tbuckley/cabot-search huggingface dataset:
A phase II, open-label study of durvalumab in combination with stereotactic body radiotherapy in androgen-intact patients with oligometastatic prostate cancer.
Authors: Isobel Porter, Thomas Eade, Andrew Kneebone, George Hruby, Sophie Mascall, Alexander P. Davis, Alexander David Guminski
Journal: Journal of Clinical Oncology (2020)

TPS263 Background: With the introduction of Ga68-PSMA PET, a new cohort of androgen-intact men with oligometastatic prostate cancer (PCa) recurrence has been identified. These men have normal traditional imaging and a disease-free interval usually measured in years from their definitive treatment. Recent data supports the use of metastasis-directed stereotactic body radiotherapy (SBRT) in oligometastatic PCa. Based on our institutional data in 57 patients treated with SBRT alone in the PSMA era, the median PSA progression free survival (PFS) is 11 months. Despite 100% local control, 80% relapsed by 18 months. Improving the PFS for these men is an important clinical need. Achieving this without the introduction of androgen deprivation therapy (ADT) will likely improve quality of life and minimise the adverse consequences of androgen deprivation. Radiotherapy results in cell stress and release of damage associated molecular patterns (DAMPs) with activation of antigen presenting cells. This stimulates a tumour antigen specific T-cell response and abscopal effect which can be heightened with PD-(L)1 inhibition. Most PD-(L)1 inhibition trials in PCa are in men with a high burden of castrate resistant disease. However, data suggests the castrate state can impair host anti-tumour immune response. PD-(L)1 inhibition combined with SBRT in androgen-intact men may result in improved PFS compared with our historical cohort treated with SBRT alone. Methods: This is a non-randomized, open label, phase II study of durvalumab (1500 mg IV every 4 weeks) starting 1 month prior to SBRT in men with recurrent PCa not immediately requiring ADT and with Ga68-PSMA PET detected oligometastasis. SBRT will be delivered with 30Gy/3# to lymph nodes or 24Gy/2# to bone metastasis. Durvalumab will be continued to a maximum of 12 months. Primary outcomes will be freedom from biochemical failure and toxicity. Secondary objectives include biochemical response rate, magnitude of response, overall survival, time and response to subsequent treatments and quality of life. The study is recruiting at Royal North Shore Hospital in Sydney with 18 of the planned 30 patients enrolled. Clinical trial information: ACTRN12619000097145.
Mannan-Allergoid Conjugate of House-Dust Mites: First Subcutaneous and Sublingual Dose-Finding Study in Humans
Authors: Miguel Casanovas, María Nieto, Ángel Mazón, María Dolores Hernández, Dah Tay Jang, Susana Calaforra, María del Carmen Pérez-Francés, Javier Montoro, Antonio de Mateo, Remedios Alamar, David El-Qutob, Javier Fernández, Luis Moral, Mónica Antón, Carmen Andreu, Ángel Ferrer, Antonio Nieto
Journal: Journal of Allergy and Clinical Immunology (2020)
Circular RNAs in the tumour microenvironment
Authors: Zhonghua Ma, You Shuai, Xiangyu Gao, Xianzi Wen, Jiafu Ji
Journal: Molecular Cancer (2020)

Abstract Background Circular RNAs (circRNAs) are a new class of endogenous non-coding RNAs (ncRNAs) widely expressed in eukaryotic cells. Mounting evidence has highlighted circRNAs as critical regulators of various tumours. More importantly, circRNAs have been revealed to recruit and reprogram key components involved in the tumour microenvironment (TME), and mediate various signaling pathways, thus affecting tumourigenesis, angiogenesis, immune response, and metastatic progression. Main body of the abstract In this review, we briefly introduce the biogenesis, characteristics and classification of circRNAs, and describe various mechanistic models of circRNAs. Further, we provide the first systematic overview of the interplay between circRNAs and cellular/non-cellular counterparts of the TME and highlight the potential of circRNAs as prospective biomarkers or targets in cancer clinics. Finally, we discuss the biological mechanisms through which the circRNAs drive development of resistance, revealing the mystery of circRNAs in drug resistance of tumours. Short conclusion Deep understanding the emerging role of circRNAs and their involvements in the TME may provide potential biomarkers and therapeutic targets for cancer patients. The combined targeting of circRNAs and co-activated components in the TME may achieve higher therapeutic efficiency and become a new mode of tumour therapy in the future.
Abstract 11401: Upregulation of Cardiac Beta3-Adrenergic Receptor-Activated Inducible Nitric Oxide Synthase (iNOS)-Coupled Pathway Promotes Diabetic Cardiomyopathy in Spontaneous Diabetic Cynomolgus Monkeys: Role of Oxidant Stress
Authors: Che Ping Cheng, Heng-Jie Cheng, Qun Shao, Li Zhang, Michael F Callahan, Dalane Kitzman, David Zhao, Janice D Wagner
Journal: Circulation (2018)

Background: Recent evidence highlights oxidative stress as an important mechanism to cardiac dysfunction in diabetic cardiomyopathy (DM) and altered β3-adrenergic receptor (AR)-activated nitric oxi...
Phenotype and outcome of pulmonary arterial hypertension patients carrying a <i>TBX4</i> mutation
Authors: Pierre Thoré, Barbara Girerd, Xavier Jaïs, Laurent Savale, Maria-Rosa Ghigna, Mélanie Eyries, Marilyne Levy, Caroline Ovaert, Amélie Servettaz, Anne Guillaumot, Claire Dauphin, Céline Chabanne, Emmanuel Boiffard, Vincent Cottin, Frédéric Perros, Gérald Simonneau, Olivier Sitbon, Florent Soubrier, Damien Bonnet, Martine Remy-Jardin, Ari Chaouat, Marc Humbert, David Montani
Journal: European Respiratory Journal (2020)

Introduction TBX4 mutation causes small patella syndrome (SPS) and/or pulmonary arterial hypertension (PAH). The characteristics and outcomes of PAH associated with TBX4 mutations are largely unknown. Methods We report the clinical, functional, radiologic, histologic and haemodynamic characteristics and outcomes of heritable PAH patients carrying a TBX4 mutation from the French pulmonary hypertension (PH) network. Results 20 patients were identified in 17 families. They were characterised by a median age at diagnosis of 29 years (0–76 years) and a female to male ratio of three. Most of the patients (70%) were in New York Heart Association (NYHA) functional class III or IV with a severe haemodynamic impairment (median pulmonary vascular resistance (PVR) of 13.6 (6.2–41.8) Wood units). Skeletal signs of SPS were present in 80% of cases. Half of the patients had mild restrictive or obstructive limitation and diffusing capacity of the lung for carbon monoxide ( D LCO ) was decreased in all patients. High-resolution computed tomography (HRCT) showed bronchial abnormalities, peri-bronchial cysts, mosaic distribution and mediastinal lymphadenopathies. PAH therapy was associated with significant clinical improvement. At follow-up (median 76 months), two patients had died and two had undergone lung transplantation. One-year, three-year and five-year event-free survival rates were 100%, 94% and 83%, respectively. Histologic examination of explanted lungs revealed alveolar growth abnormalities, major pulmonary vascular remodelling similar to that observed in idiopathic pulmonary arterial hypertension (IPAH) and accumulation of cholesterol crystals within the lung parenchyma. Conclusion PAH due to TBX4 mutations may occur with or without skeletal abnormalities across a broad age range from birth to late adulthood. PAH is usually severe and associated with bronchial and parenchymal abnormalities.
Assessment of Long-term Benefit of Intensive Blood Pressure Control on Residual Life Span
Authors: Muthiah Vaduganathan, Brian L. Claggett, Stephen P. Juraschek, Scott D. Solomon
Journal: JAMA Cardiology (2020)

<h3>Importance</h3> High blood pressure (BP) is a leading contributor to premature mortality worldwide. The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated a 27% reduction in all-cause death with intensive (vs standard) BP control. However, traditional reporting of survival benefits is not readily interpretable outside medical communities. <h3>Objective</h3> To estimate residual life span and potential survival gains with intensive compared with standard BP control in the SPRINT trial using validated nonparametric age-based methods. <h3>Design, Setting, and Participants</h3> This secondary analysis of data from an open-label randomized clinical trial included data from 102 enrolling clinical sites in the United States. Adults who were 50 years or older, were at high cardiovascular risk but without diabetes, and had a screening systolic BP between 130 and 180 mm Hg were enrolled between November 2010 and March 2013. Data analysis occurred from May 2019 to December 2019. <h3>Interventions</h3> A 1:1 randomization to intensive (target, &lt;120 mm Hg) or standard (target, &lt;140 mm Hg) systolic BP targets. <h3>Main Outcomes and Measures</h3> We calculated age-based estimates of projected survival (at a given age) using baseline age rather than time from randomization as the time axis. In each treatment arm at every year of age, residual life span was estimated using the area under the survival curve, up to a maximum of 95 years. Differences in areas under the survival curves reflect the estimated treatment benefits on projected survival. <h3>Results</h3> A total of 9361 adults were enrolled (mean [SD] age at randomization, 68 [9] years; 6029 [64.4%] were men; 5399 [57.7%] were non-Hispanic white individuals). Mean survival benefits with intensive vs standard BP control ranged from 6 months to up to 3 years. At age 50 years, the estimated residual survival was 37.3 years with intensive treatment and 34.4 years with standard treatment (difference, 2.9 years [95% CI, 0.9-5.0 years];<i>P</i> = .008). At age 65 years, residual survival was 24.5 years with intensive treatment and 23.3 years with standard treatment (difference, 1.1 years [95% CI, 0.1-2.1 years];<i>P</i> = .03). Absolute survival gains with intensive vs standard BP control decreased with age, but the relative benefits were consistent (4% to 9%). <h3>Conclusions and Relevance</h3> Intensive BP control improves projected survival by 6 months to 3 years among middle-aged and older adults at high cardiovascular risk but without diabetes mellitus. These post hoc actuarial analyses from SPRINT support the survival benefits of intensive BP control, especially among middle-aged adults at risk. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT01206062
Workplace bullying and sleep – A systematic review and meta-analysis of the research literature
Authors: Morten B. Nielsen, Anette Harris, Ståle Pallesen, Ståle V. Einarsen
Journal: Sleep Medicine Reviews (2020)

This systematic review and meta-analysis 1) clarifies and quantifies existing results on the association between exposure to workplace bullying and sleep, 2) evaluates the methodological quality of existing studies, 3) identifies theoretical frameworks used in research, 4) determines moderating and mediating variables, and 5) provides guidelines for future research. Searches for primary studies were conducted in Pubmed, Medline, Embase, PsycINFO and Web of Science. Of the 406 studies identified, 26 fulfilled the inclusion criteria for the qualitative synthesis whereas sixteen studies were included in the meta-analysis (cross sectional effect sizes: 15; N = 69,199/prospective effect sizes: 6; N = 26,164). Workplace bullying was significantly related to sleep problems in all studies. Across cross-sectional studies, targets of bullying had 2.31 higher odds of reporting sleep problems compared to non-bullied workers. The odds across the prospective studies was 1.62. The quality of evidence for the association between workplace bullying and sleep problems was low to moderate. Only eight studies had a predefined theoretical rationale for the association, and few studies examined mediating and moderating variables or bidirectional associations. The methodological quality of the studies was moderate. Further research is needed to establish the nature, directionality, mechanisms, and conditions of the association between bullying and sleep.
Alvimopan as an essential component of ERAS protocol to decrease length of hospital stay.
Authors: Peter Hanna, Arveen Kalapara, Subodh Regmi, Kalyana Srujana, Joseph Zabell, Darrel Randle, Alexander Kaizer, Luke Patten, Badrinath R. Konety, Joyce Wahr, Christopher J. Weight
Journal: Journal of Clinical Oncology (2020)

517 Background: Radical cystectomy for muscle invasive bladder cancer is the gold standard. However, it is frequently associated with a prolonged length of hospital stay (LOS). We study the effect of ERAS protocol implementations and Alvimopan use in patients undergoing radical cystectomy and its impact on length of hospital stay (LOS). Methods: Retrospective cohort study involving consecutive patients undergoing radical cystectomy for bladder cancer at our institution from 2010 through 2018. We evaluated Alvimopan use plus an ERAS protocol post radical cystectomy versus patients who underwent ERAS protocol alone versus those who were managed prior to ERAS protocol implementation. Primary outcome of interest was LOS, controlling for age, sex, smoking status and Charleson comorbidities index. Results: 146 patients (49.32 %) received standard care (non-ERAS) (group A), 102 patients (34.45 %) underwent ERAS protocol alone (group B) and 47 patients (15.87 %) underwent ERAS protocol plus Alvimopan (group C). There was no significant difference in length of stay between group A and group B (p=0.856). However, group C experienced a shorter LOS (16.6%) compared to group A (p=0.015). Similarly, group B was not significantly associated with the days to bowel movements compared to group A (p=0.112), however, group C demonstrated a significantly shorter time (16.3%) to bowel movements compared to group A (p=0.015). On other hand, group c wasn’t significantly associated with time tolerance to regular diet (p=0.068). Limitations include retrospective nature of some of the data, non-randomized approach and confounders such as a mix of robot and open approaches to cystectomy. Conclusions: Of all ERAS protocol components, Alvimopan appeared to be the most significant contributor in accelerating GI recovery and decrease LOS in our cohort.
Impact of 18F-fluciclovine PET on salvage radiotherapy plans for men with post-radical prostatectomy recurrence of prostate cancer.
Authors: Heather Ann Payne
Journal: Journal of Clinical Oncology (2020)

19 Background: Imaging options to localize lesions in men with biochemical recurrence (BCR) of prostate cancer after radical prostatectomy (RP) are limited, especially at low PSA levels. Consequently, radiation oncologists typically target the prostate bed (PB) with or without pelvic lymph nodes (LN) based on clinical or pathologic features. The FALCON study (NCT02578940) evaluated the clinical benefit of 18 F-fluciclovine PET through its impact on management plans for men with BCR. Here, we report the impact on salvage radiotherapy (RT) decisions in men post-RP. Methods: Men with a first BCR episode following curative-intent therapy who were being considered for salvage therapy underwent 18 F-fluciclovine PET at one of 6 UK sites. Physicians documented patients’ treatment plans pre- and post-scan. Imaging results and management plans were stratified by prior treatment as determined from patient records. Results: Sixty-five (63%) of the 104 FALCON patients had undergone RP. Of these, 62 (median PSA, 0.32 ng/mL) had a pre-scan plan for salvage RT. Lesions were found in 21 (34%) patients (median PSA, 0.32 ng/mL), of whom 10 (16%; median PSA, 0.54 ng/mL) had extraprostatic findings (Table). Post-scan, 25 (40%) men had a management change, 17 (68%) due to a positive scan. Of the 25 post-scan revisions, 17 (68%) were changes to the treatment modality: 8 to systemic therapy, 8 to watchful waiting, 1 other. A further 8 (32%) men had RT fields modified: PB alone modified to include a boost to a 18 F-fluciclovine-avid lesion (n = 7) or whole pelvis field refocused on a smaller area (n = 1). Conclusions: Two fifths of men scheduled to undergo salvage RT after RP had their management plan revised following 18 F-fluciclovine PET. The majority of changes involved a completely new treatment modality. Future studies to evaluate the clinical outcomes of such changes are warranted. Clinical trial information: NCT02578940. [Table: see text]
Dysbiosis-Induced Secondary Bile Acid Deficiency Promotes Intestinal Inflammation
Authors: Sidhartha R. Sinha, Yeneneh Haileselassie, Linh P. Nguyen, Carolina Tropini, Min Wang, Laren S. Becker, Davis Sim, Karolin Jarr, Estelle T. Spear, Gulshan Singh, Hong Namkoong, Kyle Bittinger, Michael A. Fischbach, Justin L. Sonnenburg, Aida Habtezion
Journal: Cell Host & Microbe (2020)
Abstract P6-02-05: Clumped vs non-clumped internal enhancement patterns in linear non-mass enhancement on breast MRI
Authors: Shu-Tian Chen, James Covelli, Satoko Okamoto, Bruce Daniel, Wendy DeMartini, Debra Ikeda
Journal: Cancer Research (2020)

Abstract Purpose To compare positive predictive values (PPVs) of clumped versus non-clumped (homogenous and heterogenous) internal enhancement on MRI detected linear non-mass enhancement (NME) on MRI-guided vacuum assisted breast biopsy (MRI-VABB). Materials and Methods With IRB approval, radiology reports were retrospectively reviewed of 598 lesions undergoing 9-gauge MRI-VABB from January 2015 to April 2018 for lesions showing linear NME, recording clumped and non-clumped internal enhancement. We reviewed the electronic medical records for MRI-guided VABB pathology, any follow up surgery and imaging and/or clinical follow-up &amp;gt;1 year (mean 1.7 years). The X2 test was performed for univariate analysis. Results There were 120/598 (20%) linear NME MRI-VABB lesions with clumped (52/120, 43%) vs non-clumped (68/120, 57%) internal enhancement, average size 1.8 cm (range 0.3-7.6 cm). On MRI-VABB, cancer was identified in 22/120 (18%) lesions, ductal carcinoma in situ (DCIS) was found in 18/22 (82%) and invasive cancer (3 IDC, 1 ILC) in 4 (18%). 31/120 (26%) were high-risk lesions with 3/31 (10%) high-risk lesions upgraded to DCIS at surgery, which comprising a total of 25/120 (21%) malignancies. Malignancy was found in 12/52 (23%) clumped lesions and in 13/68 (19%) of non-clumped lesions that showed heterogenous (5/13, 38%) or homogenous (8/13, 62%) internal enhancement. The PPV of linear NME with clumped internal enhancement (23.1%; 95% CI, 11.6-34.6) was not significantly different from the PPV of non-clumped linear NME (19.1%; 95% CI, 9.8-28.4) (p=0.597). The PPV of linear NME lesions &amp;lt;1cm (33.3%; 95% CI, 11.5-55.1) was not significantly different from the PPV of lesions ≥1cm (18.6%; 95% CI, 11.1-26.2) (p=0.157). 53/120 (44%) NME lesions were operated upon. Of the remaining 67 NME not operated upon, 2 benign findings were lost to follow up, and 65 (64 benign, 1 high-risk) showed no suspicious imaging and/or clinical features on follow up. Conclusion Linear NME showed malignancy in 21% of our series. Linear NME with clumped or non-clumped internal enhancement patterns, regardless of lesion size, should undergo MRI-VABB in appropriate clinical settings. Citation Format: Shu-Tian Chen, James Covelli, Satoko Okamoto, Bruce Daniel, Wendy DeMartini, Debra Ikeda. Clumped vs non-clumped internal enhancement patterns in linear non-mass enhancement on breast MRI [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-02-05.
Prospective observational study on pazopanib in patients treated for advanced/metastatic renal cell carcinoma (RCC): APOLON Study.
Authors: Philippe Barthelemy, Laurence Albiges, Bernard Escudier, Thierry Lebret, Pierre Bigot, Ulrich Stein, Louis-Marie Dourthe, Jeannine De La Cruz, Malka Tindel, Antoine Thiery-Vuillemin
Journal: Journal of Clinical Oncology (2020)

629 Background: Pazopanib (PZP), has been granted for advanced or metastatic RCC. In addition to pivotal clinical trials, real-world evidence (RWE) is required to evaluate effectiveness and safety in clinical routine practices. Methods: APOLON is a non-interventional, multicentric prospective study to assess PZP Progression-Free Survival (PFS) (8-month PFS rate as primary endpoint), Overall Survival (OS), Objective Response Rate (ORR), tolerability, subsequent post-pazopanib therapy sequences. It is conducted in France with 55 sites (hospital or private practitioners) in patients with mRCC, naïve to anti-VEGF therapy, who initiated PZP treatment. Data are collected at baseline and at 1, 2-3, 6, 9, 12, 18, 24, 30, 36 months (mo). Patients (n= 218) were recruited from Nov 2017 to Jan 2019. This interim analysis presents results 6 months after last patient was enrolled. Results: Patients were 71,1% males, with a median age of 69.6 years. They had clear-cell type RCC for 97.7% with a favourable (26.4%), intermediate (52.9%) or poor (20.7%) IMDC risk score. Comorbidities were: hypertension (75.1%), diabetes (26%), arterial disorders (20.1%), other pathologies (47.3%); 81.7% received co-medications. ECOG-PS was 0 (42.9%), 1 (40%), 2 (15.7%), Metastases were mainly located in lungs (62.8%), bones (28.9%), mediastinal (17.9%)/abdominal (17%) lymph nodes, glands (pancreas, thyroid, adrenals) (17.4%). Of them, 56% had an history of partial/total nephrectomy, 28.1% previous local treatments for metastases. Median PFS, assessed by investigator, was 11.3 mo ( 95% CI: 8.7-13), with an 8-mo PFS rate at 62.9%. ORR was 47.2% and 1-year OS rate was 71.2%. Treatment-related serious adverse events were reported in 17.3% of patients. No new safety signal was identified. After a median follow-up of 8.8 mo, of the 121 patients with discontinuation, 74 received post-PZP lines comprising firstly nivolumab (67.6%), cabozantinib (16.2%), sunitinib (10.8%), other (5.6%). Conclusions: APOLON study represents real-life population including elderly and frail patients with clinically meaningful ORR and PFS with PZP. Reported adverse events were consistent with known safety PZP profile.
Multimodal Abnormalities of Brain Structure and Function in Major Depressive Disorder: A Meta-Analysis of Neuroimaging Studies
Authors: Jodie P. Gray, Veronika I. Müller, Simon B. Eickhoff, Peter T. Fox
Journal: American Journal of Psychiatry (2020)

Imaging studies of major depressive disorder have reported structural and functional abnormalities in a variety of spatially diverse brain regions. Quantitative meta-analyses of this literature, however, have failed to find statistically significant between-study spatial convergence, other than transdiagnostic-only effects. In the present study, the authors applied a novel multimodal meta-analytic approach to test the hypothesis that major depression exhibits spatially convergent structural and functional brain abnormalities.