tbuckley/cabot-search huggingface dataset:
Emerging trends in pancreatic cancer and diabetes.
Authors: Seema Niphadkar, Rachel Nathan, Stuthi Perimbeti, Ya Yu Liang, Luiz Antonio Liarte Marconcini, William May Lee, Neilanjan Nandi, Maneesh Rajiv Jain, Kristine Marie Ward, Michael Styler
Journal: Journal of Clinical Oncology (2017)

e13077 Background: Risk factors for cancer and diabetes mellitus (DM) include aging, obesity, smoking, and physical inactivity. Present studies conflict on the role of DM in cancer pathogenesis; however, the link between DM and pancreatic cancer (PC) is well studied. We assessed the prevalence of DM in PC, exploring trends in demographics, length of stay (LOS), cost and inpatient mortality in teaching vs non-teaching hospitals. Methods: The Healthcare Cost and Utilization Project’s Nationwide Inpatient Sample (1999 – 2014) was queried for patients &gt; 18 with primary diagnosis of PC (excluding Whipple procedure) and secondary DM using ICD9 codes. We studied prevalence of DM and PC and compared cost of admission, LOS, mortality, and demographics between teaching and non-teaching hospitals. Chi-square test analyzed categorical variables. Results: Of 113,677 admissions for PC, 35,496 (31%) had DM. PC associated DM prevalence was higher in whites compared to blacks 57.9 % vs 12.7%, patients aged 65-79 47.7%, and southern US 37% with p &lt; 0.0001. Income disparities have decreased between 25 th percentile and &gt; 75 th percentiles from 1999 (7.3 and 32.5%) to 2014 (23.6 and 26.1%). The adjusted cost per hospitalization increased from 1999 to 2014 ($34,950 to $78,469) while LOS decreased (9.26 to 7.50 days). In teaching vs non-teaching hospitals, average cost of hospitalization ($60,465 vs $44,955) and LOS (8.8 vs 7.8 days) were higher (p &lt; 0.0001). In-hospital mortality for diabetic PC trended down from 13.09 to 6.81% and average mortality was higher in non-teaching vs teaching 11.25% vs 7.59% (all p &lt; 0.0001). Conclusions: The link between diabetes and PC has been suggested although the complete mechanism is not well understood. Our analysis showed 31% of PC cases had DM. In-hospital mortality and LOS have decreased possibly due to advances in diagnosis and treatment of both conditions. Income disparities in admissions have converged perhaps due to improved access to care for low income and outpatient management for higher income brackets. Mortality is lower in teaching hospitals but is linked with a higher cost and LOS possibly due to utilization of testing and sub-specialty access. The findings of increased white and southern prevalence are unexplained and warrant further investigation.
Prise en charge de l'hémorragie digestive liée à l'hypertension portale au cours de la cirrhose: résultats d'une enquête multicentrique
Authors: M Beauchant, J Gournay, P Bernard, F Oberti, B Bernard-Chabert, A Pauwels, P Renard, E Bartoli, JF Cadranel, JC Barbare, I Ingrand
Journal: Endoscopy (2005)

Peu d'études épidémiologiques ont été réalisées, en France comme dans les autres pays occidentaux, sur les modalités de la prise en charge de l'hémorragie digestive de la cirrhose.
Prescription opioid use in advanced COPD: benefits, perils and controversies
Authors: Nicholas T. Vozoris
Journal: European Respiratory Journal (2017)

In the ancient Roman literary masterpiece Metamorphoses , the poet Ovid writes that the god of sleep, Somnus (who had a twin brother named Thanatos, or Death), lived in a dark cave and "in front of the cave mouth a wealth of poppies flourish" [1]. This verse demonstrates that our ancestors recognised links between sleep, death and the poppy plant (from which opium is derived). Present-day population-based studies show that opioid drugs are used frequently [2, 3] and in other potentially concerning ways [2] among individuals with chronic obstructive pulmonary disease (COPD), including those with nonpalliative disease [2]. Several guidelines [4–6] support using opioids for refractory respiratory symptoms in advanced COPD, which is a commonly encountered and challenging problem. The report by Politis et al. [7] in the European Respiratory Journal describes a case of respiratory depression in an individual with advanced COPD following receipt of prescription opioids for dyspnoea, providing a timely reminder of the serious negative respiratory effects opioids can potentially have in vulnerable COPD patients. Patient and drug regimen selection important with opioid use in advanced COPD, given adverse respiratory event risk <http://ow.ly/LNXJ30bPD6C>
Entéroscopie capsulaire (EC) et maladie de Crohn: Contribution au diagnostic et impact sur la prise en charge thérapeutique
Authors: O Patron, S Sacher-Huvelin, A Bourreille, M Le Rhun, F Vavasseur, JP Galmiche
Journal: Endoscopy (2005)

L'entéroscopie capsulaire (EC) est une méthode non invasive d'exploration de l'ensemble du grêle. Dans la maladie de Crohn (MC), son apport en terme de contribution au diagnostic et au bilan d'extension de la maladie demeure mal connu. L'objectif de cette analyse rétrospective est de tenter de préciser l'impact de l'EC dans la prise en charge du patient (diagnostique et décision thérapeutique) dans une série consécutive de patients explorés en dehors d'un contexte de résection chirurgicale.
Kinin system of blood plasma as pathogenesis factor in brain tumors.
Authors: Larisa Kozlova, Elena Mikhaylovna Frantsiyants, Lyudmila Dmitriyevna Tkalya, Eduard Evgenevich Rostorguev, Dmitriy P. Atmachidi, Sergey E. Kavickij, Natalya S. Kuznetsova, David H. Porksheyan, Oleg I. Kit
Journal: Journal of Clinical Oncology (2017)

e13542 Background: The kallikrein-kinin system (KKS) does not only perform its adaptive-regulatory function; it is confirmed to be involved into pathology, neoplastic processes in particular. Our purpose was to study the kallikrein family (KLKs), pro-KLKs and carboxypeptidase N (CPN) in the blood plasma of patients with benign and malignant brain tumors. Methods: We studied citrated blood plasma of 164 patients with brain neoplasms: 37 meningiomas (M), 74 primary glioblastomas (G) and 53 brain metastases (MTS) from breast cancer. The kinetics of KKS enzymatic reactions was determined in the blood plasma before treatment using the U-2900 UV Solutions double-beam spectrophotometer (USA). The results were compared to the values in 39 healthy donors (N). The data were processed using the Statistica 10 program. The significance of differences was determined by Student's t-test. Results: Activity of KLKs in the blood plasma in patients with M exceeded N by 1.3 times (p≤0.05), in G – by 3.9 times, in MTS – by 5.1 times. Levels of pro-KLKs in M were lower than in N by 1.6 times, and in G and MTS they were similar to N. CPN activity in M was decreased compared to N by 3.1 times; in G and MTS it did not differ significantly from N. The pro-KLKs/KLKs coefficient in patients with M was lower than in N by 2 times, in G – by 3.7 times, and in MTS – by 5.1 times. Activity of KLKs in G and MTS was 3 and 4 times higher, respectively, than in M (p &lt; 0.001). It supposed realization of effects of KLKs and produced bradykinin on cells, blood enzymes and microvessel walls in malignant brain tumors to a greater extent than in benign ones. Conclusions: Activation of KKS in the blood plasma in malignant brain tumors is more intense than in benign tumors, it directly and indirectly influences cell migration, increases capillary permeability and causes an imbalance in the related enzyme systems becoming a pathogenesis factor.
Association of circulating-free DNA mutation with response of targeted therapy in HER2-positive metastatic breast cancer.
Authors: Qing Ye, Li Bian, Shaohua Zhang, Tao Wang, Yan Wang, Santai Song, Zefei Jiang
Journal: Journal of Clinical Oncology (2016)

e12083 Background: The addition of anti-HER2 targeted drug, like trastuzumab, lapatinib and TDM-1, to chemotherapy significantly improved prognosis of HER-2 positive breast cancer patients. However, it was confused that metastatic patients vary in the response of targeted drug. Therefore, methods of accurately predicting drug response were really needed. Because of the spatial and temporal limitations of needle core biopsies, we aimed to developing a higher sensitive and less invasive method of detecting mutations associated with drug response via circulating-free DNA (cfDNA) as a “liquid biopsy”. Methods: We developed a panel for detection of hotspot mutations from 50 oncogenes and tumor suppressor genes in 24 plasma samples of HER2-positive metastatic breast cancer patients who received systemic therapy from March 2014 to October 2015. Results: Totally 486 single nucleotide variants (SNV) from 46 genes were detected from 24 plasma samples. All samples harboured at least one mutation in this 50 genes panel (mean 20, range 1 to 51). Out of these 46 identified mutational genes, PIK3CA, KIT, TP53 were the top 3 mutated genes identified, with the prevalence of mutation 100%, 87.5%, 75%, respectively. And 18 genes’ mutational prevalence were under 20%. According to the treatment response about HER-2 targeted drug, 24 samples were divided into sensitive group (n = 8) and resistant group (n = 16). Comparing the SNV between two groups, we found nine gene that only occurred mutation in resistant group which was thought to be associated with targeted drug resistance. Particularly 7 samples have 11 SNVs from EGFR gene (7/16) with the mutation in exon 7, 18, 19, 20, respectively. In sensitive group, we detected a HER2 p.S855I mutation in two patients who have got long-term benefit from HER2 targeted drug. This HER2 gene mutation was probably associated with targeted drug long-term benefit. Conclusions: Targeted Next Generation Sequencing (NGS) of cfDNA has potential clinical utility to detect biomarker about HER2 targeted therapies.
Androgen receptor (AR) expression in primary breast cancer (BC): Correlations with clinical characteristics and outcomes.
Authors: Neelima Vidula, Christina Yau, Denise M Wolf, Hope S. Rugo
Journal: Journal of Clinical Oncology (2016)

1072 Background: AR is expressed in BC and may be a discrete subtype of triple negative (TN) BC. Recent trials showed modest efficacy of AR antagonists in AR+ TNBC. We investigated associations between primary BC AR gene expression (ARe), clinical characteristics, and outcomes in publically available databases. Methods: ARe was evaluated with microarray data from the neoadjuvant I-SPY 1 study (n = 149). Associations with clinical features and chemotherapy response were assessed with Kruskal-Wallis and Wilcoxon rank sum tests and recurrence free survival (RFS) by the Cox proportional hazard model. Pearson correlations between AR and selected genes were determined in I-SPY 1, METABRIC (n = 1992), and TCGA (n = 817). Results: In I-SPY1, ARe was lower in TN than hormone receptor+/HER2- and HER2+ BC (p < 0.0001). ARe was lower in basal BC (p < 0.0001) and was higher in patients > age 50 (p = 0.05). ARe correlated with grade I/II histology (p < 0.0001) and node negativity at diagnosis (p = 0.0058) but not with stage, lymphovascular invasion, or pathologic complete response. Higher ARe remained associated with better RFS upon adjustment for receptor subtype (p = 0.01). Table 1 below shows genes with significant (p < 0.05) correlations with AR in ≥ 2 datasets. Conclusions: ARe is lowest in TN and basal BC. Consistent with this finding, AR correlates with luminal genes FOXA1, ESR1, MUC1, and inversely with basal genes MYC, CRYAB, EGFR, DNA damage repair genes, mesenchymal genes KIT and CDK 6, and immune genes PD-1 and STAT5A. ARe appears to provide independent prognostic information when receptor subtypes were considered. ISPY-1 (n = 149) METABRIC (n = 1992) METABRIC TN (n = 320) TCGA (n = 817) TCGA TN (n = 101) POSITIVE Correlations (r) FOXA1 0.74 0.66 0.73 0.76 0.62 ESR1 0.56 0.50 0.23 0.63 0.40 MUC1 0.36 0.44 0.34 0.33 0.26 ERBB2 0.37 0.21 0.34 0.27 0.35 TNSF10 0.29 0.21 0.22 0.26 NS INVERSE Correlations (r) MYC -0.46 -0.31 -0.41 -0.29 -0.24 CRYAB -0.18 -0.40 -0.32 -0.45 -0.30 EGFR -0.35 -0.26 NS -0.22 NS CDK 6 -0.53 -0.48 -0.29 -0.31 NS KIT NS -0.28 -0.28 -0.12 NS PD-1 NS -0.20 NS -0.28 NS STAT5A NS -0.15 NS -0.077 NS PARPi-7 (DNA damage repair deficiency signature) N/A -0.21 -0.16 -0.42 -0.22 NS: non-significant
A common haplotype lowers PU.1 expression in myeloid cells and delays onset of Alzheimer's disease
Authors: Kuan-lin Huang, Edoardo Marcora, Anna A Pimenova, Antonio F Di Narzo, Manav Kapoor, Sheng Chih Jin, Oscar Harari, Sarah Bertelsen, Benjamin P Fairfax, Jake Czajkowski, Vincent Chouraki, Benjamin Grenier-Boley, Céline Bellenguez, Yuetiva Deming, Andrew McKenzie, Towfique Raj, Alan E Renton, John Budde, Albert Smith, Annette Fitzpatrick, Joshua C Bis, Anita DeStefano, Hieab H H Adams, M Arfan Ikram, Sven van der Lee, Jorge L Del-Aguila, Maria Victoria Fernandez, Laura Ibañez, Rebecca Sims, Valentina Escott-Price, Richard Mayeux, Jonathan L Haines, Lindsay A Farrer, Margaret A Pericak-Vance, Jean Charles Lambert, Cornelia van Duijn, Lenore Launer, Sudha Seshadri, Julie Williams, Philippe Amouyel, Gerard D Schellenberg, Bin Zhang, Ingrid Borecki, John S K Kauwe, Carlos Cruchaga, Ke Hao, Alison M Goate
Journal: Nature Neuroscience (2017)
Abstract 12827: Exercise Training Fails to Reduce Blood Pressure in Type 2 Diabetes: A Randomized Controlled Trial
Authors: Kerry J Stewart, Devon A Dobrosielski, Pamela Ouyang
Journal: Circulation (2011)

Background:  Though exercise is an integral part of diabetes care, the existing studies on exercise for BP reduction have inconsistent results. As noted in a 2010 position statement from the American Diabetes Association and American College of Sports Medicine, exercise may slightly reduce SBP and DBP reductions are less common. The evidence was rated category C, which indicates a consensus viewpoint or expert opinion rather than high-quality randomized controlled trials (RCT) or meta-analyses.   Methods:  This was a 6-month prospective RCT of a supervised moderate-intensity combined aerobic and resistance training 3 times per week; controls followed usual care physical activity and diet advice. Patients (N=140, M=81, F=59; aged 40-65 years, mean (SD) 56.4±6.1 years) had uncomplicated diabetes not requiring insulin and untreated SBP of 120 to 159 mm Hg or DBP of 85 to 99 mm Hg, or, if being treated with one or more anti-hypertensive medications, any SBP below 159 mm Hg or DBP below 99 mm Hg. Arterial stiffness was indexed by the aortofemoral pulse-wave velocity (PWV).   Results:  Fifty-three exercisers and 65 controls completed the study. Exercisers significantly improved aerobic and strength fitness, increased lean body mass and reduced general and abdominal obesity. Baseline BP was 126.3±12.3/71.7±7.9 mm Hg in exercisers and 126.0±13.5/70.3±8.7 mm Hg in controls, with no group differences p=ns. At 6-months, BP was 125.2±14.6/69.9±9.3 mm Hg in exercisers and 125.7±13.1/70.3±8.5 mm Hg in controls, with no group differences (p=ns) or change from baseline in either group (p=ns). Baseline PWV was 902.2±322.8 cm/s in exercisers and 918.4±351.0 in controls, p=ns. At 6-months, PWV was 902.7±307.0 cm/s in exercisers and 905.4±344.7 in controls, with no group differences (p=ns) or change from baseline in either group (p=ns).   Conclusions:  Exercisers achieved a training effect as evidenced by increases in fitness and lean mass and reductions in body fat yet BP remained virtually unchanged. The lack of reduction in arterial stiffness suggests that patients with type 2 diabetes may be resistant to exercise-induced reductions in SBP. Though exercise produced several health benefits, this RCT did not find a reduction in SBP or DBP in patients with type 2 diabetes.
Abstract 2978: Genotype-Phenotype Variations in Cardiomyopathies Caused by a Cardiac Troponin I Gene Mutation
Authors: Tetsuo Konno, Hidekazu Ino, Noboru Fujino, Kenshi Hayashi, Katsuharu Uchiyama, Hiromasa Katoh, Toshinari Tsubokawa, Masakazu Yamagishi
Journal: Circulation (2006)

Introduction:  It has been reported that mutations in the cardiac troponin I ( TNNI3 ) gene are associated with variable phenotypes of cardiomyopathies. However, there is no report that demonstrated 3 different phenotypes (hypertrophic cardiomyopathy; HCM, restrictive cardio-myopathy and dilated cardiomyopathy) caused by an identical mutation in the  TNNI3  gene.   Hypothesis:  We assessed the hypothesis that carriers of familial HCM with a single  TNNI3  gene mutation may show not only phenotypes of HCM, but also phenotypes of restrictive cardiomyopathy and dilated cardiomyopathy.   Methods:  Four hundred probands with HCM were screened for mutations in the  TNNI3  gene with the polymerase chain reaction and single strand conformational polymorphism analysis.   Results:  We detected a Lys183del mutation in 13 (3.3%) of 400 probands with HCM. Family studies were performed, and 54 carriers with the Lys183del mutation were identified. Besides the typical features of HCM (Figure A), such as non-dilated left ventricle and preserved systolic function (n = 30, 55% of 54 carriers), phenotypes of restrictive cardiomyopathy (Figure B) were found in 1 (1.9%) carrier, and phenotypes of dilated cardiomyopathy (Figure C, D) in 5 (9.3%) carriers. Of the 54 carriers, 18 (33%) did not manifest left ventricular hypertrophy on echocardiography.   Conclusions:  In conclusion, 3 different phenotypes of cardiomyopathies were found to be caused by an identical  TNNI3  gene mutation, suggesting a hereditary overlapping in cardiomyopathies.
Personalized, molecularly matched combination therapies for treatment-na.
Authors: Jason K. Sicklick, Brian Leyland-Jones, Shumei Kato, Michael Hahn, Casey Williams, Pradip De, Vincent A. Miller, Jeffrey S. Ross, Adam Benson, Jennifer Webster, Phil Stephens, Michael Scur, Robert Porter, Lisa Tran, Shelby Hintze Jepperson, Paul T. Fanta, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2017)

2512 Background: Precision medicine has been studied in patients (pts) with advanced, heavily-treated cancers by administering molecularly matched monotherapies. With increasing availability of large gene assays and cognate agents, we hypothesized that offering customized combination therapies to treatment-naïve tumors would be feasible and improve response rates. Methods: Investigation of Profile-Related Evidence Determining Individualized Cancer Therapy (I-PREDICT, NCT02534675) targeted metastatic and/or unresectable, untreated lethal cancers ( &gt; 50% 2-yr mortality). Comprehensive genomic profiling (CGP, Foundation Medicine; 315 genes), and, if possible, PD-(L)1 IHC, tumor mutational burden (TMB) and circulating tumor DNA were performed. A molecular tumor board discussed results immediately upon receipt, and emphasized customized combinations. Final decisions were the treating physician’s choice. Results: CGP was evaluable in 40/47 treatment-naïve pts (85.1%); 22 (46.8%) were treated [17 matched (36.2%); 5 unmatched (10.6%); 11 different diagnoses). The other 25 pts (53.2%) are awaiting therapy (8, 17%) or could not be treated (17, 36.2%), mainly due to patient deterioration or payor limitations. Each tumor had a unique genomic portfolio. The median (range) of genomic alterations/patient was 5 (1-12). TMB was available in 17 pts (12 low; 4 intermediate; 1 high). The median (range) Matching Score [(matches (#)/characterized genomic alterations (#)] was 33% (14-100%; 100% designated immunotherapy match or all alterations matched to targeted agents) [Reference PMID 2719717]. Nine/17 matched pts (53%) achieved SD &gt; 6 months (N = 2) or CR (1)/PR (6). The median progression-free survival (PFS) for matched vs. unmatched pts was 4.7 vs. 1.0 months ( P= 0.0019). There were no drug-related deaths. Conclusions: With the use of broad-based DNA sequencing assays, inclusion of pts earlier in their disease course, timely mandated molecular tumor board discussions, and increasing availability of cognate drugs for customized combinations, we report: 1) high molecular matching rates (~36%); 2) high rates of SD &gt; 6 months/CR/PR (~53%); and 3) improved PFS. Study expansion is ongoing. Clinical trial information: NCT0253467.
Abstract 19370: Are the Benefits of Quality-of-Care Improvement Programs in Acute Coronary Syndromes Maintained Once the Intervention Is Over?
Authors: Jose Barrabes, Laura Galian, Ferran Rueda, Elsa Nieto, Jaume Figueras, Josefa Cortadellas, Rosa-Maria Lidon, David Garcia-Dorado
Journal: Circulation (2010)

Objective: It has been demonstrated that participation in quality improvement programs increases hospital adherence to evidence-based recommendations for the management of patients with non-ST elevation acute coronary syndromes (NSTE-ACS). However, it is uncertain whether this effect is maintained, and for how long, after the intervention is over. Methods and Results: Our department (cardiology department in a tertiary university center) participated in the intervention arm of a multicenter, international trial assessing the effect of a quality-of-care improvement program in NSTE-ACS during 2008. Program implementation led to significant improvements in several indicators of care quality at the end of the trial. In the present study, we analyzed whether these effects were maintained throughout the following year, when no intervention was applied. A total of 303 consecutive NSTE-ACS patients ≤80 years, admitted from our Emergency Department and with either ECG changes, abnormal troponins, or both, were inc...
Blood trypsin proteinases as a new additional test in differential diagnosis of brain tumors.
Authors: Larisa Kozlova, Elena Mikhaylovna Frantsiyants, Lyudmila Dmitriyevna Tkalya, Eduard Evgenevich Rostorguev, Dmitriy P. Atmachidi, Sergey E. Kavickij, Natalya S. Kuznetsova, David H. Porksheyan
Journal: Journal of Clinical Oncology (2017)

e13543 Background: Activation of trypsin-type proteinases in cancer is a proven fact. Activity of enzymes synthesized and secreted by a malignant tumor is generally not controlled by endogenous inhibitors. Benign tumors do not come into metabolic conflict with the carrier body, at least prior to their possible malignant transformation. The purpose of the study was to analyze changes in activity of trypsin proteinases (ATP) in the blood plasma of patients to determine possible application of the parameter as an additional test in the differential diagnosis of brain tumors. Methods: The blood plasma of 164 patients was studied: 37 benign brain tumors, 74 primary glioblastomas (G) and 53 brain metastases (MTS) from breast cancer. ATP was determined before treatment using the U-2900 UV Solutions double-beam spectrophotometer (USA). The results were compared to the values in 39 healthy donors (N). The data were processed using the Statistica 10 program. Results: ATP did not differ from N in 37 of 164 patients (22.6%). After removal of the brain tumors, histological examination of surgical material showed benign brain tumors in all 37 cases. ATP in 74 of 164 patients (45.1%) exceeded N by 3.8-5.3 times (on average 4.4±0.3). Histological examination after removal of the brain tumors showed primary G in all 74 cases. ATP was 5.9-9.4 times higher than N (on average 7.3±0.5) in 53 of 164 patients (32.3%). Histological examination after removal of the brain tumors showed MTS in all 53 cases. Conclusions: ATP value similar to N indicates a benign tumor. ATP increase by 3.8-5.3 times shows the presence of a primary malignant tumor. ATP increase by 5.9-9.4 times supposes MTS.