tbuckley/cabot-search huggingface dataset:
The impact of comorbidity on cancer and its treatment
Authors: Diana Sarfati, Bogda Koczwara, Christopher Jackson
Journal: CA A Cancer Journal for Clinicians (2016)

Answer questions and earn CME/CNE Comorbidity is common among cancer patients and, with an aging population, is becoming more so. Comorbidity potentially affects the development, stage at diagnosis, treatment, and outcomes of people with cancer. Despite the intimate relationship between comorbidity and cancer, there is limited consensus on how to record, interpret, or manage comorbidity in the context of cancer, with the result that patients who have comorbidity are less likely to receive treatment with curative intent. Evidence in this area is lacking because of the frequent exclusion of patients with comorbidity from randomized controlled trials. There is evidence that some patients with comorbidity have potentially curative treatment unnecessarily modified, compromising optimal care. Patients with comorbidity have poorer survival, poorer quality of life, and higher health care costs. Strategies to address these issues include improving the evidence base for patients with comorbidity, further development of clinical tools to assist decision making, improved integration and coordination of care, and skill development for clinicians. CA Cancer J Clin 2016;66:337-350. © 2016 American Cancer Society.
Gestion endoscopique des patients atteints de polypose adénomateuse familiale refusant la colectomie
Authors: E. Coron
Journal: Endoscopy (2015)

La colectomie est le traitement préventif de choix des cancers coliques chez les patients atteints de polypose adénomateuse familiale (PAF). La quasi-totalité des patients étant opérée, l’impact de la polypectomie colique est inconnu. La question de la possibilité d’un traitement endoscopique conservateur reste donc posée.
Induction of Pulmonary Tumors in Mice With Ethyl Carbamate (Urethane)
Authors: Anderson Nettleship, Paul S. Henshaw, Henry L. Meyer
Journal: JNCI Journal of the National Cancer Institute (1943)

Journal Article Induction of Pulmonary Tumors in Mice With Ethyl Carbamate (Urethane) Get access Anderson Nettleship, Anderson Nettleship passed assistant surgeon (R) National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar Paul S. Henshaw, Paul S. Henshaw senior radiobiologist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar Henry L. Meyer Henry L. Meyer technical assistance of scientific aide National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 4, Issue 3, December 1943, Pages 309–319, https://doi.org/10.1093/jnci/4.3.309 Published: 01 December 1943
Results of a Randomised Controlled Trial Comparing Intravesical Chemohyperthermia with Mitomycin C Versus Bacillus Calmette-Guérin for Adjuvant Treatment of Patients with Intermediate- and High-risk Non–Muscle-invasive Bladder Cancer
Authors: Tom J.H. Arends, Ofer Nativ, Massimo Maffezzini, Ottavio de Cobelli, Giorgio Canepa, Fabrizio Verweij, Boaz Moskovitz, Antoine G. van der Heijden, J. Alfred Witjes
Journal: European Urology (2016)
Genetics of Coronary Artery Disease
Authors: Ruth McPherson, Anne Tybjaerg-Hansen
Journal: Circulation Research (2016)

Genetic factors contribute importantly to the risk of coronary artery disease (CAD), and in the past decade, there has been major progress in this area. The tools applied include genome-wide association studies encompassing &gt;200 000 individuals complemented by bioinformatic approaches, including 1000 Genomes imputation, expression quantitative trait locus analyses, and interrogation of Encyclopedia of DNA Elements, Roadmap, and other data sets. close to 60 common SNPs (minor allele frequency&gt;0.05) associated with CAD risk and reaching genome-wide significance ( P &lt;5×10 −8 ) have been identified. Furthermore, a total of 202 independent signals in 109 loci have achieved a false discovery rate ( q &lt;0.05) and together explain 28% of the estimated heritability of CAD. These data have been used successfully to create genetic risk scores that can improve risk prediction beyond conventional risk factors and identify those individuals who will benefit most from statin therapy. Such information also has important applications in clinical medicine and drug discovery by using a Mendelian randomization approach to interrogate the causal nature of many factors found to associate with CAD risk in epidemiological studies. In contrast to genome-wide association studies, whole-exome sequencing has provided valuable information directly relevant to genes with known roles in plasma lipoprotein metabolism but has, thus far, failed to identify other rare coding variants linked to CAD. Overall, recent studies have led to a broader understanding of the genetic architecture of CAD and demonstrate that it largely derives from the cumulative effect of multiple common risk alleles individually of small effect size rather than rare variants with large effects on CAD risk. Despite this success, there has been limited progress in understanding the function of the novel loci; the majority of which are in noncoding regions of the genome.
Slow and fast ventilated lung units in adult asthma assessed from N2 multiple-breath washouts (MBW)
Authors: Sanna Kjellberg, Olle Zetterström, Maria Ström, Birgitta Houltz, Paul Robinson, Per Gustafsson
Journal: European Respiratory Journal (2014)

Background:  3 He magnetic resonance imaging (MRI) studies in adults with bronchial asthma demonstrate the presence of markedly underventilated lung regions even when spirometry indicates normal airway function.   Aim:  To demonstrate the utilitiy of N 2  MBW, a simple and more affordable method, to quantify underventilated lung volumes in asthma.   Subjects and Methods:  62 asthmatic subjects (33 males) aged 19-67 yrs (median 50 yrs) performed triplets of N 2  MBW using the Exhalyzer D (Eco Medics AG, Duernten, Switzerland) plus spirometry. Semi-log plots of exhaled N 2  volume per breath vs. breath number were used to calculate slow and fast emptying lung compartments and their specific ventilation. All ages (Stanojevic et al 2008) spirometry reference values and LCI reference equations from 510 healthy controls were used.   Results:  Median (range) slow compartment volume was 54% (36;77) of FRC (functional residual capacity). Slow and fast compartment specific ventilation were 7.4% (3.0; 27.9) and 40.2% (15.9; 105.0), respectively. Specific ventilation of slow compartment correlated inversely with LCI (R 2 =0.55; p 1 /FVC (R 2 =0.32; p   Conclusion:  Slow and fast compartments of FRC and their specific ventilation can be derived from simple N 2  MBW curves. The degree of underventilation of the slow compartment is a determinant of global ventilation inhomogeneity and correlates to the FEV 1 /FVC ratio.
The cytotoxicity of combined paricalcitol and docetaxel in head and neck squamous cell carcinomas
Authors: T.-S. W. Huang, S. Northrup
Journal: Journal of Clinical Oncology (2004)

5609 Background: Paricalcitol is a calcitriol analog used in the treatment of secondary hyperparathyroidism. It produces less hypercalcemia compared to calcitriol and has low clinical toxicity. We have shown previously that paricalcitol is antiproliferative in head and neck squamous cell carcinomas (HNSCC) in vitro. However, its interaction with docetaxel has not been elucidated. The purpose of this study is to evaluate the combined effects of paricalcitol and docetaxel in HNSCC in vitro. Methods: The cytotoxic effects of paricalcitol and docetaxel, alone and in combination, were assessed using MTT assays after 5 days of incubation in SCC-15 and SCC-25 cells, human tongue SCC cell lines. The combined effects were evaluated by sequential application of paricalcitol for 24 hours followed by docetaxel for 5 days. CalcuSyn analyses were done to determine if the interaction between paricalcitol and docetaxel is synergistic, additive, or antagonistic. Results: Paricalcitol alone at 12.5 nM, 25 nM, and 50 nM produced growth inhibition of 26%, 40%, and 39%, respectively, in SCC-15 cells; and 13%, 25%, and 36%, respectively, in SCC 25 cells. The growth inhibitory response to docetaxel alone at 50 nM, 100 nM, and 200 nM was 42%, 47%, and 44%, respectively, in SCC-15 cells; and 34%, 41%, and 46%, respectively, in SCC 25 cells. Sequential treatment with paricalcitol (12.5, 25, or 50 nM) followed by docetaxel (50, 100, or 200 nM) produced synergistic growth inhibition for all dose combinations in both cell lines. This pattern of synergistic growth inhibition has been observed in multiple, separate MTT assays. Conclusions: Sequential application of paricalcitol and docetaxel at moderate doses produced synergistic cytotoxicity in SCC-15 and SCC-25 cells. The results of this study provide support for further investigations of combined paricalcitol and docetaxel in the treatment of head and neck cancers. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis
A phase I dose escalation study of a 2 day lapatinib chemosensitization pulse preceding weekly intravenous nanoparticle albumin-bound paclitaxel (nab-paclitaxel) in patients with advanced cancer
Authors: A. J. Chien, J. A. Illi, A. H. Ko, S. Dubey, T. M. Jahan, N. M. Hylton, B. M. Yeh, Y. Huang, K. M. Koch, M. M. Moasser
Journal: Journal of Clinical Oncology (2008)

3595 Background: The human epidermal growth factor receptor (HER) family is expressed and functionally relevant in tumor vasculature. In preclinical models tumor vascular permeability and perfusion characteristics are transiently optimized following a brief pulse of high dose HER tyrosine kinase inhibitor (TKI) therapy and chemotherapeutic efficacy is enhanced when administered in this window. Methods: To translate this treatment approach to patients, we conducted a phase I clinical study of escalating doses of the HER TKI lapatinib (Lp, Tykerb) in patients with advanced solid tumors. Lp was administered on days 1 and 2 and nab-paclitaxel (Ab, Abraxane) 100mg/m2 was administered on day 3 of weeks 1, 2, and 3 of a 4-week cycle. Lp dose was escalated in a 2-stage accelerated titration design with serum analysis of Lp bioavailability and its effect on paclitaxel pharmacokinetics at the maximum tolerated dose (MTD) of Lp. Functional MRI studies were performed before and after the Lp pulse on a subset of patients to assess Lp effects on tumor vascular function. Results: 22 patients have been treated to date including patients with lung (7), esophageal (3), prostate (3), breast (2), melanoma (2), bladder (1), sarcoma (1), ovarian (1), pancreatic (1), and mesothelioma (1) malignancies. The most common serious adverse event (SAE) and the only grade 4 events were neutropenia (4/22). Other attributable grade 3 AEs include diarrhea, nausea, fatigue, peripheral neuropathy, and neutropenia. All treatment- related AEs resolved. 2 patients experienced dose limiting toxicity consisting of grade 4 neutropenia and grade 3 vomiting despite maximal supportive care. The MTD was defined to be 5250mg/day in twice daily dosing and Lp bioavailability increased less than proportionally. 8 of 18 evaluable patients with lung (3), esophageal (2), breast (2), and prostate (1) cancer have had a partial response. These include 6 patients previously treated with taxanes and 2 patients previously treated with HER TKIs. Conclusion: A 2-day pulse of Lp preceding weekly Ab can be safely administered to patients with advanced solid tumors. There is preliminary evidence of efficacy in taxane-refractory patients. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline
Phase I trial of a sequence-specific combination of the HDAC inhibitor, valproic acid (VPA), and the topoisomerase II inhibitor, epirubicin, in advanced solid tumors: Clinical results and correlative studies
Authors: P. N. Munster, D. C. Marchion, E. Bicaku, M. L. Schmitt, B. Padilla, P. Stauffer, C. Garrett, A. Chiappori, D. M. Sullivan, A. I. Daud
Journal: Journal of Clinical Oncology (2006)

3068 Background: Multiple lines of evidence indicate that histone deacetylase inhibitors (HDACi) potentiate topoisomerase (topo) inhibitors. The HDACi-induced histone acetylation and chromatin modulation facilitates DNA access and target recruitment for topo II inhibitors. Methods: This Phase I trial explored a sequence-specific combination of VPA and epirubicin in solid tumors. A VPA loading dose and 6 oral doses (q12h) were given prior to epirubicin in 3-week cycles. Histone acetylation and topo II expression were evaluated in pre-and post-VPA peripheral blood mononuclear cells and tumor samples. Results: To date, 42 patients [median age 53 (39–78)] have been treated in 12 cohorts: IV VPA loading (mg/kg)/epirubicin (mg/m 2 ): 15/75, 30/75, 45/75, 60/75, 75/75 and 75/100, oral loading: 75/100, 90/100, 100/100, 120/100, 140/100 and 160/100. Tumor types included: breast (10), melanoma (11), lung (6), sarcoma (2), GYN (2), GI (5) and others (6). Dose-limiting toxicities included somnolence (1) and neutropenia (1). No exacerbation of epirubicin-related toxicities was observed. Objective responses were seen across different tumor types in anthracycline-resistant and -refractory tumors, despite a median number of 3 (0–6) prior regimens: Partial response; 7/37 (19%), stable disease/minor response: 16/37 (43%). Patients received a median number of 4 (1–10) treatment cycles. Study treatment was stopped despite a clinical benefit or response in 4/33 patients after reaching maximal epirubicin doses (≤750 mg/m 2 ). VPA peak and trough plasma concentrations increased linearly up to 120 mg/m 2 . MTD is being defined at 160/100 mg/kg/d VPA. H3 and H4 histone acetylation and topo II expression have been correlated with VPA dose, plasma concentration and response. Conclusion: A sequence-specific combination of VPA and epirubicin is active without exacerbation of epirubicin toxicity. VPA plasma peak and trough levels exceeding concentrations needed for biological effects and in vitro synergy are easily achievable with minimal toxicity. The noteworthy anti-tumor activity seen in this heavily pretreated Phase I population warrants further exploration. [Table: see text]
Immortal Magyar: Semmelweis, Conqueror of Childbed Fever.
Journal: Annals of Internal Medicine (1951)

A protected childhood of the Victorian era in a family of wealth and social standing was interrupted by financial disaster when the author was about eight years of age.Her mother was unprepared for the task of supporting six children but faced it gallantly, uniting her young family in a close and loyal group.She it was who decided that, somehow, Emily must go to college, and this decision was backed by the enthusiastic support of the brothers and sisters.Medical school followed, first at the Medical College of the New York
Clinical results of high-dose-rate I-192 brachytherapy combined with external beam radiotherapy for localized prostate cancer
Authors: S. Kariya, I. Yamasaki, Y. Ogawa, A. Nishioka, S. Yoshida, S. Ashida, K. Inoue, T. Shuin
Journal: Journal of Clinical Oncology (2005)

4785 Background: In recent years, high-dose-rate (HDR) brachytherapy combined with external beam radiotherapy (EBRT) has come to perform for localized prostate cancer (PC) in Japan. The aim of this study is to report the clinical control rate of patients with HDR brachytherapy combined with EBRT for localized PC. Methods: We enrolled 33 PC patients treated with HDR brachytherapy combined with EBRT between July 1999 and June 2002. Patient age ranged from 55 to 81 years (mean 73). Of the 33 patients, 9, 10, and 14 belong to low risk (stage≤T2, PSA≤10 ng/mL, and Gleason score<7), intermediate risk (stage=T3, PSA>10 ng/mL, or Gleason score≥7 (1 intermediate risk factor), and high risk group (2 or more intermediate risk factor), respectively. Nine patients had received neoadjuvant hormonal therapy, which was stopped at the beginning of RT in all cases. Patients in this series were treated on two protocols. In the initial protocol, patients in high risk group were treated with whole pelvis EBRT to 45 Gy in 25 fractions and HDR brachytherapy to 18 Gy in 3 fractions, and patients in other groups were treated with prostatic EBRT to 40 Gy in 20 fractions and HDR brachytherapy to 18 Gy. In the second protocol, patients were treated with prostatic EBRT to 40 Gy with an added staging lymphadenectomy to rule out lymph node metastasis for patients with high risk factors, and HDR brachytherapy to 18 Gy. We used the ASTRO definition for biochemical failure. Follow-up ranged from 30–65 months (median, 51 months). Results: No patients in low and intermediate groups had biochemical failure. In high risk group, 2 patients had died of heart failure and malignant lymphoma, respectively, with no biochemical failure, one patient had died of distant metastasis, and 2 patient had bone metastases with no symptoms of local recurrence. Two patients experienced RTOG Grades 3 and 4 late radiation toxicities for the gastrointestinal system, respectively. Grade 3 urethral stricture was observed in 2 patients. Acute toxicity has been modest. Conclusions: HDR brachytherapy combined with EBRT is a very effective treatment for unfavorable PC. However, in order to achieve more reliable results, additional long-term follow-up is required. No significant financial relationships to disclose.
Reducing Infant Mortality
Authors: T R Johnson
Journal: JAMA (1965)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
A pilot study of proton beam theary for mucosal melanoma of the head and neck
Authors: S. Zenda, M. Kawashima, R. Kohno, S. Arahira, T. Nishio, T. Ogino
Journal: Journal of Clinical Oncology (2009)

e17042 Background: The aim of this study is to clarify the clinical profile of proton beam therapy for mucosal melanoma of the head and neck. Methods: Patients with mucosal melanoma of the head and neck fulfilling the following criteria were enrolled: histologically confirmed malignant melanoma; N0 and M0 disease. Proton therapy was delivered three times a week with planned total dose of 60 GyE in 15 fractions. Results: From January 2004 through January 2007, thirteen patients were enrolled in this study. Patients’ characteristics were as follows: median age, 75 years (range, 56 to 79); male/female, 7/6; T1/2/3/4/rec, 3/2/0/7/1. All could receive the full dose of proton therapy. The most common acute toxicities were mucositis (grade 3: 15%) and dermatitis (grade 2: 15%). One patient had unilateral impairment of visual acuity possibly related with treatment. Initial local control rate was 77.0% (10/13, 95%CI: 46.2–95.0%). With median follow up period of 33.7 months, median progression free survival was 18.9 months and median survival time was not reached. 2-year overall survival rate was 69.7% (95%CI: 31.6–86.1%). Most frequent site of first failure was cervical lymph nodes outside of PTV. Four patients died of disease; cachexia caused by distant metastases in three and carotid blowout because of nodal disease in one. Conclusions: Proton beam therapy for mucosal melanoma of the head and neck achieved favorable results in this limited number of patients, although further investigation about late toxicity is needed. Now, the phase II study of this treatment is ongoing. No significant financial relationships to disclose.
Abstract 19358: Comparative Outcomes of Catheter-Directed Thrombolysis plus Anticoagulation versus Anti-Coagulation Alone in the Treatment of Lower Extremity Proximal Deep Vein Thrombosis
Authors: Riyaz Bashir, Chad J Zack, John Gaughan, Anthony J Comerota, Alfred A Bove
Journal: Circulation (2012)

Background: The role of catheter-directed thrombolysis (CDT) in treatment of acute proximal deep vein thrombosis (DVT) is controversial and national rates of in-hospital mortality and acute complications in these patients are unknown. Methods: We used the Nationwide Inpatient Sample (NIS) database from 2005 to 2009 to identify all patients admitted with a principal diagnosis of proximal or caval DVT. In these patients, we evaluated the trends in the utilization rates of CDT and in-hospital outcomes. We compared in-hospital outcomes between the matched groups treated with CDT plus anticoagulation (Group A - 10,730 patients) versus anticoagulation alone (Group B - 10,730). We used propensity scores and Elixhauser comorbidity risk index to match the two treatment groups. Results: Among a total of 368,974 patients admitted with lower extremity proximal or caval DVT, 3.7% (13,542) underwent CDT. The national CDT utilization rates gradually increased from 2.3% in 2005 to 5.1% in 2009. The groups that were less likely to be treated with thrombolysis included females (3.5% versus 3.9%; p &lt;0.0001), patients greater than 65 years of age (3% versus 6.6%; p &lt; 0.0001), and African Americans (2.9% versus 3.7%; p&lt;0.0001). The outcomes analysis of the matched groups showed that in-hospital mortality was similar in the CDT group than in the anti-coagulation alone group (1.2% versus 0.9%; p= 0.287). In the CDT group, a decline in mortality was noted from 2.0% in 2005 to 0.6% in 2006. The rates of blood transfusion, pulmonary embolism, intracranial bleeding, and vena caval filter placement were significantly higher in the CDT group. The CDT group also had significantly increased length of stay (7±2.3 versus 4.9±1.9 days; P &lt; 0.00001) and hospital charges ($85416 ± 67940 versus $26841 ± 43872; p&lt;0.0001) than the anticoagulation alone group. Conclusions: In this observational study we found that in-hospital morbidity with catheter-directed thrombolysis remains higher than anticoagulation alone, however recently a significant improvement in in-hospital mortality has been noted.