tbuckley/cabot-search huggingface dataset:
Amifostine pretreatment for patients with advanced colorectal cancer receiving folfox chemotherapy
Authors: F. Arena, A. Kurzyna-Solinas, R. F. Stark, A. Ohri, C. Schiffer, H. Sulzbach, D. Jemison, J. Dolat
Journal: Journal of Clinical Oncology (2007)

19663 Background: Oxaliplatin plays a key role in the treatment of advanced colorectal cancer (CRC) but is associated with dose- limiting peripheral neuropathy (PN) in &gt;20% of patients. We investigated the effects of amifostine, a cytoprotective agent, on the prevention of PN in patients receiving oxaliplatin in combination with 5-fluorouracil (5-FU) and leucovorin (LV) (FOLFOX) for the treatment of advanced (stage =III) CRC. Methods: In this ongoing prospective observational study, patients with stage =III CRC are assigned to receive FOLFOX alone (oxaliplatin 85 mg/m 2 , 5-FU 400 mg/m 2 bolus, 5-FU 1.2 or 2.4 g/m 2 continuous infusion over 46 h, LV 200 or 400 mg/m 2 ) or FOLFOX plus 500 mg subcutaneous amifostine 30 minutes before chemotherapy. Some patients also receive bevacizumab and/or panitumumab. All patients receive Ca/Mg infusion (1 g each/100 mL normal saline) before and after oxaliplatin treatment. Incidence and degree of PN are assessed during biweekly patient interviews and graded using National Cancer Institute Common Toxicity Criteria Version 3. Results: Sixteen patients have enrolled to date (9 nonamifostine, 7 amifostine; mean age, 60.2 y [range, 33–81 y]; 81% men). Currently, data for 6 patients (3 per group) who have completed 12 cycles of therapy are available. Two of 3 patients in the nonamifostine group reported PN grade =2 during treatment; 1 of these patients required multiple treatment interruptions because of grade 3 PN. The third nonamifostine patient reported grade 1 PN on only 2 occasions during treatment but experienced grade 2 PN at 3-month follow-up. No patient in the amifostine group reported grade =2 PN during the treatment period. One amifostine patient required a reduction in oxaliplatin dose after 8 cycles because of neutropenia. At 3-month follow-up, 1 amifostine-treated patient reported grade 1 tingling in his hands and is currently receiving treatment with pregabalin. Conclusions: The use of amifostine for the prevention of oxaliplatin-induced PN is investigational. Patients with advanced CRC who received amifostine with FOLFOX chemotherapy had a decreased incidence and severity of PN compared with patients who did not receive amifostine. Updated data will be available at the time of presentation; study enrollment continues. No significant financial relationships to disclose.
Abstract P171: Prevalence, Awareness and Control of Hypertension and Associated Risk Factors in Older Population in Vietnam
Authors: Nguyen C Vu, Linh T Dang, Yasuhiko Saito, Ngoc T Phan, Nga T Pham, Osuke Komazawa, Thanh-Huyen T Vu
Journal: Circulation (2020)

Background: In Vietnam, the population is aging rapidly and hypertension (HTN) is on the rise. However, no national representative data are available on HTN in Vietnam’s older population. Our study describes the current prevalence, awareness and control of HTN and examines their sociodemographic and heath behavioral determinants using baseline data from the Longitudinal Study on Aging and Health in Vietnam (LSAHVN). Methods: The baseline LSAHVN used a multistage clustered sampling to select 6,050 participants from the general population aged 60 and older in 2018-19. Systolic/diastolic blood pressures (thrice taken) were calculated using the average of the second and third measurements. Data on HTN awareness and treatment, sociodemographic characteristics, and health behaviors were collected using standard questionnaires. Definitions of HTN, awareness and control, names of risk factors, and analysis samples were showed in the Table. Adjusted prevalence ratios (PR) of HTN, awareness, and control by risk factors was estimated. Results: Population mean age was 70.8 years, 57.14% were female, 82.23% were Kinh (majority), and 33.75% lived in urban settings. The prevalence of HTN was 62.90%, 62.73% were aware of their HTN situation, 53.99% were treated, and 38.63% had HTN controlled. Generally, age, ethnicity, education levels, resident place, and BMI are risk factors for HTN prevalence, awareness, and control. For example, the PR of having HTN was 33% higher in the 80+ age group vs. the 60-69 age group; PRs of HTN awareness and control were 13% and 50% higher in urban vs. rural residents, respectively. BMI levels were associated with all 3 outcomes. Conclusion: In Vietnam’s aged 60+ population, hypertension is prevalent, with low rates of awareness, treatment, and control, and those are associated with age, socio-demographic characteristics, and BMI levels. The findings may have relevance for developing intervention strategies addressing hypertension in older people, especially in ethnic minority and rural populations.
Crystal Clots as Therapeutic Target in Cholesterol Crystal Embolism
Authors: Chongxu Shi, Tehyung Kim, Stefanie Steiger, Shrikant R. Mulay, Barbara M. Klinkhammer, Tobias Bäuerle, Maria Elena Melica, Paola Romagnani, Diana Möckel, Maike Baues, Luying Yang, Sanne L.N. Brouns, Johan W. M. Heemskerk, Attila Braun, Twan Lammers, Peter Boor, Hans-Joachim Anders
Journal: Circulation Research (2020)

Cholesterol crystal embolism can be a life-threatening complication of advanced atherosclerosis. Pathophysiology and molecular targets for treatment are largely unknown.We aimed to develop a new animal model of cholesterol crystal embolism to dissect the molecular mechanisms of cholesterol crystal (CC)-driven arterial occlusion, tissue infarction, and organ failure.C57BL/6J mice were injected with CC into the left kidney artery. Primary end point was glomerular filtration rate (GFR). CC caused crystal clots occluding intrarenal arteries and a dose-dependent drop in GFR, followed by GFR recovery within 4 weeks, that is, acute kidney disease. In contrast, the extent of kidney infarction was more variable. Blocking necroptosis using mixed lineage kinase domain-like deficient mice or necrostatin-1s treatment protected from kidney infarction but not from GFR loss because arterial obstructions persisted, identifying crystal clots as a primary target to prevent organ failure. CC involved platelets, neutrophils, fibrin, and extracellular DNA. Neutrophil depletion or inhibition of the release of neutrophil extracellular traps had little effects, but platelet P2Y12 receptor antagonism with clopidogrel, fibrinolysis with urokinase, or DNA digestion with recombinant DNase I all prevented arterial occlusions, GFR loss, and kidney infarction. The window-of-opportunity was <3 hours after CC injection. However, combining Nec-1s (necrostatin-1s) prophylaxis given 1 hour before and DNase I 3 hours after CC injection completely prevented kidney failure and infarcts. In vitro, CC did not directly induce plasmatic coagulation but induced neutrophil extracellular trap formation and DNA release mainly from kidney endothelial cells, neutrophils, and few from platelets. CC induced ATP release from aggregating platelets, which increased fibrin formation in a DNase-dependent manner.CC embolism causes arterial obstructions and organ failure via the formation of crystal clots with fibrin, platelets, and extracellular DNA as critical components. Therefore, our model enables to unravel the pathogenesis of the CC embolism syndrome as a basis for both prophylaxis and targeted therapy.
Drug Approved to Aid Youths With Peanut Allergy
Authors: Rebecca Voelker
Journal: JAMA (2020)

A newly approved drug is intended to lessen allergic reactions, including anaphylaxis, in children and adolescents who are allergic to peanuts. An FDA advisory committee supported approval of the treatment, Peanut (Arachis hypogaea) Allergen Powder-dnfp, during a September 2019 meeting.
Tumor specific antibodies for the early diagnosis of lung cancer
Authors: T. V. Pedchenko, R. Mernaugh, P. P. Massion
Journal: Journal of Clinical Oncology (2007)

18068 Background: The survival rates in lung cancer vary significantly by stage, the earlier the better. However, only 16% of patients are diagnosed at stage I. This implies an urgent need to identify a panel of biomarkers for the early detection of lung cancer in order to offer an improve chance for cure. We hypothesized that a unique phage-display recombinant antibody library approach will allow us to capture from serum and evaluate cancer antibodies as novel diagnostic biomarkers of non-small cell lung cancer. Methods: Immunoglobulins G (IgG) were purified from 3 groups of pooled serum: 10 diagnosed with adenocarcinoma, 10 squamous carcinomas, and 10 controls. A naïve rodent scFv (single chain fragment variable) phage-displayed recombinant antibody library (∼2.9 x 10 9 members) was used to select scFv specific for cancer human IgG. Individual bacterial colonies obtained after two rounds of subtractive biopanning on purified normal IgG and cancer IgG were picked and induced to express soluble E-tagged ScFv antibodies. An ELISA was used to screen ScFv for binding activity to pooled normal and cancer serum IgG. Single scFv clones that showed preferential binding to cancer IgG in ELISA were further validated for binding specificity by dot blot. ScFv were assayed against individual serum samples obtained from 120 normal, 60 adenocarcinoma, 56 squamous carcinoma, and 35 other, non-small cell, lung cancers. Dot blot signal intensity was quantified using Typhoon 8600 imaging system. Results: Seventy-five individual bacterial clones produced scFv that, by ELISA, distinguished purified normal from cancer IgG from pooled serum samples. Selected scFv antibodies show significantly higher binding activity to cancer-related IgG as compared to normal IgG. Twenty-five scFv were further validated for binding activity in individual human serum samples by dot blot assays. Ten scFv clearly differentiated cancer immunoglobulins from normal in human serum by dot blot, with preferential binding either to adeno- or squamous carcinoma. Conclusions: In this preliminary dataset, we identified scFv antibodies that interact with immunoglobulins present in human cancer serum samples. We show that this is a feasible and promising approach to discover cancer-specific immunoglobulins as candidate diagnostic biomarkers. No significant financial relationships to disclose.
Evaluation of barriers to clinical trial enrollment through a novel pharmacy quality assurance tool
Authors: D. C. Vamos, M. P. Kane, J. Nishioka, S. Lisi, J. R. Neceskas, E. H. Rubin, J. Aisner, W. Shih, M. Todd, S. Goodin
Journal: Journal of Clinical Oncology (2007)

17026 Background: Clinical trials offer the best treatment for patients with cancer, yet less than 5 percent of adults and less than 60 percent of children are enrolled on clinical trials. To determine reasons for lack of enrollment on clinical trials and to assess areas for potential trial development, we designed a ‘non-protocol’ form for use at our center. Our goal was to assess deficiencies in our menu of trials, identify other barriers to enrollment, and to indirectly increase awareness of trials. Methods: Completion of a ‘non-protocol’ form was required by the pharmacy with the first set of new chemotherapy orders for all Cancer Institute of New Jersey ambulatory patients who were not enrolled on a clinical trial. The form required completion of one of three areas for lack of enrollment: trial availability, reason for ineligibility, or other reason for not enrolling the patient. Results: From June 2003 through December 2005, 474 forms were collected for patients not enrolled on a clinical trial. The median age of patients not enrolled on trial was 56 years (range 1 to 88 years) and females outnumbered males (69% vs 31%). Lack of trial availability limited enrollment for 51% of patients (n=241) while administration of standard therapy was listed for 10 patients. Of those patients where a trial was available (n=223), 65% (n=145) of patients were not eligible, most commonly due to performance status (n=55). The remaining 78 patients refused participation. To determine if implementation of this pharmacy service changed the reasons for lack of enrollment, the data was evaluated by year: Conclusion: Lack of trial availability has been a rate-limiting factor in enrollment on clinical trials at our center. The data generated from the implementation of this novel pharmacy service is of strategic importance to the center. It is reviewed with the tumor-focused groups of the cancer center to identify areas for developing clinical trials. [Table: see text] No significant financial relationships to disclose.
Cirrhosis as new indication for statins
Authors: Jaime Bosch, Jordi Gracia-Sancho, Juan G Abraldes
Journal: Gut (2020)

In the recent years, there have been an increasing number of reports on favourable effects of statins in patients with advanced chronic liver disease. These include reduction in portal pressure, improved liver sinusoidal endothelial and hepatic microvascular dysfunction, decreased fibrogenesis, protection against ischaemia/reperfusion injury, safe prolongation of ex vivo liver graft preservation, reduced sensitivity to endotoxin-mediated liver damage, protection from acute-on-chronic liver failure, prevention of liver injury following hypovolaemic shock and preventing/delaying progression of cirrhosis of any aetiology. Moreover, statins have been shown to have potential beneficial effects in the progression of other liver diseases, such as chronic sclerosing cholangitis and in preventing hepatocellular carcinoma. Because of these many theoretically favourable effects, statins have evolved from being considered a risk to kind of wonder drugs for patients with chronic liver diseases. The present article reviews the current knowledge on the potential applications of statins in chronic liver diseases, from its mechanistic background to objective evidence from clinical studies.
The Sequelae Of Early Life Pneumonia And Pleurisy On Lung Function From Childhood To Middle Age
Authors: JL Perret, EH Walters, M Matheson, DP Johns, A Lowe, JA Burgess, BR Thompson, JJ Pretto, J Markos, I Feather, S Morrison, CF McDonald, PS Thomas, MJ Abramson, SC Dharmage
Journal: American Journal of Respiratory and Critical Care Medicine (2014)
Pharmacotherapy for the Treatment of Cannabis Use Disorder
Authors: Karli K. Kondo, Benjamin J. Morasco, Shannon M. Nugent, Chelsea K. Ayers, Maya E. O'Neil, Michele Freeman, Devan Kansagara
Journal: Annals of Internal Medicine (2020)

Background: Cannabis use disorder (CUD) is a growing concern, and evidence-based data are needed to inform treatment options. Purpose: To review the benefits and risks of pharmacotherapies for the treatment of CUD. Data Sources: MEDLINE, PsycINFO, Cochrane Database of Systematic Reviews, and clinical trial registries from inception through September 2019. Study Selection: Pharmacotherapy trials of adults or adolescents with CUD that targeted cannabis abstinence or reduction, treatment retention, withdrawal symptoms, and other outcomes. Data Extraction: Data were abstracted by 1 investigator and confirmed by a second. Study quality was dually assessed, and strength of evidence (SOE) was determined by consensus according to standard criteria. Data Synthesis: Across 26 trials, the evidence was largely insufficient. Low-strength evidence was found that selective serotonin reuptake inhibitors (SSRIs) do not reduce cannabis use or improve treatment retention. Low- to moderate-strength evidence was found that buspirone does not improve outcomes and that cannabinoids do not increase abstinence rates (moderate SOE), reduce cannabis use (low SOE), or increase treatment retention (low SOE). Across all drug studies, no consistent evidence of increased harm was found. Limitations: Few methodologically rigorous trials have been done. Existing trials are hampered by small sample sizes, high attrition rates, and heterogeneity of concurrent interventions and outcomes assessment. Conclusion: Although data on pharmacologic interventions for CUD are scarce, evidence exists that several drug classes, including cannabinoids and SSRIs, are ineffective. Because of increasing access to and use of cannabis in the general population, along with a high prevalence of CUD among current cannabis users, an urgent need exists for more research to identify effective pharmacologic treatments. Primary Funding Source: U.S. Department of Veterans Affairs. (PROSPERO: CRD42018108064)
Abstract P284: Higher Bitter Taste Perception is Associated With Lower Diabetes Risk Among Older Adults With Metabolic Syndrome - The PREDIMED-PLUS Trial
Authors: Julie E Gervis, Oscar Coltell, José V Sorlí, Dolores Corella, Alice H Lichtenstein
Journal: Circulation (2020)

Background: Beyond taste perception, taste receptors in the mouth and gastrointestinal tract have been linked to the regulation of energy balance, endocrine function and glucose homeostasis. Despite this, little is known about the relationship between perception for the 5 tastes (sweet, salt, sour, bitter and umami) and diet-related chronic disease risk. Objective: To investigate the association between perception for the 5 tastes and diabetes status. Methods: A cross-sectional baseline analysis was performed on older (55-75 years), overweight (BMI, ≥27-&lt;40) adults diagnosed with metabolic syndrome who were participating in the PREDIMED-PLUS Valencia trial (N=367). Taste perception was measured by challenging participants with standard solutions representing sweet, salt, sour, bitter and umami (400 mM sucrose, 200 mM NaCl, 34 mM citric acid, 5.6 mM phenylthiocarbamide [PTC], 200 mM monopotassium glutamate, respectively) and was evaluated on a 0-5 unit scale. Diabetes status was determined by self-reported clinical diagnosis. Multivariable logistic regression models that included all 5 tastes were used to test the association between taste perception and diabetes status. Results: The prevalence of diabetes in this cohort was 38%. Compared to individuals without diabetes, individuals with diabetes had significantly lower bitter taste perception (unadjusted means: 1.6 versus 1.1 units, respectively) (t-test p&lt;0.001). After adjusting for age, sex, smoking status, physical activity, BMI and medication use, a 1 unit increase in bitter taste perception was associated with a 42% lower odds of being diagnosed with diabetes (adjusted odds ratio [aOR] = 0.58; 95% CI = [0.38, 0.84], p&lt;0.001). Although mean perceptions for sweet, salt, sour and umami were also lower in individuals with diabetes, the associations did not reach statistical significance. Conclusions: Among older adults with metabolic syndrome, higher bitter taste perception was associated with lower odds of being diagnosed with diabetes. Further investigations are warranted to confirm these observations and to determine whether bitter taste receptors may provide a possible therapeutic target for diabetes prevention and treatment.
Individualized versus fixed dosing of L-asparaginase during intensification therapy in children treated on Dana-Farber Cancer Institute (DFCI) ALL Consortium Protocol 00–001
Authors: C. Waghorne, K. E. Stevenson, D. S. Neuberg, S. E. Sallan, M. V. Relling, J. G. Supko, J. Kutok, L. B. Silverman
Journal: Journal of Clinical Oncology (2007)

20000 Background: Asparaginase (ASP) is an important agent in the treatment of ALL, but is associated with multiple toxicities. In an attempt to reduce toxicity and improve ASP tolerability, we investigated individualizing the dose to maintain nadir serum ASP levels at the minimum concentration (0.01 - 0.014 IU/ml) required to achieve asparagine depletion. Methods: 399 children (1–18 years) with newly diagnosed ALL were randomized to receive intramuscular E.coli ASP either as fixed dose (FD) (N=201; 25,000 IU/m 2 /week) or individualized dose (ID) (N=198; 12,500 IU/m 2 /week starting dose, adjusted up or down every 3 weeks based upon nadir serum ASP level) for 30 weeks during post-induction intensification. We report here on 365 randomized patients (pts) who had 7-day nadir ASP levels measured (185 FD and 180 ID). Serum ASP levels were measured prior to ASP doses 2, 4 and every third subsequent dose. ASP-antibodies (ab) were measured every six weeks. Results: The median dose for ID pts was17,500 IU/m 2 (range 6,000–28,000 IU/m 2 ). The median ASP concentration was 0.11 IU/ml (range &lt; 0.025- 2.16 IU/ml) for FD (N=1190 samples) and 0.08 IU/ml (range &lt; 0.025–0.74 IU/ml) for ID (N= 1238 samples) (p&lt;0.01). The interpatient variability in ASP concentration was smaller for ID vs. FD at all 10 time points measured. The proportion of pts who had detectable E.coli-ASP antibodies did not differ between the two arms (35% FD vs. 40% ID) (p= 0.33). The median ASP concentration was lower for ab-positive pts (0.08 IU/ml vs. 0.1 IU/ml, (p&lt;0.01). Toxicity was similar in the two arms: local allergy: 6% FD vs. 8% ID (p= 0.55); systemic allergy: 12% FD vs. 14% ID (p= 0.54); pancreatitis: 5% FD vs. 7% ID (p= 0.66); thrombosis: 8% FD vs. 7% ID (p= 0.84). No association was observed between nadir ASP levels and either pancreatitis or thrombosis. Conclusions: Individualized dosing of E.coli ASP during intensification therapy reduced peak nadir ASP levels and interpatient variability but did not significantly decrease the incidence of ASP-related toxicity. Longer follow-up is necessary to determine event-free survival of the randomized pts. No significant financial relationships to disclose.
A phase II trial of dacarbazine (DTIC) and bevacizumab in patients with metastatic melanoma
Authors: E. Munzone, A. Testori, I. Minchella, M. Mosconi, C. Passoni, E. Verri, M. Cossu Rocca, A. Lambiase, A. Goldhirsch, F. Nolè
Journal: Journal of Clinical Oncology (2007)

8579 Background: Dacarbazine (DTIC) has been approved for treating metastatic melanoma in the 1970s, and as a single agent gives a response rate of about 20%. There have been efforts to ameliorate this poor result by using DTIC in different combinations without a significant improvement. In addition, new studies with melanoma cells in vitro show that DTIC causes transcriptional up-regulation of vascular endothelial growth factor (VEGF), suggesting a potential clinical benefit from the concomitant treatment of DTIC and anti-VEGF therapy. The purpose of this study is to determine whether a combination therapy of bevacizumab and DTIC is safe and can increase response rate and progression-free survival in patients (pts) with metastatic melanoma. Methods: From June 2006 to December 2006, 8 chemo-naive pts (1 female and 7 males) with metastatic melanoma were enrolled in the study. The median age was 53 (43–74) and PS was 0–1. Patients received DTIC 800 mg/m 2 iv every 4 weeks and bevacizumab 10 mg/kg iv every 2 weeks. A treatment cycle consisted of 28 days. Results: Among 5 evaluable pts there were 1 partial response, 2 stable disease and 2 progressions, 3 pts were not evaluable because it is too early. Median number of administered cycles was 2 (2–6). The toxicity profile was particularly favourable with no G3/G4 haematological toxicity. Other most commonly seen toxicities were: nausea/vomiting (22%), mucositis (13%), diarrhea (9%). Proteinuria 1+ was reported in 3 cycles (13%). One patient with an early progression had also a G2 increase in blood pressure with a dilatative cardiomyopathy. Conclusions: The combination treatment resulted well tolerated and with a sufficient anti-tumor activity to warrant the continuing of enrolment. Updated efficacy and safety data will be presented. No significant financial relationships to disclose.