tbuckley/cabot-search huggingface dataset:
Healthy Lifestyle Is Associated With Reduced Mortality in Patients With Inflammatory Bowel Diseases
Authors: Chun-Han Lo, Hamed Khalili, Mingyang Song, Paul Lochhead, Kristin E. Burke, James M. Richter, Edward L. Giovannucci, Andrew T. Chan, Ashwin N. Ananthakrishnan
Journal: Clinical Gastroenterology and Hepatology (2020)
Barriers to breast cancer risk screening
Authors: A. Zwaagstra, K. Hoskins
Journal: Journal of Clinical Oncology (2007)

1505 Background: The U. S. Preventive Services Task Force has recommended that physicians assess and discuss breast cancer risk with their female patients. With this recommendation comes the need to develop strategies for providing breast cancer risk-screening and a need to identify potential barriers to the successful implementation of a risk-screening strategy. Methods: A personalized breast cancer risk profile was offered to all women presenting for a screening mammogram at a community hospital. The profile included a Gail model estimate and analysis of family cancer history to detect hereditary breast cancer syndromes utilizing a pedigree assessment tool developed by the authors. Women with 5 year Gail estimates ≥ 1.66%, lifetime Gail estimate ≥ 15% or increased score with the pedigree assessment tool were considered at increased breast cancer risk. Women in the increased risk cohort received written notification of their risk status and were advised to undergo formal risk assessment either through a free consultation with an advanced practice nurse with expertise in cancer risk assessment or with their primary physician. We analyzed compliance with this recommendation over the 6 month period of time after subjects received the risk notification letter. Results: For the three month study period, 242 women met criteria for the increased risk cohort. Of these, 201 (83%) failed to follow through with the advanced practice nurse for formal risk assessment. Surveys were mailed to all 201 non-compliant subjects to identify reasons for non-compliance and 80 surveys were returned (40%). Reasons given for failure to follow- through with formal risk assessment included: self-perception of “average” breast cancer risk (75%), recent normal screening mammogram (55%), primary care physician had not referred them (18%), absence of breast symptoms (15%), and time constraints (15%). Only 11 subjects (14%) indicated that they had discussed risk results with their physician. Conclusions: The majority of women in our study who requested breast cancer risk estimates failed to act on that information. These results could have implications for design and implementation of a successful breast cancer risk-screening program, and point to the need for better patient education and involvement of primary care physicians in the risk assessment process. No significant financial relationships to disclose.
Neoadjuvant trastuzumab in locally advanced breast cancer (NOAH): Antitumour and safety analysis
Authors: L. Gianni, V. Semiglazov, G. M. Manikhas, W. Eiermann, A. Lluch, S. Tjulandin, A. Feyereislova, B. Vanhauwere, P. Valagussa, J. Baselga
Journal: Journal of Clinical Oncology (2007)

532 Background: NOAH (NeOAdjuvant Herceptin) is a Phase III trial of neoadjuvant trastuzumab; H) in combination with chemotherapy in patients (pts) with HER2-positive locally advanced breast cancer (LABC). Methods: 228 pts with centrally confirmed HER2-positive (IHC 3+ or FISH+) LABC received 3 cycles of doxorubicin-paclitaxel (AT: A 60 mg/m 2 , T 150 mg/m 2 q3w), 4 cycles of T (175 mg/m 2 q3w) and 3 cycles of cyclophosphamide/methotrexate/5-fluorouracil (CMF: C 600 mg/m 2 , M 40 mg/m 2 , F 600 mg/m 2 q4w) on days 1 and 8, with (n=115) or without (n=113) concomitant H (8 mg/kg loading dose then 6 mg/kg q3w for 1 year) before surgery. Pts with HER2- negative disease (IHC 0/1+; n=99) were treated in parallel with AT/T/CMF. The primary end point was event-free survival (EFS); secondary end points included overall response rate (ORR), pathological complete response (pCR) rate and safety. Results: Baseline characteristics were well balanced for randomised pts. Median tumour size was 5.5 cm (range 1.5–20.0). Inflammatory breast cancer (IBC) was present in 40% of HER2-positive vs 14% of HER2-negative tumours, while 35% vs 65%, respectively, were hormone receptor positive. Left ventricular ejection fraction (LVEF) at baseline was similar in all 3 groups. Adding H to AT/T/CMF improved ORR (81% vs 73%; p=0.18) and significantly increased pCR rate (43% vs 23%; p=0.002). This response pattern was also seen in IBC pts. ORR (66%) and pCR rate (17%) for pts with HER2-negative disease were similar to pt responses in the HER2-positive group who did not receive H. The most common serious adverse event was febrile neutropenia (8% with H vs 4% without). Only 11% of pts receiving H had absolute LVEF decreases of =10% and 1 pt treated with H experienced a cardiac event with an LVEF value of &lt;45%. One pt with HER2-negative disease died after surgery due to pulmonary embolism. Conclusions: Neoadjuvant H plus AT/CMF-containing chemotherapy significantly improved the pCR rate of LABC vs chemotherapy alone. Treatment was well tolerated with acceptable cardiac safety. Follow-up is ongoing and EFS is maturing. [Table: see text]
Extent of lymphadenectomy (LA) and outcome for patients with stage I non-small cell lung cancer (NSCLC)
Authors: M. M. DeCamp, A. Recht, M. Nikolov, J. C. Flickinger, J. M. Varlotto
Journal: Journal of Clinical Oncology (2007)

7604 Background: It is uncertain if LA affects overall survival (OS) or disease-free survival (DFS) rates for patients with stage I NSCLC and, if performed, what is the minimum number of nodes that should be recovered. Methods: 24,273 patients with stage I NSCLC diagnosed from 1992–2002 underwent a definitive surgical procedure and were included in the SEER data-base. For patients diagnosed from 1998–2002, outcome was examined separately for patients having only N1 (2,683 patients) or N2 nodal (1,019 patients) dissections. Results: For the entire population, LA was associated with an increase in the 5-year OS rate from 41.7% to 58.4% (p &lt;0.0001) and in DFS from 58.4% to 72.9%, compared to not having LA. For patients undergoing only N1 dissection, LA was also associated with significant improvements in OS and DFS, compared to no LA (p=0.056 and 0.043). The maximum difference between those with no LA and those with only N1 dissection was when 11–16 nodes were removed (4-year OS, 40.0% vs. 68.2%; DFS, 40.0% vs. 60.4%). For patients undergoing only N2 dissection, LA was associated with a significant improvement in OS (p=0.045) and a trend for a DFS benefit (p=0.086), with the maximum difference between those with no LA and those with 7–10 nodes removed (4-year OS, 75.0% vs. 77.7%; DFS, 75.0% vs. 85.0%). Those patients undergoing removal of ≥ 11 N2 nodes were found to have a significantly increased risk of death to cardiopulmonary/infectious causes (5.56% vs 1.79%) as compared to those patients having &lt; 11 nodes removed (p = 0.023). Conclusions: LA was associated with increased rates of OS and DFS, compared to no LA. Our results also suggest the minimum number of recovered nodes needed to see the maximum staging accuracy of LA. No significant financial relationships to disclose.
Subpopulation analyses in a worldwide treatment-use trial of sunitinib (SU) in GIST patients (pts) with resistance or intolerance to prior imatinib (IM) therapy
Authors: P. Reichardt, Y. K. Kang, W. Ruka, B. Seddon, C. M. Baum, G. D. Demetri
Journal: Journal of Clinical Oncology (2007)

10022 Background: SU is an oral, multitargeted TKI of KIT, PDGFRs, VEGFRs, RET and FLT3, approved multinationally for the treatment of IM-resistant/-intolerant GIST. The aims of this study are to provide access to SU to GIST pts who were ineligible for SU clinical trials or for whom SU is unavailable prior to regulatory approval in their country, and to collect safety/efficacy data in a large number of GIST pts. Methods: In this ongoing open-label study, pts with advanced GIST and prior IM failure receive SU at a starting dose of 50 mg/d in 6-wk cycles (4 wks on treatment, 2 wks off). Assessments include safety/tolerability measures, response (per local standard of care) and OS. Because of the variability of response evaluations, treatment duration (TD; time from first dose to the earlier of termination date or 2 wks after last dose) was analyzed as a surrogate efficacy measure. Results: As of March 1, 2006, 768 pts enrolled at 96 centers in 33 countries had received =1 dose of SU (ITT population). Of these, 362 had discontinued treatment (lack of efficacy: 25%; AE: 12%). Median TD (ITT population) was 126 d (range: 1–618); 55% of pts had received =3 mos of treatment; 32%, =6 mos and 16%, =9 mos. Median TD was similar for pts irrespective of tumor histological subtype (epithelioid: 125 d, n=85; spindle cell: 127 d, n=414; mixed: 126 d, n=100; other subtypes: 114 d, n=158; P=0.17). Median TD was longer in pts with ECOG PS 0/1 (127 d, n=637) vs 2 (84 d, n=96; P&lt;0.0001) and pts aged &lt;65 (127d, n=486) vs =65 yrs (97d, n=281; P=0.011). Median OS has not been reached. The impact of baseline factors on survival will be presented. The most common AEs of any cause were fatigue (42%), diarrhea (38%) and nausea (32%), which were usually grade 1/2. The most common grade =3 AEs of any cause were abdominal pain (4%), vomiting (3%) and dehydration (2%). 3% of pts have demonstrated hypothyroidism. Hematologic AEs (total, grade 3/4) included anemia (56%, 5%), thrombocytopenia (35%, 5%) and neutropenia (22%, 10%). Conclusions: In this ongoing study of a large, relatively heterogeneous population of IM-resistant/-intolerant GIST pts, SU demonstrated acceptable tolerability and clinical efficacy that is highly consistent with prior studies. No significant financial relationships to disclose.
Sustained colonoscopy quality improvement using a simple intervention bundle
Authors: Laura J. Neilson, James E. East, Praveen T. Rajasekhar, Paul Bassett, Simon Dunn, Roisin Bevan, Shyju Paremal, Shiran Esmaily, Colin J. Rees
Journal: Endoscopy (2020)

Abstract Background Unacceptable variation in colonoscopy quality exists. The Quality Improvement in Colonoscopy (QIC) study in 2011 improved quality by introducing an evidence-based “bundle” of measures into routine colonoscopy practice. The QIC bundle included: minimal cecal withdrawal time of ≥ 6 minutes; hyoscine butylbromide use; supine patient position for transverse colon examination; rectal retroflexion. Colonoscopy quality was measured by adenoma detection rate (ADR). The current study measured whether these effects led to a sustained change in practice 3 years following implementation. Methods This observational study collected data from eight hospital trusts (sites) in the United Kingdom for a 6-month period, 3 years following QIC bundle implementation. Use of the antispasmodic, hyoscine butylbromide, was measured as a marker of bundle uptake. Bundle effectiveness was measured by ADR change. Comparisons were made between data before and immediately after implementation of the bundle. Results 28 615 colonoscopies by 188 colonoscopists were studied. Hyoscine butylbromide use increased from 15.8 % pre-implementation to 47.4 % in the sustainability phase (P &lt; 0.01) indicating sustained engagement with QIC measures. ADR was higher in the sustainability period compared with pre-intervention, but only reached statistical significance among the poorest-performing colonoscopists. Conclusions The introduction of a simple, inexpensive, pragmatic intervention significantly changed practice over a sustained period, improving colonoscopy quality as measured by ADR, particularly in poorer performers. QIC demonstrates that an easy-to-implement quality improvement approach can deliver a sustained change in practice for many years post intervention.
A woman with spreading erythema after caesarean section
Authors: Oscar Johnson, Anna Louise Pouncey, Sonya Gardiner, David Ross
Journal: BMJ (2020)

A 26 year old woman presented to the emergency department six days after having a caesarean section with an area of spreading erythema extending from her wound site over the infra-umbilical abdomen (fig 1). She had a body mass index of 30 and gestational diabetes, and during labour had experienced premature rupture of membranes. She reported that the area of erythema had doubled in size over the preceding 12 hours and an area of dark bruising had appeared over the last four hours. The wound had become increasingly painful, despite regular analgesia, with a pain score of …
Abstract 36: The Role of Sleep as a Cardiovascular Health Metric: Does It Improve Cardiovascular Disease Risk Prediction? Results From The Multi-Ethnic Study of Atherosclerosis
Authors: Nour Makarem, Cecilia Castro-Diehl, Marie-Pierre St-Onge, Susan Redline, Steven Shea, Donald M Lloyd-jones, Hongyan Ning, Brooke Aggarwal
Journal: Circulation (2020)

Background: The AHA Life’s Simple 7 (LS7) is a measure of cardiovascular health (CVH). Sufficient and healthy sleep has been linked to higher LS7 scores and lower cardiovascular disease (CVD) risk, but sleep has not been included as a CVH metric. Hypothesis: A CVH score that includes the LS7 plus sleep metrics would be more strongly associated with CVD outcomes than the LS7 score. Methods: Participants were n=1920 diverse adults (mean age: 69.5 y) in the MESA Sleep Study who completed 7 days of wrist actigraphy, overnight in-home polysomnography, and sleep questionnaires. Logistic regression and Cox proportional hazards models were used to compare the LS7 score and 4 new CVH scores that incorporate aspects of sleep in relation to CVD prevalence and incidence (Table). There were 95 prevalent CVD events at the Sleep Exam and 93 incident cases during a mean follow up of 4.4y. Results: The mean LS7 score was 7.3, and the means of the alternate CVH scores ranged from 7.4 to 7.8. Overall, 63% of participants slept &lt;7h, 10% had sleep efficiency &lt;85%, 14% and 36% reported excess daytime sleepiness and insomnia, respectively, 47% had obstructive sleep apnea, and 39% and 25% had high night-to-night variability in sleep duration and sleep onset timing. The LS7 score was not significantly associated with CVD prevalence or incidence (Table). Those in the highest vs. lowest tertile of CVH score 1, that included sleep duration, and CVH score 2, that included sleep characteristics linked to CVD in the literature, had lower odds of prevalent CVD. Those in the highest vs. lowest tertile of CVH scores 3 and 4, which included sleep characteristics linked to cardiovascular risk in MESA, had lower odds of prevalent CVD and lower risk of developing CVD. Conclusions: CVH scores that include sleep were more strongly associated with CVD prevalence and incidence than the traditional LS7 score. The incorporation of sleep as a metric of CVH, akin to other health behaviors, may improve CVD risk prediction. Findings warrant confirmation in larger samples and over longer follow-up.
Post-resection CA 19–9 predicts overall survival (OS) in patients treated with adjuvant chemoradiation: A secondary endpoint of RTOG 9704
Authors: A. C. Berger, K. Winter, J. Hoffman, W. Regine, R. Abrams, H. Safran, A. Konski, A. Benson, J. MacDonald, C. Willet
Journal: Journal of Clinical Oncology (2007)

4522 Background: CA 19–9 is an important tumor marker in pancreatic adenocarcinoma. Several single institutional studies have demonstrated post-resection CA 19–9 to be an important prognostic factor. A secondary endpoint of RTOG 9704, a phase III adjuvant chemoradiation trial for pancreatic cancer, was to prospectively evaluate the ability of post-resectional CA 19–9 to predict survival. Methods: A total of 538 patients were accrued to this trial, of which 385 had evaluable CA 19–9 levels. These were analyzed using ELISA GI-MA kits provided by Diagnostic Products Corporation, a Siemens Company. CA 19–9 expression was analyzed as a dichotomized variable (&lt;180 vs. =180). Cox proportional hazards models were utilized to characterize the contribution of CA 19–9 expression on OS. The following additional variables were included in the multivariate analysis: treatment, nodal involvement, tumor diameter (&lt; or &gt; 3cm), and margin status. Actuarial estimates for OS were calculated using Kaplan-Meier methods. Results: Most patients had CA 19–9 &lt; 180 (n=220, 57%), while 34% were Lewis Antigen negative (unable to express CA 19–9) and 33 (9%) patients had levels &gt;180. Survival was statistically significantly improved among patients with CA 19–9 &lt;180 compared with those whose CA 19–9 =180 (HR=3.58(95% CI=2.40–5.34), p&lt;0.0001) ( table ). This corresponds to a 72% reduction in the risk of death. This improvement was observed among patients with pancreas head and non-head tumors when analyzed separately. The multivariate analysis confirms that CA 19–9 is a highly significant predictor of OS in patients with resected pancreatic cancer. Conclusions: This prospective analysis of CA 19–9 in 385 patients treated with adjuvant chemoradiation definitively confirms the importance of post-resectional CA 19–9 in pancreatic cancer patients who have undergone resection. Patients with post-resection CA 19–9 &gt;180 should be considered for additional therapy. [Table: see text] No significant financial relationships to disclose.
State of the Art: Toward Improving Outcomes of Lung and Liver Tumor Biopsies in Clinical Trials—A Multidisciplinary Approach
Authors: Elliot B. Levy, Maria I. Fiel, Stanley R. Hamilton, David E. Kleiner, Shannon J. McCall, Peter Schirmacher, William Travis, Michael D. Kuo, Robert D. Suh, Alda L. Tam, Shaheen U. Islam, Katherine Ferry-Galow, Rebecca A. Enos, James H. Doroshow, Hala R. Makhlouf
Journal: Journal of Clinical Oncology (2020)

PURPOSE National Cancer Institute (NCI)–sponsored clinical trial network studies frequently require biopsy specimens for pharmacodynamic and molecular biomarker analyses, including paired pre- and post-treatment samples. The purpose of this meeting of NCI-sponsored investigators was to identify local institutional standard procedures found to ensure quantitative and qualitative specimen adequacy. METHODS NCI convened a conference on best biopsy practices, focusing on the clinical research community. Topics discussed were (1) criteria for specimen adequacy in the personalized medicine era, (2) team-based approaches to ensure specimen adequacy and quality control, and (3) risk considerations relevant to academic and community practitioners and their patients. RESULTS AND RECOMMENDATIONS Key recommendations from the convened consensus panel included (1) establishment of infrastructure for multidisciplinary biopsy teams with a formalized information capture process, (2) maintenance of standard operating procedures with regular team review, (3) optimization of tissue collection and yield methodology, (4) incorporation of needle aspiration and other newer techniques, and (5) commitment of stakeholders to use of guideline documents to increase awareness of best biopsy practices, with the goal of universally improving tumor biopsy practices.
Research and development of drug delivery systems based on drug transporter and nano-formulation
Authors: Yi Peng, Lu Chen, Sheng Ye, Yu Kang, Junqing Liu, Su Zeng, Lushan Yu
Journal: Asian Journal of Pharmaceutical Sciences (2020)

In recent years, the continuous occurrence of multi-drug resistance in the clinic has made people pay more attention to the transporter. Changes in the expression and activity of transporters can cause corresponding changes in drug pharmacokinetics and pharmacodynamics. The drug-drug interactions (DDI) caused by transporters can seriously affect drug effectiveness and toxicity. In the development of pharmaceutical preparations, people have increasingly concerned about the effects and regulation of transporters in drug effects. To improve the targeting and physicochemical properties of drugs, the development of targeted agents is very rapid. Among them, novel nano-formulations are the best. With the continuous innovation and development of nano-formulation, its application has become more and more extensive. Nano-formulation has exerted certain advantages in the drug development based on transporters, and is also involved in the combination of targeted transporters. This review focuses on the application of novel nano-agents targeting transporters and the introduction of drug-transporter-based nano-formulations.
A potent peptide-steroid conjugate accumulates in cartilage and reverses arthritis without evidence of systemic corticosteroid exposure
Authors: Michelle L. Cook Sangar, Emily J. Girard, Gene Hopping, Chunfeng Yin, Fiona Pakiam, Mi-Youn Brusniak, Elizabeth Nguyen, Raymond Ruff, Mesfin M. Gewe, Kelly Byrnes-Blake, Natalie W. Nairn, Dennis M. Miller, Christopher Mehlin, Andrew D. Strand, Andrew J. Mhyre, Colin E. Correnti, Roland K. Strong, Julian A. Simon, James M. Olson
Journal: Science Translational Medicine (2020)

A scorpion-derived peptide-steroid conjugate accumulates in cartilage and reverses inflammation in a rat model of arthritis without steroid toxicity.
Endoscopic coil embolization of major intrahepatic biliary leak
Authors: Sandra Baile-Maxía, Lucía Medina-Prado, Maryana Bozhychko, Carolina Mangas-Sanjuan, Juan Antonio Casellas, José Ramón Aparicio
Journal: Endoscopy (2020)

A 45-year-old man who had undergone surgery for a giant hepatic hydatid cyst 1 month ago presented to the emergency room with abdominal pain and fever. Computed tomography (CT) revealed a right pleural effusion and a collection in the right hepatic lobe, suggestive of a biliary leak ([Fig. 1]).
Abstract MP68: Dietary Lignan and Cardio-metabolic Risk: Exploring the Role of the Gut Microbiome
Authors: Yanping Li, Jun Li, Kerry L Ivey, Jeremy E Wilkinson, Dong Wang, Gang LIU, Ruifeng Li, Andrew Chan, Curtis Huttenhower, F Hu, Qi Sun, Eric B Rimm
Journal: Circulation (2020)

Background and Study Purpose: The conversion of plant lignans to enterolignans for absorption is mediated through the gut microbiota. We explored the interconnections between the intake of dietary lignans, circulating concentrations of plasma enterolignans, the gut microbiome, and cardio-metabolic risk factors (LDL-cholesterol, HDL-cholesterol, &amp; triglycerides). Design and method: The study was a repeated cross-sectional survey of up to 4 stool samples. Dietary lignan intake was assessed by two 7 day weighed records administered to coincide with fecal sample collection. DNA was extracted from 916 samples provided by 301 participants, and RNA was extracted from 369 samples from a subgroup of 96 participants. P&lt;0.25 after false discovery rate correction was considered statistically significant. Results: A high ratio of plasma enterolactone to dietary lignan was significantly associated with the relative abundance of 35 species (24 enriched and 11 depleted species), including 8 Bacteroidetes and 13 Firmicutes species. Greater dietary lignan was only significantly associated with a lower plasma ratio of triglyceride to HDL when plasma enterolactone was high. The association between dietary lignans and ratio of TG to HDL was mainly mediated by plasma enterolactone level (mediation effect: 74.3%, P=0.002), which was partially captured by the weighted species score (mediation effect: 28.6%, P=0.02). We observed several significant interactions between dietary lignans and presence of species on ratio of TG to HDL, suggesting that the protective effect of dietary lignans on CVD risk factor depends on the presence/abundance of certain microbiota. The relative abundance of microbial pathways involved in I-isoleucine biosynthesis and glutaryl-coa degradation pathways were significantly greater in in participants with a higher level of plasma enterolactone. Conclusion: The health benefits of dietary lignans on lipid levels may be modified by the greater enrichment of biologically relevant microbiota species. FIGURE