tbuckley/cabot-search huggingface dataset:
Volume-controlled Ventilation Does Not Prevent Injurious Inflation during Spontaneous Effort
Authors: Takeshi Yoshida, Susumu Nakahashi, Maria Aparecida Miyuki Nakamura, Yukiko Koyama, Rollin Roldan, Vinicius Torsani, Roberta R. De Santis, Susimeire Gomes, Akinori Uchiyama, Marcelo B. P. Amato, Brian P. Kavanagh, Yuji Fujino
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Rationale: Spontaneous breathing during mechanical ventilation increases transpulmonary pressure and Vt, and worsens lung injury. Intuitively, controlling Vt and transpulmonary pressure might limit injury caused by added spontaneous effort.Objectives: To test the hypothesis that, during spontaneous effort in injured lungs, limitation of Vt and transpulmonary pressure by volume-controlled ventilation results in less injurious patterns of inflation.Methods: Dynamic computed tomography was used to determine patterns of regional inflation in rabbits with injured lungs during volume-controlled or pressure-controlled ventilation. Transpulmonary pressure was estimated by using esophageal balloon manometry [Pl(es)] with and without spontaneous effort. Local dependent lung stress was estimated as the swing (inspiratory change) in transpulmonary pressure measured by intrapleural manometry in dependent lung and was compared with the swing in Pl(es). Electrical impedance tomography was performed to evaluate the inflation pattern in a larger animal (pig) and in a patient with acute respiratory distress syndrome.Measurements and Main Results: Spontaneous breathing in injured lungs increased Pl(es) during pressure-controlled (but not volume-controlled) ventilation, but the pattern of dependent lung inflation was the same in both modes. In volume-controlled ventilation, spontaneous effort caused greater inflation and tidal recruitment of dorsal regions (greater than twofold) compared with during muscle paralysis, despite the same Vt and Pl(es). This was caused by higher local dependent lung stress (measured by intrapleural manometry). In injured lungs, esophageal manometry underestimated local dependent pleural pressure changes during spontaneous effort.Conclusions: Limitation of Vt and Pl(es) by volume-controlled ventilation could not eliminate harm caused by spontaneous breathing unless the level of spontaneous effort was lowered and local dependent lung stress was reduced.
Quality and Safety in Health Care, Part XXII
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2017)

Large databases from multiple sources have been highly useful in studying and improving the quality of health care in the United States. The American College of Surgeons National Surgical Quality Improvement Program, the Society of Vascular Surgery Vascular Quality Initiative and its component regional groups such as the Vascular Study Group of New England, and the National (Nationwide) Inpatient Sample are some of the sources of information that have been helpful to improve quality in vascular surgery.
PDTB-09. ORGANOTYPIC TUMOR SLICE CULTURE FOR EVALUATING TREATMENT OF MEDULLOBLASTOMA
Authors: James Felker, Abhinav Dey, Tobey MacDonald, Anna Kenney
Journal: Neuro-Oncology (2016)

Medulloblastoma (MB) is the most common malignant brain tumor of childhood. Current treatments leave the majority of survivors with long term cognitive impairment; thus, more effective tumor-targeting strategies are needed. Unfortunately, in vivo preclinical drug testing is cumbersome, time consuming, and relies on in vitro screens, which lack the tumor microenvironment. To counter these issues, we developed a new preclinical assay, organotypic ex vivo brain tumor slice culture, which retains the microenvironment, and thus we hypothesize will be a more robust predictive method for the evaluation of the efficacy and toxicity of specific tumor-targeting drug combinations. Our lab previously found STAT3 and Hippo (YAP/YB1) pathways to interact and be important to the survival of SHH-type MB cells. We therefore tested the STAT3 inhibitor (WP1066), YB1 inhibitor (Fisetin), and Shh pathway inhibitor (LDE225), as a single agent and in combination, in this assay to assess efficacy, toxicity, and to test for novel molecular interactions that may be amenable for future targeting. 300 µm sections of murine SmoA1 SHH MB were generated using a vibratome. Slices were placed on trans-well inserts, cultured, and treated with vehicle or increasing concentrations of LDE225, Fisetin, or WP1066, with or without radiation. Slices were immunostained for markers of cell death (cleaved caspase-3) and cancer stem-like cells (CD15). Samples were imaged by confocal microscopy, and staining quantified with ImageJ software. We observed a dose-dependent increase in cell death with WP1066, LDE225, and Fisetin (p<.01). Healthy brain tissues were not affected. WP1066 also increased CD15-positive tumor stem cell death when combined with radiation. In vivo validation studies of the ex-vivo assay results are ongoing. In conclusion, our ex vivo brain tumor slice culture method is a promising new assay for rapid preclinical testing of SHH MB-targeting drug combinations.
Comparative Genomic Hybridization, Gene Expression Profiling and Whole Genome Sequencing Analysis of Disease Progression in Myeloma Reveals Vigorous Clonal Evolution in Patients with High Baseline Genetic Risk.
Authors: Jan Egan, Jonathan J Keats, P. Leif Bergsagel, Rodger E. Tiedemann, John Carpten, A. Keith Stewart
Journal: Blood (2009)
Dysregulated ADAM10-Mediated Processing of APP during a Critical Time Window Leads to SynapticDeficits in Fragile X Syndrome
Authors: Emanuela Pasciuto, Tariq Ahmed, Tina Wahle, Fabrizio Gardoni, Laura D’Andrea, Laura Pacini, Sébastien Jacquemont, Flora Tassone, Detlef Balschun, Carlos G. Dotti, Zsuzsanna Callaerts-Vegh, Rudi D’Hooge, Ulrike C. Müller, Monica Di Luca, Bart De Strooper, Claudia Bagni
Journal: Neuron (2015)
Muscle Involvement of Multiple Myeloma Revealed by FDG PET/CT
Authors: Meng Liang, Minggang Su, Rang Wang, Weiya Wang, Chengzhong Fan
Journal: Clinical Nuclear Medicine (2017)

Extramedullary myeloma can occur in variety of organs; however, muscle involvement is rarely reported. Here we present a case of a multiple myeloma patient with muscle involvement found by 18F-FDG PET/CT, which is sensitive in detecting extramedullary lesions of multiple myeloma. Plasmacytoma was confirmed by pathological biopsy afterwards.
Dasatinib (BMS354825) Inhibits IgE-Dependent Activation and Histamine Release in Human Blood Basophils.
Authors: Michael Kneidinger, Peter Valent, Karoline V. Gleixner, Stefan Florian, Alexandra Boehm, Karoline Sonneck, Margit Weghofer, Christian Lupinek, Susanne Vrtala, Anja Vales, Rudolf Valenta, Giulio Superti-Furga, Francis Y. Lee
Journal: Blood (2006)
SANDPIPER: Phase III study of the PI3-kinase (PI3K) inhibitor taselisib (GDC-0032) plus fulvestrant in patients (pts) with oestrogen receptor (ER)-positive, HER2-negative locally advanced or metastatic breast cancer (BC) enriched for pts with PIK3CA-mutant tumours
Authors: J. Baselga, J. Cortes Castan, M. De Laurentiis, V. Dieras, N. Harbeck, J. Hsu, H. Jin, F. Schimmoller, T.R. Wilson, Y.-H. Im, W. Jacot, I.E. Krop, S. Verma
Journal: Annals of Oncology (2016)
Risk of heart failure after community acquired pneumonia: prospective controlled study with 10 years of follow-up
Authors: Dean T Eurich, Thomas J Marrie, Jasjeet K Minhas-Sandhu, Sumit R Majumdar
Journal: BMJ (2017)

Objective To determine the attributable risk of community acquired pneumonia on incidence of heart failure throughout the age range of affected patients and severity of the infection.Design Cohort study.Setting Six hospitals and seven emergency departments in Edmonton, Alberta, Canada, 2000-02.Participants 4988 adults with community acquired pneumonia and no history of heart failure were prospectively recruited and matched on age, sex, and setting of treatment (inpatient or outpatient) with up to five adults without pneumonia (controls) or prevalent heart failure (n=23 060).Main outcome measures Risk of hospital admission for incident heart failure or a combined endpoint of heart failure or death up to 2012, evaluated using multivariable Cox proportional hazards analyses.Results The average age of participants was 55 years, 2649 (53.1%) were men, and 63.4% were managed as outpatients. Over a median of 9.9 years (interquartile range 5.9-10.6), 11.9% (n=592) of patients with pneumonia had incident heart failure compared with 7.4% (n=1712) of controls (adjusted hazard ratio 1.61, 95% confidence interval 1.44 to 1.81). Patients with pneumonia aged 65 or less had the lowest absolute increase (but greatest relative risk) of heart failure compared with controls (4.8% v 2.2%; adjusted hazard ratio 1.98, 95% confidence interval 1.5 to 2.53), whereas patients with pneumonia aged more than 65 years had the highest absolute increase (but lowest relative risk) of heart failure (24.8% v 18.9%; adjusted hazard ratio 1.55, 1.36 to 1.77). Results were consistent in the short term (90 days) and intermediate term (one year) and whether patients were treated in hospital or as outpatients.Conclusion Our results show that community acquired pneumonia substantially increases the risk of heart failure across the age and severity range of cases. This should be considered when formulating post-discharge care plans and preventive strategies, and assessing downstream episodes of dyspnoea.
Genetic influence of EGFR-PI3K-mTOR pathway and other loci in triple-negative breast cancer
Authors: C. Cabrera, M.J. Arranz, M.L. Surralles Calnge, A. Salas, X. Tarroch, L. Ibañez, A. Garcia, S. Gonzalez Jimenez, M. Campayo, L. Cirera
Journal: Annals of Oncology (2016)
The role of preoperative breast magnetic resonance (MR) imaging for surgical decision in patients with triple-negative breast cancer
Authors: T.J. Kwon, H.Y. Park, J.H. Jung, W.W. Kim, S.O. Hwang, Y.S. Chae, S.J. Lee, J.-Y. Park, J.H. Chung, J. Lee
Journal: Annals of Oncology (2016)
STAT5-Regulated miRNA193b Controls Hematopoietic Stem and Progenitor Cell Expansion By Fine Tuning Cytokine Signaling
Authors: Nadine Haetscher, Yonatan D Feuermann, Susanne Wingert, Maike Rehage, Christian Weiser, Frederic B. Thalheimer, Hanibal Bohnenberger, Timm Schroeder, Hubert Serve, Thomas Oellerich, Lothar Hennighausen, Michael A. Rieger
Journal: Blood (2014)
Genomic Alterations in Hodgkin’s and Reed/Sternberg (HRS) Cells at Disease Onset Reveals Distinct Signatures for Chemosensitive and Primary Refractory Hodgkin’s Lymphoma.
Authors: Marilyn L. Slovak, Victoria Bedell, Dolores Bobadilla, Norma J Nowak, Maria L. Delioukina, Lawrence M. Weiss, David Smith, Stephen J. Forman
Journal: Blood (2008)
Role of the <i>HLA-C*06</i> allele in clinical response to ustekinumab: evidence from real life in a large cohort of European patients
Authors: M. Talamonti, M. Galluzzo, J.M. van den Reek, E.M. de Jong, J.L.W. Lambert, P. Malagoli, L. Bianchi, A. Costanzo
Journal: British Journal of Dermatology (2017)

Little is known about the role of the HLA‐C*06 allele in the response to psoriasis treatments. To confirm the role of HLA‐C*06 as a pharmacogenetic marker of response to ustekinumab in a new, large cohort of patients involving four European centres. In this retrospective multicentre study we reviewed data of 255 patients with psoriasis genotyped for HLA‐C*06 who started ustekinumab treatment between January 2014 and March 2015. The severity of psoriasis and response to treatment were evaluated using the Psoriasis Area and Severity Index (PASI) score at baseline and then at follow‐up visits on weeks 4, 12, 28, 40 and 52. The primary end point was the proportion of patients achieving ≥ 50% reduction in PASI score (PASI 50) at week 4. A ≥ 75% reduction in PASI score (PASI 75) and a ≥ 90% reduction in the PASI score (PASI 90) after 12 weeks were secondary end points. At week 4, PASI 50 was seen in 71·7% of HLA‐C*06‐positive (C*06POS) and 35·2% of HLA‐C*06‐negative (C*06NEG) patients. At week 12, PASI 75 was reached by 69.1% of C*06POS patients and 40·5% of C*06NEG patients. After 52 weeks, PASI 75 was reached by 83.7% of C*06POS patients and 58.8% of C*06NEG patients. The results from our new, large cohort of European patients treated with ustekinumab in daily clinical practice confirm the role of HLA‐C*06 as a potential predictor of response to ustekinumab.
IMST-27. CD70–A CRITICAL MEDIATOR OF TUMOR PROGRESSION AND IMMUNOSUPPRESSION IN GLIOMAS
Authors: Haitao Ge, Linchun Jin, Changlin Yang, Yu Long, Yifan Chang, Luyan Mu, Elias Sayour, Gabriel DeLeon, Jeffrey Drake, Paul Kubilis, Hongbo Bao, Songsong Xia, Dunyue Lu, Yingjun Kong, Li Hu, Yibo Yin, Yujiao Shang, Chencheng Jiang, Jing Nie, Shimin Li, Jiping Qi, Yunhe Gu, Jiahang Sun, Zhiguo Lin, Duane Mitchell, Jianping Huang
Journal: Neuro-Oncology (2016)

For patients with glioblastoma (GBM) in particular, current treatment modalities (surgery, chemotherapy/radiation) are rarely curative. Cancer immunotherapy has been one of the most promising new treatment strategies for patients with GBM, yet finding better treatment options especially by identifying clinically useful targets for immunotherapy are desperately needed. We demonstrate here that CD70 is only constitutively expressed by tumors in primary and recurrent low-grade gliomas (LGG) and GBM. Relatively higher gene expression of CD70 was observed in a subgroup of LGG (IDH wild-type) and GBM (mesenchymal), and was inversely correlated with the overall survival of LGG (hazard ratio: 3.52, P < .001) and GBM (hazard ratio: 1.8, P < .05) patients. Intriguingly, glioma-specific and dramatically lower levels of CD8 gene transcripts (30-fold) as well as fewer viable tumor-infiltrating CD8+ T cells were found in primary GBM, as compared to CD4 transcript/CD4+ T cells, and CD70 was found to be the key factor that was directly involved in this skewed numbers of CD4 vs. CD8. Results from in vitro experiments using CD70-manipulated GBM lines co-culturing with allogenic PBMCs showed that CD70 tumor expression specifically induced CD8+ T-cell death and maintained T regulatory cells. Furthermore, CD70 expression in GBM was highly associated with cytokine/chemokine-signaling pathways by enhancing IL-8, CCL2, and CCL20 productions from the tumor cells, which potentiate the attraction of immunosuppressive infiltrates in GBM. In summary, our data suggest that CD70 is a key mediator of glioma tumor immunosuppression and progression, and that therapeutic approaches targeting CD70 may help treat patients with gliomas.
SURG-28. COMBINATION OF INTRAOPERATIVE MRI WITH ELECTROPHYSIOLOGICAL MONITORING FOR ENHANCED BRAIN TUMOR RESECTION
Authors: Ryan Planchard, Daniel Shepherd
Journal: Neuro-Oncology (2016)

Intraoperative MRI (iMRI) has been shown to increase both extent of resection and survival in patients with low and high-grade glioma, with no differences in postoperative neurological deficits following surgery. Much of the work has been done with high-grade gliomas as these are usually contrast-enhancing. Coupling iMRI with intraoperative electrophysiological mapping (EPM) provides a potential opportunity to further reduce neurological injury. In this study, 203 patients undergoing craniotomy and tumor resection with iMRI by a single surgeon were followed to determine outcomes. Among these, 124 also underwent electrophysiological mapping of motor (65 of 203), speech (3 of 203) or both (56 of 203). There were no significant differences in age, gender or comorbidities among the participants. Patients undergoing combined motor and speech mapping were less likely to obtain a gross total resection (18% versus 32% of patients undergoing motor mapping only and 42% who received surgery without intraoperative mapping). However, when controlled for tumor location and multifocality, all statistical significance disappeared. Similarly, postoperative deficits were more common among patient undergoing combined speech and motor electrophysiological mapping. However, when the preoperative deficits were factored, no significant differences were found in outcome as determined by delta KPS score. This is despite carrying out surgery in disparate eloquent areas. There were no statistically significant differences in 30-day mortality or permanent neurological deficits. This preliminary data suggests that EPM in combination with iMRI is a safe adjunct that does not lead toward any deleterious outcomes for patients and provides yet another tool to guide the surgeon during resection. This data has not demonstrated a clear benefit on extent of resection or postoperative deficits. More work needs to be done to determine the utility of EPM in combination with iMRI to help guide the extent of resection.
Cost-effectiveness of KRAS, EGFR and ALK testing for therapeutic decision making of advanced stage non-small cell lung cancer (NSCLC): the French IFCT-PREDICT.amm study
Authors: A. Drezet, S. Loubière, M. Wislez, M. Beau-Faller, I. Nanni-Métellus, S. Garcia, M.-P. Chenard, J.-P. Ghnassia, R. Lacave, M. Antoine, M. Duruisseaux, S. Friard, E. Fabre, C. Daniel, P. Missy, F. Morin, F. Barlesi, P. Auquier, J. Cadranel
Journal: Annals of Oncology (2016)
FOLFOXIRI plus bevacizumab (bev) as upfront treatment for metastatic colorectal cancer (mCRC) patients (pts) with initially unresectable liver-limited disease (LLD)
Authors: M. Casagrande, C. Cremolini, G. Zucchelli, F. Bergamo, L. Ferrari, F. Pietrantonio, S. Lonardi, F. Loupakis, G. Masi, N. Pella, R. Intini, L. Salvatore, G. Tomasello, F. Pagani, A. Pellino, E. Dell'Aquila, L. Ginocchi, M. Milione, E. Fea, A. Pellegrinelli, A. Falcone
Journal: Annals of Oncology (2016)
A phase Ib study of second-line therapy with panitumumab, irinotecan, and everolimus (PIE) in metastatic colorectal cancer (mCRC) with KRAS wild type (WT).
Authors: Amanda Rose Townsend, Louise Pirc, Pamela Cooper, Niall C. Tebbutt, Christos Stelios Karapetis, Nimit Singhal, Timothy Jay Price
Journal: Journal of Clinical Oncology (2013)

e14506 Background: The mammalian target of rapamycin (mTOR) is a key downstream protein activated via PI3K-AKT pathway, and regulates cell growth, proliferation, and survival. Inhibition of mTOR in addition to EGFR may overcome upstream resistance to EGFR inhibitors in CRC. This is a phase Ib study to determine the maximum tolerated dose (MTD) of the PIE combination. Methods: Patients with KRAS WT mCRC following failure of first line fluoropyrimidine based therapy received IV irinotecan and panitumumab every 2 weeks, and everolimus orally throughout a 14 day cycle. Dose finding used a standard 3+3 design with the MTD defined as the dose with dose limiting toxicity (DLT) in ≤1/6 patients. A DLT is any of the following in the first 28 days; febrile neutropenia, G3/G4 neutropenia &gt; 14 days, any G4 thrombocytopenia, any non-haematologic event of G4 or of G3 for &gt;7 days, treatment delays of &gt;14 days. Dose level 1; irinotecan 200mg/m2, panitumumab 6mg/kg, everolimus 5mg alternate days. Dose level 2; irinotecan 200mg/m2, panitumumab 6mg/kg, and everolimus 5mg daily. Results: 15 patients have been enrolled into the study, 2 withdrew prior to receiving any therapy. Five patients were enrolled at dose level 1. Two patients were not evaluable. Of the three evaluable patients there was no DLT. Three patients were then treated at dose level 2. Following one DLT (grade 3 mucositis &gt;7 days), the cohort was expanded to 5 evaluable patients but suspended after a further DLT (grade 3 mucositis &gt; 7 days). Other grade 3 toxicities were anorexia, rash, vomiting, and hypersensitivity. There were no grade 4 toxicities. Dose level 1 was expanded by 3, to a total of 6 evaluable patients. Grade 3 toxicities were mucositis (17%), fatigue (17%), diarrhoea (33%), rash (17%), hypomagnesemia (17%), and neutropenia (17%). There was no DLT. Conclusions: Dose level 2 exceeded the MTD. Dose level 1 appears tolerable and warrants further investigation. The phase II component of the study is ongoing. Clinical trial information: NCT01139138.
Final Report on Tandem Autologous Stem Cell Transplantation for Patients with Primary Progressive or Poor Risk Recurrent Hodgkin Lymphoma - A Two Institution Study.
Authors: Henry C. Fung, Patrick Stiff, A. Nademanee, E. Smith, C. Cutrone, M. Parthasarathy, A. Krishnan, J. Klein, A. Molina, C. Ruel, D. Smith, T. Rodriquez, P. Falk, A. Toor, J. Schriber, J. Rosenthal, B. Ivers, G. Somlo, N. Kogut, N. Vora, K. Margolin, R. Spielberger, Stephen J. Forman
Journal: Blood (2005)
Metronomic vinorelbine, cyclophosphamide plus capecitabine (VEX) combination: a phase II study for metastatic breast cancer patients
Authors: E. Montagna, A. Palazzo, G. Cancello, M. Iorfida, A. Sciandivasci, A. Cardillo, M. Mazza, E. Munzone, G.M. Campennì, N. Bianco, G. Sortino, L. Rinaldi, A. Esposito, M. Colleoni
Journal: Annals of Oncology (2016)
EXTH-51. BREVICAN-SPECIFIC PEPTIDES FOR THE DEVELOPMENT OF NEXT-GENERATION TARGETED THERANOSTICS FOR MALIGNANT GLIOMAS
Authors: Choi-Fong Cho, Kazue Kasai, Justin Wolfe, Kalvis Hornburg, Fernanda Bononi, Leonard Luyt, Bradley Pentelute, Mariano Viapiano, E. Antonio Chiocca, Sean E. Lawler
Journal: Neuro-Oncology (2016)

High-grade gliomas are deadly cancers, and current standard-of-care has demonstrated limited success. The ability to specifically target glioma cells can allow for the development of improved theranostic agents leading to better detection methods and safer anti-cancer therapies. Brevican (BCAN), a CNS-specific extracellular matrix protein is upregulated in glioma cells and its expression correlates with tumor progression. Particularly, a plasma membrane bound BCAN isoform lacking normal glycosylation, called B/bΔg is a unique glioma marker and is not expressed in non-cancerous tissues. Therefore, B/bΔg represents a valuable target for anti-cancer strategies. We describe here the discovery of novel high-affinity B/bΔg-Targeted Peptides (BTP) using rapid combinatorial library screens. Briefly, a one-bead-one-compound (OBOC) peptide library was screened against small magnetic particles decorated with B/bΔg. Positive “hit” beads labeled with magnetic particles were isolated using a high-throughput in-house microfluidic magnetic-activated sorter of our own design. These hits were exposed to cells expressing B/bΔg, and beads/peptides with the highest cell association were isolated and sequenced. Seven novel peptides were identified. Cell uptake and blocking studies revealed that 5 of these peptides displayed specific affinity for B/bΔg-overexpressing cells. These candidates displayed nano-/micromolar binding affinity for recombinant B/bΔg protein. Further analyses of these candidates using confocal microscopy revealed increased peptide binding/uptake in patient-derived glioma stem cells compared with primary human astrocytes. Flow cytometry analysis using GBM-X6 cells revealed BTP-2, 7 and 8 as the top three candidates. For in vivo evaluation, GBM-X6 tumors were established intracranially in nude mice, and tumor formation was verified by magnetic resonance imaging. We observed that upon systemic administration, BTP-7 displayed the highest and most rapid tumor uptake, followed by BTP-2 and then, BTP-8. Our data here provides strong evidence that these peptides can serve as tumor-specific agents, and offer substantial promise in the development of highly efficacious and safe brain cancer therapeutics.