tbuckley/cabot-search huggingface dataset:
Are Patients in Favour of General Health Screening?
Authors: J A Levine
Journal: Journal of the Royal Society of Medicine (1991)

In order to determine whether patients are in favour of general health screening, two sex-matched groups of patients of similar age from a general practice were studied; a group of 315 consecutive patients who attended the practice and 93 individuals who had not attended the practice for at least 12 months were studied. Individuals in both groups were provided with a short, anonymous questionnaire about their desire for general health screening. Although roughly equal proportions of the attenders (93%) and non-attenders (88%) indicated that general health screening was a 'good idea', a significantly greater proportion of the attenders (83%) indicated that they would make an appointment and attend the practice for health screening compared to the non-attenders (66%) (P less than 0.002). Similarly, a significantly greater proportion of the attenders (33%) indicated that they would seek general health screening, even if not contacted by their doctor, when compared with the non-attenders (16%) (P less than 0.001). Thus patients in this study were greatly in favour of general health screening. However, patients who attended the general practice infrequently may represent a population who are relatively resistant to health screening.
Real-Time Visualization of Left Lung Consolidation Relief Using Lung Ultrasound
Authors: Maxime Nguyen, Salima Benkhadra, Christophe Douguet, Bélaïd Bouhemad
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Lung ultrasound (LUS) is increasingly used at the bedside by intensivists for evaluation of cardiopulmonary failure. It allows rapid and reliable diagnosis of lung consolidation, pleural effusion, or interstitial–alveolar syndrome (1). Thus, any therapeutic maneuvers that effectively increase lung aeration can be seen in real time using LUS. To simplify, four LUS patterns (Figure 1), corresponding to increasing loss of aeration, can be used to monitor lung aeration semiquantitatively: (1) presence of horizontal artifact A-lines beyond the pleural line characterizes normal pulmonary aeration, (2) presence of multiple and well-separated vertical B-lines corresponds to moderate decrease in lung aeration resulting from interstitial syndrome, (3) presence of coa-lescent B-lines corresponds to a more severe decrease in lung aeration resulting from partial filling of alveolar spaces, and (4) presence of lung consolidation corresponds to complete loss of aeration with persisting aeration of distal bronchioles (dynamic bronchograms) (2). Figure 1. Lung ultrasound patterns corresponding to progressive loss of aeration. (A) Normal pattern. The pleural line (thick arrow) can be seen with multiple horizontal A-lines (thin arrow). (B) The pleural line is visible (arrow) with separated B-lines (*) arising from the pleural line and spreading down to the edge of the screen. This pattern corresponds to moderate lung aeration loss resulting from interstitial syndrome. (C) The pleural line is visible (arrow) with coalescent B-lines (between circles) arising therefrom. This pattern results from partial filling of alveolar spaces by pulmonary edema. (D) Transverse view of a consolidated lower lobe. The lung has a tissue-like echotexture (L). Hyperechoic images (*) can be seen within the consolidation corresponding to dynamic air bronchograms (air-filled bronchi). Ple = pleural effusion.
Long-Lasting Complete Responses in Patients with Metastatic Melanoma after Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes and an Attenuated IL2 Regimen
Authors: Rikke Andersen, Marco Donia, Eva Ellebaek, Troels Holz Borch, Per Kongsted, Trine Zeeberg Iversen, Lisbet Rosenkrantz Hölmich, Helle Westergren Hendel, Özcan Met, Mads Hald Andersen, Per thor Straten, Inge Marie Svane
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Adoptive cell transfer therapy (ACT) based on autologous tumor-infiltrating lymphocytes (TIL) has achieved impressive clinical results in several phase I and II trials performed outside of Europe. Although transient, the toxicities associated with high-dose (HD) bolus IL2 classically administered together with TILs are severe. To further scrutinize whether similar results can be achieved with lower doses of IL2, we have carried out a phase I/II trial of TIL transfer after classical lymphodepleting chemotherapy followed by an attenuated IL2 regimen. Experimental Design: Twenty-five patients with progressive treatment-refractory metastatic melanoma, good clinical performance, age &amp;lt; 70 years, and at least one resectable metastasis were eligible. TIL infusion was preceded by standard lymphodepleting chemotherapy and followed by attenuated doses of IL2 administered in an intravenous, continuous decrescendo regimen (ClinicalTrials.gov Identifier: NCT00937625). Results: Classical IL2-related toxicities were observed but patients were manageable in a general oncology ward without the need for intervention from the intensive care unit. RECIST 1.0 evaluation displayed three complete responses and seven partial responses (ORR 42%). Median overall survival was 21.8 months. Tumor regression was associated with a higher absolute number of infused tumor-reactive T cells. Moreover, induction and persistence of antimelanoma T-cell responses in the peripheral blood was strongly correlated to clinical response to treatment. Conclusions: TIL-ACT with a reduced IL2 decrescendo regimen results in long-lasting complete responses in patients with treatment-refractory melanoma. Larger randomized trials are needed to elucidate whether clinical efficacy is comparable with TIL-ACT followed by HD bolus IL2. Clin Cancer Res; 22(15); 3734–45. ©2016 AACR.
A novel in situ hydrophobic ion pairing (HIP) formulation strategy for clinical product selection of a nanoparticle drug delivery system
Authors: Young Ho Song, Eyoung Shin, Hong Wang, Jim Nolan, Susan Low, Donald Parsons, Stephen Zale, Susan Ashton, Marianne Ashford, Mir Ali, Daniel Thrasher, Nicholas Boylan, Greg Troiano
Journal: Journal of Controlled Release (2016)
M24 Prevalence of anxiety and patient characteristics from a randomised controlled trial (RCT) to identify if cognitive behavioural therapy (CBT) by respiratory nurses reduces anxiety in COPD: Abstract M24 Table 1
Authors: K Heslop-Marshall, C Baker, D Carrick-Sen, SC Stenton, J Newton, GP Burns, A De Soyza
Journal: Thorax (2015)

<h3>Introduction</h3> Anxiety and depression are common co-morbidities in COPD. Anxiety is associated with increased breathlessness, lower levels of self-efficacy, impaired health status, poorer treatment outcomes and reduced survival, increased risk of hospitalisation, longer in-patient stay, readmissions and unhealthy behaviours such as smoking and lack of exercise. The aim of this abstract is to present prevalence data, engagement and baseline patient characteristics from the largest RCT on CBT in COPD. <h3>Study design</h3> A multicentre RCT with follow up at 3, 6 and 12 months (ISCRCTN55206395). Outcome measures include mean HADS-A (anxiety) and HADS-D (depression) score,<sup>1</sup> EuroQol -5D Questionnaire,<sup>2</sup> COPD Clinical Assessment Tool<sup>3</sup> and admission prevention at three, six and 12 months post intervention. <h3>Approach</h3> 1,518 patients were screened for symptoms of anxiety using the Hospital Anxiety and Depression Scale (HADS). Two thirds, 705 (59%) patients scored ≥8 for anxiety and were approached. <h3>Intervention</h3> Up to 6 CBT sessions provided by one of four respiratory nurses were offered. Self-help leaflets on anxiety and depression were provided as standard care. <h3>Usual care</h3> Self- help leaflets only. <h3>Results</h3> 42% of eligible patients consented to take part. Groups were well matched at baseline (Table 1) with no correlation between FEV1 and anxiety. A median of 4 CBT sessions (range 2–6) was delivered. Retention was high: 85% at 3 months and 72% at 6 months. <h3>Conclusion</h3> The prevalence of anxiety and depression is high in patients with COPD and screening is therefore recommended. Affected patients were willing to engage in CBT in this large study. Results from 3, 6 and 12 months data will be will be available in November 2015 and will be reported. Results will include the cost effectiveness of CBT in COPD delivered by respiratory nurses. <h3>Funding</h3> NIHR fellowship. <h3>References</h3> 1 Zigmond AS, Snaith RP. The hospital anxiety and depression scale.<i> Acta Psychiatr Scand</i>. 1983;<b>67</b>(6):361–370 2 EQ-5D. www.euroqol.org/about-eq5d/how-to-use-eq-5d.html. Accessed 11.4.2015 3 Jone PW, Harding G, Berry P, Wiklund I, Chen WH, Kline LN. Development and first validation of the COPD Assessment Test.<i> Eur Respir J</i>. 2009;<b>34</b>(3):648–654
Abstract 17811: Inhibition of Mitochondrial Fission and Cardioprotection: Does Activation of Necroptosis Play a Confounding Role?
Authors: Yi Dong, Vishnu V Undyala, Karin Przyklenk
Journal: Circulation (2014)

Background:  Emerging evidence suggests that ischemia-reperfusion-induced translocation of dynamin-related protein 1 (DRP1) to mitochondria, and subsequent fragmentation (i.e., fission) of mitochondria, contributes to myocyte death. However, recent data from our group revealed a complex temporal relationship between fission and cell fate: pretreatment with Mdivi-1 (specific DRP1 inhibitor) attenuated both apoptotic and total cell death, while ‘delayed’ treatment (at reoxygenation) attenuated apoptosis but  exacerbated  necrosis. There are reports that caspase inhibition can up-regulate an alternative, kinase-mediated form of cell death termed ‘necroptosis’. Accordingly, we propose that the paradox seen with ‘delayed’ Mdivi-1 treatment may be explained by Mdivi-1-triggered caspase inhibition and resultant activation of necroptosis.   Methods:  Cultured HL-1 cells underwent 2 hrs of hypoxia + reoxygenation (R) or a matched normoxic period. In Protocol 1, cells received: i) Mdivi-1 (50 μM) at 1 hr before hypoxia; ii) Mdivi-1 (50 μM) at R; or iii) vehicle. In Protocol 2, Necrostatin-1 (inhibitor of RIP1, a key kinase involved in necroptosis: 50 μM) + Mdivi-1 were co-administered at R, while, in Protocol 3, Necrostatin-1 alone was given at R. Endpoints included expression of cleaved caspase 3 (harbinger of apoptosis), and cell viability (by trypan blue staining).   Results:  We confirmed that Mdivi-1attenuated caspase 3 cleavage irrespective of the timing of treatment (Fig A: left), but decreased (rather than increased) cell viability when given at R (Fig A: right). Necrostatin-1 partially rescued the exacerbated cell death seen with ‘delayed’ Mdivi-1 treatment (Fig B), but had no effect when given alone (Fig C).   Conclusion:  These data: i) suggest that Mdivi-1, given at reoxygenation, exacerbates myocyte death by up-regulation of necroptosis; and ii) underscore the complex temporal interplay between inhibition of mitochondrial fission and myocyte viability.
Equal access to innovative therapies and precision cancer care
Authors: Agnès Buzyn, Jean-Yves Blay, Natalie Hoog-Labouret, Marta Jimenez, Frédérique Nowak, Marie-Cécile Le Deley, David Pérol, Christian Cailliot, Jacques Raynaud, Gilles Vassal
Journal: Nature Reviews Clinical Oncology (2016)
Clonal Expansion of β-T Lymphocytes With Inverted Jβ1 Bias in Familial Hemophagocytic Lymphohistiocytosis
Authors: Mitsuyuki Nagano, Nobuhiro Kimura, Eiichi Ishii, Nobuyuki Yoshida, Tetsuya Yoshida, Masahiro Sako, Shigeyoshi Hibi, Shinsaku Imashuku, Sumio Miyazaki, Toshiro Hara, Shuki Mizutani
Journal: Blood (1999)
Exploratory analysis of safety by histology and efficacy in a nonsquamous NSCLC subgroup in REVEL: A randomized phase III study of ramucirumab (RAM) plus docetaxel (DOC) vs DOC for second-line treatment of stage IV non-small-cell lung cancer (NSCLC).
Authors: Luis Paz-Ares, Maurice Perol, Tudor-Eliade Ciuleanu, Ruben Dario Kowalyszyn, Martin Reck, Conrad R. Lewanski, Konstantinos N. Syrigos, Oscar Arrieta, Kumar Prabhash, Keunchil Park, Joanna Pikiel, Tuncay Göksel, Pablo Sang Lee, Annamaria Zimmerman, Joseph Treat, David Ferry, Allen S. Melemed, Gebra Cuyun Carter, Ekaterine Alexandris, Edward B. Garon
Journal: Journal of Clinical Oncology (2015)

8055 Background: REVEL, a study inclusive of nonsquamous (NSQ) and squamous (SQ) NSCLC, led to FDA approval of second-line RAM+DOC for patients (pts) with metastatic NSCLC based on improved survival. Neutropenia, febrile neutropenia, gastrointestinal and pulmonary hemorrhage events were similar across histologies. Additional outcomes are presented. Methods: A total of 1,253 pts with SQ or NSQ NSCLC received DOC (75 mg/m2) plus RAM (10 mg/kg; N = 628) or placebo (N = 625) after disease progression on platinum-based therapy (NCT01168973). Endpoints evaluated in specified histologic subgroups were OS, PFS, response rates, safety, and QoL. OS and PFS were analyzed using Kaplan-Meier (KM) method and Cox proportional hazard model. Response was compared using the Cochran-Mantel-Haenszel test. The primary QoL analysis was time to deterioration (TtD) of the Lung Cancer Symptom scale (LCSS) using the KM method. Results: Of the 73% (N = 912) of NSQ tumors, the majority were adenocarcinoma (79%; N = 725). Efficacy outcomes for pts with adenocarcinoma were similar to the NSQ population (see table). Incidences of pts with ≥ 1 treatment-emergent adverse event (TEAE), ≥ 1 serious adverse event, TEAEs grade ≥ 3, and TEAEs leading to dose adjustment or discontinuation were similar between treatment arms and across NSQ and SQ histologies. The TtD for total LCSS score was similar between treatment arms in NSQ and SQ subgroups. Conclusions: REVEL demonstrated an acceptable benefit/risk profile for RAM+DOC, with favorable efficacy and manageable safety outcomes seen across the major histologic subtypes of NSCLC. Clinical trial information: NCT01168973. NSQ ITT NSQ Adenocarcinoma RAM+DOC (N = 465) PBO+DOC (N = 447) HR (95% CI) RAM+DOC (N = 377) PBO+DOC (N = 348) HR (95% CI) Median OS, mos 11.1 9.7 0.83 (0.71, 0.97) 11.2 9.8 0.83 (0.69, 0.99) Median PFS, mos 4.6 3.7 0.77 (0.67, 0.88) 4.5 3.9 0.75 (0.64, 0.88) DCR (CR+PR+SD), % 66 55 65 56 ORR (CR+PR), % 22 15 19 15 CR = complete response; DCR = disease control rate; HR = hazard ratio; ITT = intent-to-treat; ORR = overall response; PBO = placebo; PR = partial response; SD = stable disease.
Abstract 19686: Nox4-Dependent Increase in Mitochondrial Reactive Oxygen Species Levels Contributes to Aging-Associated Increase in Cardiovascular Disease
Authors: Aleksandr E Vendrov, Nageswara R Madamanchi, Marschall S Runge
Journal: Circulation (2012)

The incidence of cardiovascular diseases (CVD) increases with age. Elevated ROS levels and resulting vascular inflammation were implicated in this process. We previously reported that inhibition of Nox1/Nox2 NADPH oxidases in p47phox deficient apoE-/- mice was not sufficient to reduce aging-associated increase in vascular reactive oxygen species (ROS) levels and atherosclerosis, aortic stiffness and cardiac dysfunction. This loss of protection is associated with increased total as well as mitochondrial ROS (mtROS) levels in the vasculature of aged apoE-/- and apoE-/-/p47phox-/- mice. Here we investigated the mechanisms and impact of aging-associated increase in oxidative stress in mouse and human CVD. Vascular smooth muscle cells (VSMC) isolated from aged wild-type and p47phox-/- mice had higher total and mtROS levels compared to VSMC from respective young mice (p&lt;0.01 for both total and mtROS). Nox4 expression was increased in the aortic wall of aged apoE-/- and apoE-/-/p47phox-/- mice and in mitochondria of VSMC from both aged mice (p&lt;0.05). Nox4 knockdown with shRNA resulted in decreased mtROS levels in aged wild-type VSMC (p&lt;0.05). Increased oxidation and dysfunction of mitochondrial proteins were observed in VSMC from aged mice. Vcam1 expression, which was increased in the aged VSMC was abrogated on treatment with MitoTEMPO, a mitochondria targeted antioxidant (p&lt;0.05). Increased mtROS levels in aortic VSMC from aged subjects were associated with enhanced mitochondrial Nox4 expression. Expression of Nox4 in the human carotid artery wall correlated with subjects’ age (r2 = 0.59, p&lt;0.0001) and atherosclerotic lesion complexity (p&lt; 0.0001). In addition, a significant association was observed between mitochondrial DNA damage index and CVD (r=0.45, p=0.013). In conclusion, Nox4-dependent increase in mitochondrial oxidative stress may contribute to mitochondrial DNA damage, mitochondrial dysfunction, vascular inflammation and increased incidence of CVD in aging, suggesting that selective targeting of mtROS in aging is beneficial.
So-Called C Marker Chromosome and Epstein-Barr Virus
Authors: J. Whang-Peng, P. Gerber, T. Knutsen
Journal: JNCI Journal of the National Cancer Institute (1970)

Detailed cytogenetic studies were performed on cell lines AV1 and NC37, which were purposely infected with Epstein-Barr virus (EBV), and on lines P3-HR1K and NHDL8, which originally contained the EBV although one had a negligible amount. Particular emphasis was placed on the presence of gaps and secondary constrictions. In each cell line the incidence of gaps and secondary constrictions increased as the total number of chromosomal aberrations increased. Only 1–2% of the cells in lines with 20–90% EBV-infected cells had the so-called C marker chromosome and there was no evidence that this abnormality was related to EBV. We believe the C marker chromosome aberration is not a true secondary constriction but a random gap or break that could have been caused by a nonspecific viral infection.
Promising the Moon!
Authors: Margaret Tempero
Journal: Journal of the National Comprehensive Cancer Network (2016)

Dr. Tempero is a Professor of Medicine and Director of the UCSF Pancreas Center, and the editorin-chief of JNCCN. Her research career has focused on pancreatic ductal adenocarcinoma, especially in the area of investigational therapeutics. Dr. Tempero has served on the ASCO Board of Directors and as ASCO President. She co-directed the AACR/ASCO Methods in Clinical Cancer Research and taught this course and similar courses in Europe and Australia. She was founding Chair of the NCI Clinical Oncology Study Section (CONC) and served as a member and chair of the NCI Board of Scientific Counselors Subcommittee A. She is on the External Advisory Boards of the Pancreas SPOREs at Mayo Clinic and at UAB/Minnesota and the GI SPORE at the University of Arizona. She is, or has been, on the Scientific Advisory Boards of the Lustgarten Foundation, the Pancreatic Cancer Action Network, the V Foundation, The Alberta Canada Cancer Board, and the EORTC. She served as a member of the Oncology Drug Advisory Committee for the FDA. She has served as Deputy Director and Interim Director for the UNMC Eppley Cancer Center. She is Chief Emeritus of the Division of Medical Oncology at UCSF and served as Deputy Director and Director of Research Programs at the UCSF Helen Diller Family Comprehensive Cancer Center. Promising the Moon!
A multicenter randomized study of adjuvant heat-shock protein peptide-complex 96 (HSPPC-96) vaccine in patients with high-risk of recurrence after nephrectomy for renal cell carcinoma (RCC)-a preliminary report
Authors: C. G. Wood, B. Escudier, S. Gorelov, K. Krajka, L. Lacombe, S. Fossa, A. Hoos, R. Flanigan, R. Figlin, P. Srivastava
Journal: Journal of Clinical Oncology (2004)

2618 Background: HSPPC-96 is an autologous, polyvalent vaccine produced from resected cancer tissue. This trial investigates the use of HSPPC-96 versus observation in patients with RCC at high-risk for recurrence after nephrectomy. Methods: Eligible patients have AJCC (1997) stage I/II (clinical tumor size ≥5cm; Fuhrman grade 3/4), stage III, or stage IV (non-metastatic) RCC, ECOG score 0 or 1, clear cell carcinoma (≥25%), and ≥7g of viable tumor tissue for vaccine production. Randomized and eligible patients receive HSPPC-96 intradermally once weekly x4 and in 2-week intervals thereafter or are followed by observation. Endpoints are recurrence-free survival and overall survival. Follow-up occurs in 3-month intervals for the first year and in 6-month intervals for the 2nd and 3rd years. Results: 132 medical centers in North America, Western and Eastern Europe are accruing patients with a randomization rate of 20–50 per month. In September 2003, 1491 patients were screened and 644 patients were randomized (43%). Frequent reasons for ineligibility among 847 patients (57%) were T1/2 tumors with grade 1/2, RCC with ≤25% clear cells or other histology, or evidence of metastases. Randomized patients: 63% male and 37% female; median age of 59 years (28–86); Fuhrman grade was low (1/2) in 33% and high (3/4) in 67%, while 11% were pT1, 25% pT2, 13% pT3unspecified, 27% pT3a, 22% pT3b, 2% pT3c or pT4 (non-metastatic) and 92% were pN0 and 8% pN+; vaccine could be produced for 92% and median number of vaccinations was 10 (1–39). Conclusion: This trial represents the largest randomized study to date in this adjuvant setting. Accrual is rapid and vaccine production rate is high. Patient accrual continues and updated information will be available upon presentation. No significant financial relationships to disclose.
Factors predicting survival in amyotrophic lateral sclerosis patients on non-invasive ventilation
Authors: Núria González, Enric Prats, Esther Giro, Lluis Mateu, Jordi Dorca, Eva Farrero
Journal: European Respiratory Journal (2013)

AIM: to determine prognostic factors of survival in patients with amyotrophic lateral sclerosis (ALS) who initiated non-invasive ventilation (NIV).  METHODS: retrospective analysis (1999-2012). We included all patients with diagnosis of ALS treated with NIV. Data were collected at initiation of NIV. Variables collected included: sex, age, site of disease onset, time from first symptoms to diagnosis, time from diagnosis to NIV, Forced Vital Capacity percentage (FVC%), PaO2, PaCO2, bulbar involvement at initiation of NIV, NIV compliance. We determined the median survival from initiation of NIV and factors predicting survival. Statistical analysis was performed using the Kaplan-Meier test and Cox proportional hazard models.  RESULTS: 175 patients were included; 60% men, age 64 (9) years. 72% of the cases the disease onset was limb. PaO2 76.73 (12) mmHg, PaCO2 45.9 (9) mmHg, FVC 52.9% (16), mean NIV compliance 9.6 h/day. Mean time form first symptoms to diagnosis 11.7 months. 34% of patients had a moderate-severe bulbar involvement at initiation of NIV. Median survival was 14.9 months (mean 19.5 months). In univariate analysis variables associated with survival were delay in diagnosis (HR 0.977, p 0.018), bulbar involvement at initiation of NIV (HR 1.92, p 0.000) and FVC% (HR 0.987, p0.048). Site of onset tended to be associated with survival, without reaching the statistical significance. In multivariate analysis the only covariate that had significant independent prognostic value was bulbar involvement (HR 1.78, p 0.0004).  CONCLUSIONS: In our study moderate-severe bulbar involvement at initiation of NIV was the main prognostic factor independent for survival in ALS patients after NIV.