tbuckley/cabot-search huggingface dataset:
Phase II study of a combination therapy of nivolumab, bevacizumab and paclitaxel in patients with HER2-negative metastatic breast cancer as a first-line treatment (WJOG9917B, NEWBEAT trial).
Authors: Yukinori Ozaki, Koji Matsumoto, Masato Takahashi, Toru Mukohara, Manabu Futamura, Norikazu Masuda, Junji Tsurutani, Kenichi Yoshimura, Hironobu Minami, Toshimi Takano
Journal: Journal of Clinical Oncology (2018)

TPS1110 Background: In recent years, an immune checkpoint inhibitor, anti-PD-1 antibody, has been developed for various cancer types including breast cancer. The synergic effect of combination of nivolumab, paclitaxel and bevacizumab has been anticipated based on various preclinical data. Therefore, we initiated this investigator-initiated trial to evaluate the efficacy and safety of nivolumab + paclitaxel + bevacizumab therapy as a first-line treatment in patients with metastatic or recurrent HER2-negative breast cancer. Methods: This is a Phase II, multi-center, single-arm study to evaluate the efficacy and safety of nivolumab + paclitaxel + bevacizumab combination therapy as a first-line treatment for HER2-negative advanced metastatic or inoperable recurrent breast cancer. Patients will receive nivolumab 240 mg/body on day 1, 15, paclitaxel 90 mg/m2 on day1, 8, 15, and bevacizumab 10 mg/kg on day1, 15 every 4 weeks until the protocol treatment is determined to be ineffective or may not be continued. The primary endpoint is the objective response rate (ORR) and key secondary endpoints include progression free survival, overall survival, and the toxicity of the protocol treatment. The threshold and expected ORR are 55% and 70%, respectively, and 47 patients are needed to ensure a statistical power of 80% (α = 0.10). A total of 51 patients will be enrolled and duration of enrollment will be one year. Tumor tissue will be evaluated for the amount and phenotypes of TILs, PD-L1 expression, and gene expression analysis. Peripheral blood will be evaluated for immune status and cytokine profiling. This trial opened to accrual in February 2018. Clinical trial information: UMIN000030242.
For Patients With Type 2 Diabetes, What’s the Best Target Hemoglobin A<sub>1C</sub>?
Authors: Jennifer Abbasi
Journal: JAMA (2018)

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An inhibitor of oxidative phosphorylation exploits cancer vulnerability
Authors: Jennifer R. Molina, Yuting Sun, Marina Protopopova, Sonal Gera, Madhavi Bandi, Christopher Bristow, Timothy McAfoos, Pietro Morlacchi, Jeffrey Ackroyd, Ahmed-Noor A. Agip, Gheath Al-Atrash, John Asara, Jennifer Bardenhagen, Caroline C. Carrillo, Christopher Carroll, Edward Chang, Stefan Ciurea, Jason B. Cross, Barbara Czako, Angela Deem, Naval Daver, John Frederick de Groot, Jian-Wen Dong, Ningping Feng, Guang Gao, Jason Gay, Mary Geck Do, Jennifer Greer, Virginia Giuliani, Jing Han, Lina Han, Verlene K. Henry, Judy Hirst, Sha Huang, Yongying Jiang, Zhijun Kang, Tin Khor, Sergej Konoplev, Yu-Hsi Lin, Gang Liu, Alessia Lodi, Timothy Lofton, Helen Ma, Mikhila Mahendra, Polina Matre, Robert Mullinax, Michael Peoples, Alessia Petrocchi, Jaime Rodriguez-Canale, Riccardo Serreli, Thomas Shi, Melinda Smith, Yoko Tabe, Jay Theroff, Stefano Tiziani, Quanyun Xu, Qi Zhang, Florian Muller, Ronald A. DePinho, Carlo Toniatti, Giulio F. Draetta, Timothy P. Heffernan, Marina Konopleva, Philip Jones, M. Emilia Di Francesco, Joseph R. Marszalek
Journal: Nature Medicine (2018)
When will I feel normal again? Quality of life trajectories after first-line chemotherapy for ovarian cancer.
Authors: Penelope M Webb, Vanessa Beesley, Christina Nagle, Peter T. Grant, Anna deFazio, Andreas Obermair, Michael Friedlander
Journal: Journal of Clinical Oncology (2018)

172 Background: Patients often ask if/when they will feel normal again following treatment for ovarian cancer (OC). There is a paucity of data on the trajectories of quality of life (QoL), physical (PWB), social (SWB), emotional (EWB) and functional (FWB) wellbeing over time following chemotherapy and especially regarding those who have persistent problems. Our aim was to quantify the proportion of women with significantly lower QoL/wellbeing than the general population at the end of treatment and determine if/when they return to normal. Methods: The OPAL (Ovarian cancer Prognosis &amp; Lifestyle) Study is a prospective study of Australian women diagnosed with invasive OC from 2012-15 who agreed to complete regular questionnaires after diagnosis. 580 participants who received ≥3 cycles of platinum-based chemotherapy as primary treatment and completed a questionnaire while on or &lt; 6 weeks after completing chemotherapy (baseline) were included. FACT-G data came from questionnaires at baseline and ~3, 6, 9 &amp; 18 months post-baseline. Group-based trajectory models were used to identify groups with distinct patterns of QoL/wellbeing over time. Results: Overall, 44% (254) of women had QoL scores significantly lower than the general population at baseline; 35% (88) returned to normal by 3 months after treatment, 73% by 6 months and 27% (69) had not returned to normal by 18 months. The Table shows the comparable figures for the wellbeing subscales. Conclusions: While &gt; 50% of women with OC can expect similar QoL, FWB and EWB to the general population at the end of chemotherapy, PWB was compromised in 3 of 4 women. For most, wellbeing recovered within 6 months but a substantial proportion reported ongoing deficits. A particularly prolonged impact was seen for those with poor EWB at baseline, warranting early intervention in this subset. [Table: see text]
Abstract 20275: A Novel Engineered Hepatocyte Growth Factor Analog Released via a Temperature-Responsive, Shear-Thinning Hydrogel Enhances Post-Infarction Ventricular Function
Authors: Amanda N Steele, Lei Cai, Andrew B Goldstone, Bryan B Edwards, Aaron C Mitchell, Anahita Eskandari, Lyndsay M Stapleton, Masashi Kawamura, Jay Patel, Michael Hopkins, Jennifer R Cochran, Sarah C Heilshorn, Y. Joseph Woo
Journal: Circulation (2016)

Objective:  Hepatocyte growth factor is cardioprotective, anti-apoptotic, and pro-angiogenic; yet, is limited in clinical translation due to its high manufacturing cost and low stability. We encapsulated an engineered HGF fragment (HGFf) in an engineered shear-thinning, temperature-responsive, injectable hydrogel (SHIELD). We hypothesized SHIELD would facilitate targeted, sustained intramyocardial delivery of HGFf, thereby attenuating myocardial injury and post-infarction remodeling.   Methods:  HGFf elution was tracked for 2 weeks via fluorophore conjugation. Cytoprotective effects of HGFf on rat cardiomyocytes were assessed with a WST-1 cell viability assay after a 48hr serum starvation. Adult male Wistar rats (n=21) underwent sham surgery or permanent ligation of the LAD followed by borderzone injection of 60μL PBS, SHIELD alone, or SHIELD encapsulating 10μg HGFf. Ventricular geometry and function, infarct size, and angiogenic response were assessed 4-weeks post-infarction.   Results:  HGFf elution was sustained for 14 days in vitro (Fig. 1A), remained active, and improved cardiomyocyte viability by 22% during serum starvation (Fig. 1B). SHIELD remained localized within the heart at day 16 following injection. Treatment with SHIELD-HGFf reduced infarct size and significantly increased ejection fraction compared to that of the controls (Fig. 1C and D). The improvements in function in SHIELD-HGFf treated animals were coupled with a significant increase in arterial density compared to that of the other study groups (Fig. 1E and F).   Conclusions:  Sustained delivery of a stable, protein engineered HGFf limits post-infarction adverse ventricular remodeling by increasing angiogenesis and reducing fibrosis. Combining HGFf with SHIELD improves clinical translatability by enabling catheter-based delivery and subsequent retention of this novel, potent angiogenic protein analog.
Text messaging and activity tracker motivation program to increase physical activity in cancer survivors.
Authors: Bridget F. Koontz, Erica Levine, Frances McSherry, Tykeytra Dale, Martin Streicher, Junzo P. Chino, Christopher Ryan Kelsey, Kim Ward, Katie Little, Lynda Owen, Gary Bennett, William Kraus, Bercedis Peterson, Kathryn I. Pollak, Linda Sutton
Journal: Journal of Clinical Oncology (2018)

92 Background: Cancer survivors have high rates of sedentary behavior leading to obesity and cardiovascular disease. Physical activity improves quality of life (QOL) and reduces morbidity and mortality. However, cancer survivors commonly cite motivation as a barrier to increasing physical activity. We hypothesized that a motivational text-messaging feedback system linked to a Fitbit Flex activity tracker would increase the activity level of survivors and those undergoing cancer treatment. Methods: 29 participants were enrolled in an IRB-approved single-institution study. Eligibility allowed any cancer/stage, ≤2 days of exercise per week, life expectancy of 12+ months, and smartphone access. After baseline fitness/QOL testing, participants were provided a Fitbit Flex activity tracker. A text-messaging program automatically uploaded data from the tracker via an application programming interface and provided personalized text message feedback to subject’s smartphone daily for 3 months. Primary endpoint was change in step count from baseline to 3 months, with additional endpoints of change in 6 minute walk/QOL measures at 3 months, and continued exercise/use of tracker at 6 months. Results: To date, 24 have completed the 3 month program. Both academic and community sites participated, including areas with limited internet access. Most participants were female (71%) and white (63%). Eight cancer types and all stages were represented. Three participants withdrew – one because of lost tracker, one cancer death, and one “disappointed” with tracker function. Median daily steps at baseline were 3773 (IQR 2928) and 4365 at 3 months (IQR 4864). 42% had at least a 20% increase in median step count at 3 months. Improvement was noted in 45% of survivors and 38% of active treatment participants. Participants frequently used research nurses for guidance on use of wearable tracker (e.g. syncing, charging, features). Conclusions: Activity tracker with personalized daily feedback via text message successfully motivates cancer patients to increase daily activity. Patients are interested in health technology, but require technical support and coaching to maintain use. Clinical trial information: NCT02627079.
Abstract 15540: NRF2 Upregulation Attenuates Post-Infarct Ventricular Remodeling by Modifying Redox Signalling
Authors: Kristen J Bubb, Cindy Kok, Owen Tang, Nathalie B Rasko, Thomas Hansen, Rebecca Ritchie, Ravinay Bhindi, Scott A Reisman, Colin Meyer, Keith Ward, Keyvan Karimi Galougahi, Gemma Figtree
Journal: Circulation (2016)

Background: Adverse remodeling following myocardial infarction (MI) contributes to substantial morbidity, including heart failure and arrhythmia. Reactive oxygen species (ROS) play an important rol...
Restrictive lung defects: parenchymal, chest wall and neuromuscular
Authors: Anne-Marie Shanks, Sujal R Desai, Alexandra Rice, Stephen R Thomas, Michael I Polkey, Peter M George
Journal: Thorax (2018)

Sarcoidosis is a multisystem condition which may affect a number of organs and, within the cardiopulmonary system, most commonly manifests as parenchymal, airway-centred, nodal, vascular or cardiac disease. Pleural involvement is rare, but well described, and often presents as pleural effusions or pleural thickening. Here, we present the first case of active sarcoidosis manifesting as bilateral pleural calcification. We highlight the importance of a nuanced understanding of pulmonary physiology when dissecting coexistent extrathoracic and intrathoracic pulmonary restriction. We demonstrate the value of positron emission tomography scanning for identification of sites of sarcoid activity, in this case the pleura, to ensure tissue confirmation of this rare but functionally important manifestation of disease. Sarcoidosis should be considered within the differential diagnosis for patients with pleural calcification, not explained by more common causes.
Long-term albumin administration in decompensated cirrhosis (ANSWER): an open-label randomised trial
Authors: Paolo Caraceni, Oliviero Riggio, Paolo Angeli, Carlo Alessandria, Sergio Neri, Francesco G Foschi, Fabio Levantesi, Aldo Airoldi, Sergio Boccia, Gianluca Svegliati-Baroni, Stefano Fagiuoli, Roberto G Romanelli, Raffaele Cozzolongo, Vito Di Marco, Vincenzo Sangiovanni, Filomena Morisco, Pierluigi Toniutto, Annalisa Tortora, Rosanna De Marco, Mario Angelico, Irene Cacciola, Gianfranco Elia, Alessandro Federico, Sara Massironi, Riccardo Guarisco, Alessandra Galioto, Giorgio Ballardini, Maria Rendina, Silvia Nardelli, Salvatore Piano, Chiara Elia, Loredana Prestianni, Federica Mirici Cappa, Lucia Cesarini, Loredana Simone, Chiara Pasquale, Marta Cavallin, Alida Andrealli, Federica Fidone, Matteo Ruggeri, Andrea Roncadori, Maurizio Baldassarre, Manuel Tufoni, Giacomo Zaccherini, Mauro Bernardi, Marco Domenicali, Ferdinando A Giannone, Manuela Merli, Stefania Gioia, Silvano Fasolato, Antonietta Sticca, Daniela Campion, Alessandro Risso, Giorgio M Saracco, Daniela Maiorca, Agostino Rizzotto, Arianna Lanzi, Elga Neri, Anna Visani, Antonio Mastroianni, Alberto B Alberti, Chiara Mazzarelli, Marcello Vangeli, Marco Marzioni, Francesca Capretti, Alba Kostandini, Giulia Magini, Maria Colpani, Giacomo Laffi, Tommaso Gabbani, Maria Marsico, Marianna Zappimbulso, Josè Petruzzi, Vincenza Calvaruso, Giovanni Parrella, Nicola Caporaso, Francesco Auriemma, Maria Guarino, Fabio Pugliese, Antonio Gasbarrini, Pietro Leo, Francesco De Leonardis, Alessandra Pecchioli, Piera Rossi, Giovanni Raimondo, Elisa Negri, Marcello Dallio, Carmelina Loguercio, Dario Conte, Natascia Celli, Roberto Bringiotti, Nicola M Castellaneta, Francesco Salerno
Journal: The Lancet (2018)
Major hazelnut and peanut allergens are potent in basophil activation and cross‐react at T‐cell level
Authors: L. J. N. Masthoff, S. G. M. A. Pasmans, H. van Doorn, C. F. den Hartog Jager, K. Geneugelijk, E. F. Knol, C. A. F. M. Bruijnzeel‐Koomen, J. Lidholm, A. C. Knulst, E. Hoffen
Journal: Allergy (2018)

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Infantile Pulmonary Teratoid Tumor
Authors: Leanne de Kock, Somayyeh Fahiminiya, Pierre O Fiset, Itziar Astigarraga, Van-Hung Nguyen, Steffen Albrecht, William D Foulkes
Journal: New England Journal of Medicine (2018)

Infantile Pulmonary Teratoid Tumor Pleuropulmonary blastoma is a childhood tumor related to DICER mutations. The authors identify a new cancer, infantile pulmonary teratoid tumor, that has some his...
Energetics of Blood Flow in Cardiovascular Disease
Authors: Friso M. Rijnberg, Mark G. Hazekamp, Jolanda J. Wentzel, Patrick J.H. de Koning, Jos J.M. Westenberg, Monique R.M. Jongbloed, Nico A. Blom, Arno A.W. Roest
Journal: Circulation (2018)

Visualization and quantification of the adverse effects of distorted blood flow are important emerging fields in cardiology. Abnormal blood flow patterns can be seen in various cardiovascular diseases and are associated with increased energy loss. These adverse energetics can be measured and quantified using 3-dimensional blood flow data, derived from computational fluid dynamics and 4-dimensional flow magnetic resonance imaging, and provide new, promising hemodynamic markers. In patients with palliated single-ventricular heart defects, the Fontan circulation passively directs systemic venous return to the pulmonary circulation in the absence of a functional subpulmonary ventricle. Therefore, the Fontan circulation is highly dependent on favorable flow and energetics, and minimal energy loss is of great importance. A focus on reducing energy loss led to the introduction of the total cavopulmonary connection (TCPC) as an alternative to the classical Fontan connection. Subsequently, many studies have investigated energy loss in the TCPC, and energy-saving geometric factors have been implemented in clinical care. Great advances have been made in computational fluid dynamics modeling and can now be done in 3-dimensional patient-specific models with increasingly accurate boundary conditions. Furthermore, the implementation of 4-dimensional flow magnetic resonance imaging is promising and can be of complementary value to these models. Recently, correlations between energy loss in the TCPC and cardiac parameters and exercise intolerance have been reported. Furthermore, efficiency of blood flow through the TCPC is highly variable, and inefficient blood flow is of clinical importance by reducing cardiac output and increasing central venous pressure, thereby increasing the risk of experiencing the well-known Fontan complications. Energy loss in the TCPC will be an important new hemodynamic parameter in addition to other well-known risk factors such as pulmonary vascular resistance and can possibly be improved by patient-specific surgical design. This article describes the theoretical background of mechanical energy of blood flow in the cardiovascular system and the methods of calculating energy loss, and it gives an overview of geometric factors associated with energy efficiency in the TCPC and its implications on clinical outcome. Furthermore, the role of 4-dimensional flow magnetic resonance imaging and areas of future research are discussed.
Flow-related right ventricular to pulmonary arterial pressure gradients during exercise
Authors: Stephen P Wright, Alexander R Opotowsky, Tayler A Buchan, Sam Esfandiari, John T Granton, Jack M Goodman, Susanna Mak
Journal: Cardiovascular Research (2018)

The assumption of equivalence between right ventricular (RV) and pulmonary arterial systolic pressure is fundamental to several assessments of RV or pulmonary vascular haemodynamic function. Our aims were to (i) determine whether systolic pressure gradients develop across the RV outflow tract in healthy adults during exercise, (ii) examine the potential correlates of such gradients, and (iii) consider the effect of such gradients on calculated indices of RV function.Healthy untrained and endurance-trained adult volunteers were studied using right-heart catheterization at rest and during submaximal cycle ergometry. RV and pulmonary artery (PA) pressures were simultaneously transduced, and the cardiac output was determined by thermodilution. Systolic pressures, peak and mean gradients, and indices of chamber, vascular, and valve function were analysed offline. Summary data are reported as mean ± standard deviation or median (interquartile range). No significant RV outflow tract gradients were observed at rest [mean gradient = 4 (3-5) mmHg], and the calculated effective orifice area was 3.6 ± 1.0 cm2. The increase in right ventricular systolic pressure during exercise was greater than the PA systolic pressure. Accordingly, mean gradients were developed during light exercise [8 (7-9) mmHg] and increased during moderate exercise [12 (9-14) mmHg, P < 0.001]. The magnitude of the mean gradient was linearly related to the cardiac output (r2 = 0.70, P < 0.001).In healthy adults without pulmonic stenosis, systolic pressure gradients develop during exercise, and the magnitude is related to the blood flow rate.
IMpower131: Primary PFS and safety analysis of a randomized phase III study of atezolizumab + carboplatin + paclitaxel or nab-paclitaxel vs carboplatin + nab-paclitaxel as 1L therapy in advanced squamous NSCLC.
Authors: Robert M. Jotte, Federico Cappuzzo, Ihor Vynnychenko, Daniil Stroyakovskiy, Delvys Rodriguez Abreu, Maen A. Hussein, Ross A. Soo, Henry Jacob Conter, Toshiyuki Kozuki, Carlos Silva, Vilma Graupner, Shawn Sun, Ray S Lin, Claudia Kelsch, Marcin Kowanetz, Tien Hoang, Alan Sandler, Mark A. Socinski
Journal: Journal of Clinical Oncology (2018)

LBA9000 Background: Atezolizumab (atezo; anti–PD-L1) demonstrated OS benefit vs docetaxel in 2L+ NSCLC regardless of PD-L1 status or tumor histology. Because cytotoxic agents can exhibit positive immunomodulatory effects, combining atezo with chemotherapy may further improve outcomes. IMpower131 (NCT02367794) was designed to evaluate atezo + carboplatin (carbo) + paclitaxel (pac) or nab-paclitaxel (nab-pac) in 1L stage IV squamous NSCLC. Methods: Patients (pts) were randomized 1:1:1 to Arm A (atezo 1200 mg q3w + carbo AUC 6 q3w + pac 200 mg/m 2 q3w), Arm B (atezo + carbo + nab-pac 100 mg/m 2 weekly) or Arm C (carbo + nab-pac). Pts received chemotherapy for 4 or 6 cycles and atezo until loss of clinical benefit. We present the primary analysis of investigator (INV)-assessed PFS per RECIST v1.1 in the ITT population for Arm B vs Arm C. Data cutoff: 22 January 2018. Results: 338 pts (Arm A), 343 pts (Arm B) and 340 pts (Arm C) were enrolled. Minimum follow-up was 9.8 mo. INV-assessed median PFS was 6.3 mo in Arm B vs 5.6 mo in Arm C (HR, 0.715; 95% CI: 0.603, 0.848; P = 0.0001). PFS benefit was enriched in all PD-L1–positive IHC subgroups and was most pronounced in TC3 or IC3. AEs related to any treatment (TRAEs) were 91.3% (Arm A), 94.6% (Arm B) and 90.7% (Arm C); Grade 3-4 TRAEs were 42.8% (Arm A), 68.0% (Arm B) and 56.9% (Arm C); serious TRAEs were 22.3% (Arm A), 20.4% (Arm B) and 10.5% (Arm C). Preliminary OS data will be presented. Conclusions: IMpower131 met its co-primary endpoint of INV-assessed PFS in the ITT population in Arm B vs Arm C. The safety profile of atezo + carbo + nab-pac or pac was consistent with the known risks of the individual treatment components; no new safety signals were identified. Clinical trial information: NCT02367794. [Table: see text]
Treatment and secondary prophylaxis with ethanol lock therapy for central line-associated bloodstream infection in paediatric cancer: a randomised, double-blind, controlled trial
Authors: Joshua Wolf, Tom G Connell, Kim J Allison, Li Tang, Julie Richardson, Kristen Branum, Eloise Borello, Jeffrey E Rubnitz, Aditya H Gaur, Hana Hakim, Yin Su, Sara M Federico, Francoise Mechinaud, Randall T Hayden, Paul Monagle, Leon J Worth, Nigel Curtis, Patricia M Flynn
Journal: The Lancet Infectious Diseases (2018)
Regulation of epithelial injury and bile duct obstruction by NLRP3, IL-1R1 in experimental biliary atresia
Authors: Li Yang, Tatsuki Mizuochi, Pranavkumar Shivakumar, Reena Mourya, Zhenhua Luo, Sridevi Gutta, Jorge A. Bezerra
Journal: Journal of Hepatology (2018)