tbuckley/cabot-search huggingface dataset:
Abstract 11339: Association of Statin With Total and Non-HDL Cholesterol is Enhanced in Adult Whole Grain Consumers
Authors: Huifen Wang, Paul F Jacques, Martha S Morris
Journal: Circulation (2012)

Background Studies have demonstrated the cholesterol-lowering effects of whole grains, but the potential for a diet rich in whole grains to enhance the effects of statins on lipoprotein profiles has not been investigated. Methods In this cross-sectional study, we used data from the National Health and Nutrition Examination Survey (NHANES) 1999-2002 to assess the interaction between statins and whole grain intake in relation to cholesterol levels in adults aged>40 years with reliable dietary data. Whole-grain intake was estimated from a 24-hour diet recall using the MyPyramid Equivalents Database, and participants who consumed>16g whole grain ingredients (i.e. 1oz equivalent) were defined as consumers. Participants self-reported their statin use. Total cholesterol (TC) and HDL were measured in serum samples from all adult participants. Non-HDL cholesterol levels were calculated as TC minus HDL. Adults who took cholesterol-lowering drugs other than statins were excluded. Results Median [range] whole grain i...
Abstract 20097: Shear-Sensitive Lipid Phosphate Phosphatase 3 Maintains Nitric Oxide-Mediated Flow-Induced Dilation In Healthy Human Arterioles
Authors: Dawid Chabowski, Karima Ait-Aissa, Andrew Kadlec, Joseph Hockenberry, Andreas Beyer, David Gutterman
Journal: Circulation (2016)

Shear-stimulated release of nitric oxide (NO) is the most important physiological endothelium-dependent vasodilator response (flow-induced dilation; FID) in the arteriolar circulation. However, in ...
Laparoscopic vs. open left lateral sectionectomy: An update meta-analysis of randomized and non-randomized controlled trials
Authors: Rodrigo Luiz Macacari, Fabricio Ferreira Coelho, Wanderley Marques Bernardo, Jaime Arthur Pirola Kruger, Vagner Birk Jeismann, Gilton Marques Fonseca, Danielle Menezes Cesconetto, Ivan Cecconello, Paulo Herman
Journal: International Journal of Surgery (2018)
Changes in health‐related quality of life with long‐term eltrombopag treatment in adults with persistent/chronic immune thrombocytopenia: Findings from the EXTEND study
Authors: Abderrahim Khelif, Mansoor N. Saleh, Abdulgabar Salama, Maria do Socorro O. Portella, Mei Sheng Duh, Jasmina Ivanova, Kelly Grotzinger, Anuja N. Roy, James B. Bussel
Journal: American Journal of Hematology (2018)

Patients with persistent/chronic immune thrombocytopenia (cITP) have low platelet counts, increased risk of bleeding and bruising, and often suffer from reduced health-related quality of life (HRQoL). cITP treatments may either improve HRQoL by increasing platelet counts or decrease it because of side effects. The open-label EXTEND study (June 2006 to July 2015) evaluated long-term safety, tolerability, and efficacy of eltrombopag (an oral thrombopoietin-receptor-agonist) in adults with cITP who completed a previous eltrombopag ITP trial. The final results of EXTEND were published and used to assess changes in patient-reported HRQoL over time and association between HRQoL and platelet response. Four validated HRQoL instruments were administered: SF-36v2 including physical component summary (PCS) and Mental Component Summary; Motivation and Energy Inventory Short Form (MEI-SF); Fatigue Subscale of FACIT (FACIT-Fatigue); and FACT-Thrombocytopenia Subscale Six-Item Extract (FACT-Th6). For the 302 patients enrolled, median duration of eltrombopag treatment was 2.37 years. All 4 HRQoL instruments demonstrated positive mean changes from baseline over time adjusted for patient baseline characteristics and rescue therapy use, and had positive association with platelet response (platelet count ≥30 × 109 /L; ≥50 × 109 /L; and ≥50 × 109 /L and >2 times baseline). Improvements from baseline started within 3 months and persisted through 5 years of treatment for FACIT-Fatigue and FACT-Th6 (P <.05 for nearly all time points); through 2.5 years for SF-36v2 PCS and less consistently for the MEI-SF. In conclusion, in addition to eltrombopag increasing platelet counts and reducing bleeding/bruising, it also alleviated fatigue, concerns about bleeding and bruising, and improved physical function in many patients, especially responders.
Merkel cell polyomavirus-specific immune responses in patients with Merkel cell carcinoma receiving anti-PD-1 therapy
Authors: Natalie J. Miller, Candice D. Church, Steven P. Fling, Rima Kulikauskas, Nirasha Ramchurren, Michi M. Shinohara, Harriet M. Kluger, Shailender Bhatia, Lisa Lundgren, Martin A. Cheever, Suzanne L. Topalian, Paul Nghiem
Journal: Journal for ImmunoTherapy of Cancer (2018)

<h3>Background</h3> Merkel cell carcinoma (MCC) is an aggressive skin cancer that frequently responds to anti-PD-1 therapy. MCC is associated with sun exposure and, in 80% of cases, Merkel cell polyomavirus (MCPyV). MCPyV-specific T and B cell responses provide a unique opportunity to study cancer-specific immunity throughout PD-1 blockade therapy. <h3>Methods</h3> Immune responses were assessed in patients (<i>n</i> = 26) with advanced MCC receiving pembrolizumab. Peripheral blood mononuclear cells (PBMC) were collected at baseline and throughout treatment. MCPyV-oncoprotein antibodies were quantified and T cells were assessed for MCPyV-specificity via tetramer staining and/or cytokine secretion. Pre-treatment tumor biopsies were analyzed for T cell receptor clonality. <h3>Results</h3> MCPyV oncoprotein antibodies were detectable in 15 of 17 (88%) of virus-positive MCC (VP-MCC) patients. Antibodies decreased in 10 of 11 (91%) patients with responding tumors. Virus-specific T cells decreased over time in patients who had a complete response, and increased in patients who had persistent disease. Tumors that were MCPyV(+) had a strikingly more clonal (less diverse) intratumoral TCR repertoire than virus-negative tumors (<i>p</i> = 0.0001). <h3>Conclusions</h3> Cancer-specific T and B cell responses generally track with disease burden during PD-1 blockade, in proportion to presence of antigen. Intratumoral TCR clonality was significantly greater in VP-MCC than VN-MCC tumors, suggesting expansion of a limited number of dominant clones in response to fewer immunogenic MCPyV antigens. In contrast, VN-MCC tumors had lower clonality, suggesting a diverse T cell response to numerous neoantigens. These findings reveal differences in tumor-specific immunity for VP-MCC and VN-MCC, both of which often respond to anti-PD-1 therapy.
Discontinuation of poly(adenosine diphosphate-ribose) polymerase inhibitors due to adverse events in patients with recurrent ovarian cancer: A meta-analysis of three phase III trials.
Authors: Kyaw Zin Thein, Anita Sultan, Myo Zaw, Sriman Swarup, Myat M. Han, Yin Mon Myat, Catherine Jones, Fred L. Hardwicke, Sanjay Awasthi
Journal: Journal of Clinical Oncology (2018)

118 Background: Ovarian cancer is the fifth leading cause of cancer-related death among women. Poly adenosine diphosphate ribose polymerase (PARP) inhibitors maintenance has shown to improve survival in patients with recurrent ovarian cancer. Yet, there are notable adverse events which led to treatment discontinuation, interruption, or dose reduction. We conducted a systematic review and meta-analysis of randomized controlled trials (RCT) to determine the risk of PARP inhibitors discontinuation due to adverse events. Methods: MEDLINE, EMBASE databases and meeting abstracts from inception through June 2018 were queried. Phase III RCTs which employed PARP inhibitors maintenance in ovarian cancer and mentioned treatment interruption, dose reduction and treatment discontinuation due to adverse events were included. Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Random effects model was applied. Results: Three phase III RCTs with a total of 1,401 patients with recurrent ovarian cancer were eligible. The study arm used olaparib or niraparib or rucaparib while the control arm utilized placebo. The randomization ratio was 2:1 in all studies. The incidence of treatment interruption due to adverse events was 578 (61.8%) in study group versus 46 (9.8%) in control arm. The relative risk for treatment interruption was statistically significant at 5.87 (95% CI: 2.24 – 15.36, P &lt; 0.001). The reduction in dose was reported in 496 (53.1%) in PARP inhibitors arm versus 37 (7.9%) in control group. The pooled RR for dose reduction was 7.49 (95% CI: 3.44 – 16.29, P &lt; 0.001). The treatment discontinuation rate was 11.4% higher with PARP inhibitors than with control arm (RR - 6.84; 95% CI: 3.51 – 13.34, P &lt; 0.001). Conclusions: Our study showed that patients on PARP inhibitors experienced some adverse events which led to significant drop outs although the definitive advantage to PARP inhibitors is still shown in the studies. Preemptive measures with proper supportive care will aide in reducing those toxicities, improve patients’ quality of life and may probably affect patients’ compliance.
Towards photomechanical therapy: intracellular photodisruption of double-targeted cancer cells with microbubbles from laser induced optical breakdown of dendrimer nanocomposites
Authors: Christine Tse, Marwa Zohdy, Jing Yong Ye, Matthew O'Donnell, Wojciech Lesniak, Lajos Balogh
Journal: Cancer Research (2008)

5604  We have reported that nanosized metal clusters in metal/dendrimer nanocomposites enhance nonlinear energy absorption from femtosecond lasers in and decrease breakdown threshold of organic materials by two magnitudes. Above the threshold, laser induced optical breakdown (LIOB) occurs and short-lived microbubbles form. We have also reported that dendrimers and dendrimer nanocomposites can be used to make composite nanodevices (CNDs) in regulated size, surface charge and with multiple targeting moieties that can deliver payloads to multiple types of cancer cells expressing specific surface receptors. Simultaneous geometrical and biochemical targeting of CNDs to cancer cells followed by CND internalization and laser irradiation offers selective destruction of cells by microbubbles that damage only those cells they formed at, but do not affect their neighbors. To distinguish from photodynamic therapy (PDT) and nanoshells or nanorods (photothermal therapy, PTT), we name this method photomechanical therapy (PMT). In this study we present the first in vitro demonstration of this principle.  Purpose: To investigate the in vitro feasibility of selective destruction of cancer cells by intracellularly created microbubbles.  Experimental Procedures: The surface of dendrimer templates was made biocompatible by partially reacting the terminal amines with glycidol then covalently attaching folic acid molecules as targeters. From the above templates, we fabricated folate targeted silver/dendrimer composite nanodevices (for short: FA-{Ag(0)}) and targeted these CNDs to KB cells (a human oral epidermoid cancer cell line that is known to overexpress folate receptors) followed by irradiation using a near IR femtosecond laser. To detect and characterize breakdown dynamics in cells, transient bubble events were monitored using a high-frequency ultrasonic system. Preferential uptake of the FA-{Ag(0)} was visualized with confocal microscopy and TEM. Images show that CND internal localization and distribution varies with treatment concentration and surface functionality. Cells that bind FA-{Ag(0)} demonstrate a reduction in LIOB threshold and much reduced laser fluences are needed to break down labeled cells.  Results: We observed a considerable increase in the uptake of composite nanoparticles by KB cells as a result of targeting. CND localization and distribution varies with treatment concentration and surface functionality. Cells incubated with 500 nM of FA-{Ag(0)} exhibit a significant decrease of breakdown threshold when irradiated.  Conclusions: Selective photodisruption of cancer cells targeted with silver/dendrimer composite nanodevices was demonstrated in vitro. After further in vivo validation, photomechanical therapy has potential use in many diagnostic and therapeutic applications.
FDG-PET/CT for Detecting an Infection Focus in Patients With Bloodstream Infection
Authors: Jordy P. Pijl, Andor W. J. M. Glaudemans, Riemer H. J. A. Slart, Derya Yakar, Marjan Wouthuyzen-Bakker, Thomas C. Kwee
Journal: Clinical Nuclear Medicine (2018)

To investigate the diagnostic performance of F-fluoro-2-deoxy-D-glucose (FDG) PET/ CT for the detection of an infection focus in patients with a bloodstream infection (BSI) and to identify factors influencing the diagnostic yield of FDG-PET/CT.This retrospective single-center study included 185 consecutive patients with a BSI who underwent an FDG-PET/CT scan for the detection of an infection focus between 2010 and 2017. The final diagnosis at hospital discharge was used as reference standard. Diagnostic performance of FDG-PET/CT for the detection of an infection focus was assessed, and logistic regression analyses were performed to identify factors associated with FDG-PET/CT yield.An infection focus was identified on FDG-PET/CT in 120 (64.8%) of 185 patients. FDG-PET/CT achieved a sensitivity of 80.2%, specificity of 79.6%, positive predictive value of 90.8%, and a negative predictive value of 61.4% for detecting an infection focus in patients with a BSI. Blood cultures positive for enterococci (odds ratio, 0.14; P = 0.019) and days of antibiotic treatment before FDG-PET/CT (odds ratio, 0.94 per day increase; P = 0.014) were statistically significant independent predictors of a lower odds of detecting an infection focus on FDG-PET/CT. In patients who received antibiotics for less than 7 days before FDG-PET/CT, an infection focus was found in 71% (56/79). In patients who received antibiotics for 8 to 14 days before FDG-PET/CT, an infection focus was found in 52% (22/42). After 15 to 21 days of antibiotic treatment, an infection focus was found in 61% (8/13), and for 22 days or more, this declined to 38% (5/13).FDG-PET/CT is a useful method for detecting an infection focus in patients with BSI. However, longer duration of antibiotic treatment before FDG-PET/CT and bacteremia with enterococci reduce the diagnostic yield of FDG-PET/CT. These factors should be taken into account when considering an FDG-PET/CT scan for this indication.
Energy drinks: evidence doesn’t support ban on sales to children, say MPs
Authors: Nigel Hawkes
Journal: BMJ (2018)

A ban on the sale of “energy drinks” to children is unwarranted by the evidence, a House of Commons committee has reluctantly concluded.1

The Science and Technology Committee did not hide its view that controls of some sort should be imposed on children’s consumption of energy drinks containing caffeine. But the evidence of harm falls short of that needed to justify a statutory ban.

The committee suggested, however, that “societal harms” could justify the government going beyond the evidence and imposing a ban. If it did so, said the committee chairman Norman Lamb, it should explain how it reached its decision.

Energy drinks contain caffeine and sugar and are sold on the basis that they provide a …
Opioid dose reduction and pain control with medical cannabis.
Authors: Ajaz Bulbul, Emilio Araujo Mino, Masoud Khorsand-Sahbaie, Lisa Lentkowski
Journal: Journal of Clinical Oncology (2018)

189 Background: The use of medical cannabis (MC) for palliation of symptoms is on the rise in cancer and rheumatological patients. Whether there is a potential for opioid dose reduction (ODR) and or quality of life improvements (QOL) is unclear. Methods: A retrospective cohort was evaluated to understand the pattern of care and QOL outcomes with MC use across rural multidisciplinary practices in New Mexico. MC use (&gt; 1 mo.), EMR interrogation, urine toxicology screening were used to identify patients. QOL questionnaire included a graded pain scale. Morphine equivalent (ME) dose was used to estimate changes in opioid dose. ODR was defined as any reduction of baseline opioid dose. A chi-square was performed to evaluate associations. Results: A total of 133 patients were identified between Jan 2017- May 2017. (M/F) 65/68; median age of 53 (range 20 - 84). Nineteen percent (25/133) had a cancer diagnosis. Pain score improved in 80 % of patients with cancer and in 75% (64/89) of non-cancer patients (x2 0.24 p = 0.62). ODR was achieved in 41% (54/133) of all patients on MC. Of these, 63% (34/54) had a 25% ODR and 37% (20/54) had 26% or more ODR (x2 12.8 p = 0.002). In cancer patients, a 25% ODR was achieved in 73% (x2 0.51 p = 0.771). All patients (15/15) using MC and high dose opioid (morphine equivalent ≥ 50 mg/day) had some ODR. Co-adjuvant NSAIDs with MC improved pain score in 67% of all cases vs 33% among non-NSAID cohort (x2 10.7 p = 0.001). ODR was achieved in 32% of patients with active depression vs 68% of patients without (x2 0.044 p = 0.83). Conclusions: In this rural cohort, MC use led to ODR in 41% of all patients. Depression was a negative predictor of ODR. NSAID use facilitated ODR. It will be important to assess MC toxicity before considering this intervention. This study did not include toxicity data due to the retrospective nature of this study and its inherent limitations. Prospective data are needed to confirm these findings.
Efficacy of intravenous (IV) NEPA, a fixed NK<sub>1</sub>/5-HT<sub>3</sub> receptor antagonist combination, for prevention of emesis following highly emetogenic chemotherapy (HEC).
Authors: Eric Roeland, Richard J. Gralla, Li Zhang, Paul Joseph Hesketh, Lee Steven Schwartzberg
Journal: Journal of Clinical Oncology (2018)

194 Background: An IV formulation of NEPA (fixed combination of fosnetupitant 235 mg and palonosetron 0.25 mg) was recently approved offering clinicians an additional antiemetic treatment option. Approval of IV NEPA was based on showing pharmacokinetic bioequivalence and comparable safety to oral NEPA. This post-hoc analysis presents the efficacy of IV NEPA relative to that of oral NEPA and other NK 1 RAs in the HEC setting. Methods: Data is compiled from 3 pivotal NEPA registration studies in a total of 951 adult chemotherapy-naïve patients with solid tumors undergoing predominantly cisplatin-based HEC. All studies had similar inclusion/exclusion criteria. IV NEPA was administered as a single 30-min infusion and a single capsule of oral NEPA was given prior to HEC. All patients received dexamethasone (DEX) on Days 1-4. Data is also compiled from registration HEC trials on other NK 1 RA (aprepitant, fosaprepitant, rolapitant) regimens. No emesis rates are summarized for the overall phase (0-120h) of the initial cycle of HEC for each study and also pooled for oral NEPA. No formal statistical comparisons were performed. Results: The overall no emesis rate was 84.2% for IV NEPA and 81.6% for oral NEPA for the pooled studies. The no emesis rates for aprepitant, fosaprepitant and rolapitant regimens ranged from 66.0% to 77.7%. Clinical trial information: NCT02517021. Conclusions: Both IV and oral formulations of NEPA represent effective and convenient single-dose prophylactic antiemetics targeting two distinct CINV pathways, offering comparable options for clinicians/patients in different settings.[Table: see text]
Pricing a Year of Progression-Free Survival
Authors: Sarah S. P. DiMagno, Ezekiel J. Emanuel
Journal: JAMA Dermatology (2018)

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Willingness to bear adversity and beliefs about the curability of advanced cancer.
Authors: Kah Poh Loh, Supriya Gupta Mohile, Ronald M. Epstein, Colin McHugh, Marie Anne Flannery, Eva Culakova, Lianlian Lei, Megan Wells, Nikesha Gilmore, Dilip Sankar Babu, Alison Katherine Conlin, Melanie B. Thomas, Jeffrey L. Berenberg, Paul Duberstein
Journal: Journal of Clinical Oncology (2018)

20 Background: Older patients with advanced cancer who are certain that they could be cured pose unique challenges for physicians who wish to help them prepare for death. By estimating the prevalence of absolute certainty about curability (ACC) and examining its correlates we aim to inform the development of interventions to improve end of life care. We hypothesized that patients who report greater willingness to bear adversity in exchange for longevity will be more likely to demonstrate ACC. Methods: This is a cross-sectional analysis of a nationwide geriatric assessment trial. Patients were asked: “What are the chances the cancer will go away and never come back with treatment [100% (ACC), &gt; 50%, 50/50, &lt; 50%, 0%, or unclear].” We assessed willingness to bear adversity using two types of trade-off questions. For trade-offs between treatment-related adverse reactions and survival, five statements on specific adverse reactions (nausea/vomiting, assistance with activities, bedbound state, confusion, worsening memory) were administered. For trade-off preferences between quality of life (QoL) and survival, patients answered the following statement: “Maintaining my QoL is more important to me than living longer”. Logistic regression was used to assess the independent associations of patient trade-off preferences with ACC, after controlling for covariates. Results: 349 older patients were included; 8.0% had ACC. 7.4% of respondents disagreed/strongly disagreed with the statement “Maintaining my QoL is more important than living longer.” Patients who were willing to trade QoL for survival were more likely to demonstrate ACC (AOR 4.43, 95% CI 1.13-17.42). Trade-off preferences between adverse reactions and survival were not associated with ACC. Non-white race, &lt; high school education, lower household income, lack of social support, intact functional status, and no polypharmacy were associated with ACC (p &lt; 0.05). Conclusions: Patients with advanced cancer who are more willing to accept a decreased QoL for survival are more likely to be certain that they will be cured. Beyond sharing prognosis, clinicians might help patients improve prognostic understanding by helping them identify and articulate their values and beliefs.
Telomere Length and Telomerase Complex Mutations Predict Fatal Treatment Toxicity after Stem Cell Transplantation in Patients with Myelodysplastic Syndrome
Authors: Mikko Myllymaki, Robert A. Redd, Corey S. Cutler, Wael Saber, Zhen-Huan Hu, Tao Wang, Stephen R. Spellman, Christopher J. Gibson, Maxine M Chen, Esther Orr, David P. Steensma, Joseph H. Antin, Immaculata De Vivo, Donna S Neuberg, Suneet Agarwal, R. Coleman Lindsley
Journal: Blood (2018)