tbuckley/cabot-search huggingface dataset:
Thresholds for Arterial Wall Inflammation Quantified by 18F-FDG PET Imaging
Authors: Fleur M. van der Valk, Simone L. Verweij, Koos A.H. Zwinderman, Aart C. Strang, Yannick Kaiser, Henk A. Marquering, Aart J. Nederveen, Erik S.G. Stroes, Hein J. Verberne, James H.F. Rudd
Journal: JACC. Cardiovascular imaging (2016)

This study assessed 5 frequently applied arterial 18fluorodeoxyglucose (18F-FDG) uptake metrics in healthy control subjects, those with risk factors and patients with cardiovascular disease (CVD), to derive uptake thresholds in each subject group. Additionally, we tested the reproducibility of these measures and produced recommended sample sizes for interventional drug studies. 18F-FDG positron emission tomography (PET) can identify plaque inflammation as a surrogate endpoint for vascular interventional drug trials. However, an overview of 18F-FDG uptake metrics, threshold values, and reproducibility in healthy compared with diseased subjects is not available. 18F-FDG PET/CT of the carotid arteries and ascending aorta was performed in 83 subjects (61 ± 8 years) comprising 3 groups: 25 healthy controls, 23 patients at increased CVD risk, and 35 patients with known CVD. We quantified 18F-FDG uptake across the whole artery, the most-diseased segment, and within all active segments over several pre-defined cutoffs. We report these data with and without background corrections. Finally, we determined measurement reproducibility and recommended sample sizes for future drug studies based on these results. All 18F-FDG uptake metrics were significantly different between healthy and diseased subjects for both the carotids and aorta. Thresholds of physiological 18F-FDG uptake were derived from healthy controls using the 90th percentile of their target to background ratio (TBR) value (TBRmax); whole artery TBRmax is 1.84 for the carotids and 2.68 in the aorta. These were exceeded by >52% of risk factor patients and >67% of CVD patients. Reproducibility was excellent in all study groups (intraclass correlation coefficient >0.95). Using carotid TBRmax as a primary endpoint resulted in sample size estimates approximately 20% lower than aorta. We report thresholds for physiological 18F-FDG uptake in the arterial wall in healthy subjects, which are exceeded by the majority of CVD patients. This remains true, independent of readout vessel, signal quantification method, or the use of background correction. We also confirm the high reproducibility of 18F-FDG PET measures of inflammation. Nevertheless, because of overlap between subject categories and the relatively small population studied, these data have limited generalizability until substantiated in larger, prospective event-driven studies. (Vascular Inflammation in Patients at Risk for Atherosclerotic Disease; NTR5006)
ESMO consensus conference on malignant lymphoma: general perspectives and recommendations for prognostic tools in mature B-cell lymphomas and chronic lymphocytic leukaemia
Authors: M. Ladetto, C. Buske, M. Hutchings, M. Dreyling, G. Gaidano, S. Le Gouill, S. Luminari, C. Pott, A. Zamò, E. Zucca, C. Buske, M. Dreyling, A.J.M. Ferreri, P. Fields, G. Gaidano, V. Goede, M. Hutchings, M. Ladetto, S.L. Gouill, S. Luminari, U. Mey, P.d.N. Brown, M. Pfreundschuh, C. Pott, N. Schmitz, P. Soubeyran, M. Spina, R. Stauder, A.S. Balari, M. Trněný, G.v. Imhoff, J. Walewski, U. Wedding, A. Zamò, E. Zucca
Journal: Annals of Oncology (2016)
Induction of MAPK phosphatase-1 by hypothermia inhibits TNF- -induced endothelial barrier dysfunction and apoptosis
Authors: Dan Yang, Ping Xie, Shubin Guo, Huihua Li
Journal: Cardiovascular Research (2009)

Hypothermia therapy has been shown to confer robust protection against brain injury and cardiac arrest. However, the mechanisms underlying endothelial cell protection of hypothermia have not yet been completely elucidated. Here, we investigated molecular effects of hypothermia on tumour necrosis factor-alpha (TNF-alpha)-induced endothelial barrier dysfunction and apoptosis.Human umbilical vein endothelial cells (HUVECs) treated with TNF-alpha were incubated under normothermia (37 degrees C) or hypothermia (33 degrees C). [corrected] Endothelial permeability, actin alterations, and apoptosis were examined. The protein levels were determined by immunoblot analysis. Treatment of HUVECs with TNF-alpha resulted in a significant increase of permeability, actin reorganization, and apoptosis. Hypothermia markedly attenuated TNF-alpha-induced effects. The inhibitory action of hypothermia on stress fibre formation was mediated via inactivation of p38 mitogen-activated protein kinase (MAPK)/heat shock protein 27 (HSP27), and the decrease in TNF-alpha-induced apoptosis by hypothermia was associated with inhibition of p38 MAPK and c-Jun N-terminal kinase (JNK) activity. Hypothermia had no action on p38 MAPK and JNK upstream kinases MAPK kinase 3/6 (MKK3/6) and MAPK kinase 7 (MKK7), but it markedly induced the expression of MAPK phosphatase-1 (MKP-1). Furthermore, siRNA experiments showed that MKP-1 was an important mediator of hypothermia in reducing TNF-alpha-induced inflammatory responses and activation of p38 MAPK and JNK in HUVECs.These results for the first time demonstrate that hypothermia protects against TNF-alpha-induced endothelial barrier dysfunction and apoptosis through an MKP-1-dependent mechanism.
Acute Adaption to Oral or Intravenous Phosphate Requires Parathyroid Hormone
Authors: Linto Thomas, Carla Bettoni, Thomas Knöpfel, Nati Hernando, Jürg Biber, Carsten A. Wagner
Journal: Journal of the American Society of Nephrology (2016)

Phosphate (Pi) homeostasis is regulated by renal, intestinal, and endocrine mechanisms through which Pi intake stimulates parathyroid hormone (PTH) and fibroblast growth factor-23 secretion, increasing phosphaturia. Mechanisms underlying the early adaptive phase and the role of the intestine, however, remain ill defined. We investigated mineral, endocrine, and renal responses during the first 4 hours after intravenous and intragastric Pi loading in rats. Intravenous Pi loading (0.5 mmol) caused a transient rise in plasma Pi levels and creatinine clearance and an increase in phosphaturia within 10 minutes. Plasma calcium levels fell and PTH levels increased within 10 minutes and remained low or high, respectively. Fibroblast growth factor-23, 1,25-(OH) 2 -vitamin D 3 , and insulin concentrations did not respond, but plasma dopamine levels increased by 4 hours. In comparison, gastric Pi loading elicited similar but delayed phosphaturia and endocrine responses but did not affect plasma mineral levels. Either intravenous or gastric loading led to decreased expression and activity of renal Pi transporters after 4 hours. In parathyroidectomized rats, however, only intravenous Pi loading caused phosphaturia, which was blunted and transient compared with that in intact rats. Intravenous but not gastric Pi loading in parathyroidectomized rats also led to higher creatinine clearance and lower plasma calcium levels but did not reduce the expression or activity of Pi transporters. This evidence suggests that an intravenous or intestinal Pi bolus causes rapid phosphaturia through mechanisms requiring PTH and downregulation of renal Pi transporters but does not support a role of the intestine in stimulating renal clearance of Pi.
Randomized Comparison of Weekly Administration and Daily Courses of Cladribine in Patients with Hairy Cell Leukemia - Updated Results.
Authors: Tadeusz Robak, Marek Kasznicki, Joanna Gora-Tybor, Jadwiga Dwilewicz-Trojaczek, Anna Dmoszynska, Maria Wojtaszko, Barbara Zdziarska, Malgorzata Calbecka, Andrzej Hellmann, Beata Stella-Holowiecka, Kazimierz Sulek, Aleksander Skotnicki, Krystyna Zawilska, Janusz Kloczko, Krzysztof Warzocha, Lech Konopka
Journal: Blood (2004)
Myeloid-derived suppressor cell quantity prior to treatment with ipilimumab at 10mg/kg to predict for overall survival in patients with metastatic melanoma.
Authors: Shigehisa Kitano, Michael Andrew Postow, Czrina Cortez, Teresa Rasalan, Humilidad F. Gallardo, Katherine Panageas, Jianda Yuan, Jedd D. Wolchok, Alexander M. Lesokhin
Journal: Journal of Clinical Oncology (2012)

2518 Background: Ipilimumab, an antibody that blocks the function of the immune inhibitory molecule cytotoxic T lymphocyte antigen 4 (CTLA-4), significantly prolongs survival in patients with metastatic melanoma. Approximately 30% of patients derive clinical benefit from therapy. Defining biomarkers of response to ipilimumab therapy would enable selection of patients more likely to respond and is relevant for both practicing clinicians and for clinical trial design. We performed a pilot correlative study evaluating myeloid derived suppressor cells (MDSC), a population of immune suppressive monocytic cells, as a biomarker of clinical outcome. Methods: Peripheral blood from 26 patients with stage IV melanoma treated with ipilimumab 10mg/kg every 3 weeks for 4 doses at our center, as part of an expanded access program (BMS CA184-045) was assessed for MDSC quantity (%CD14 + ,HLA-DR low/- cells) pre-treatment, at week 7, week 12, and week 24 by flow cytometry. MDSC ability to inhibit T cell proliferation was tested using an in vitro suppression assay. Results: We found that lower MDSC quantity pre-treatment predicted for improved overall survival (Hazard ratio 1.07 (1.03, 1.11) p=0.002) and trended toward associating with clinical benefit measured at week 24 imaging (p=0.09). This effect was independent of pre-treatment or week 7 absolute lymphocyte counts (ALC) and pre-treatment LDH when evaluated in a multivariate model with ALC and MDSC quantity HR 1.10; 95% CI 1.04, 1.17 p=0.0006 and LDH and MDSC quantity HR 1.06; 95% CI 1.01, 1.11 p = 0.013. Furthermore, a general trend of increasing MDSC number by week 24 from the pre-treatment baseline was associated with patients that did not achieve clinical benefit. MDSC suppressed peripheral blood T cell proliferation as measured by CFSE dilution in response to anti-CD3 antibody stimulation. Conclusions: Pre-treatment MDSC quantity may predict clinical response following ipilimumab therapy. Further studies evaluating MDSC as a biomarker of ipilimumab therapy are warranted both retrospectively and prospectively in a broader group of patients.
Identifying people at higher risk of melanoma across the U.K.: a primary-care-based electronic survey
Authors: J.A. Usher-Smith, A.P. Kassianos, J.D. Emery, G.A. Abel, Z. Teoh, S. Hall, R.D. Neal, P. Murchie, F.M. Walter
Journal: British Journal of Dermatology (2016)

Melanoma incidence is rising rapidly worldwide among white populations. Defining higher‐risk populations using risk prediction models may help targeted screening and early detection approaches. To assess the feasibility of identifying people at higher risk of melanoma using the Williams self‐assessed clinical risk estimation model in U.K. primary care. We recruited participants from the waiting rooms of 22 general practices covering a total population of > 240 000 in three U.K. regions: Eastern England, North East Scotland and North Wales. Participants completed an electronic questionnaire using tablet computers. The main outcome was the mean melanoma risk score using the Williams melanoma risk model. Of 9004 people approached, 7742 (86%) completed the electronic questionnaire. The mean melanoma risk score for the 7566 eligible participants was 17·15 ± 8·51, with small regional differences [lower in England compared with Scotland (P = 0·001) and Wales (P < 0·001), mainly due to greater freckling and childhood sunburn among Scottish and Welsh participants]. After weighting to the age and sex distribution, different potential cut‐offs would allow between 4% and 20% of the population to be identified as higher risk, and those groups would contain 30% and 60%, respectively of those likely to develop melanoma. Collecting data on the melanoma risk profile of the general population in U.K. primary care is both feasible and acceptable for patients in a general practice setting, and provides opportunities for new methods of real‐time risk assessment and risk stratified cancer interventions.
Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis
Authors: Didier Keh, Evelyn Trips, Gernot Marx, Stefan P. Wirtz, Emad Abduljawwad, Sven Bercker, Holger Bogatsch, Josef Briegel, Christoph Engel, Herwig Gerlach, Anton Goldmann, Sven-Olaf Kuhn, Lars Hüter, Andreas Meier-Hellmann, Axel Nierhaus, Stefan Kluge, Josefa Lehmke, Markus Loeffler, Michael Oppert, Kerstin Resener, Dirk Schädler, Tobias Schuerholz, Philipp Simon, Norbert Weiler, Andreas Weyland, Konrad Reinhart, Frank M. Brunkhorst
Journal: JAMA (2016)

Adjunctive hydrocortisone therapy is suggested by the Surviving Sepsis Campaign in refractory septic shock only. The efficacy of hydrocortisone in patients with severe sepsis without shock remains controversial.To determine whether hydrocortisone therapy in patients with severe sepsis prevents the development of septic shock.Double-blind, randomized clinical trial conducted from January 13, 2009, to August 27, 2013, with a follow-up of 180 days until February 23, 2014. The trial was performed in 34 intermediate or intensive care units of university and community hospitals in Germany, and it included 380 adult patients with severe sepsis who were not in septic shock.Patients were randomly allocated 1:1 either to receive a continuous infusion of 200 mg of hydrocortisone for 5 days followed by dose tapering until day 11 (n = 190) or to receive placebo (n = 190).The primary outcome was development of septic shock within 14 days. Secondary outcomes were time until septic shock, mortality in the intensive care unit or hospital, survival up to 180 days, and assessment of secondary infections, weaning failure, muscle weakness, and hyperglycemia (blood glucose level >150 mg/dL [to convert to millimoles per liter, multiply by 0.0555]).The intention-to-treat population consisted of 353 patients (64.9% male; mean [SD] age, 65.0 [14.4] years). Septic shock occurred in 36 of 170 patients (21.2%) in the hydrocortisone group and 39 of 170 patients (22.9%) in the placebo group (difference, -1.8%; 95% CI, -10.7% to 7.2%; P = .70). No significant differences were observed between the hydrocortisone and placebo groups for time until septic shock; mortality in the intensive care unit or in the hospital; or mortality at 28 days (15 of 171 patients [8.8%] vs 14 of 170 patients [8.2%], respectively; difference, 0.5%; 95% CI, -5.6% to 6.7%; P = .86), 90 days (34 of 171 patients [19.9%] vs 28 of 168 patients [16.7%]; difference, 3.2%; 95% CI, -5.1% to 11.4%; P = .44), and 180 days (45 of 168 patients [26.8%] vs 37 of 167 patients [22.2%], respectively; difference, 4.6%; 95% CI, -4.6% to 13.7%; P = .32). In the hydrocortisone vs placebo groups, 21.5% vs 16.9% had secondary infections, 8.6% vs 8.5% had weaning failure, 30.7% vs 23.8% had muscle weakness, and 90.9% vs 81.5% had hyperglycemia.Among adults with severe sepsis not in septic shock, use of hydrocortisone compared with placebo did not reduce the risk of septic shock within 14 days. These findings do not support the use of hydrocortisone in these patients.clinicaltrials.gov Identifier: NCT00670254.
Measles and Measles Vaccination
Authors: Johan Christiaan Bester
Journal: JAMA Pediatrics (2016)

Measles is a highly communicable viral infection with serious complications. There have been continued outbreaks of measles in countries in which measles is considered to be eliminated, such as the United States and the Netherlands, and measles remains endemic in some countries. Health care professionals play an important role in diagnosing and managing acute cases of measles, preventing spread during outbreaks, and vaccination uptake.To provide an overview of measles and vaccination for health care professionals.MEDLINE and PubMed were searched from January 1, 1980, to April 30, 2016, in addition to the data repositories of the Centers for Disease Control and Prevention and World Health Organization.Seven systematic reviews, 15 reviews, 15 observational studies, 1 qualitative study, 5 epidemiologic reports, and 2 books were included, in addition to World Health Organization and Centers for Disease Control and Prevention data, position papers, and statements. Transmission of measles is dependent on person-to-person spread through respiratory droplets or direct contact. Diagnosis is based on recognizing the clinical picture and can be confirmed with results of laboratory testing, such as serologic tests or polymerase chain reaction. Measles infection leads to immune suppression for weeks to months. Complications of measles are of high frequency and severity. There is no specific antiviral treatment for measles; treatment with vitamin A is recommended for younger children to decrease mortality from measles. Vaccination against measles is effective, cost-effective, and safe. There is no link between the measles vaccination and autism. Measles can be eliminated from a population; this outcome requires coverage with 2 doses of vaccine at rates of 93% to 95% of the population. Countries with high rates of measles vaccination experience outbreaks by virtue of imported cases causing transmission through susceptible groups of individuals who are not immune to the measles virus. Endemic transmission can be reestablished if rates of vaccination fall below the elimination threshold.Measles remains of high clinical importance. Health care professionals should be able to diagnose and manage an acute case and assist in prevention of the spread of measles during an outbreak. Health care professionals also play an important role in uptake of measles vaccination through establishing trusting relationships with parents, offering vaccination at indicated times, and engaging parents in discussion on facts and concerns about vaccination.
Combination of Idelalisib and ONO/GS-4059 in Lymphoma Cell Lines Sensitive and Resistant to BTK Inhibitors
Authors: Stacey Tannheimer, Jia Liu, Rick Sorensen, Anella Yahiaoui, Sarah Meadows, Li Li, Peng Yue, Kathleen S Keegan, Jamie Bates, Daniel Tumas, Christophe Queva
Journal: Blood (2015)
Clinical and pathological predictors of Advanced Breast Carcinoma with Luminal subtype (ABC-Lum) identifying prognostic ‘outliers’: multicenter retrospective analysis in the ‘real-world’ scenario
Authors: I. Sperduti, L. Carbognin, M. Ciccarese, A. Fabi, L. Petrucelli, S. Vari, R.C. Forcignanò, J. Furlanetto, C. Vicentini, R. Nortilli, M. Brunelli, A. Nottegar, D. Giannarelli, G. Tortora, E. Bria
Journal: Annals of Oncology (2015)
P2.36: Nivolumab (nivo) in Patients (pts) With Advanced (adv) NSCLC and Central Nervous System (CNS) Metastases (mets)
Authors: Jonathan W. Goldman, Lucio Crino, Everett E. Vokes, Esther Holgado, Karen Reckamp, Adam Pluzanski, David Spigel, Martin Kohlhaeufl, Marina Garassino, Laura Qm Chow, Scott Gettinger, David E. Gerber, Libor Havel, Suresh S. Ramalingam, Grace K. Dy, William J. Geese, Ang Li, Anne Blackwood-Chirchir, Diane Healey, Julie Brahmer, Gilberto Lopes
Journal: Journal of Thoracic Oncology (2016)
Smart nanoparticles with a detachable outer shell for maximized synergistic antitumor efficacy of therapeutics with varying physicochemical properties
Authors: Tingjie Yin, Jiyong Liu, Zekai Zhao, Lihui Dong, Han Cai, Lifang Yin, Jianping Zhou, Meirong Huo
Journal: Journal of Controlled Release (2016)
Docetaxel (Do) and liposomal pegylated doxorubicin in metastatic breast cancer (MBC) patients (pts): The French GINECO group experience
Authors: J. P. Guastalla, R. Largillier, J. F. Geay, A. C. Hardy-Bessard, S. Kirsher, B. Slama, J. Cretin, H. Orfeuvre, Y. Goubely, E. Pujade-Lauraine
Journal: Journal of Clinical Oncology (2006)

10589 Background: Taxanes and anthracyclins are among the most effective agents in MBC. Ca has a favourable cardiac toxicity profile and we tested Ca in combination with Do. Methods: Two successive Ca-Do regimens (Reg) were evaluated in first line MBC pts with performance status ≤ 2, and good organ function including normal MUGA scan. Reg A (n = 53 pts): Ca 35 mg/m 2 /d1 q4wks + Do 40 mg/m 2 /d1 q2wks according to previous phase I study results (Guastalla JP et al, Proc Am Soc Clin Onc 2004) and Reg B (n = 14 pts): Ca 30 mg/m 2 /d1 + Do 75 mg/m 2 /d2 every 3wks (Alexopoulos A et al, Ann Oncol 2004). Pyridoxine (250 mg/d) was given continuously during treatment (Tt). Results: The 67 pts had a median age of 58 yrs (range 37–77 yrs); others characteristics (%): ER+ (75), PR+ (51), HER2+ (9), adjuvant anthracyclin (54) and hormonotherapy (60), visceral disease (78). Both regimens induced unbearable toxicities (Tox) leading to premature stopping of the trial. Dose reduction, Tt delay and early stopping due to Tox were noted (% pts) in A:68, 36, 48 and B:57, 64, 54. Mucositis-skin Tox was the most severe Tox (% Gr2/3; A:40/15, B:43/21) and was observed in 21 and 40% of pts at cycle 2 and 4. Hematotoxicity was worse in reg B: Gr3/4 neutropenia (A:28/9, B:14/57), anemia (A:0/0, B:7/7) and thrombopenia (A:0/0, B:14/0), febrile neutropenia (A:6, B:14), Gr2–3 infection (A:13, B:28). Others Gr2–3 toxicities (&gt; 10%) included alopecia (A:64, B:78), fatigue (A:54, B:57), nausea/vomiting (A:19, B:50). Three pts had a reduction of LVEF without clinical cardiac toxicity Conclusions: The combination of Do and Ca according to the 2 schedules tested in this study induced an unexpected high rate of mucositis and skin toxicity. No significant financial relationships to disclose.
Specific PML Isoforms and SATB1 Affect HLA Expression In Classical Hodgkin Lymphoma
Authors: Yuxuan Liu, Anke Van Den Berg, Bea Rutgers, Rianne Veenstra, Debora de Jong, Gertrud Kortman, Gustaaf van Imhoff, Lydia Visser, Arjan Diepstra
Journal: Blood (2013)