tbuckley/cabot-search huggingface dataset:
Why Less Is Always More in the Treatment of Alcohol Use Disorders
Authors: David J. Nutt, Antoni Gual, Peter Anderson, Jürgen Rehm
Journal: JAMA Psychiatry (2019)

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Preliminary results of a two stage phase II study of <sup>18</sup>F-DCFPyL PET-MR for enabling oligometastases ablative therapy in subclinical prostate cancer.
Authors: Rachel Glicksman, Ur Metser, Doug Vines, Rosanna Chan, John Valliant, Peter W. M. Chung, Mary K. Gospodarowicz, Andrew Bayley, Charles N Catton, Padraig Richard Warde, Joelle Antoine Helou, Nafisha Lalani, David E Green, Nathan Perlis, Neil Eric Fleshner, Robert James Hamilton, Alexandre Zlotta, Antonio Finelli, David A. Jaffray, Alejandro Berlin
Journal: Journal of Clinical Oncology (2019)

250 Background: Despite maximal local therapies (MLT) (radical prostatectomy followed by radiotherapy [RT]), 20-30% of men will have incurable progression of prostate cancer (PC). Most recurrences in this scenario are characterized by continuous PSA rises and failure of standard imaging (bone scan [BS] and computed tomography [CT]) to detect recurrence sites. We conducted a phase II trial for men with rising PSA after MLT using 18 F-DCFPyL PET-MR followed by targeted ablation of PET positive foci. We report the results of our pre-defined analysis. Methods: Patients with rising PSA (0.43.0 ng/mL) after MLT, negative BS/CT and no prior salvage ADT were eligible. All patients underwent 18 F-DCFPyL PET-MR followed by immediate PET-CT acquisition. Those with limited disease, where possible, underwent stereotactic ablative RT (SABR) or surgery. No ADT was used. The primary endpoint was biochemical response rate (complete [undetectable PSA] or partial [PSA decline ≥50% compared to baseline]). A Simon’s two stage study design was employed. Stage 1 included 12 response evaluable patients, requiring 1 or more responses in the absence of grade 3+ toxicities to proceed to stage 2 (additional 25 response evaluable patients). Results: After a median of 58 months (range 29-120) post MLT, 20 patients underwent PET-MR/CT to have 12 response evaluable patients. Median PSA at enrollment was 1.3 ng/mL (range 0.4-2.8). Three patients had negative PET-MR/CT, while 17 had positive scans, of which 12 (60%) were amenable to response evaluable ablation. The median number of detected lesions in those treated was 2 (range 1-5). Ten patients underwent SABR (27-30 Gy/3 fractions) and 2 had surgery. One patient (8%) had complete and 4 (33%) had partial PSA responses at a median of 3.3 months (range 2.8-6.0) after ablation, while the remaining 7 (59%) did not have biochemical response. No grade 3+ toxicities were observed. Conclusions: 18 F-DCFPyL PET/MR has high detection rates in men with rising PSA after MLT. We observed favorable early results with SABR or surgery (41% RR). Trial completion will inform if this approach offers potential for cure in an early molecularly-defined PC oligometastatic state. Clinical trial information: NCT03160794.
High PD-1 and Tim-3 Expression Concurrent with Exhausted CD4+ and CD8+ T Cells in Bone Marrow Compared with Peripheral Blood from Patients with Multiple Myeloma
Authors: Jiaxiong Tan, Shaohua Chen, Jingying Huang, Youchun Chen, Lijian Yang, Jun Zhong, Yuhong Lu, Yangqiu Li
Journal: Blood (2017)
The value of primary tumor resection in patients with metastatic colorectal cancer received chemotherapy plus bevacizumab: Results from the single center, retrospective study.
Authors: Zhiming Wang, Li Lian, Yuhong Zhou, Tian Shu Liu
Journal: Journal of Clinical Oncology (2015)

e14615 Background: The role of primary tumor resection ( PTR ) in colorectal cancer patients with synchronous unresectable metastases are still controversial. The addition of bevacizumab to chemotherapy brings out further improvement in disease control rate and overall survival among patients with metastatic colorectal cancer, which might change the role of primary tumor resection in the multidisciplinary treatment. The purpose of this study was to investigate the clinical benefit of PTR in colorectal cancer patients with synchronous unresectable metastases who received chemotherapy combined with bevacizumab. Methods: We performed a retrospective study of 191 colorectal cancer patients with synchronous unresectable metastases and performance status 0-2 received chemotherapy (mFOLFOX/XELOX) combined with bevacizumab. Between October 2011 to November 2013, the patients were enrolled to either the group ( n = 118 ) with PTR or the group ( n = 73 ) with IPT ( intact primary tumor ) by doctors/patients choice. The patients were followed up to January 2015. Progress free survival ( PFS ), overall survival (OS), and severe clinical events (such as emergent surgery, radiation therapy, stent plantation) were analyzed. Results: There were no significant differences of the clinical characteristics of age, sex, performance status, KRAS mutation, colon or rectum, the number of distant metastatic organs in the two groups. The median PFS of the group with PTR was superior to the group with IPT (10.0 vs 7.8 months, p < 0.01 ), and the median OS as the same (22.4 vs 17.7 months, p < 0.01). The incidences of adverse events associated with chemotherapy were similar in the two groups. There were 16 patients ( 21.9%, 16/73 ) with IPT developed significant primary tumor-related complications including bleeding, obstruction or even perforation. Conclusions: The colorectal cancer patients with synchronous unresectable metastases received chemotherapy plus bevacizumab who underwent primary tumor resection had significantly longer PFS and survival, decreased severe clinical events and improved the quality of life compared those without prophylactic surgery.
Can we avoid radiotherapy with 18FCH PET/CT?
Authors: Julieta Iorio, Martin Eleta, Florencia Bambacci, Lucrecia Cuneo, Constanza Montenegro, Maria Agustina Brisco
Journal: Journal of Clinical Oncology (2019)

282 Background: The aim of this study was to assess the utility of 18 fluorocholine (FCH) positron emission tomography (PET)/computed tomography (CT) in detecting local recurrence in patients with prostate carcinoma treated with radical prostatectomy surgery. Methods: 432 patients with prostate cancer were enrolled in our institution between July 2015 and August 2018. 176 were treated with radical prostatectomy surgery and presented elevated levels of PSA (0.02-1600 ng/ml). All of them underwent “Dual phase” PET-CT consisting of initial pelvis starting 20 minutes after the injection of 18 F-Choline followed by 1 hour delayed PET of the whole body. 18 F-Colina PET/TC findings were compared with other imaging techniques and/or clinical monitoring. Patients were divided in three subgroups according to PSA levels: &lt;1 ng/ml; ≥1-5ng/ml y &gt;5 ng/ml. Results: 39 (22%) patients had PSA levels &lt;1 ng/ml; 90 (51%) had between 1-5 ng/ml and 47 (27%) &gt;5 ng/ml. 120 (68%) patients showed radiotracer uptake, on the other hand, 56 (32%) patients had negative PET-CT. 153 lesions showed increased uptake on FCH-PET, only 36 (23%) of them were interpretated as local recurrence the rest of them were interpretated as extraprostatic involment (table). Conclusions: 18 FCH PET/CT has clinical implications in patients with prostate carcinoma treated with radical prostatectomy surgery not only because it avoids unnecessary radiotherapy in the surgical wound, but also, it has the ability to detect local recurrent disease and lymphatic/haematogenous involvement. [Table: see text]
Abstract MP72: The Effects of Antihypertensive Class on Falls, Syncope, and Orthostatic Hypotension in Older Adults: the ALLHAT Trial
Authors: Stephen P Juraschek, Lara M Simpson, Barry R Davis, Jennifer L Beach, Anthony Ishak, Kenneth J Mukamal
Journal: Circulation (2019)

Background: Hypertension treatment is believed to contribute to falls, syncope, and orthostatic hypotension (OH), common events among older adults. Whether choice of antihypertensive agent influences the incidence of these adverse outcomes is unknown. Hypothesis: Chlorthalidone and atenolol are associated with higher risk of fall, syncope, and OH, compared with amlodipine or lisinopril. Methods: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a randomized clinical trial that compared the effects of first-step therapy with amlodipine, lisinopril, or chlorthalidone on fatal coronary heart disease or nonfatal myocardial infarction (1994-2002). We linked participants to CMS and VA claims to determine the incidence of fall, syncope, OH, or a composite outcome (any of fall, syncope, or OH), using Cox regression. The association of baseline or 1-month add-on atenolol use with outcomes was determined via Cox models adjusted for age, sex, race, and randomized drug assignment. Results: Among 23,964 participants (mean age 70.4 ± 6.7 years, 43% women, 31% black), 927 participants took atenolol at baseline. Over a mean follow-up of 4.9 years, there were 267 fall, 755 syncope, 249 OH, and 1,157 composite claims with no significant differences in the cumulative incidence of events across randomized drug assignments ( Figure ). Compared with chlorthalidone, amlodipine and lisinopril were not associated with falls (HR [95%CI]: 1.36 [0.90-2.05] and 0.80 [0.47-1.36], respectively), syncope (0.96 [0.77-1.21] and 1.07 [0.85-1.34], respectively), OH (0.98 [0.66-1.45] and 1.24 [0.87-1.76], respectively), or the composite outcome (1.01 [0.84-1.21] and 1.07 [0.92-1.22], respectively). Similarly, atenolol use was not associated with any of the 3 individual or composite claims. Conclusions: Choice of antihypertensive agent has no effect on risk of fall, syncope, or OH in older adults. This observation should simplify the choice of initiating antihypertensive therapy in this population.
Abstract P036: Association Between Circulating Galectin-3 and Arterial Stiffness in the Atherosclerosis Risk in Communities Study
Authors: Xiaoming Jia, Hirofumi Tanaka, Christie M Ballantyne, Wensheng Sun, Amil M Shah, Ron C Hoogeveen, David Aguilar, Chiadi E Ndumele, Eric Boerwinkle, Salim Virani, Elizabeth Selvin, Gerardo Heiss, Vijay Nambi
Journal: Circulation (2019)

Introduction: Galectin-3 (gal-3) is a B-galactoside-binding lectin and is associated with increased risk of heart failure and other adverse cardiovascular outcomes. Circulating gal-3 has been implicated in promoting tissue fibrosis, leading to vascular remodeling and resultant arterial stiffening. Hypothesis: Plasma gal-3 levels will be associated with central arterial stiffness in a community-based population. Methods: We conducted a cross-sectional analysis of 4,073 participants from the Atherosclerosis Risk in Communities (ARIC) Study who attended visit 5 (2011-2013), with a mean age of 75.1±5.0 years. Central arterial stiffness was measured by carotid-femoral pulse wave velocity (cfPWV). Association between gal-3 and arterial stiffness was assessed using multivariable linear regression models with gal-3 (log transformed) and adjustment first for age, sex, race-center, heart rate, current smoking, mean arterial pressure and use of anti-hypertensive medication (model 1), then for model 1 plus body mass index (BMI), diabetes, hypertension, LDL cholesterol and estimated glomerular filtration rate (eGFR) (model 2). Results: The median gal-3 concentration was 16.5 ng/mL (p25, p75: 13.8, 19.8) and mean cfPWV was 1163 (SD, 303) cm/s. Higher gal-3 concentrations corresponded with higher mean cfPWV and central pulse pressure (p-trends &lt;0.001). Higher gal-3 levels were also associated with higher BMI, diabetes, hypertension, LDL cholesterol, cholesterol lowering medication use, prevalent coronary artery disease, and lower eGFR. In regression analysis, gal-3 was significantly associated with cfPWV in model 1 (ß=46.0; 95% CI 15.4-76.6, per natural log higher gal-3, p=0.003). Further adjustment in model 2 strongly attenuated the association and the coefficient was no longer significant (ß=25.0; 95% CI -8.2-58.2, per natural log increase in gal-3, p=0.14). Conclusions: Higher levels of gal-3, a known promoter of tissue fibrosis, were associated with greater central arterial stiffness. In addition, circulating gal-3 levels were also associated with many traditional risk factors such as BMI, diabetes, hypertension and eGFR; adjustment for these factors attenuated the association of gal-3 with arterial stiffness measures, suggesting mediation of the gal-3 association.
Poor mobilization of peipheral blood stem cells (PBSC) in patients undergoing autologous stem cell transplantation (ASCT): A prospective study.
Authors: Rakesh Reddy, Sameer Bakhshi, Atul Sharma, Ranjit Sahoo, Ajay Gogia, Prabhat Singh Malik, Sobuhi Iqbal, Sainath Bhethanabhotla, Mukesh Patekar, Mercy Thomas, Lalit Kumar
Journal: Journal of Clinical Oncology (2015)

e18013 Background: PBSC dose of 2×106cells /Kg body weight is considered adequate to allow prompt and persistent hematopoietic recovery. We prospectively studied factors predictive of poor mobilization. Methods: Between Feb 2014 to Jan 2015, 79 Patients underwent ASCT. Patients received inj. G-CSF 5mcg/kg/d twice a day for 5 days followed by large volume stem cell harvest on d5 and d6. Peripheral blood CD34 counts were enumerated on d4. Median age of the patients was 44 years (range, 4-68); M:F is 56:23. 54 patients had multiple myeloma (MM), NHL-7, HL-7, AML-4, neuroblastoma -3, PNET-3 and GCT-1. Poor mobilization was defined as a failure to collect stem cell dose of <2×106cells /Kg body weight after a maximum of 3 apharesis sessions. Results: The mean harvest yield is 3.35×106cells /Kg (range, 0.58-15.88). Median number of harvest session is 1. Thirteen (16%) patients had poor mobilization. Other factors like gender, platelet count, number of lines of prior therapy, exposure to lenalidomide and melphalan for myeloma patients, prior radiation to marrow bearing areas, treatment duration prior to transplant, bone marrow involvement with disease and cellularity pre-transplant were not significant predictors. A day 4 PBCD34 count of > 20/µL predicted a successful mobilization in all the patients. Conclusions: Age >50 years, diagnosis of lymphoma (NHL&HL), pre-transplant disease status of <CR and day 4 PBCD34 count of ≤20/µL were important predictors of poor mobilization. Factors impacting adequate mobilization. Variables Poor mobilization (n) Adequate mobilization (n) p value AGE ≤50 years >50 years 5 8 51 23 0.014 HISTOLOGY Lymphoma (NHL&HL) Others 7 6 7 59 0.001 Disease status at transplant CR <CR 4 9 55 11 0.027 D4-PB CD34 ≤20/µL >20/µL 13 0 12 54 0.0001
Publisher Correction: Clonal analysis of Salmonella-specific effector T cells reveals serovar-specific and cross-reactive T cell responses
Authors: Giorgio Napolitani, Prathiba Kurupati, Karen Wei Weng Teng, Malick M. Gibani, Margarida Rei, Anna Aulicino, Lorena Preciado-Llanes, Michael Thomas Wong, Etienne Becht, Lauren Howson, Paola de Haas, Mariolina Salio, Christoph J. Blohmke, Lars Rønn Olsen, David Miguel Susano Pinto, Laura Scifo, Claire Jones, Hazel Dobinson, Danielle Campbell, Helene B. Juel, Helena Thomaides-Brears, Derek Pickard, Dirk Bumann, Stephen Baker, Gordon Dougan, Alison Simmons, Melita A. Gordon, Evan William Newell, Andrew J. Pollard, Vincenzo Cerundolo
Journal: Nature Immunology (2019)
Correlation of dynamic <sup>18</sup>FET-PET with IDH 1 mutation for prediction of outcome in anaplastic astrocytoma WHO° III independently from tumor vascularisation.
Authors: Bogdana Suchorska, Nathalie Lisa Jansen, Theo Kraus, Armin Giese, Peter Bartenstein, Joerg Tonn
Journal: Journal of Clinical Oncology (2015)

2037 Background: Patients with an anaplastic glioma (WHO III°) without IDH1 mutation have a comparable disease course to glioblastoma. Dynamic 18FET-PET has been shown to provide prognostic information in malignant glioma independent of other clinical parameters. Here, we analyzed whether dynamic parameters acquired from 18FET-PET imaging correlate with IDH1 mutation status or tumor vessel density regarding the clinical course in anaplastic astrocytoma. Methods: 96 patients with a glioma WHO III ° who received a 18FET-PET at primary diagnosis were analyzed with respect to IDH1/2 mutation, MGMT promoter methylation, LOH 1p/19q status and vascularity (vessel density quantified by CD34-positive tumor area). The maximum
Simple Magnetic Resonance Scores Associate With Outcomes of Patients With Primary Sclerosing Cholangitis
Authors: Sara Lemoinne, Nora Cazzagon, Sanaâ El Mouhadi, Palak J. Trivedi, Anthony Dohan, Astrid Kemgang, Karima Ben Belkacem, Chantal Housset, Yves Chretien, Christophe Corpechot, Gideon Hirschfield, Annarosa Floreani, Raffaella Motta, Benoit Gallix, Alan Barkun, Jeffrey Barkun, Olivier Chazouillères, Lionel Arrivé
Journal: Clinical Gastroenterology and Hepatology (2019)
First-in-human phase I administration of YS110, a monoclonal antibody directed against the CD26 immunostimulatory molecule in advanced cancer patients.
Authors: ERIC ANGEVIN, Nicolas Isambert, Veronique N. Trillet-Lenoir, Benoit You, Jérôme Alexandre, Gerard Zalcman, Philippe Viehl, Françoise Farace, Fanny Valleix, Thomas Podoll, Yu Kuramochi, Itaru Miyashita, Osamu Hosono, Nam H. Dang, Kei Ohnuma, Taketo Yamada, Yutaro Kaneko, Chikao Morimoto
Journal: Journal of Clinical Oncology (2015)

2519 Background: YS110 is a recombinant humanized IgG1 monoclonal antibody that selectively binds with high affinity to the extracellular domain of the CD26 antigen. Preclinical evaluations of YS110 have demonstrated promising anti-tumor effects in cancer cell lines and xenografts expressing the CD26 antigen without significant side effects in toxicology studies (up to 100 mg/kg as single dose or 30 mg/kg for 5 weekly doses in monkeys). Methods: Escalating doses of YS110, using a standard 3+3 escalation scheme, were administered intravenously once every 2 weeks for 3 doses at 0.1, 0.4, 1 and 2 mg/kg and then based on PK data, once every week for 5 doses at 2, 4 and 6 mg/kg in solid tumors pts with confirmed CD26+tumor expression ( ≥ 20% of the tumor cells). This FIH study was designed to determine the MTD and RD, assess tolerance, PK and PDs of YS110. Results: 34 heavily pre-treated pts, including 23 pts with mesothelioma and 10 with renal cell carcinoma, were enrolled. A total of 232 infusions (median 3 [range 1-30]) of YS110 were administered across 6 dose levels ranging from 0.1 to 6 mg/Kg. MTD was not reached and 2 DLTs (1 pt with Gr 3 anaphylactic reaction at 1 mg/kg and 1 pt with Gr 3 allergic reaction at 2 mg/kg) were reported. Recovery was obtained with dose omission. Pts with a medical history of allergy were excluded and corticoids prophylaxis improved safety profile. No dose-dependent AEs were observed. Low grade asthenia (33.3%), hypersensitivity (30.0%), chills (13.3%), pyrexia (13.3%), nausea (13.3%), vomiting (10.0%), and headache (10.0%) were reported. Blood exposure PK parameters (AUC and Cmax) increased in proportion with the dose. Cytokines and immunophenotyping indicated CD26 target modulation. Prolonged stabilization was observed in 13 pts out of 25 evaluable pts. Conclusions: YS110 is well tolerated with preliminary evidence of activity. Combination with chemotherapy will be investigated. Clinical trial information: 2008-004407-56.
Abstract P357: Subclinical Hypothyroidism Alters Autonomous Nervous System. The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)
Authors: Rosangela Hoshi, Paulo A Lotufo, Eduardo Dantas, Rodrigo Varejao, J.Geraldo Mill, Isabela M Bensenor
Journal: Circulation (2019)

Introduction: Lifetime stressful conditions have been related to a higher risk of coronary heart diseases events. One recognized way is related to the disbalance of a parasympathetic and sympathetic system that can be mediated by several humoral factors, including thyroid hormones. Although the role of thyroid hormones on cardiovascular system regulation on the autonomous nervous system was very well-defined decades ago for normal conditions and there is scarce information concern to the association between subclinical thyroid disorders and the autonomous nervous system. Hypothesis: Subclinical thyroid dysfunctions are associated with autonomic disturbances assessed by the heart rate variability evaluated by linear and nonlinear variables following postural changes. Methods: At baseline of the ELSA-Brasil study (15105 adults aged 35-74 years old), we evaluated the heart variability rate at the supine position for everyone, and sampled 855 participants to repeat a standing measure of the heart rate variability. Subclinical hypothyroidism was defined as thyroid-stimulating hormone &gt;4 IU/ml for people with normal free-thyroxine levels. The cardiac autonomic nervous function was evaluated by linear time and frequency domain analyses (standard deviation of consecutive RRi - SDNN; root mean square of successive differences between adjacent regular R-R intervals - RMSSD; low frequency - LF; high frequency - HF; LF/HF ratio) as well as by nonlinear symbolic dynamics (patterns with no variation - “0V”; patterns with one variation - “1V”; patterns with two variations - 2V). Results: After exclusions, 666 (93.8%) euthyroid and 44 (6.2%) participants with subclinical hypothyroidism were eligible for analyses. At the baseline, supine rest measurement, the “0V” symbolic pattern, which reflects sympathetic modulation, was higher (31.8 vs. 24.2; P= .01) and “2V”, representing parasympathetic activity, was lower than in the euthyroid group (18.0 vs. 25.3; P= .02). Comparing the variation between positions, the “0V” pattern showed a lower delta in subclinical hypothyroidism than in euthyroid subjects (6.8 vs. 14.2%; P= .04). Additionally, it is suggested that a symbolic analysis of heart rate dynamics is an alternative and, possibly, a more sensitive method for cardiac autonomic assessment following standing position in this population. Conclusion: Subclinical hypothyroidism presented lower sympathetic and parasympathetic tonus at rest and a blunted sympathetic response to active postural change, marked by reduced variation in the “0V” of symbolic analysis.