tbuckley/cabot-search huggingface dataset:
The accuracy of colposcopy in diagnostic and screening settings
Authors: S. B. Cantor, M. Cárdenas-Turanzas, M. Follen, D. D. Cox
Journal: Journal of Clinical Oncology (2007)

1545 Background: We sought to determine the accuracy of colposcopy to diagnose cervical precancer in screening and diagnostic settings. Methods: As part of a larger clinical trial, 1850 patients were recruited into a diagnostic group or a screening group depending on their history of abnormal Papanicolaou smear results. For all patients, colposcopic examination was performed and biopsies were obtained from abnormal and normal colposcopic sites. The gold standard of test result accuracy was the histologic report of biopsies. Results: The diagnostic group had a 29.0% prevalence of high-grade squamous intraepithelial lesions (HGSIL) or cancer, and the screening group had a 2.2% prevalence of HGSIL or cancer. Using a disease threshold of HGSIL or worse, the diagnostic group had a sensitivity of 71.4% and a specificity of 81.3%, and the screening group had a sensitivity of 19.1% and a specificity of 96.1%. The areas under the receiver operating characteristic (ROC) curves for the diagnostic and screening groups at the same disease threshold were 0.854 and 0.511, respectively. Conclusions: We demonstrated that colposcopy performs well in the diagnostic setting and poorly in the screening setting. Colposcopy should not be used for the screening of cervical intraepithelial neoplasia. No significant financial relationships to disclose.
Initial Glycemic Control and Care Among Younger Adults Diagnosed With Type 2 Diabetes
Authors: Anjali Gopalan, Pranita Mishra, Stacey E. Alexeeff, Maruta A. Blatchins, Eileen Kim, Alan Man, Andrew J. Karter, Richard W. Grant
Journal: Diabetes Care (2020)

OBJECTIVE The prevalence of type 2 diabetes is increasing among adults under age 45. Onset of type 2 diabetes at a younger age increases an individual’s risk for diabetes-related complications. Given the lasting benefits conferred by early glycemic control, we compared glycemic control and initial care between adults with younger onset (21–44 years) and mid-age onset (45–64 years) of type 2 diabetes. RESEARCH DESIGN AND METHODS Using data from a large, integrated health care system, we identified 32,137 adults (aged 21–64 years) with incident diabetes (first HbA1c ≥6.5% [≥48 mmol/mol]). We excluded anyone with evidence of prior type 2 diabetes, gestational diabetes mellitus, or type 1 diabetes. We used generalized linear mixed models, adjusting for demographic and clinical variables, to examine differences in glycemic control and care at 1 year. RESULTS Of identified individuals, 26.4% had younger-onset and 73.6% had mid-age–onset type 2 diabetes. Adults with younger onset had higher initial mean HbA1c values (8.9% [74 mmol/mol]) than adults with onset in mid-age (8.4% [68 mmol/mol]) (P &amp;lt; 0.0001) and lower odds of achieving an HbA1c &amp;lt;7% (&amp;lt;53 mmol/mol) 1 year after the diagnosis (adjusted odds ratio [aOR] 0.70 [95% CI 0.66–0.74]), even after accounting for HbA1c at diagnosis. Adults with younger onset had lower odds of in-person primary care contact (aOR 0.82 [95% CI 0.76–0.89]) than those with onset during mid-age, but they did not differ in telephone contact (1.05 [0.99–1.10]). Adults with younger onset had higher odds of starting metformin (aOR 1.20 [95% CI 1.12–1.29]) but lower odds of adhering to that medication (0.74 [0.69–0.80]). CONCLUSIONS Adults with onset of type 2 diabetes at a younger age were less likely to achieve glycemic control at 1 year following diagnosis, suggesting the need for tailored care approaches to improve outcomes for this high-risk patient population.
Abstract P230: Association of Accelerometer-Measured Physical Activity and Cardiovascular Health in the Hispanic Community Health Study/Study of Latinos
Authors: Priscilla Vasquez, Ramon A Durazo-Arvizu, David Marquez, Maria Argos, Melissa Lamar, Angela Odoms-Young, Linda Gallo, Daniela Sotres-Alvarez, Sheila F Castaneda, Krista Perreira, Denise Vidot, Carmen R Isasi, Marc Gellman, Martha L Daviglus
Journal: Circulation (2020)

Background: Detailed information on associations between accelerometer-measured moderate-vigorous physical activity (MVPA) and cardiovascular (CV) health among Hispanic/Latino adults are unavailable. Methods: Cross-sectional data from 12,008 Hispanic/Latino adults aged 18-74 years in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) 2008-2011 were analyzed using complex survey design methods. Poisson regression models were used to examine the associations between accelerometer-measured MVPA and CV health indicators (blood glucose, total cholesterol, blood pressure, body mass index [BMI], and smoking) and a composite of low CV risk. Results: Compared to high MVPA, low MVPA was associated with a higher prevalence of diabetes, hypercholesterolemia, obesity, smoking, but not hypertension. Low MVPA was associated with lower prevalence of ideal blood glucose, blood pressure, BMI and low CV risk. Similar results were observed with non-adherence of PA guideline recommendations. Conclusions: Overall in Hispanic/Latino adults, high accelerometer-measured MVPA and meeting PA guideline recommendations were associated with favorable CV health.
Results of a phase II evaluation of nanoparticle albumin bound paclitaxel (nab-paclitaxel) in platinum-sensitive patients with recurrent ovarian, peritoneal, or fallopian tube cancer
Authors: M. G. Teneriello, P. C. Tseng, M. Crozier, C. Encarnacion, K. Hancock, M. J. Messing, K. A. Boehm, A. Williams, D. Ilegbodu, L. Asmar
Journal: Journal of Clinical Oncology (2007)

5525 Background: Patients (pts) with recurrent ovarian, peritoneal, or fallopian tube cancer generally have a poor outcome with current therapies. There are no reports of albumin-bound paclitaxel (nab-paclitaxel) in pts with platinum sensitive recurrent disease. We are reporting our preliminary efficacy and toxicity results with nab-paclitaxel in this group. Methods: 47 pts were enrolled (44 available for analysis). Main inclusion criteria: histologically or cytologically confirmed epithelial cancer of the ovary, fallopian tube, or peritoneum (any stage, grade 2–3 if stage I) and measurable disease by RECIST or elevated CA-125 (&gt;70 units/mL) in the absence of measurable disease; nonepithelial disease was excluded. Pts received 260 mg/m 2 of nab-paclitaxel IV over 30 minutes Day 1 of each 21-day cycle. Pts continued until progressive disease (PD) up to a maximum of 6 cycles. Results: Median age was 65.5 years (range, 42- 84), Stage IIIC (53%) or IV (23%); ECOG PS=0 (87%), and prior surgery (94%). For evaluable pts the overall response rate (ORR) was 50% (13 CR and 9 PR in 44 pts). In pts followed by RECIST only, the ORR was 27% (1 CR and 2 PR in 11 pts). In pts with only CA-125, it was 64% (5 CR and 2 PR in 11 pts). In pts meeting both RECIST and CA-125 criteria, the ORR was 54.5 % (7 CR and 5 PR in 22 pts. Median time to response was 1.8 months (range, 1 to 2.1). The most frequent Grade 3–4 treatment-related toxicities were: neutropenia (8.7%) and fatigue, diarrhea, and dyspepsia (2.2%, each); alopecia (Grades 1–2) occurred in 84.8%. All other adverse events were Grade 1–2. To date, 46 pts are surviving; one death was related to progressive disease. Conclusions: Nab-paclitaxel was very active in this group of pts with recurrent ovarian, peritoneal, or fallopian tube cancer. The ORR was 50%. Toxicities were minimal and manageable. Response and survival analysis and review of the methods of disease assessment are ongoing. Further studies of nab-paclitaxel are warranted. This research was supported, in part, from a research grant from Abraxis BioScience, Inc., Santa Monica, CA. [Table: see text]
Abstract P3-02-09: Vulnerabilities in glutamine metabolism define triple-negative from Luminal A breast cancer subsets
Authors: Michelle van Geldermalsen, Lake-Ee Quek, Nigel Turner, Seher Balaban, Andrew Hoy, Angel Pang, Yi Fang Guan, Kanu Wahi, Qian Wang, Jeff Holst
Journal: Cancer Research (2020)

Abstract Although a nonessential amino acid in normal cells, the demand for glutamine is dramatically increased throughout malignant transformation to support increased metabolic demands; namely, provision of catabolic substrates for ATP production and anabolic substrates for the citric acid cycle and subsequent macromolecule biosynthesis, as well as potentiating the uptake of other critical amino acids by acting as an obligate exchange substrate. Elevated expression of glutamine metabolism-related genes, MYC-driven transcriptional events, and increased consumption and reliance on glutamine are all associated with aggressive breast cancers, including the high-risk triple-negative (TN) subtype. We recently showed that in breast cancer cells, glutamine uptake by the small neutral amino acid transporter, ASCT2, is required to sustain TN cell growth in vitro and in vivo. We therefore hypothesised that highly proliferative TN breast cancers that are sensitive to ASCT2 inhibition may have unique metabolic signatures that could be additionally exploited for therapeutic purposes. Using radiolabelled and stable isotope tracing methods, we analysed in detail glutamine catabolism and its conversion into various metabolic products such as tricarboxylic acid (TCA) cycle intermediates, lipids, nucleotides, and amino acids in human breast cancer cell lines in vitro and ex vivo. These analyses revealed distinct metabolic effects across cell lines representing different subtypes of breast cancer, both at baseline and when glutamine uptake was blocked in vitro by L-gamma-glutamyl-p-nitroanilide (GPNA), a pharmacological inhibitor of ASCT2. These data confirm a broad reliance on glutamine availability in TN breast cancers, where glutamine anapleurosis was significantly greater than in the Luminal A subtype. Analysis of gene expression data from the METABRIC and TCGA patient datasets and the CCLE cell line dataset showed a specific upregulation of multiple glutamine metabolism enzymes in TN breast cancer patient samples and cell lines compared to the Luminal A subtype. These data suggest a rewiring of glutamine metabolism in TN breast cancer that utilises their addiction to glutamine to fuel cell growth. Furthermore, these data provide an additional suite of glutamine metabolic enzymes that may be therapeutically targeted in the hard-to-treat TN breast cancer subset. Citation Format: Michelle van Geldermalsen, Lake-Ee Quek, Nigel Turner, Seher Balaban, Andrew Hoy, Angel Pang, Yi Fang Guan, Kanu Wahi, Qian Wang, Jeff Holst. Vulnerabilities in glutamine metabolism define triple-negative from Luminal A breast cancer subsets [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 P3-02-09.
UK will still attract overseas doctors despite ending free movement, government insists
Authors: Gareth Iacobucci
Journal: BMJ (2020)

The government has insisted that it will continue to attract doctors from overseas despite publishing legislation to end free movement of people following the UK’s exit from the European Union.

The Immigration Bill1 introduced on 5 March will pave the way for the biggest shake-up of the UK’s immigration system for decades, creating a new points based system from 1 January 2021 that grants visas based on people’s skills, qualifications, salaries, and profession.

In November last year the Conservative Party pledged to introduce a special NHS visa to ease fears that the health service would struggle to …
Assessment of the MMRpredict model for prediction of DNA mismatch repair gene mutations (Lynch Syndrome)
Authors: S. K. Nigon, N. M. Lindor
Journal: Journal of Clinical Oncology (2007)

4127 Background: The MMRpredict model, developed at the University of Edinburgh, is a web-based model developed to predict which patients diagnosed with colorectal cancer (CRC) under age 55 years have germline mutations in a DNA mismatch repair (MMR) gene [Barnetson et al., NEngJMed 2006;354:2751–63]. Stage 1 MMRpredict estimates the carrier probability for MMR mutations from clinical parameters (age of diagnosis of colorectal cancer, proximal vs distal site, family history, multiple primary CRCs). We evaluated the performance of Stage 1 of this model in a well characterized cohort of colorectal cancer patients. Methods: Cases with CRC were identified through the Minnesota Cancer Surveillance System (MCSS), a population based registry and Mayo Clinic Rochester, a clinical practice. All were consented participants in the Mayo Colon Cancer Family Registry. Of 342 cases tested for MMR mutations (MLH1, MSH2, MSH6), 45 had insufficient information on colon site and 62 were older than 55 and could not be used in the study. The remaining 235 included 110 females/125 males; 90 cases with proximal site/145 with distal site; 229/235 were self-identified as White. Results: We defined 5 probability risk groups based on output from the MMRpredict web model Stage 1: 1–10%, 11–25%, 26–50%, 51–75%, and 76–100%. In our study, the number of cases in each of these groups was 60, 45, 65, 34, and 31, respectively. The corresponding number of mutations in each group was 1 (1.7%), 4 (8.9%), 9 (13.8%), 3 (8.8%), and 11 (35.5%). Overall, 28/235 patients were found to have mutations (11.9%), compared to predicted range of 62–107 (26–45%). Conclusion: MMRpredict Stage 1 over-estimated the probability of detecting a MMR gene mutation in this study. This may reflect ascertainment issues or genetics of different populations. No significant financial relationships to disclose.
Exploring the Possible Impact of Unbalanced Open-Label Drop-In of Glucose-Lowering Medications on EXSCEL Outcomes
Authors: M. Angelyn Bethel, Susanna R. Stevens, John B. Buse, Jasmine Choi, Stephanie M. Gustavson, Nayyar Iqbal, Yuliya Lokhnygina, Robert J. Mentz, Rishi A. Patel, Peter Öhman, Guntram Schernthaner, Albert Lecube, Adrian F. Hernandez, Rury R. Holman
Journal: Circulation (2020)

EXSCEL (Exenatide Study of Cardiovascular Event Lowering) assessed the impact of once-weekly exenatide 2 mg versus placebo in patients with type 2 diabetes mellitus, while aiming for glycemic equipoise. Consequently, greater drop-in of open-label glucose-lowering medications occurred in the placebo group. Accordingly, we explored the potential effects of their unbalanced use on major adverse cardiovascular events (MACE), defined as cardiovascular death, nonfatal myocardial infarction or nonfatal stroke, and all-cause mortality (ACM), given that some of these agents are cardioprotective.Cox hazard models were performed by randomized treatment for drug classes where >5% open-label drop-in glucose-lowering medication occurred, and for glucagon-like peptide-1 receptor agonists (GLP-1 RAs; 3.0%) using three methodologies: drop-in visit right censoring, inverse probability for treatment weighting (IPTW), and applying drug class risk reductions.Baseline glucose-lowering medications for the 14 752 EXSCEL participants (73.1% with previous cardiovascular disease) did not differ between treatment groups. During median 3.2 years follow-up, open-label drop-in occurred in 33.4% of participants, more frequently with placebo than exenatide (38.1% versus 28.8%), with metformin (6.1% versus 4.9%), sulfonylurea (8.7% versus 6.9%), dipeptidyl peptidase-4 inhibitors (10.6% versus 7.5%), SGLT-2i (10.3% versus 8.1%), GLP-1 RA (3.4% versus 2.4%), and insulin (13.8% versus 9.4%). The MACE effect size was not altered meaningfully by right censoring, but the favorable HR for exenatide became nominally significant in the sulfonylurea and any glucose-lowering medication groups, while the ACM HR and p-values were essentially unchanged. IPTW decreased the MACE HR from 0.91 (P=0.061) to 0.85 (P=0.008) and the ACM HR from 0.86 (P=0.016) to 0.81 (P=0.012). Application of literature-derived risk reductions showed no meaningful changes in MACE or ACM HRs or P values, although simulations of substantially greater use of drop-in cardioprotective glucose-lowering agents demonstrated blunting of signal detection.EXSCEL-observed HRs for MACE and ACM remained robust after right censoring or application of literature-derived risk reductions, but the exenatide versus placebo MACE effect size and statistical significance were increased by IPTW. Effects of open-label drop-in cardioprotective medications need to be considered carefully when designing, conducting, and analyzing cardiovascular outcome trials of glucose-lowering agents under the premise of glycemic equipoise. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01144338.
NETS of the lung (non SC): Experience of lung cancer working group E. Morelli Hospital Sondalo
Authors: G. Valmadre, R. Delfanti, M. Robustellini, G. Rossi, C. Della Pona, R. Epis, A. Pastorini, A. Buscemi
Journal: Journal of Clinical Oncology (2007)

18191 Background: pulmonary NETS are typical carcinoid (TC), atypical carcinoid (AC), large-cell neuroendocrine carcinoma (LCNC), and SCLC. Purpose: to evalue prognosis of pulmonary NET (non SC) according by histotype, treatment and serum CgA. Methods: From 1996 to 2006 our lung cancer working group followed 42 pulmonary NETs, none carcinoid syndrome and 1 metastatic (CgA 100xN) at diagnosis. 39/42 underwent radical surgical resection with adenectomy. 2/42 TC had endobronchial laser, the metastatic any treatment. 31/42 (73.8%) are TC. 10/42 (23.8 %) are AC, 1/42 (2%) undetermined. Results: In dec 06 we reviewed 37/42 cases (20 clinical examination and 17 by phone). 2/5 missing were dead: 1 AC 7 years later with liver metastasis, high CgA without syndrome and 3 years of octreotide. 2 TC, 1 AC drop-out. Of 20 pts seen, 3 had high CgA, but Octreoscan negative. 32 pts (86.5%) had only surgery: 15 with more than 5 years DFS. 7 had preoperating CgA: 4 normal, 2 high (1 had hepatic metastasis, in 1 normalized and 36 months DFS), 1 ongoing. 2 pts without surgery are alive after 17 and 8 months. The metastatic pt has PR with octreotide. 1 TC had gastric carcinoma at 7 years. 3 TC had progressive disease. 1 TC (IA and high pre-lobectomy CgA), had persistent high CgA and positive octreoscan hepatic lesion 4 months later: PR after 6 months of octreotide. Another with normal pre-lobectomy CgA (TC IB) had carcinoid syndrome with high CgA and octreoscan positivity, 4 months later: negative restaging at 22 months with one-year of octreotide. A sixteen girl - TC IB - with high CgA (normal after pneumonectomy) developed octreoscan positive thoracic lesions, 18 months later. PR after 44 months with radiometabolic therapy. Conclusion: NETS are heterogeneous and with better prognosis (except SC) than other lung cancers. AC radically resected had good prognosis (1/10 metastasis ), sometimes TC gave metastasis and progression (2/31). For the 2 subtypes OS is high. Octreotide- and radiometabolic therapy can control the metastatic disease. CgA is not indicative of relapse but well correlates with the extension of metastatic disease. High CgA values are not predictive of carcinoid syndrome. It is important to evalue CgA before and 2–3 months after surgery. Carcinoid syndrome is rare in lung NET. We don’t have any LCNL. No significant financial relationships to disclose.
Quality Measurement in Cancer Care: A Review and Endorsement of High-Impact Measures and Concepts
Authors: Thomas A. D’Amico, Lindsey A.M. Bandini, Alan Balch, Al B. Benson, Stephen B. Edge, C. Lyn Fitzgerald, Robert J. Green, Wui-Jin Koh, Michael Kolodziej, Shaji Kumar, Neal J. Meropol, James L. Mohler, David Pfister, Ronald S. Walters, Robert W. Carlson
Journal: Journal of the National Comprehensive Cancer Network (2020)

Although oncology care has evolved, outcome assessment remains a key challenge. Outcome measurement requires identification and adoption of a succinct list of metrics indicative of high-quality cancer care for use within and across healthcare systems. NCCN established an advisory committee, the NCCN Quality and Outcomes Committee, consisting of provider experts from NCCN Member Institutions and other stakeholders, including payers and patient advocacy, community oncology, and health information technology representatives, to review the existing quality landscape and identify contemporary, relevant cancer quality and outcomes measures by reevaluating validated measures for endorsement and proposing new measure concepts to fill crucial gaps. This manuscript reports on 22 measures and concepts; 15 that align with existing measures and 7 that are new.
AKT and AMPK signaling pathways in adipose tissue from patients with metabolic unhealthy obesity
Authors: J.A. Suárez-Cuenca, K.G. Carvajal-Aguilera, L.C. Camacho-Castillo, D.G. Ruíz-Dangú, C.B. Romero-Hernández, K. De La Vega-Moreno, R. Pérez-Cabeza De Vaca, O. Felipe-Gaytán, J. Montoya-Ramírez, M. Salamanca-García, P. Mondragón-Terán
Journal: Metabolism (2020)
Computer simulation of pharmacokinetic analysis of 161,051 drugs after intraperitoneal (IP) or intravenous (IV) administrations
Authors: Y. Miyagi, K. Fujiwara, S. Nagao, J. Kigawa, K. Miyake, T. Oda, Y. Miyagi
Journal: Journal of Clinical Oncology (2007)

16042 Background: Recent clinical studies for ovarian cancer have demonstrated the survival benefit of intraperitoneal (IP) administration of anti-cancer drugs, such as platinum agents, or paclitaxel. It is of great interest to investigate whether IP administration of other cytotoxic agents are more effective compared with intravenous (IV) administration. In this study we investigated the pharmacological advantage of IP administration using anti-cancer drugs, of which cytocidal effect is determined by the value of the area under the time concentration curve (AUC), by using computer simulation model. Methods: The 3-compartment pharmacokinetic computer model was used and 161,051 sets of the rate constants were substituted into the model. Because one set of the rate constants determines a pharmacokinetic behavior of one drug, it was considered to simulate over 160,000 drugs in this study. The constants were referred to ones of carboplatin. The simulations were made after 210 mg/body of the drugs were administered. The values of the AUC in the serum and in the IP cavity after IP or IV administration were calculated for each set, and then, these two administration methods were compared. Results: The values of the AUC in the serum by IP vs IV administration were 6.675 ± 21.603 (mean±SD); [0.08 - 106.155 (range)] vs 6.663 ± 21.541; [0.183 - 105.726]. The values of the AUC in the cavity after IP vs IV administration were 128.799 ± 344.491; [0.342 - 2288.48] vs 90.700 ± 283.946; [0.002 - 2259.32]. The ratios of AUC in the serum after IP or IV administrations were 0.995 ± 0.023; [0.401 - 1.020]. 147,201 sets (91.4%) were between 0.99 and 1.01. On the other hand, the ratios in the IP cavity were 25.327 ± 86.515; [1.003 - 548.976]. All the IP/IV ratios in the cavity were more than 1. Conclusions: The simulated probability clearly indicated that IP administration is not a local but a systemic chemotherapy for most drugs. All of the chemotherapeutic agents should be investigated for IP administration as well as conventional IV administration in clinical research protocol, especially in phase I/II study to clarify the effects and toxicities. No significant financial relationships to disclose.