designated BMclaims-90) or at any time during follow up (designated BMclaims-ever). BM identified using SEER was based on an indicator for bone metastasis at diagnosis using the AJCC M1b classification (designated BMseer). We calculated the sensitivity and specificity of BM at diagnosis in claims (BMclaims-90) with respect to the incident BM data in SEER, assuming BMseer to be the gold standard. Results: Application of inclusion/exclusion criteria resulted in 3,664 stage IV (M1) PCa pts. Average age was 79 years, 13% were African American, and 61% had poorly/un-differentiated tumors. BMseer (n=2,301; 63%) was higher than BMclaims-90 (n=1,979; 54%) and lower than BMclaims-ever (n=2,878; 79%). Assuming BMseer as the standard measure of BM at diagnosis, BMclaims-90 had 58.8% sensitivity (n=1,353), 54.1% specificity (n=737), and 68.4% positive predictive value for identifying BM at diagnosis. Among men with BM identified using BMseer, 84% (1,931) had BMclaims-ever and the median (min; max; average) time to the first BM claim was 0.9 (-2.6; 57.1; 3.9) months. Among men with BM identified using BMclaims-90, the median (min; max; average) time to the first BM claim was 0.6 (-1.0; 2.0; 0.7) months. Conclusions: The incidence of BM in PCa pts differs between a commonly-used algorithm to identify BM in claims data and the AJCC staging information in tumor registry data. There was moderate concordance between the claims-based measure and the SEER-based measure of BM at diagnosis.
Four drug firms are fined £3.4m for fixing price of nortriptyline
Authors: Clare Dyer
Journal: BMJ (2020)

Four drug companies have been fined a total of £3.4m (€3.9m; $4.4m) for illegal information sharing and illegally carving up the market for an antidepressant used by thousands of NHS patients every day. After an investigation by the Competition and Markets Authority (CMA), the NHS will also receive a direct payment of £1m from two of the companies—only the second time this has happened as a result of a CMA probe.

The investigation found that King Pharmaceuticals and Auden Mckenzie colluded to share the market and fix quantities and prices in …
Relation of ANGPTL4 with the Concentration of LPL and Hepatic Fibrosis in Patients with NAFLD
Authors: Gabriela Alexandra Domínguez-Pérez, Eduardo Vera-Gómez, Alejandro Hernández-Patricio, Juan Ariel Gutiérrez-Buendía, Karen De la Vega-Moreno, Carlos Ramiro Zamora-Alemán, Moisés Salamanca-García, Jesús Montoya-Ramírez, Omar Felipe Gaytán-Fuentes, Paul Mondrágón-Terán, Rebeca Pérez-Cabeza de Vaca, Juan Antonio Suárez-Cuenca
Journal: Metabolism (2020)
A phase I study of SDX-102 for the treatment of patients with MTAP-deficient recurrent malignant gliomas
Authors: S. Phuphanich, M. Chamberlain, T. Mikkelsen, X. Ye, S. A. Grossman, T. Batchelor, G. Lesser, J. D. Fisher, S. Desideri
Journal: Journal of Clinical Oncology (2007)

2063 Background: De novo purine biosynthesis entails two metabolic pathways of which one pathway is frequently impaired in cancer due to gene deletion of the rate limiting enzyme, methythioadenosine phosphorylase (MTAP). In MTAP-deficient cancers, SDX-102 inhibits purine biosynthesis by blocking the remaining synthetic pathway. This study was to determine the maximum tolerated dose (MTD), toxicity and pharmacokinetic activity of SDX-102 in the treatment of recurrent MTAP-deficient malignant gliomas. Methods: Eligible patients had recurrent supratentorial MTAP-deficient malignant gliomas treated previously with surgery, radiation and = 2 regimens of chemotherapy. Dose escalation was conducted separately for patients taking enzyme inducing anti-seizure drugs (EIASD+) and for those not (EIASD-). The starting dose in both groups was 80 mg/m 2 /day continuous infusion for 5 days every 3 weeks, cycle length was 3 weeks. Dose escalation was in a stepwise fashion in cohorts of three patients, up to a maximum dose of 125 mg/m 2 /day. Results: 118 patients were screened of which 39 (33%) had MTAP-deficient tumors. 21 patients (14 males/7 females) were enrolled between 9/17/04 and 3/17/06. Median age was 50 years (23–76); median KPS was 90 (60–100); 16 patients (76%) had GBM. Two dose levels of SDX-102 were tested in the EIASD+ group: 80 mg/m 2 /day (n=4) and 100 mg/m 2 /day (n=3), 3/3 dose limiting toxicity (DLT) were noted with grade 3 mucositis at 100 mg/m 2 /day , so in the EIASD+ group the MTD was 80 mg/m 2 /day. Three dose levels were tested in the EIASD- group: 80 mg/m 2 /day (n=4), 100 mg/m 2 /day (n=7), 1/3 patients had DLT (Grade 4 mucositis) at 100 mg/m 2 /day and the cohort was expanded for additional 3 patients without DLT noted; and 125 mg/m 2 /day (n=3) amongst whom no DLT was observed. No MTD was determined in the EIASD- group because the MTAP assay became unavailable through the sponsor. There were a range of 1–14 cycles administered in this patient population. Conclusions: SDX-102 infusion is safe and feasible in patients with recurrent MTAP-deficient malignant gliomas. The MTD in EIASD+ patients is 80 mg/m 2 /day. The EIASD-group MTD has not been determined however the highest dose tested is 125 mg/m 2 /day. No significant financial relationships to disclose.
Successful biliary cannulation using a novel rotatable sphincterotome in a patient with situs inversus totalis
Authors: Akihiro Yoshida, Kosuke Minaga, Osami Takeda, Hajime Hanno, Shigenori Takayanagi, Toshio Dozaiku, Masatoshi Kudo
Journal: Endoscopy (2020)

Situs inversus totalis (SIT) is a rare congenital deformity involving complete transposition of all of the viscera. Endoscopic retrograde cholangiopancreatography (ERCP) is challenging in patients with SIT owing to anatomical anomalies [1]. Here we present the case of a patient with SIT who successfully underwent biliary cannulation by ERCP using a novel rotatable sphincterotome.
Systematic Integration of Structural and Functional Data into Multi-scale Models of Mouse Primary Visual Cortex
Authors: Yazan N. Billeh, Binghuang Cai, Sergey L. Gratiy, Kael Dai, Ramakrishnan Iyer, Nathan W. Gouwens, Reza Abbasi-Asl, Xiaoxuan Jia, Joshua H. Siegle, Shawn R. Olsen, Christof Koch, Stefan Mihalas, Anton Arkhipov
Journal: Neuron (2020)
Abstract P5-02-06: Improved histologic grading of breast cancer by a novel deep learning-based model
Authors: Mattias Rantalainen, Yinxi Wang, Balázs Ácz, Stephanie Robertson, Johan Hartman
Journal: Cancer Research (2020)

Abstract Breast cancer histologic grade is a well-established prognostic factor utilized in clinical decision making. In current clinical practice grading is conducted manually by pathologists and this procedure is associated with a substantial inter-observer variability. Furthermore, patients classified as histologic grade 2 has been reported to exhibit an intermediate recurrence risk, resulting in less prognostic value. With the aim of improving patient stratification, we have developed a model-based approach for histological grading using deep convolutional neural networks (CNNs). In this study, we developed a CNN model for improved histologic grading, with a focus on further stratification of grade 2 patients into high and low risk groups. Histopathology images from the Clinseq breast cancer study and the Cancer Genome Atlas (TCGA) containing 730 patients were scanned at 40X magnification and tiled into patches at 20X. In total, we obtained 5.3 million patches of size 299 × 299 pixels. Using image annotations of invasive cancer regions in Clinseq study, we trained a deep CNN model to segment cancer regions in TCGA data. Subsequently, the cancer regions from both Clinseq and TCGA were used to optimize a second deep CNN model for classification of grade 1 and 3, this model was applied to re-classify 291 patients with histologic grade 2 into low and high risk. The CNN model classified cancer and non-cancer with area under the receiver operating characteristic curve (AUC) of 0.941. The second CNN model achieved an AUC of 0.910 in terms of classification of grade 1 and 3 tumors (cross-validation). For grade 2 tumors (independent test data), 184 were re-classified into the lower risk group whereas 107 were classified as high risk. The risk of recurrence for the grade 2 higher risk group is significantly higher than that in lower risk group, with an estimated hazard ratio of 2.86 (95% confidence interval: 1.21-6.69) after adjusting for age, tumor size, estrogen receptor status and lymph node status. In conclusion, we found that the deep CNN model demonstrated a high capability to distinguish between breast cancer with histologic grade 1 and 3. We also found that re-stratification of Grade 2 patients into high and low risk groups was significantly associated with risk of recurrence. Improved histological grading, and further risk stratification of grade 2 patients, by deep CNN models could contribute towards a reduction of both over- and under-treatment of breast cancer patients. Citation Format: Mattias Rantalainen, Yinxi Wang, Balázs Ácz, Stephanie Robertson, Johan Hartman. Improved histologic grading of breast cancer by a novel deep learning-based model [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-02-06.
Abstract P526: Bariatric Surgery is Associated With Slower Decline in Kidney Function, Estimated by Multiple Filtration Markers
Authors: Alex R CHANG, G. C Wood, Adam Cook, Xin Chu, Morgan Grams
Journal: Circulation (2020)

Background: Persons with morbid obesity are at increased risk for end-stage kidney disease, and prior studies have shown an association between bariatric surgery and improvements in creatinine-based estimated glomerular filtration rate (eGFR cr ). However, eGFR cr could be biased by loss of muscle mass after surgery, and creatinine-cystatin C estimated glomerular filtration rate (eGFR cr-cyc ) has been shown to be more accurate in this setting. Methods: We matched 144 patients who underwent bariatric surgery on pre-surgery age, sex, race, body mass index (BMI), and eGFR cr with 144 morbidly obese non-surgery patients at Geisinger with serial biobanked serum samples. We measured filtration markers (creatinine, cystatin C, beta-2 microglobulin [B2M] and beta-trace protein [BTP], and calculated eGFR cr-cyc using the CKD-EPI combined equation. Using mixed effects models with random intercepts, we compared changes in filtration markers and eGFR cr-cyc between surgery and non-surgery groups. Results: Mean (SD) values for age, BMI, and eGFR cr were 48.2 (10.4) years, 45.2 (6.3) kg/m 2 , and 91.7 (17.5) ml/min/1.73m 2 ; 87.5% were female, 0.7% were black, 50.3% had hypertension, and 41.0% had type 2 diabetes. Mean eGFR cr-cyc slope in the surgery group was -0.41 ml/min/1.73m 2 /yr (95% CI: -0.74, -0.08) over a mean follow-up of 9.2 (1.4) years, compared to -1.43 ml/min/1.73m 2 /yr in the non-surgery group over a mean follow-up of 8.2 (1.1) years. Bariatric surgery was associated with a 1.02 ml/min/1.73m 2 /yr slower decline in eGFR cr-cyc , and smaller increase in all 4 filtration markers (p&lt; 0.02 for all comparisons). Conclusions: Bariatric surgery is associated with slower decline in kidney function, as assessed by eGFR cr-cyc , B2M and BTP.
Abstract P441: Oral Glucose Tolerance Test Detects Diabetes at Early Stages
Authors: Mitra Mosslemi, Nathan D Wong
Journal: Circulation (2020)

Introduction: Diabetes is a significant risk factor for cardiovascular disease (CVD) and one of the leading causes of death in the USA. The progression to type 2 diabetes, as the major type, is known to be gradual and remissible by intervention at early stages. However, despite the diabetes epidemic over the past few decades in the US, diabetes detection at the early stages has received insufficient attention. Assessing which diabetes diagnostic test can detect progression to diabetes at early stages may help to improve diagnostic recommendations for the at-risk population. Hypothesis: We hypothesize that the Oral Glucose Tolerance Test (OGTT) can detect diabetes at earlier stages compared with Hemoglobin A1c (HbA1c) and Fasting Plasma Glucose (FPG) tests. Therefore, the diabetes cases which are diagnosable only by OGTT have a better CVD risk profile. Methods: We extracted diabetes cases with laboratory evidence of diabetes OGTT ≥ 200 or FPG ≥ 126 or HbA1c ≥ 6.5% who reported themselves as undiagnosed by a doctor from the National Health and Nutrition Survey (NHANES) 2005-2014. We compared the CVD risk factors in the undiagnosed diabetes group between the subgroup, which was diagnosable only by OGTT and the subgroup, which was diagnosable by HbA1c or FPG. Results: Among the total of 953 undiagnosed diabetes cases (projected to 26.4 million) from NHANES 2005-2014, 207 (6.1 million, 23%) had a normal HbA1c and FPG, but OGTT ≥ 200. After adjustment for gender and race, the subgroup who were only diagnosable by OGTT had a better glycemic profile and considerably milder insulin resistance compared with the subgroup who were diagnosable by other diagnostic tests (table). Conclusions: The results indicate that OGTT can assess diabetes at earlier stages compared with HbA1c and FPG, providing opportunities for earlier preventive strategies.
Wasteful Health Care Spending in the United States—Reply
Authors: William H. Shrank, Natasha Parekh
Journal: JAMA (2020)

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
Gene expression levels of ribonucleotide reductase subunit M1 (RRM1), tyrosyl-DNA phosphodiesterase (Tdp1), nuclear factor of activated T-cells (NFAT), and BubR1 mRNA expression in completely resected chemo-naive non-small cell lung cancer (NSCLC) patients
Authors: I. Chaib, E. Jassem, M. Spkrzypski, R. Rosell, M. Taron, L. Perz-Roca, A. Szymanowska, W. Rzyman, G. Gulida, J. Jassem
Journal: Journal of Clinical Oncology (2007)

18016 Background: A relationship between gene transcripts and survival in operable NSCLC is now emerging. RRM1 is involved in DNA repair, Tdp1 is implicated in the repair of CPT-induced topoisomerase damage, and NFAT promotes cancer invasion. BubR1 is a key spindle checkpoint gene, and altered BubR1 mRNA levels are associated with lymph node metastasis and chromosome instability. Methods: In order to identify p with a high risk of relapse, we examined the expression of these four genes in frozen resected tumors from 126 resected NSCLC p by real-time quantitative PCR. Gene expression was normalized using β-actin expression as internal reference. Results: Adenocarcinoma (adeno), 33 p; squamous cell carcinoma (SCC), 93 p. Stage: IA, 18 p; IB, 53 p; IIB, 33 p; IIIA, 22 p. Tumor transcript expression: RRM1, 2.10; Tdp1, 1.77; NFAT, 0.56; BubR1, 16.40. Expression of RRM1, Tdp1 and BubR1 was higher in SCC than in adeno (P&lt;0.001). Median time to relapse (TTR) was longer for p with low levels of RRM1 (P=0.11), Tdp1 (P=0.86), NFAT (P=0.29), or BubR1 (P=0.44) (Table). A significant trend towards longer survival was also observed in stage I p with low RRM1 P=0.06). In a multivariate Cox model, tumor size &gt; 4 cm and stage III predicted shorter TTR and survival. Conclusion: Increased mRNA expression of these genes is associated with shorter TTR; this knowledge could be useful for customizing adjuvant chemotherapy. [Table: see text] No significant financial relationships to disclose.
Impact of Gene Mutation Regions of HERG Channel, Pore or Nonpore, on Clinical Course of LQTS
Authors: Sakamoto Yuichiro, Ino Hidekazu, Fujino Noboru, Uchiyama Katsuharu, Hayashi Kenshi, Konno Tetsuo, Masuta Eiichi, Tsubokawa Toshinari, Katoh Hiromasa, Funada Akira, Nakashima Keisuke, Higasida Haruhiro, Yamagishi Masakazu
Journal: Circulation (2007)
Dietary fibre and whole grains in diabetes management: Systematic review and meta-analyses
Authors: Andrew N. Reynolds, Ashley P. Akerman, Jim Mann
Journal: PLoS Medicine (2020)

Fibre is promoted as part of a healthy dietary pattern and in diabetes management. We have considered the role of high-fibre diets on mortality and increasing fibre intake on glycaemic control and other cardiometabolic risk factors of adults with prediabetes or diabetes.
Renal safety of intravenous ibandronate 6mg infused over 15 or 60 minutes in patients with breast cancer and bone metastases: A randomized, open-label study
Authors: R. von Moos, B. Thürlimann, C. B. Caspar, R. Inauen, R. Greil, F. Schütz, L. Flores, B. Bergstrom, K. Schmieding, M. Pecherstorfer
Journal: Journal of Clinical Oncology (2007)

1114 Background: Clinical data show that a single 15-minute intravenous infusion of ibandronate (IA) 6mg is associated with no significant changes in renal functioning. The aim of this study was evaluation of renal safety of repeated 15-minute intravenous infusions of IA 6mg in women with breast cancer and bone metastases. Methods: Patients (n=127) were randomized to receive treatment with intravenous ibandronate as a 15-minute infusion (n=101) or as a 60-minute infusion (n=26) every 3–4 weeks. Patients were stratified according to previous treatment and the presence or absence of visceral metastases. All patients had serum creatinine within normal limits and calculated creatinine clearance =50mL/min as assessed prior to each infusion throughout the trial. The primary endpoint was the percentage of patients with an increase in serum creatinine from baseline of =44.2μmol/L (0.5mg/dL) at any point in the study. Results: Three percent of patients in the 15 minute infusion (3/101) met the primary endpoint with either hydronephrosis due to tumor, severe diarrhea or pre-existing diabetes with urinary tract infection. No patients in the 60-minute infusion arm (0/26) had an increase in serum creatinine that met the primary endpoint. No clinically relevant changes were seen in serum creatinine, calculated or measured creatinine clearance, or levels of N-acetyl-β-D- glucosaminidase, a1-microglobulin or microalbumin in either arm. There were no marked changes in mean bone pain or analgesic requirement scores. A slight increase in mean WHO performance status score was seen in both arms. Most adverse events were mild or moderate. No clinically-relevant mean changes were observed in vital signs, hematology, blood chemistry including renal function or urinalysis parameters. Renal impairment was related to IA in the 3 patients with increased serum creatinine. Conclusions: IA 6mg administered as a 15- minute intravenous infusion every 3–4 weeks had a renal safety profile consistent with that of the 60-minute infusion, suggesting that a 15-minute infusion of ibandronate 6mg is well-tolerated in patients with breast cancer and bone metastases. No significant financial relationships to disclose.
Abstract 24: Amyloidogenic V122I Transthyretin Variant is Associated With Progression of Adverse Cardiac Mechanics in Middle-aged African American Adults: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Arjun Sinha, Yinan Zheng, Yishu Qu, Drew Nannini, Lifang Hou, Sanjiv J Shah, Clyde W Yancy, Donald M Lloyd-Jones, Laura Rasmuseen-Torvik, Sadiya S Khan
Journal: Circulation (2020)

Introduction: Direct-to-consumer testing (e.g. 23andme) reports now include common pathogenic variants in the transthyretin (TTR) gene, such as V122I. TTR cardiac amyloidosis due to V122I is an autosomal dominant disease known to be of variable penetrance in elderly African Americans. However, the association of carrier status for V122I with echocardiographic measures of cardiac mechanics in middle-age African Americans is not known. Hypothesis: Presence of V122I TTR mutation is associated with adverse cardiac mechanics in middle-aged African Americans. Methods: All African Americans from the CARDIA study with imputed genetic data (R 2 = 0.98) and echocardiography at year 25 (Y25) were included. Echo parameters at Y25 and change from Y25 to Y30 were compared between V122I heterozygote carriers and controls using linear regression models. The analysis was adjusted for age, sex, and top 3 principal components of ancestry. Analysis for change from Y25 to Y30 was adjusted for baseline Y25 echo parameters. Results: Of 874 included participants, mean age was 50.2 (3.6) years at Y25. There were 843 controls and 31 carriers for the V122I genotype (3.5% prevalence). There was no difference in age, sex, or clinical characteristics. Carriers of the V122I variant had worse diastolic function as measured by early diastolic tissue Doppler velocity (e’) at Y25 (9.2 [2.1] vs. 10.2 [2.4], p=0.048). From Y25 to Y30, V122I carriers had greater progression of left ventricular (LV) volume and mass as well as greater decline in subclinical LV systolic function as measured by circumferential strain (Table). Conclusions: Prevalence of the carrier status of the V122I genotype in CARDIA is relatively high and consistent with prior studies. Our findings suggest that the V122I mutation may be a unique risk enhancer for heart failure in middle-aged African Americans. Further data are needed for clarity on risk associated with carrier status of V122I and implications for cascade screening given emerging therapies for TTR cardiac amyloidosis.