tbuckley/cabot-search huggingface dataset:
Evaluation of daily breakthrough chemotherapy-induced nausea and vomiting (CINV) rates in a phase III study of NEPA versus an aprepitant (APR)/granisetron (GRAN) regimen.
Authors: Eric Roeland, Gary Binder, Joseph Ma, Corinna Lanzarotti, Li Zhang
Journal: Journal of Clinical Oncology (2017)

120 Background: Antiemetic trials typically evaluate CINV control during acute (Day 1), delayed (Days 2-5), and overall (Days 1-5) phases post-chemotherapy; the daily course of events is often unstudied in the delayed phase. In a head-to-head study evaluating NK 1 RA-containing regimens, a single dose of NEPA, an oral fixed combination of the NK 1 RA netupitant and 5-HT 3 RA palonosetron, was non-inferior to a 3-day regimen of APR and GRAN for overall complete response (no emesis/no rescue use) rates (74% NEPA vs 72% APR/GRAN) in 828 patients receiving cisplatin-based highly emetogenic chemotherapy (HEC). This secondary analysis explores daily rates of breakthrough CINV in this study. Methods: This was a double-blind study in chemotherapy-naïve patients with solid tumors. Daily rates of breakthrough CINV, defined as the % of patients with emesis and/or rescue use were calculated with differences between treatment groups evaluated by the Cochran-Mantel-Haenszel method stratified by sex. Results: While daily rates of patients with breakthrough CINV remained stable between 13%-15.1% for APR/GRAN, they declined from 15.5% to 8% over the 5 days for NEPA, with the difference between groups reaching statistical significance on Day 5 (Table). Percent of total patient days with CINV events were 11.7% [NEPA] and 14.0% [APR/GRAN]. The % of patients with ≥ 3 days of breakthrough CINV were 8.5% and 12.3%, respectively. Conclusions: In this study evaluating guideline-recommended antiemetic regimens for HEC, CINV was prevented in most patients during the overall phase yet breakthrough CINV on individual days differed between treatment groups. APR/GRAN showed a relatively constant rate over time, while NEPA rates decreased and patients had fewer total days with breakthrough. This suggests the need for close monitoring of CINV events during the delayed phase. [Table: see text]
Evolução epidemiológica da doença por meningococos em Espanha 1989-1997
Authors: S Mateo, R Cano, C García
Journal: Eurosurveillance (1997)

Nos anos 80, as infeccoes por meningococos em Espanha, caracterizavam-se por um predominio do serotipo B (1). No entanto, desde o inicio do anos 90, tem-se vindo a isolar um numero crescente de estirpes do serotipo C, em certas localidades do oeste do pais (2), ainda que, inicialmente, nao se tenha acompanhado de um aumento da incidencia.
Possible mechanism of chemo-resistance under hypoxia and the effect of expressed ASC on hypoxia-mediated cell death in pancreatic cancer
Authors: Takao Ohtsuka, Mayumi Mitsuno, Takao Ide, Yoshihiko Kitajima, Kohji Miyazaki
Journal: Cancer Research (2008)

LB-49  We previously demonstrated that an apoptosis-associated speck-like protein, ASC, can regulate p53-mediated chemosensitivity and TNF-α-induced apoptosis (Nature Cell Biol 2004, Oncogene 2006). We also showed the preliminary data that ASC is inducible by hypoxia, and regulates hypoxia-mediated cell death (AACR 2006). Others have demonstrated that hypoxia causes chemo-resistance and accelerates the tumor progression, invasiveness, and metastasis in pancreatic cancer, and thus, one of the reasons for the poor prognosis of pancreatic cancer is considered to be a hypoxic circumstance due to its hypovascularity. In this study, we investigated more detailed roles of ASC under hypoxia- mediated cell death using pancreatic cancer cells. ASC expression was preserved in 5 of 7 pancreatic cancer cell lines (71%). Among them, PK-1 was suitable for our experiment because expressions of ASC, wild-type p53, hypoxia-inducible factor (HIF)-1α, and other apoptosis-related genes were well preserved. ASC induction under 1% hypoxic condition was HIF1α-dependent but p53-independent. Two representative chemotherapeutic agents for pancreatic cancer, 5-FU and Gemcitabine, promoted cell death of PK-1 with p53-dependent manner; however, 1% hypoxia caused chemo-resistance to these drugs. Western blot of this condition showed that a pro-apoptotic gene, Bax, decreased and anti-apoptotic genes, IAP-2 and survivin, increased under hypoxia. These results suggest that although hypoxia induces both pro-apoptotic (ASC induction) and anti-apoptotic condition (Bax repression, and IAP-2 and survivn inductions), total balance seemed to be anti-apoptotic dominant, which might be explanation for chemo-resistance. To overcome this anti-apoptotic dominant condition, adenovirus expressing ASC were infected into PK-1 cells. Expressed ASC induced cell death even under the 20% normoxia, and hypoxia enhanced such ASC-mediated cell death. Our data demonstrate the possible mechanism of chemo-resistance under hypoxia in pancreatic cancer cells, and suggest that ASC might become a new treatment strategy for pancreatic cancer.
Palliative care from cancer diagnosis for all: Memorial Sloan Kettering’s “One-Two-Three” program.
Authors: Andrew S. Epstein, Virginia M. Klimek, Kimberly Chow, Anjali V. Desai, Peter Justin Wan, Kelley Anderson, Coleen Ranghan, Molly Okpako, Robin Rawlins-Duell, Dana Kramer, Jessica Goldberg, Debra O'Shea, Judith Eve Nelson
Journal: Journal of Clinical Oncology (2017)

111 Background: Early, universal palliative care is an unmet need for cancer patients. Our new program aims to provide palliative care, by primary oncology teams with support from palliative care specialists, from diagnosis as an institutional standard. Methods: One-Two-Three is a structured program of assessment and response addressing palliative care needs regardless of cancer stage or prognosis starting with the first 3 visits after diagnosis. Assessments include patient physical/emotional/spiritual symptoms (10 symptoms, self-reported 0-10), communication needs (information preferences, illness understanding), and proactive care planning through exploration of core values. As first responders, oncology nurses are guided by “ready responses” in an empathic framework and coaching or direct patient consultation by palliative care specialists. Feasibility, acceptability, and impact on patient, caregiver, and utilization outcomes are evaluated quantitatively and qualitatively. Results: Assessments were piloted with 25 consecutive, newly-diagnosed patients in blood cancer and solid tumor clinics. Symptom and communication assessments each took &lt; 5 minutes and showed high prevalence of moderate/severe distress ( &gt; 50% for 8/10 symptoms, 144 assessments), variation in information preferences (76% wanting detail, 24% broad overview only), and unmet communication needs. All but 1 patient without a health care proxy chose one. Oncology nurses engaged patients in structured discussions ( &lt; 15 minutes) of core values. Clinic workflow was maintained. Patients, families, and oncology clinicians endorsed the initiative. As palliative care skills of oncology teams improved, specialists focused on more complex issues. Conclusions: Routine interprofessional primary palliative care with specialist support from diagnosis is feasible and acceptable in our center’s high-volume outpatient oncology clinics. Ongoing evaluations will assess other outcomes (e.g., quality of life); impact on clinicians/ processes; and utilization (e.g., ED/hospital visits, hospice use).
Abstract #1636: Cisplatin resistant germ cell tumors are characterized by microsatellite instability, mismatch repair deficiency and BRAF mutation
Authors: Leendert Looijenga, Friedemann Honecker, Hendrik Wermann, Frank Mayer, Ad Gillis, Hans Stoop, Karin Oechsle, Ewout Steyerberg, Jorg Hartmann, Winand Dinjens, Carsten Bokemeyer, Wolter Oosterhuis
Journal: Cancer Research (2009)

Purpose: Mismatch repair (MMR) deficiency and microsatellite instability (MSI) are associated with cisplatin resistance in human germ cell tumors (GCTs).  BRAF  mutation (V600E) is found in MSI colorectal cancers. The role of  RAS/RAF  pathway mutations in GCT treatment response is unknown. Methods: Two patient cohorts were investigated: 100 control GCTs (50 seminomas and 50 non-seminomas), and 35 cisplatin-based chemotherapy resistant GCTs. MMR-proteins were analysed by immunohistochemistry, and eight microsatellite loci were examined for MSI. Tumors were assessed for specific  BRAF  and  KRAS  mutations. Results: Resistant tumors showed a higher incidence of MSI than controls: 26% versus 0% in \#8805;2 loci (p KRAS , and two controls (2%) contained a  KRAS  mutation. There was a significantly higher incidence of  BRAF  V600E mutation in resistant tumors compared to controls: 26% versus 1% (p BRAF  mutations highly correlated with MSI (p=0.006), and MSI and mutated  BRAF  correlated with weak or absent staining for hMLH1 (p=0.017 and p=0.008). Low or absent staining of hMLH1 was correlated with promoter hypermethylation (p BRAF  V600E - and cisplatin resistance in non-seminomatous GCTs. Furthermore a correlation between MMR deficiency, MSI and treatment failure is confirmed.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1636.
Post-transcriptional regulation of Bax and Bak protein expression in rituximab and chemotherapy resistant B-cell non-Hodgkin’s lymphoma (NHL) cells
Authors: Scott H. Olejniczak, James L. Clements, Francisco J. Hernandez-Ilizaliturri, Naveen Bangia, Myron S. Czuczman
Journal: Cancer Research (2006)

4085   The balance between pro-apoptotic (Bax,Bak) and anti-apoptotic (Bcl-2, Bcl-xL, Mcl-1) Bcl-2 family proteins is essential for the maintenance of B-cell homeostasis. Disruption of this critical balance occurs in the majority of B-cell neoplasms. Clinically, high Bcl-2/Bak and Bcl-2/Bax ratios have been associated with decreased median survival (7.3 years and 3.8 years, respectively) in follicular lymphoma patients 1 . Recent work in mouse embryonic fibroblasts deficient for the multi-domain pro-apoptotic Bcl-2 family proteins Bax and Bak has shown that they are essential for induction of cell death following apoptotic stimuli that act through the mitochondrial (intrinsic) pathway 2 . The vast majority of clinically available anti-neoplastic agents, including rituximab, are known to induce cell death via this pathway and therefore likely rely on Bax and/or Bak to exert their anti-tumor effects. Alteration in expression of Bax and/or Bak could therefore underlie acquired resistance to chemotherapy and/or rituximab in NHL patients. We have focused on studying the mechanisms of resistance to rituximab and developed several rituximab-resistant cell lines (RRCL). RRCL were generated by exposing Raji, SU-DHL-4 and RL cells to escalating doses of rituximab human serum and subsequently cloning by limited dilution. Interestingly, we demonstrated that RRCL are resistant to various chemotherapy agents. In our present work we studied the intrinsic apoptotic pathway in an attempt to explain shared mechanisms of resistance to chemotherapy and rituximab. We found that RRCL have dramatically reduced levels of both Bax and Bak proteins by Western blot while levels of Bcl-2, Bcl-xL and Mcl-1 protein were comparable to parental cells. Additionally, Bax and Bak were only detected in sensitive parental cells following a short (30’)  35 S-methionine label of parental or RRCL. Interestingly, quantitative real-time PCR revealed that the level of  Bax  and  BAK1  message is equivalent when comparing RRCL to parental cells. In summary our data suggest that Bax and Bak protein expression in RRCL is regulated post-transcriptionally and may be regulated at the level of translation. Currently we are attempting to determine whether post-transcriptional regulation of Bax and Bak occurs in primary non-Hodgkin’s lymphoma patient samples and to further define the mechanism(s) underlying the down-regulation of Bax and Bak seen in RRCL.  1 Wei M.C.  et al . 2001 Science 292(5517):727–30.  2 Gulmann C.,  et al . 2005. Clin Cancer Res. 11(16):5847–55.
<i>Unanticipated Outcomes: A Medical Memoir</i>—A Book Review
Authors: Vinay Prasad
Journal: JAMA Internal Medicine (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
P3.02b-058 Second-Line Therapy in EGFR Activating Mutation Positive Advanced NSCLC: Analysis from a Randomized Phase III First-Line Trial
Authors: Anant Ramaswamy, Vijay Patil, Amit Joshi, Vanita Noronha, Anuradha Chougule, Abhishek Mahajan, Supriya Goud, Sucheta More, Ashay Karpe, Nikhil Pande, Arun Chandrasekharan, Alok Goel, Vikas Talreja, Kumar Prabhash
Journal: Journal of Thoracic Oncology (2017)
Abstract 15352: Plasma Levels of BNP are Lower in Patients With Heart failure With Preserved EF (HFpEF) as Compared With Those With Reduced EF (HFrEF)
Authors: Eisaku Harada, Yuji Mizuno, Makoto Shono, Hiroyuki Maeda, Naotsugu Yano, Yoshimi Tokunaga, Hirofumi Yasue
Journal: Circulation (2015)

Introduction: Heart failure with preserved ejection fraction (HFpEF) is increasing in prevalence and causes substantial morbidity, mortality, and resource utilization in the aging population. The plasma level of B-type natriuretic peptide (BNP) is used as a marker of HF with reduced EF (HFrEF). However, the role of BNP in HFpEF is not well known. The purpose of the present study was to compare the levels of BNP together with the echocardiographic findings between HFpEF and HFrEF. Methods: The study subjects consisted of 1574 patients with HF and early diastolic flow velocity (E)/velocity of early diastolic mitral annular motion (e′) or E/e′≥15 (as a measure of elevated left atrial pressure) (574 men and 1000 women, mean age 78.8±10.7) admitted at our hospital. They were divided into 1238 patients with HFpEF (373 men and 865 women, mean age 79.7±10.2) [left ventricular (LV) EF≥50% and E/e′≥15] and 336 patients with HFrEF (201 men and 135 women, mean age 75.4±11.8) (LVEF&lt;50%). Echocardiographic parameters, age, gender, and BNP were examined. Results: The levels of BNP were lower [107(47, 225) pg/ml vs. 296(121, 626) pg/ml, P&lt;0.001] in the HFpEF group than in the HFrEF group. The frequencies of female gender, age, EF, LV posterior wall thickness were higher (all P&lt;0.001, respectively) and LV mass, LV end-diastolic diameter (LVDd), LV end-systolic diameter (LVDs) and left atrial diameter (LAD) were lower (all P&lt;0.001, respectively) in the HFpEF group than in the HFrEF group. A multiple regression analysis revealed EF (t=-17.0), age (t=11.2), E/e′ (t=10.5), LAD (t=9.0), LV mass (t=7.9), and LVDd (t=-5.3) were independent predictors (all P&lt;0.001, respectively) for the BNP level (P&lt;0.001, R2=0.40) in this order. Conclusions: HFpEF was associated with lower levels of BNP and smaller heart and was more prevalent in the elders and women as compared with HFrEF. Predictors for the levels of BNP were EF, age, and E/e′ in this order. These findings imply that the plasma levels of BNP reflect LVEF more than LV diastolic function (E/e′) and thus are lower in the HFpEF group than in the HFrEF group. These findings suggest that the role of BNP in HF may be different between HFpEF and HFrEF.
Interaction between alcohol consumption and metabolic syndrome in predicting severe liver disease in the general population
Authors: Fredrik Åberg, Jaana Helenius‐Hietala, Pauli Puukka, Martti Färkkilä, Antti Jula
Journal: Hepatology (2017)

The metabolic syndrome and alcohol risk use are both associated with a high prevalence of hepatic steatosis, but only a minority develop liver failure or liver cancer. Few general population studies have analyzed metabolic predictors of such severe liver complications. We studied which metabolic factors best predict severe liver complications, stratified by alcohol consumption, in 6732 individuals without baseline liver disease who participated in the Finnish population‐based Health 2000 Study (2000‐2001), a nationally representative cohort. Follow‐up data from national registers until 2013 were analyzed for liver‐related admissions, mortality, and liver cancer. Baseline alcohol use and metabolic factors were analyzed by backward stepwise Cox regression analysis. Eighty‐four subjects experienced a severe liver event during follow‐up. In the final multivariate model, factors predictive of liver events were age (hazard ratio [HR], 1.02; 95% confidence interval [CI], 1.004‐1.04), sex (women: HR, 0.55; 95% CI, 0.34‐0.91), alcohol use (HR, 1.002; 95% CI, 1.001‐1.002), diabetes (HR, 2.73; 95% CI, 1.55‐4.81), low‐density lipoprotein (LDL) cholesterol (HR, 0.74; 95% CI, 0.58‐0.93), and homeostasis model assessment of insulin resistance (HOMA‐IR) (HR, 1.01; 95% CI, 1.004‐1.02). Among alcohol risk users (≥210 g/week for men, ≥ 140 g/week for women), diabetes (HR, 6.79; 95% CI, 3.18‐14.5) was the only significant predictor. Among nonrisk drinkers, age, alcohol use, smoking, waist circumference, low LDL cholesterol and HOMA‐IR were significant independent predictors. The total‐to‐LDL cholesterol ratio and waist circumference‐to‐body mass index ratio emerged as additional independent predictors. Conclusion : Multiple components of the metabolic syndrome independently affected the risk for severe liver disease. Alcohol was significant even when average alcohol consumption was within the limits currently defining nonalcoholic fatty liver disease. (H epatology 2018;67:2141‐2149)
Fiction as a bridge to action
Authors: Melanie C. Green, Kaitlin Fitzgerald
Journal: Behavioral and Brain Sciences (2017)

Abstract We propose an extension of the Distancing-Embracing model to the use of stories for prosocial ends. Specifically, audiences may find stories of individuals in need too emotionally overwhelming. Audiences may attempt to regulate or reduce negative emotions, which can reduce empathy and willingness to help. Through distancing, fictionalized accounts may counteract this tendency and thus increase prosocial behavior.
Patient-Reported Symptom Monitoring During Chemotherapy—Reply
Authors: Ethan Basch, Allison M. Deal, Amylou C. Dueck
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 15892: Machine Learning Techniques for Risk Stratification of Non-ST-Elevation Acute Coronary Syndrome: The Role of Diabetes and Age
Authors: Beatrice Ricci, Mihaela van der Schaar, Jinsung Yoon, Edina Cenko, Zorana Vasiljevic, Maria Dorobantu, Marija Zdravkovic, Sasko Kedev, Oliver Kalpak, Davor Milicic, Olivia Manfrini, Lina Badimon, Raffaele Bugiardini
Journal: Circulation (2017)

Introduction: Patients with diabetes and NSTE-ACS exhibit a highly variable risk of mortality and morbidity, even when undergoing similar therapeutic strategies. Machine-learning (ML) algorithms re...
Abstract 21103: Annual Trends Outcomes and Disparities of Hemodynamic Support Utilization for Ventricular Tachycardia Ablation in Congestive Heart Failure Population in United States
Authors: Venkat Vuddanda, Mohammad-Ali Jazayeri, Mohit K. Turagam, Zubair Shah, Sudarshan Balla, Bhanu Harshita Settipalle, Sindhu Reddy Avula, Seth H Sheldon, Madhu Reddy Yeruva, Dhanunjaya R. Lakkireddy
Journal: Circulation (2017)

Introduction: There is limited real world data evaluating the role of hemodynamic support (HS) during ventricular tachycardia (VT) ablation in congestive heart failure (CHF) patients. Hypothesis: We sought to investigate the annual trends, gender and racial disparities in utilization of HS and hospital mortality after VT ablation with HS in CHF population. Methods: Using the U.S. National Inpatient Sample (NIS) database from 2010-2014, we identified all discharge records with CHF (CCS code 108) and a primary diagnosis of VT (ICD-9-CM diagnosis code 427.1) undergoing catheter ablation (ICD-9-CM procedure code 37.34). Records with diagnosis of supraventricular arrhythmia and cardiogenic shock were excluded. Patients receiving HS on the day of VT ablation were identified using respective ICD-9-CM procedure codes, percutaneous ventricular assist device [pVAD] 37.68, and extracorporeal membrane oxygenation [ECMO] 39.65. Statistical analyses were performed using R (Vienna, Austria). To account for the single cluster stratified random sampling design of NIS, R survey package was used to obtain national estimates. Proportions were compared with Chi-Square test, and p trend computed using Mann-Kendall test. Results: Of 6,837 VT ablations, 353 (5.1%) were performed with HS. Use of HS consistently increased over the study period (0.37% vs. 3.64%; p trend &lt;0.001). Age adjusted hospital mortality was higher in patients receiving HS (4.2% vs. 2.0%; p &lt; 0.001). Men and minority races (blacks, hispanics) had higher use of HS. Among patients who received HS, women and minority races had higher age adjusted hospital mortality (Figure) . Conclusion: Utilization of HS for VT ablation is increasing in this nationally representative population. Unadjusted rates show disparities in the use of HS, with lower use in women and caucasians. Hospital mortality was higher in patients receiving HS, with disproportionately high rates in women and minorities.
Abstract 18124: Left Heart Decompression on Veno-Arterial Extracorporeal Membrane Oxygenation is Associated With Decreased Mortality in Children With Myocarditis: An Extracorporeal Life Support Organization Registry Review
Authors: Tarif A Choudhury, George Ofori-Amanfo, Jaeun Choi, Shivanand Medar, Scott I Aydin
Journal: Circulation (2017)

Introduction: Goals for veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in pediatric cardiogenic shock are to decrease myocardial wall stress and enhance myocardial recovery. Left heart...