tbuckley/cabot-search huggingface dataset:
Association of PD-L2 expression in human tumors with atezolizumab activity.
Authors: Peter Schmid, Priti S. Hegde, Wei Zou, Marcin Kowanetz, Sanjeev Mariathasan, Luciana Molinero, Shirish M. Gadgeel, Thomas Powles, Michiel Simon Van Der Heijden, Marcella Fasso, Carol O'Hear, Marcus Ballinger, Gregg Daniel Fine, Alan Sandler, Daniel S. Chen, F. Stephen Hodi
Journal: Journal of Clinical Oncology (2016)

11506 Background: Atezolizumab (atezo, MPDL3280A) is a humanized IgG1 mAb that prevents the interaction of the ligand PD-L1 with PD-1 and B7.1 and can reinvigorate anticancer T-cell responses. Atezo does not inhibit the interaction of an alternative ligand PD-L2 with PD-1. PD-L2 is associated with Th2 immune responses but its role in anticancer immunity is unclear. Here we characterize the association between these ligands and patient (pt) outcome following atezo treatment across tumor types. Methods: Expression of PD-L1 and PD-L2 transcripts in tumor specimens from pts before starting atezo treatment was assessed using Fluidigm platform or RNAseq. Pts from PCD4989g (melanoma, n = 38; RCC, n = 59), POPLAR (NSCLC, n = 112) and cohort 2 of IMvigor210 (urothelial carcinoma [UC], n = 251) trials were included in the analysis. Results: A close Spearman correlation was observed for PD-L1 and PD-L2 transcripts in melanoma (0.8), UC (0.77), NSCLC (0.74) but less so in RCC (0.43). Overall survival HRs and odds ratios (ORs) of being a responder using the median expression of PD-L1 and PD-L2 across 4 cancer types are listed (Table). High expression of either ligand in these tumors was associated with improved OS benefit to atezo treatment. Neither ligand had an association with OS benefit of docetaxel (doc) in NSCLC pts. OS HR of PD-L2 high in the randomized trial (POPLAR) of atezo vs doc was 0.50 (95% CI: 0.31-0.83), favoring atezo. Conclusions: Clinical outcomes in 4 distinct cancer types showed that high expression of PD-L2 was associated with improved benefit of atezo therapy.These data show that blocking the PD-L1:PD-1 and PD-L2:B7.1 axes but not PD-L2: PD-1 axis is highly efficacious in PD-L2 high pts. Further evidence is required to understand the role of PD-L2 in cancer. Clinical efficacy of atezo monotherapy. N PD-L1 PD-L2 Events/N OS HRa 95% CI ORb Events/N OS HRa 95% CI ORb BM high BM low BM high BM low Melanoma 38 8/19 11/19 0.52 0.21-1.29 2.19 7/19 12/19 0.28 0.11-0.72 3.88 RCC 59 13/30 17/29 0.62 0.3-1.28 2.7 12/30 18/29 0.5 0.24-1.06 7 UC 251 73/126 83/125 0.76 0.55-1.04 1.9 72/126 84/125 0.73 0.54-1.01 2.13 NSCLC 112 27/56 34/56 0.72 0.44-1.2 3.18 26/56 35/56 0.61 0.37-1.02 3.18 BM, biomarker aBM high vs low bOdds ratio for response, including CR and PR per RECIST v1.1.
Pharmacokinetic (pk) guide for dose adjustments in cancer patients (pts) treated with 5-fluoruracil (5-fu) infusions. Preliminary results
Authors: M. S. Gonzalez, J. Rebollo, V. Escudero, B. Valenzuela, R. Nalda, M. Duart, A. Brugarolas
Journal: Journal of Clinical Oncology (2008)

13550 Background: 5-FU efficacy and toxicity depends on steady-state 5-FU plasma concentration (ss[5-FU]) and AUC 5-FU concentration-time curve. However a wide interindividual variability of plasma 5-FU levels can be found. Methods: A PK guide for 5-FU infusions-dose adjustments have been initiated since June’07. Plasma samples have been collected at multiple time points from 60 to 150 minutes after 5-FU initiation and have been analyzed by HLPC. Individual PK parameters were calculated using a Bayesian algorithm which included a population-based PK model previously published. Dose adjustments were done in subsequent cycles (if clinically allowed) to achieve a target ss[5-FU] of 0.31–0.83 ug/ml. Results: Forty seven cycles (median 3, range 2–6) in 12 consecutive pts (M age 61 y, r 40–84 y) treated with 24-hrs 2.6 gr/m2 5-FU infusions have been monitored. Two pts required a 10% and 3 pts a 5% increase in the 5-FU dose in the second cycle. One pt had a 10% decrease in the dose because of toxicity with a PK recommendation of no modification. Mean (±SD) ss[5-FU] in the first two cycles have been 0.44 (0.18) ug/ml and 0.49 (0.18) ug/ml, respectively. ss[5-FU] increased 33.05% in the 5 pts with a dose increment to obtain a Mean (±SD) ss[5-FU] of 0.49(0.10) ug/ml without an additional toxicity, and decreased 38.14% in 6 pts without dose modification. Conclusions: Five out of 12 pts required a 5–10% 5-FU dose increment in the first cycle according to PK recommendations with no added toxicity with this regimen. Intrapatient variability in ss[5-FU] observed in 6 pts without dose modifications suggests that PK monitoring must be done in subsequent cycles for further dose adjustments to achieve the optimal ss[5- FU]. No significant financial relationships to disclose.
Case 16-1973
Authors: Richard C. Cabot, Benjamin Castleman, Robert E. Scully, Betty U. McNeely, Aubrey Leatham, Bruce D. Ragsdale
Journal: New England Journal of Medicine (1973)

Presentation of CaseA 71-year-old woman was admitted to the hospital because of chest pain.She was known to have a heart murmur since birth and for many years had complained of dyspnea, with sighing, sharp substernal pain and palpitation. Periodic examinations by a cardiologist had revealed a loud pulmonic systolic murmur, right ventricular hypertrophy and aneurysmal dilatation of the pulmonary artery. She had refused the repeated recommendation that she undergo cardiac catheterization and consideration of surgical repair. Three months before admission she began to experience "weariness" in the legs and arms and a mild "pulling" sensation in the left . . .
The thoracic oncology specialist: curriculum recommendations in thoracic oncology training
Authors: Anne-Pascale Meert, Julie-Lyn Noël, Fernando Gamarra
Journal: European Respiratory Journal (2016)

The power of one, if fearless and focused, is formidable, but the power of many working together is better. HERMES proposes a detailed, interprofessional and multidisciplinary curriculum for training in thoracic oncology <http://ow.ly/H1A9301jVpx> The members of the Thoracic Oncology HERMES Task Force are Alessandro Brunelli (Dept of Thoracic Surgery, St James's University Hospital, Leeds, UK), Anne-Marie C. Dingemans (Maastricht University Medical Centre, Pulmonology, Maastricht, the Netherlands), Enriqueta Felip (Hospital Univer. Vall d'Hebron, Barcelona, Spain), Mina Gaga (Athens Chest Hospital, 7th Respiratory Medicine Dept, Athens, Greece), Bogdan Dragos Grigoriu (University of Medicine and Pharmacy Iasi, Regional Institute of Oncology Iasi, Iasi, Romania), Georgia Hardavella (Dept of Respiratory Medicine, King's College Hospital, and Dept of Thoracic Medicine, University College London, London, UK), Rudolf M. Huber (Division of Respiratory Medicine and Thoracic Oncology, University of Munich, and Thoracic Oncology Centre Munich, Member of the German Centre for Lung Research (DZL CPC-M), Munich, Germany), Samuel Janes (University College London, Centre for Respiratory Research, London, UK), Gilbert Massard (Dept of Thoracic Surgery, Hôpitaux Universitaires de Strasbourg, Strasbourg, France), Paul Martin Putora (Kantonsspital St Gallen, Dept of Radiation Oncology, St Gallen, Switzerland), Jean-Paul Sculier (Institut Jules Bordet, Intensive Care and Thoracic Oncology (ULB), Brussels, Belgium), Philipp A. Schnabel (Institut für Allgemeine und spezielle Pathologie, Universität des Saarlandes, Homburg/Saar, Germany), Sara Ramella (Campus Bio-Medico University, Radiation Oncology, Rome, Italy) and Dirk Van Raemdonck (Dept of Thoracic Surgery, University Hospital Leuven, Leuven, Belgium).
Effects of vandetanib on body composition in patients with advanced medullary thyroid carcinomas: Results from a placebo-controlled study.
Authors: Marie-Helene Massicotte, Isabelle Borget, Sophie Leboulleux, Eric Baudin, Vickie E. Baracos, Merad Mansouriah, Martin Schlumberger, Sami Antoun
Journal: Journal of Clinical Oncology (2012)

5569 Background: Muscle (MT) and adipose tissue (AT) share common intra cellular pathways with tumor, thus it is not surprising to observe metabolic consequences with targeted therapies. The aim of the study was to assess the effects of vandetanib, a tyrosine kinase inhibitor (TKI) which demonstrated efficacy for the treatment of advanced medullary thyroid carcinoma (MTC), on MT and AT. Methods: 33 patients (25 men and 8 women, mean age of 54 years) with metastatic MTC received vandetanib 300 mg/d (n=23) or placebo (n=10) in the setting of the ZETA study. Cross-sectional areas (cm 2 ) of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and MT were assessed by computed tomography imaging at 3rd lumbar vertebra and were indexed for height (cm 2 /m 2 ). Comparisons between treatment and placebo were made at 3 months, and long-term evolution was evaluated over 12 months. Results: At 3 months, compared to baseline, patients treated with vandetanib gained 1.5 kg, 1.3 cm 2 /m 2 of MT, 5.1 cm 2 /m 2 of VAT and 4.5 cm 2 /m 2 of SAT. In contrast, patients under placebo lost 1.5 kg (p=0.02), 1.0 cm 2 /m 2 of MT (p=0.009), 5.5 cm 2 /m 2 of SAT (p=0.004) and gained significantly less VAT (0.6 cm 2 /m 2 ) (p=0.02). At 12 months, compared to baseline, patients treated with vandetanib gained 2 kg (NS), lost 0.3 cm 2 /m 2 MT (NS), gained 3.4 cm 2 /m 2 of VAT (NS) and 8.7 cm 2 /m 2 of SAT (95% CI, 1.1 to 16.2). A significant decrease of calcitonin (defined as ≤50% compared to baseline) was associated with higher weight (p=0.01), VAT (p=0.01), and total adipose tissue (p=0.02). Conclusions: Beyond its proved efficacy in MTC treatment, and despite common intracellular pathways, vandetanib is the only studied TKI to preserve MT and to restore AT. Further research is needed to explore whether the relationship between changes of VAT and vandetanib treatment results from a direct metabolic action of vandetanib or is a consequence of biochemical tumor control.
A Phase 2 Open-Label Safety and Tolerability Study of Single Intravenous (IV) Escalating Doses of 90 Yttrium-Labeled Antiferritin Antibodies (90 Y-Antiferritin) in Patients with Relapsed or Refractory Hodgkin Lymphoma
Authors: Didier Decaudin, Alain Pecking, François Lokiec, Jean Kadouche, Stephane E. Allard
Journal: Blood (2014)
Evolution of Spitz naevi: a dermoscopic and confocal follow-up of 26 cases
Authors: C. Ferrari, C. Longo, I. Stanganelli, S. Magi, L. Mazzoni, G. Pellacani, G. Argenziano, S. Ribero, E. Moscarella
Journal: British Journal of Dermatology (2016)

A conservative management of Spitz nevi (SN) in children is currently adopted by many pediatric dermatologists in case of flat to slightly palpable lesions, clinically and dermoscopically diagnosed as SN (1-5). The aim of the current study was to analyze the dermoscopic and reflectance confocal microscopy (RCM) in vivo changes observed over time, during the sequential follow up of a series of SN.

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Mortality in HIV-infected women, heterosexual men, and men who have sex with men in Rio de Janeiro, Brazil: an observational cohort study
Authors: Lara Coelho, Beatriz Grinsztejn, Jessica L Castilho, Raquel De Boni, Marcel S B Quintana, Dayse P Campos, Sayonara R Ribeiro, Antonio G Pacheco, Valdilea G Veloso, Paula M Luz
Journal: The Lancet HIV (2016)
Only minor differences in renal osteodystrophy features between wild-type and sclerostin knockout mice with chronic kidney disease
Authors: Daniel Cejka, Diego Parada-Rodriguez, Stefanie Pichler, Rodrig Marculescu, Ina Kramer, Michaela Kneissel, Thomas Gross, Andreas Reisinger, Dieter Pahr, Marie-Claude Monier-Faugere, Martin Haas, Hartmut H. Malluche
Journal: Kidney International (2016)
Phase II Investigator-Initiated Study of Brentuximab Vedotin in Mycosis Fungoides or Sezary Syndrome: Final Results Show Significant Clinical Activity and Suggest Correlation with CD30 Expression
Authors: Youn H. Kim, Mahkam Tavallaee, Sima Rozati, Uma Sundram, Katrin Salva, Gary S. Wood, Shufeng Li, Michael Krathen, Seema Nagpal, Sunil Reddy, Randall Armstrong, Richard T. Hoppe, Melissa Pulitzer, Ranjana H Advani, Steven M. Horwitz
Journal: Blood (2014)
Cytomegalovirus Infection Is Associated with Expansions of CD8 T Cells and Highly Oligoclonal Vdelta1 Gamma/Delta T Cells in Patients Treated with Dasatinib for Chronic Myelogenous Leukaemia
Authors: David Lewis, Guy Pratt, David A Price, Tessa Holyoake, Kristin Ladell, Heather Jorgensen, Annette Pachnio, Mike Griffiths, Charles Craddock, Paul Moss
Journal: Blood (2014)
Secondary Infection in Patients With Sepsis—Reply
Authors: Lonneke A. van Vught, Peter MC Klein Klouwenberg, Tom van der Poll
Journal: JAMA (2016)

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Imaging Microglial Activation in Untreated First-Episode Psychosis: A PET Study With [<sup>18</sup>F]FEPPA
Authors: Sina Hafizi, Huai-Hsuan Tseng, Naren Rao, Thiviya Selvanathan, Miran Kenk, Richard P. Bazinet, Ivonne Suridjan, Alan A. Wilson, Jeffrey H. Meyer, Gary Remington, Sylvain Houle, Pablo M. Rusjan, Romina Mizrahi
Journal: American Journal of Psychiatry (2016)

Objective: Neuroinflammation and abnormal immune responses are increasingly implicated in the pathophysiology of schizophrenia. Previous positron emission tomography (PET) studies targeting the translocator protein 18 kDa (TSPO) have been limited by high nonspecific binding of the first-generation radioligand, low-resolution scanners, small sample sizes, and psychotic patients being on antipsychotics or not being in the first episode of their illness. The present study uses the novel second-generation TSPO PET radioligand [18F]FEPPA to evaluate whether microglial activation is elevated in the dorsolateral prefrontal cortex and hippocampus of untreated patients with first-episode psychosis. Method: Nineteen untreated patients with first-episode psychosis (14 of them antipsychotic naive) and 20 healthy volunteers underwent a high-resolution [18F]FEPPA PET scan and MRI. Dynamic PET data were analyzed using the validated two-tissue compartment model with arterial plasma input function with total volume of distribution (VT) as outcome measure. All analyses were corrected for TSPO rs6971 polymorphism (which is implicated in differential binding affinity). Results: No significant differences were observed between patients and healthy volunteers in microglial activation, as indexed by [18F]FEPPA VT, in either the dorsolateral prefrontal cortex or the hippocampus. There were no significant correlations between [18F]FEPPA VT and duration of illness, clinical presentation, or neuropsychological measures after adjusting for multiple testing. Conclusions: The lack of significant differences in [18F]FEPPA VT between groups suggests that microglial activation is not present in first-episode psychosis.
Abstract 3391: Prevalence Of Hypertrophic Cardiomyopathy In Elite Athletes
Authors: Sandeep Basavarajaiah, Mathew Wilson, Agnes Chlebinska, Arash Yavari, Gordon Jackson, Gregory Whyte, Ajay Shah, Sanjay Sharma
Journal: Circulation (2007)

Objectives: The prevalence of HCM in the general population is estimated to be around 1 in 500. The exact prevalence of HCM in athletes has never been reported and has important implications with regards to potential future national pre-participation screening programme in countries such as United Kingdom, where currently there is no such programme for junior athletes. Methods: Between 1996 and 2006, 3500 asymptomatic and normotensive elite athletes (70% males) aged between 14–35 years (mean: 20.5±5.80) and a mean body surface area of 1.86±0.16 m 2 (range1.36–2.29) underwent 12-lead EKG and 2D-echocardiography. Cardiac dimensions and function were measured using conventional methods. Results: Of the 3500 athletes, 53 (2%) had maximal left ventricular wall thickness (LVWTd) &gt; 12 mm (mean: 13.6 ± 0.9, range: 13–16). All 53 were male athletes and all except 3 of them had associated dilated LV cavity (58.5 ± 5.14 mm, range 52– 65) implying physiological left ventricular hypertrophy (LVH). This was also supported by normal indices of diastolic function and absence of family history of HCM or sudden cardiac death (SCD). However, there were 3 athletes with LVWT &gt; 12mm who had a relatively non-dilated LV cavity (range:45– 46) and bizarre EKG changes (deep T-wave inversion) that that raised the suspicion of HCM. But none of them exhibited any other phenotypic feature of HCM on further testing with 48-hour EKG recording, cardiopulmonary exercise testing and assessment of their first-degree family members. Only one of the 3 athletes agreed to detrain for 12-weeks, which resulted in regression of LVH and complete resolution of EKG changes. Conclusion: In our study, only 3 athletes had echocardiographic findings that could have been consisted with the diagnosis of HCM but further investigations failed to support the diagnosis. These results indicate that the prevalence of HCM in highly trained athletes is extremely rare. The structural and functional changes associated with HCM precludes generation of large amounts of cardiac output that are required during exercise selecting out most of these individuals from competitive sports. Our findings also questions the validity of previous data which proposes that HCM is the commonest cause of exercise related SCD in young athletes.
Early invasive versus non-invasive treatment in patients with non-ST-elevation acute coronary syndrome (FRISC-II): 15 year follow-up of a prospective, randomised, multicentre study
Authors: Lars Wallentin, Lars Lindhagen, Elisabet Ärnström, Steen Husted, Magnus Janzon, Søren Paaske Johnsen, Frederic Kontny, Tibor Kempf, Lars-Åke Levin, Bertil Lindahl, Mats Stridsberg, Elisabeth Ståhle, Per Venge, Kai C Wollert, Eva Swahn, Bo Lagerqvist
Journal: The Lancet (2016)
Tumor response and patient survival after intralesional therapy with low-dose GM-CSF and IL-2 in metastatic and primary cutaneous melanoma: An exploratory study.
Authors: E. George Elias, Bhuvnesh K Sharma
Journal: Journal of Clinical Oncology (2014)

e20002 Background: Dermal and subdermal metastatic melanoma can give us an excellent opportunity to evaluate the local and systemic effects of intralesional therapy. While GM-CSF administration can activate and induce autologous dendretic cells (APCs), IL-2 administration can stimulate autologous T cells at the tumor site. Methods: Patients with derma and subdermal metastases, regardless to the extent of their disease or previous therapy, who consented to the study, each received intralesional GM-CSF 500 μg once/week for 4-6 weeks. If no complete clinical response (CR) was observed at the injection sites, intralesional IL-2 was substituted at 18 million IU weekly for the same length of time. One patient with primary invasive melanoma with a satellite lesion and regional lymph node (LN) metastasis, who remained a surgical candidate, received both cytokines at th skin lasions one week before surgery. Results: Four patients had > 126 small in-transit metastases, each lesion measuring few mm up to 1 cm. All had CR confirmed pathologically 6-8 weeks after cessation of therapy, with disease-free survival of 37-54 months. Another three patients with large sclerotic skin lesions failed to respond to either cytokine. One of two patients with distant metastases who had palpable subdermal tumors had CR of all metastases for 6 months. The resected tissues from the patient with primary melanoma with a satellite lesion revealed complete tumor necrosis at both injection sites with massive pigmented histiocytosis at the skin sites and in some LNs. Immunohistochemical studies showed overexpression of CD3+, CD4+, CD8+ and CD83+ cells at the primary site, the satellite and in some of the LNs. This patient is alive disease-free for over 48 months. Conclusions: Intralesional therapy seemed to utilize the tumor site as a source for tumor-specific antigens giving rise to autoimmunization with strong antitumor response regardless of tumor antigenic or genetic profiles. These observations open up new aspects for clinical trials to standardize the management of in-transit metastases and to initiate new approaches to adjuvant therapy in high-risk melanoma patients.
Intranasal flu vaccine provides similar protection to injected flu vaccine, finds study
Authors: Susan Mayor
Journal: BMJ (2016)

Intranasal live attenuated influenza vaccine achieves similar protection against infection with influenza in children, as well as similar herd immunity, as giving inactivated flu vaccine by injection, a randomised study has shown.1

The effectiveness of flu vaccines made headlines in June when the US Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices recommended against vaccinating children against flu in the 2016-17 flu season because, for the past three flu seasons, the inhaled …