tbuckley/cabot-search huggingface dataset:
The incidence of anxiety and depression in adult cancer outpatients in an area of social deprivation.
Authors: Hannah Louise Chapman, Lucinda Melcher, Justin Shute
Journal: Journal of Clinical Oncology (2013)

e20709 Background: Psychological distress is common in cancer patients and negatively impacts patient quality of life. Untreated depression predicts early death in patients with advanced cancer. Anxiety and depression may be unrecognised in cancer patients as symptoms can be mistakenly attributed to the underlying malignancy. We assessed the incidence of anxiety and depression in patients attending two hospitals located in areas of significant social deprivation and ethnic diversity. Methods: Patients attending the oncology department at North Middlesex University Hospital and Princess Alexandra Hospital during a one week period were invited to complete a questionnaire. We collected socio-demographic data. The rest of the questionnaire consisted of the Hospital Anxiety and Depression Scale (HADS). HADS is a 14 question, validated screening tool. Total scores range from 0-42, but can be divided into two subscales: HADS-D for depression and HADS-A for anxiety. Interpretation is based primarily on cut-off scores suggested by the test’s authors. In a previously reported non-clinical sample, mean total HADS was 9.82, HADS-D 3.68 and HADS-A 6.14. Results: 96 patients completed the questionnaire. 64 out of 96 patients (67%) were aged between 50 and 79 years. The majority were of white UK ethnicity. The most common types of cancer were breast and colorectal. Seventy five patients (78%) had a ‘normal’ total HADS (≤14). The mean scores for total HADS, HADS-D and HADS-A were 10.53, 4.61 and 5.93, respectively. On the HADS-A subscale, 14 patients had mild anxiety, 12 had moderate and 2 patients had severe anxiety. Depression scores were slightly lower: 12 patients had mild depression and 4 had moderate depression. No patient had severe depression. Only 6 (6%) patients reported taking anti-depressant medication. Conclusions: We demonstrate lower levels of anxiety and depression in a mixed group of cancer patients than previously reported. We explore the possible causes for this difference. Thresholds set to identify ‘cases’ in a non-clinical population may be too high for cancer patients. HADS is a useful screening tool in oncology patients but should be combined with clinical assessment to improve sensitivity and specificity.
Randomized phase II study of sunitinib + CXCR4 inhibitor LY2510924 versus sunitinib alone in first-line treatment of patients with metastatic renal cell carcinoma.
Authors: John D. Hainsworth, Joseph Ronald Mace, James Andrew Reeves, Edward J. Crane, Oday Hamid, John R Stille, Amy Flynt, John Polzer, Alvin Milner, Stephanie Roberson, Edward Arrowsmith
Journal: Journal of Clinical Oncology (2015)

4547 Background: Sunitinib is a standard first-line treatment for patients (pts) with metastatic renal cell carcinoma (RCC). CXCR4 and its only known ligand, SDF-1, are both overexpressed in tumor and vascular cells of clear cell RCC. LY2510924 is a selective peptide antagonist of CXCR4. We compared the results of open-label treatment with LY2510924 + sunitinib vs sunitinib alone. Methods: Previously untreated metastatic clear cell RCC pts were randomized (2:1) to receive standard-dose sunitinib (50 mg qd for 4 weeks [wk], then 2 wk off) + LY2510924 (20 mg sc, qd) (Arm A) or sunitinib alone (Arm B). Pts were evaluated (per RECIST v.1.1) every 8 wk. The primary analysis was done when all pts completed 72 wk of treatment, discontinued, progressed, or died and compared progression-free survival (PFS) between arms using a Bayesian time to event analysis incorporating prior information about sunitinib along with the trial data. PFS was also analyzed using the hazard ratio (HR) with only trial data. The Bayesian design was simulated to size the trial. The objective response rates (ORR) in each arm were compared using the chi-squared test. Results: 72 and 36 pts were treated in Arms A and B, respectively. Key pt characteristics (ECOG PS, Motzer risk score, prior nephrectomy) were similar in Arms A and B. Median number of cycles administered in each arm was 5. Median PFS was 8.1 and 12.3 months in Arms A and B, respectively (HR [95% CI]: 1.19 [0.73, 1.94]). The ORR (95% CI) was 30.6% (19.9%, 41.2%) in Arm A and 38.9% (23.0%, 54.8%) in Arm B. The most frequent ( > 5% Arm A) grade 3/4 AEs (Arm A, Arm B) were hypertension (13.9%, 19.4%), fatigue (9.7%, 13.9%), diarrhea (6.9%, 16.7%), thrombocytopenia (8.3%, 5.6%), and anemia (8.3%, 2.8%). Of interest, there were more bleeding-related events (mostly grade 1 or 2) in Arm A than B (39%, 14%). More pts in Arm A discontinued treatment due to AE (18.1%, 8.3%). Two deaths in Arm A were due to adverse events (pulmonary edema/respiratory arrest/cardiac arrest and intracranial tumour hemorrhage). Conclusions: Adding the CXCR4 inhibitor LY2510924 to sunitinib as first-line treatment for metastatic RCC was tolerated but did not improve efficacy. Clinical trial information: NCT01391130.
RAINBOW: A global, phase III, randomized, double-blind study of ramucirumab plus paclitaxel versus placebo plus paclitaxel patients with previously treated gastric or gastroesophageal junction (GEJ) adenocarcinoma: Quality-of-life (QoL) results.
Authors: Salah-Eddin Al-Batran, Eric Van Cutsem, Sang Cheul Oh, Gyorgy Bodoky, Yasuhiro Shimada, Shuichi Hironaka, Naotoshi Sugimoto, Oleg N. Lipatov, Tae-You Kim, David Cunningham, Philippe Rougier, Kei Muro, Astra M. Liepa, Shaila Ballal, Michael Emig, Atsushi Ohtsu, Hansjochen Wilke
Journal: Journal of Clinical Oncology (2014)

4058 Background: Ramucirumab (RAM) added to paclitaxel (PTX) resulted in statistically significantly improved overall survival, progression-free survival and response rate for previously treated patients (pts) with advanced gastric or GEJ cancer (Wilke et al, GI Cancer Symposium 2014). Here we present the secondary endpoint of QoL. Methods: Pts who had previously received fluoropyrimidine- and platinum-based therapy were randomized to receive RAM 8 mg/kg IV or placebo (PL) on Days 1 and 15 every 4 weeks (wks); both arms received PTX 80 mg/m2on Days 1, 8 and 15. Pts completed the EORTC QLQ-C30 (v3) at baseline, every 6 wks from start of therapy and at discontinuation. Time to deterioration (TtD) in each QoL parameter was defined as randomization to first worsening of ≥10 points (on 100-point scale). Hazard ratios (HRs) for treatment effect were estimated using stratified Cox proportional hazards models. In addition, scores were classified as improved or worsened if changed by ≥10 points relative to baseline, otherwise classified as stable. Results: Of 665 pts randomized, 322/330 (98%) of RAM+PTX and 328/335 (98%) of PL+PTX pts provided baseline (BL) QoL data and 87% and 81%, respectively, provided both BL and post-BL data. BL scores were similar between arms. Of the 15 QoL parameters, 14 had HRs <1, indicating similar or longer TtD in QoL for RAM+PTX. HRs <0.75 were observed for emotional functioning and nausea/vomiting and >1 for diarrhea. For all QoL parameters and at all on-therapy assessment times, the proportion of pts reporting improved or stable scores was numerically greater for RAM+PTX; in general, more pts were classified as stable than improved. Conclusions: For pts with advanced gastric cancer, addition of RAM to PTX did not impair QoL. Compared with PL+PTX, QoL was maintained for a longer time and more pts reported stable or improved scores. Clinical trial information: NCT01170663. Rates of improvement/stability for select QoL parameters. RAM+PTX (N=330) PL+PTX (N=335) Wk 6 Wk 12 Wk 6 Wk 12 Global QoL 53% 36% 50% 27% Physical functioning 56% 41% 47% 28% Fatigue 45% 35% 42% 25% Pain 56% 41% 49% 27% Appetite loss 60% 43% 54% 30%
Not all of the patients with hepatitis B-related hepatocellular carcinoma require endoscopic screening for esophageal varices: a large cohort study
Authors: C.-Y. Chang, C.-W. Su, P.-H. Chen, M.-C. Hou, P.-C. Lee, H.-C. Lin, Y.-H. Huang, T.-I. Huo, J.-C. Wu
Journal: Journal of Hepatology (2017)
Improved virological outcomes and excellent safety profile in genotype 3 HCV-infected cirrhotic patients after an extended 24-weeks course of daclatasvir, sofosbuvir + ribavirin: insights from a real-life multicenter study
Authors: R. Lionetti, I. Lenci, M. Siciliano, M. Pompili, U.V. Comandini, M. Milana, C. Taibi, M. Montalbano, A.R. Garbuglia, P. Begini, B. Imperatrice, M. Angelico, G. D’Offizi
Journal: Journal of Hepatology (2017)
P1.01-016 An International Epidemiological Analysis of Young Patients Diagnosed with NSCLC (AduJov - CLICaP)
Authors: Luis Corrales-Rodriguez, Oscar Arrieta, Luis Mas, Omar Castillo-Fernandez, Normand Blais, Claudio Martin, Ludwing Bacon, Allan Ramos-Esquivel, Mauricio Cuello, Leonardo Rojas, Melissa Juárez, Andrés Cardona
Journal: Journal of Thoracic Oncology (2017)
Field evaluation of Xpert ® HCV Viral Load point-of-care test for detection of hepatitis C virus infection by venipuncture-collected and finger-stick capillary whole-blood samples
Authors: J. Grebely, F. Lamoury, B. Hajarizadeh, Y. Mowat, A. Marshall, S. Bajis, P. Marks, J. Amin, J. Smith, M. Edwards, C. Gorton, N. Ezard, D. Persing, M. Kleman, P. Cunningham, B. Catlett, G. Dore, T.L. Applegate
Journal: Journal of Hepatology (2017)
Impact of sustained virologic response on liver fibrosis in recurrent hepatitis C after liver transplantation
Authors: E. Mauro, G. Crespo, M.C. Londoño, A. Diaz, P. Ruiz, C. Montironi, J. Lombardo, L. Sastre, J. Aguirre, J. Colmenero, X. Forns, M. Brunet, M. Navasa
Journal: Journal of Hepatology (2017)
Treatment uptake and real world effectiveness of sofosbuvir/ ledipasvir and paritaprevir/ritonavir/ombitasvir/dasabuvir among HCV-infected persons with chronic kidney disease
Authors: M.M. Alkadi, Y. Ren, A. Puenpatom, R. Kumar, J.M. Arduino, A.-B. Abou-Samra, A.A. Butt
Journal: Journal of Hepatology (2017)
Clinical outcomes in BRAFV600-mutant metastatic melanoma with sequential treatment with immunotherapy and BRAF inhibitors or vice versa.
Authors: Francisco Aya, Aranzazu Fernandez, Iván Victoria, Lydia Gaba, Estela Pineda, Ana M Arance
Journal: Journal of Clinical Oncology (2015)

e20030 Background: Limited data exists on the sequencing of BRAF inhibitors (BRAFi) and immunotherapy (IT) in patients (pts) with BRAFV600-mutant metastatic melanoma (BRAFV600MM). The aim of this analysis was to determine the overall survival (OS) of pts treated with both agents sequentially in this population. Methods: This was a retrospective, single-institution analysis of pts treated with BRAFi (vemurafenib or dabrafenib) and IT (ipilimumab, pembrolizumab or nivolumab) as part of a clinical trial, expanded access program or via commercial use. Eligible patients were positive for the BRAFV600 mutation and had sequentially received treatment with BRAFi followed by IT (cohort A), or vice versa (cohort B). Response rate (RR), according to immune-related response criteria for IT and to RECIST v1.1 for BRAFi, OS and survival rates, upon both sequences were evaluated. Descriptive statistics were used to analyze patient baseline characteristics. Median follow-up were compared by U Mann-Whitney test. RR were compared by exact Fisher test. OS were estimated by the Kaplan-Meier method. Results: A total of 23 pts were eligible, 14 pts received BRAFi prior to IT (cohort A); and 9 pts, IT followed by BRAFi (cohort B). No differences were found in baseline characteristics between each cohort before the start of either treatment. Median follow-up were 16.8 and 26.5 months (p =.791) for cohorts A and B, respectively. Pts treated with a BRAFi before or after progression to IT showed similar RR (71 vs 78%, p = 1.00). Nine pts treated first with IT showed no response compared to 6 pts treated with IT after a BRAFi (0 vs 43%, p = 0.048). Median OS for cohort A was 31 months and not reached for B (with only 4 events reported). Seventy-six versus 89% of pts were alive at 12 months in cohort A and B; and 54 and 51% at 24 months in cohort A and B, respectively. Conclusions: This study suggests that BRAFi induce a similar RR independently of the sequence of treatment administered. Administration of a BRAFi prior to IT may enhance response to IT. Most importantly it suggests that BRAFi and IT are optimal first-line options in pts with BRAFV600MM based on similar long term outcomes.
Biomarkers and Clinical Prediction Rules in the Diagnosis of Suspected Deep Vein Thrombosis: A Comparison of Cancer and Non-Cancer Patients
Authors: Jordan K. Schaefer, Dana E. Angelini, Angela Hawley, Susan A. Blackburn, Elizabeth Lusk, Thomas M. Braun, Thomas W. Wakefield, Suman L. Sood
Journal: Blood (2016)
NAFLD as an indication for liver transplantation in the Nordic countries – a cohort study during 1982-2015
Authors: M. Holmer, E. Melum, H. Isoniemi, B.-G. Ericzon, M. Castedal, A. Nordin, N.A. Schultz, A. Rasmussen, P.-D. Line, P. Stål, W. Bennet, H. Hagström
Journal: Journal of Hepatology (2017)
Upregulation of MATE-1 transporter by obeticholic acid correlates with increased biliary excretion of asymmetric dimethylarginine during hepatic ischemia/reperfusion injury
Authors: L.G. Di Pasqua, C. Berardo, V. Siciliano, V. Rizzo, L. Adorini, P. Richelmi, A. Ferrigno, M. Vairetti
Journal: Journal of Hepatology (2017)
Gene expression profiling to predict the prognosis of neuroblastoma and its application to a diagnostic microarray of clinical use
Authors: Miki Ohira-Ichikawa, Shigeyuki Oba, Yohko Nakamura, Eriko Isogai, Takahiro Hirata, Yasuko Yoshida, Misa Fuchioka, Shin Ishii, Akira Nakagawara
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4491 

Neuroblastoma (NBL) is an enigmatic tumor with heterogeneous clinical behaviors including maturation, regression, and aggressive growth. Recent progress in therapeutic strategies against advanced NBL has improved patient survival, however, their long-term outcomes are still poor. In addition, the intermediate risk group in advanced stages (i.e. stage 3 or 4 without MYCN amplification) has been difficult to predict its prognosis. In order to predict the prognosis of NBL patients efficiently and choose a better therapeutic protocol, we have developed an in-house, microceramic pump-based ink-jet-printed cDNA microarray carrying 5,340 genes obtained from primary NBL cDNA libraries and applied it for the expression profiling of 136 NBL tumors. A combination of ’weighted voting’ supervised machine learning and ’leave-two-out’ cross validation process has selected the 70 predictor gene set which showed its strongest power (with accuracy of approximately 89%, sensitivity of 87%, and specificity of 89%) to predict patient prognosis at 5-years after the diagnosis. Compared to the existing prognosis markers, the supervised microarray analysis showed the best sensitivity-specificity balance among the prognostic factors. We then constructed a probabilistic output ’posterior’ probability to indicate the reliability of each sample’s outcome prediction. Each posterior takes a real number between 0 and 1, and corresponds to the expected 5-year survival rate. When we divided samples by the posterior value of 0.5, Kaplan-Meier analysis indicated 5-year survivals for 33% and 94% of patients with unfavorably and favorably predicted NBLs, respectively (p<10–5). Of clinical interest, the intermediate risk type of NBL, whose cumulative survival rate was 74%, was divided by our microarray into two subgroups with better (89%) and worse (36%) prognoses (p<10–5). Based on these results, we made a practical mini-chip carrying top-ranked 200 genes for clinical use, which gave a highly comparable result (88% of prediction accuracy) to that obtained from the 5,340 cDNA microarray in the independent test by using 50 additional samples. Further tests of the mini-chip diagnosis system are currently ongoing. Thus, our microarray system made its practical use feasible at the bedside to predict the prognosis of the patient with NBL. Our findings will provide a new strategy to find patients who need early intensive therapy.
Virological and clinical significance of detectable HCV-RNA below limit of quantification at End-of-Treatment in patients treated with direct antiviral agents
Authors: U.V. Comandini, D. Lapa, R. Lionetti, C. Taibi, L. Loiacono, M. Montalbano, M. Capobianchi, G. D’Offizi, A.R. Garbuglia
Journal: Journal of Hepatology (2017)
<i>EGFR</i> and <i>KRAS</i> mutations during anti-EGFR monoclonal antibody treatment in metastatic colorectal cancer: Clinically relevant?
Authors: Lucie Karayan-Tapon, Aurelie Ferru, Ulrich Cortes, Claire Villalva, Jean Marc Tourani, Christine Silvain, Pierre Levillain, David Tougeron
Journal: Journal of Clinical Oncology (2013)

3513 Background: It is well-established that only patients with wild-type KRAS metastatic colorectal cancer (mCRC) benefit from treatment with an epidermal growth factor receptor monoclonal antibody (anti-EGFR mAb). Recently, in patients with tumor progression after anti-EGFR mAb, occurrence of EGFR mutation (n=2/10) [Montagut C et al., Nat Med 2012] or KRAS mutation (n=6/10) [Misale S et al., Nature 2012] in metastases has been identified. These mutations could explain treatment resistance but still need to be confirmed with simultaneous analysis of KRAS and EGFR mutations. Methods: We analyzed 37 tumor samples after anti-EGFR mAb treatment for mCRC (34 from metastasis lesions and 3 from primary tumors). We analyzed KRAS (codons 12 and 13), BRAF V600E and EGFR S492R mutations using a highly sensitive technique, pyrosequencing (TheraScreen KRAS Pyro Kit, Qiagen). All tumors were KRAS, BRAF V600E and EGFR S492R wild-type before anti-EGFR mAb treatment. Results: The majority of patients were treated using anti-EGFR mAb in first-line chemotherapy (70%) and combined with cytotoxic chemotherapy (96%). Cetuximab was used in 86% and panitumumab in 14% of the cases. Among the 37 tumor specimens, 8 were collected after disease progression, and the others after disease control. No EGFR S492R mutation was detected. No tumors developed BRAF mutation but one tumor acquired a KRAS mutation. Nevertheless, the KRAS mutation in this patient (G12V) was detected, after 5-fluorouracil plus cetuximab therapy, only in the primary tumor in the colon but not in the liver metastasis. Moreover, there was a disease control (partial response). Conclusions: Our results suggest that EGFR S492R and acquired KRAS mutations during anti-EGFR mAb therapy are not the only factors accounting for anti-EGFR resistance. Moreover, occurrence of KRAS mutation during anti-EGFR therapy could differ between primary tumor and metastases.
Transjugular intrahepatic portosystemic shunt before planned abdominal surgery in cirrhotic patients
Authors: N. Tabchouri, L. Barbier, B. Menahem, J.-M. Perarneau, F. Muscari, J. Dumortier, L. D’Alteroche, J. Lubrano, A. Alves, C. Bureau, E. Salamé
Journal: Journal of Hepatology (2017)
Hepatic uptake of conjugated bile acids is mediated by both sodium taurocholate cotransporting polypeptide and organic anion transporting polypeptides and modulated by intestinal sensing of plasma bile acid levels in mice
Authors: Davor Slijepcevic, Reinout L.P. Roscam Abbing, Takeshi Katafuchi, Antje Blank, Joanne M. Donkers, Stéphanie van Hoppe, Dirk. R. de Waart, Dagmar Tolenaars, Jonathan H.M. van der Meer, Manon Wildenberg, Ulrich Beuers, Ronald P.J. Oude Elferink, Alfred H. Schinkel, Stan F.J. van de Graaf
Journal: Hepatology (2017)

The Na + ‐taurocholate cotransporting polypeptide (NTCP/ SLC10A1 ) is believed to be pivotal for hepatic uptake of conjugated bile acids. However, plasma bile acid levels are normal in a subset of NTCP knockout mice and in mice treated with myrcludex B, a specific NTCP inhibitor. Here, we elucidated which transport proteins mediate the hepatic uptake of conjugated bile acids and demonstrated intestinal sensing of elevated bile acid levels in plasma in mice. Mice or healthy volunteers were treated with myrcludex B. Hepatic bile acid uptake kinetics were determined in wild‐type (WT), organic anion transporting polypeptide (OATP) knockout mice (lacking Slco1a/1b isoforms), and human OATP1B1‐transgenic mice. Effects of fibroblast growth factor 19 (FGF19) on hepatic transporter mRNA levels were assessed in rat hepatoma cells and in mice by peptide injection or adeno‐associated virus–mediated overexpression. NTCP inhibition using myrcludex B had only moderate effects on bile acid kinetics in WT mice, but completely inhibited active transport of conjugated bile acid species in OATP knockout mice. Cholesterol 7α‐hydroxylase Cyp7a1 expression was strongly down‐regulated upon prolonged inhibition of hepatic uptake of conjugated bile acids. Fgf15 (mouse counterpart of FGF19 ) expression was induced in hypercholanemic OATP and NTCP knockout mice, as well as in myrcludex B–treated cholestatic mice, whereas plasma FGF19 was not induced in humans treated with myrcludex B. Fgf15/FGF19 expression was induced in polarized human enterocyte‐models and mouse organoids by basolateral incubation with a high concentration (1 mM) of conjugated bile acids. Conclusion : NTCP and OATPs contribute to hepatic uptake of conjugated bile acids in mice, whereas the predominant uptake in humans is NTCP mediated. Enterocytes sense highly elevated levels of (conjugated) bile acids in the systemic circulation to induce FGF15/19, which modulates hepatic bile acid synthesis and uptake. (H epatology 2017;66:1631–1643).
Vitamin D serum levels are only marginally lower in hepatic steatosis and do not correlate with Vitamin D dietary ingestion
Authors: J. Leitão, S. Carvalhana, A. Silva, F. Velasco, I. Medeiros, A.C. Alves, M. Bourbon, B. Oliveiros, A. Carvalho, H. Cortez-Pinto
Journal: Journal of Hepatology (2017)
F<scp>ifty</scp> Y<scp>ears of</scp> R<scp>esearch in</scp> ARDS.Genomic Contributions and Opportunities
Authors: John P. Reilly, Jason D. Christie, Nuala J. Meyer
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Clinical factors alone poorly explain acute respiratory distress syndrome (ARDS) risk and ARDS outcome. In the search for individual factors that may influence ARDS risk, the past 20 years have witnessed the identification of numerous genes and genetic variants that are associated with ARDS. The field of ARDS genomics has cycled from candidate gene association studies to bias-free approaches that identify new candidates, and increasing effort is made to understand the functional consequences that may underlie significant associations. More recently, methodologies of causal inference are being applied to maximize the information gained from genetic associations. Although challenges of sample size, both recognized and unrecognized phenotypic heterogeneity, and the paucity of early ARDS lung tissue limit some applications of the rapidly evolving field of genomic investigation, ongoing genetic research offers unique contributions to elucidating ARDS pathogenesis and the paradigm of precision ARDS medicine.
INTER-COLLaborative HEPatitis C: real-world treatment of hepatitis C patients by non-expert specialist providers in small and medium size Portuguese hospitals
Authors: J. Ramos, R. Silva, J. Firmino-Machado, P. Carrola, A. Moutinho, S. Carvalho, S. Tavares, C. Oliveira, D. Coutinho, S. Nunes, J. Velez, F. Freitas, F. Campante, A. Formigo, A. Cardoso, L. Tavares, C. Vieira, M. Sousa, R. Valente, J. Nunes, A. Loba, A. Pinto, R. Corga, J. Andrade, I. Cotrim, C. Martins, P. Marcos, S. Barbeiro, C. Monteverde, P. Fortes, M.J. Banza, D. Moura, F. Alçada, C. Pinto, A. Gonçalves, L. Carvalho, A. Banhudo, L.C. Matos, I. Pinho
Journal: Journal of Hepatology (2017)