tbuckley/cabot-search huggingface dataset:
Abstract 14981: Home Healthcare Services for Heart Failure Patients and Family Caregivers Dyads at End of Life
Authors: Judith E Hupcey, Lisa Kitko, Maureen Palese, Casey Pinto
Journal: Circulation (2012)

Background: Home healthcare services, including nursing, palliative care and hospice, have been recommended to meet the needs of patient-caregiver dyads throughout the end-of-life (EOL) heart failure trajectory. Although the number of end-stage HF patients referred to hospice has significantly increased since 2000, according to CDC statistics, heart disease accounted for only 11% of hospice admissions and only 6.4% were for heart failure. For other home healthcare services, which include a wide-range of medical and therapeutic services, only 4.3% of admissions were for heart failure. There are many reasons why patients and caregivers do not receive these services. In addition to not being offered these services during discharge after an acute heart failure exacerbation, dyads (as a whole or one member of the dyad), at times, refuse to accept these home healthcare services or when accepted; it is within days of the patient’s death. Methods: Fifty dyads, who are part of a longitudinal qualitative study of h...
A phase I pharmacokinetic and safety analysis of epothilone folate (BMS-753493): A first-in-human clinical experience of a folate receptor-targeted chemotherapeutic agent dosed once daily on days 1, 2, 3, and 4 of a 21-day cycle.
Authors: P. P. Peethambaram, L. C. Hartmann, G. D. Goss, D. J. Jonker, R. Plummer
Journal: Journal of Clinical Oncology (2010)

e13005 Background: The high-affinity folate receptor alpha is selectively overexpressed in some epithelial tumors, including ovarian, endometrial, renal, and breast, and in a few nonepithelial neoplasms such as anaplastic ependymomas, pituitary tumors, and mesothelioma. BMS- 753493, a folate conjugate of epothilone analog BMS-748285, was designed to target folate receptor-expressing tumor cells. Methods: BMS-753493 was investigated in two parallel first-in-human phase I/II multiple ascending dose studies in subjects with advanced solid cancers. These studies differed only in dosing schedule. Both studies dosed 4 times during each 21 day cycle and followed a 3+3 open-label dose escalation scheme during phase I. CA190-002 dosed once daily on days 1-4 and is reported here, while CA190-001 (companion abstract) dosed once daily on days 1, 4, 8, and 11. Results: Phase I enrollment was completed, and a maximum tolerated dose of 15 mg was achieved. Dose-limiting toxicities (DLTs) were seen in two of four subjects treated at 17 mg. The first DLT consisted of grade 3 ALT and grade 2 AST, requiring dose reduction from 17 mg to 12 mg. The second DLT consisted of grade 3 nausea and grade 3 fatigue. An intermediate dose of 15 mg was expanded to 12 subjects, with two DLTs identified. The first DLT consisted of grade 3 mucositis. The other DLT consisted of grade 3 AST elevation. The most common AEs included fatigue, diarrhea, nausea, vomiting, anorexia, and ALT/AST elevations. Although no responses occurred, target lesion shrinkage up to 23% from baseline was observed. Plasma exposures (Cmax and AUC) of BMS-753493 and BMS-748285 on day 1 and day 4 increased in a dose-related manner in the dose range of 2.5 to 17 mg. All data are preliminary. Conclusions: At the doses and schedules tested, BMS-753493 demonstrated at best moderate activity with manageable toxicity. Pharmacokinetic data: BMS-753493, day 4 Dose (mg) N Cmax(ng/ml) GeoMean (CV%) AUC(O-T) (ng*h/mL) GeoMean (CV%) 2.5 3 424 (20) 120.5 (20) 5 3 962 (34) 271.2 (31) 8 3 1,342 (8) 496.5 (37) 12 5 1,596 (43) 786.8 (32) 15 14 2,068 (39) 1,122.7 (47) 17 3 3,367 (28) 1,672.3 (30) Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb
Tubular fluid concentrations and kidney contents of angiotensins I and II in anesthetized rats.
Authors: L G Navar, L Lewis, A Hymel, B Braam, K D Mitchell
Journal: Journal of the American Society of Nephrology (1994)

Previous micropuncture studies have reported nanomolar concentrations of angiotensin II in proximal tubular fluid and have indicated that angiotensin II or a precursor may be secreted into the tubular lumen. Further experiments were performed to determine if proximal tubular fluid angiotensin I concentrations are also greater than plasma and kidney levels and to estimate the degree of intrarenal compartmentalization of the angiotensin peptides. Free-flow proximal tubular fluid samples were collected in micropipets and were pooled for each animal. At the end of each experiment, a blood sample was collected and the micropunctured left kidney was harvested and homogenized in methanol. The angiotensin I concentration in proximal tubular fluid samples averaged 6.1 +/- 1.2 pmol/mL, whereas the angiotensin II concentration averaged 8.1 +/- 1.6 pmol/mL (N = 13). HPLC analysis of a separate sample pooled from collections in five rats indicated that the immunoreactive angiotensin I and angiotensin II primarily represented authentic angiotensin I and II. Plasma concentrations of angiotensin I and angiotensin II averaged 0.39 +/- 0.09 and 0.15 +/- 0.03 pmol/mL, respectively. The kidney contents of angiotensin I and angiotensin II were 1.28 +/- 0.24 and 0.97 +/- 0.17 pmol/g of kidney, respectively. These findings indicate that proximal tubular fluid contains nanomolar concentrations of angiotensin I as well as angiotensin II. These high tubular fluid concentrations, which greatly exceed the plasma and kidney levels, likely reflect net secretion of the angiotensin peptides by proximal tubule cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract P307: Chitin-Glucan Fiber Effects on Oxidized Low-Density Lipoprotein: A Randomized Controlled Trial
Authors: Joseph L Evans, Harold Bays, Kevin C Maki, Mal Evans, Veronique Maquet, Raymond Cooper, James W Anderson
Journal: Circulation (2012)

Oxidized low-density lipoprotein (OxLDL) is believed to play a role in the progression of atherosclerotic coronary heart disease (CHD) and the development of diabetes complications. This randomized, double-blind, placebo-controlled study of a novel insoluble fiber derived from the mycelium Aspergillus niger , chitin-glucan (CG) (ARTINIA™), evaluated 135 patients with fasting LDL-cholesterol 130-189.9 mg/dl and fasting glucose &lt;=125 mg/dl. Participants were randomly assigned to receive CG (4.5 g/day; n=34), CG (1.5 g/day; n=33), CG (1.5 g/day) plus olive extract (n=33), or matching placebo (n=35) for 6 weeks. The primary outcome measure was the between-group difference in OxLDL. Secondary outcome measurements included effects upon lipid, glucose, insulin, and F2-isoprostane levels. After 6 weeks, CG 4.5 g/day (CG-4.5) significantly reduced mean OxLDL 3.8 U/L compared to baseline (58.0 U/L vs 61.8 U/L, respectively; P =0.006), and reduced OxLDL 4.97 U/L compared to placebo (P=&lt;0.05). Other treatment groups generally had no significant effect upon OxLDL. CG treatment groups reduced LDL-cholesterol levels 3.2–;6.5% compared to placebo (P&lt;0.05). In this study population without diabetes mellitus or elevated glucose levels, CG did not significantly affect high density lipoprotein cholesterol, triglycerides, glucose, insulin, F2-isoprostanes, or the homeostasis model assessment of insulin resistance. Treatments were well tolerated and with adverse experiences comparable to placebo. These results suggest that chitin-glucan, a novel insoluble fiber, may significantly reduce OxLDL and LDL-cholesterol levels, which may have therapeutic implications for patients at risk for CHD or other diabetes complications.
Disclosing Pleiotropic Effects During Genetic Risk Assessment for Alzheimer Disease
Authors: Kurt D. Christensen, J. Scott Roberts, Peter J. Whitehouse, Charmaine D.M. Royal, Thomas O. Obisesan, L. Adrienne Cupples, Jacqueline A. Vernarelli, Deepak L. Bhatt, Erin Linnenbringer, Melissa B. Butson, Grace-Ann Fasaye, Wendy R. Uhlmann, Susan Hiraki, Na Wang, Robert Cook-Deegan, Robert C. Green
Journal: Annals of Internal Medicine (2016)

Background: Increasing use of genetic testing raises questions about disclosing secondary findings, including pleiotropic information. Objective: To determine the safety and behavioral effect of disclosing modest associations between apolipoprotein E (APOE) genotype and coronary artery disease (CAD) risk during APOE-based genetic risk assessments for Alzheimer disease (AD). Design: Randomized, multicenter equivalence clinical trial. (ClinicalTrials.gov: NCT00462917) Setting: 4 teaching hospitals. Participants: 257 asymptomatic adults were enrolled, 69% of whom had 1 AD-affected first-degree relative. Intervention: Disclosure of genetic risk information about AD and CAD (AD+CAD) or AD only (AD-only). Measurements: Primary outcomes were Beck Anxiety Inventory (BAI) and Center for Epidemiologic Studies Depression Scale (CES-D) scores at 12 months. Secondary outcomes were all measures at 6 weeks and 6 months and test-related distress and health behavior changes at 12 months. Results: At 12 months, mean BAI scores were 3.5 in both the AD-only and AD+CAD groups (difference, 0.0 [95% CI, −1.0 to 1.0]), and mean CES-D scores were 6.4 and 7.1 in the AD-only and AD+CAD groups, respectively (difference, 0.7 [CI, −1.0 to 2.4]). Both confidence bounds fell within the equivalence margin of ±5 points. Among carriers of the APOE ε4 allele, distress was lower in the AD+CAD groups (difference, −4.8 [CI, −8.6 to −1.0]) (P = 0.031 for the interaction between group and APOE genotype). Participants in the AD+CAD groups also reported more health behavior changes, regardless of APOE genotype. Limitations: Outcomes were self-reported by volunteers without severe anxiety, severe depression, or cognitive problems. Analyses omitted 33 randomly assigned participants. Conclusion: Disclosure of pleiotropic information did not increase anxiety or depression and may have decreased distress among persons at increased risk for 2 conditions. Providing risk modification information about CAD improved health behaviors. Findings highlight the potential benefits of disclosure of secondary genetic findings when options exist for decreasing risk. Primary Funding Source: National Human Genome Research Institute.
Surface Immunoglobulin on Leukemic, Leukemoid, and Normal Granulocytes 2
Authors: Paul K. Pattengale, Barbara K. Schneider, John W. Parker, Barbara H. Tindle, Stebbins Chandor, Robert J. Lukes
Journal: JNCI Journal of the National Cancer Institute (1976)

Journal Article Surface Immunoglobulin on Leukemic, Leukemoid, and Normal Granulocytes Get access Paul K. Pattengale, M.D., Paul K. Pattengale, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Barbara K. Schneider, M.D., Barbara K. Schneider, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar John W. Parker, M.D., John W. Parker, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Barbara H. Tindle, M.D., Barbara H. Tindle, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Stebbins Chandor, M.D., Stebbins Chandor, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert J. Lukes, M.D. Robert J. Lukes, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 56, Issue 6, June 1976, Pages 1269–1270, https://doi.org/10.1093/jnci/56.6.1269 Published: 01 June 1976 Article history Received: 12 September 1975 Accepted: 13 December 1975 Published: 01 June 1976
Association of Frailty and 1-Year Postoperative Mortality Following Major Elective Noncardiac Surgery
Authors: Daniel I. McIsaac, Gregory L. Bryson, Carl van Walraven
Journal: JAMA Surgery (2016)

Single-center studies identify frailty as a risk factor for 30-day postoperative mortality. The long-term and population-level effect of frailty on postoperative mortality is, to our knowledge, poorly described, as are the interactions of frailty with important predictors of mortality.To measure the population-level effect of patient frailty on, and its association with, 1-year postoperative mortality.Population-based retrospective cohort study in Ontario, Canada, with data collected between April 1, 2002 and March 31, 2012. Analysis was performed from December 2014 to March 2015. All patients were community-dwelling individuals aged 65 years or older on the day of elective, major noncardiac surgery.Frailty, as defined by the Johns Hopkins Adjusted Clinical Groups (ACG) frailty-defining diagnoses indicator. The ACG frailty-defining diagnoses indicator is a binary variable that uses 12 clusters of frailty-defining diagnoses.One-year all-cause postoperative mortality.Of 202 811 patients, 6289 (3.1%) were frail (mean [SD] age, 77 [7] years). Within 1 year, 13.6% (n = 855) of frail and 4.8% (n = 9433) of nonfrail patients died. Adjustment for sociodemographic and surgical confounders resulted in a hazard ratio of 2.23 (95% CI, 2.08-2.40). The interaction between frailty and postoperative time demonstrated an increased relative hazard for death in frail patients (hazard ratio, 35.58; 95% CI, 29.78-40.19) on postoperative day 3. The association between frailty and increased risk of death decreased with patient age (HR, 2.66; 95% CI, 2.28-3.10 at age 65; HR, 1.63; 95% CI, 1.36-1.95 at age 90). Significant variations in the increased risk for death in frail patients existed between different surgery types and was strongest after total joint arthroplasty (HR, 3.79; 95% CI, 3.21-4.47 for hip replacement; HR, 2.68; 95% CI, 2.10-3.42 for knee replacement).At a population level, preoperative frailty-defining diagnoses were associated with a significantly increased risk of 1-year mortality that was particularly notable in the early postoperative period, in younger patients, and after joint arthroplasty.
Long-term disease-free survival in small-cell carcinoma of the lung: a study of clinical determinants.
Authors: K Osterlind, H H Hansen, M Hansen, P Dombernowsky, P K Andersen
Journal: Journal of Clinical Oncology (1986)

The influence of treatment and of pretreatment patient characteristics on the probability of long-term disease-free survival in small-cell lung cancer (SCLC) was investigated in a consecutive series of 874 patients. The patients were included in six controlled treatment trials from 1973 to 1981, using different combinations of chemotherapy with or without irradiation. All patients underwent pretreatment staging, including bronchoscopy, peritoneoscopy with liver biopsy, and bone marrow examination. The same procedures were repeated in patients without overt signs of disease 18 months from initiation of treatment, and patients without evidence of SCLC were regarded as long-term survivors. Seventy-two patients were disease-free at restaging, corresponding to 13% of 443 patients with limited-stage disease and 3% of 431 patients with extensive-stage disease. The possible relationship between different pretreatment variables and the probability of 18 months' disease-free survival was investigated by multiple regression analysis. Disease extent was the most important determinant of long-term survival. Being a woman was a positive factor and hypouricemia had negative influence on the long-term results, while features such as performance status and serum lactate dehydrogenase (LDH) did not have significant influence in the regression model. Differences between the efficacy of the applied treatment regimens were less in limited disease than they were in extensive disease, in which six-agent regimens of alternating chemotherapy was significantly better than treatment with three- or four-agent regimens. Accordingly, disease extent seems to be the most pivotal determinant of long-term survival in SCLC, but influence of the patient's sex and serum urate concentration should also be considered.
Molecular Pathways: Isocitrate Dehydrogenase Mutations in Cancer
Authors: Owen Clark, Katharine Yen, Ingo K. Mellinghoff
Journal: Clinical Cancer Research (2016)

IDH1 and IDH2 are homodimeric enzymes that catalyze the conversion of isocitrate to α-ketoglutarate (α-KG) and concomitantly produce reduced NADPH from NADP(+) Mutations in the genes encoding IDH1 and IDH2 have recently been found in a variety of human cancers, most commonly glioma, acute myeloid leukemia (AML), chondrosarcoma, and intrahepatic cholangiocarcinoma. The mutant protein loses its normal enzymatic activity and gains a new ability to produce the "oncometabolite" R(-)-2-hydroxyglutarate (R-2-HG). R-2-HG competitively inhibits α-KG-dependent enzymes which play crucial roles in gene regulation and tissue homeostasis. Expression of mutant IDH impairs cellular differentiation in various cell lineages and promotes tumor development in cooperation with other cancer genes. First-generation inhibitors of mutant IDH have entered clinical trials, and have shown encouraging results in patients with IDH-mutant AML. This article summarizes recent progress in our understanding of the role of mutant IDH in tumorigenesis.Clin Cancer Res; 22(8); 1837-42. ©2016 AACR.
Unimolecular Pentavalent (Globo-H-Gm2-Stn-Tf-Tn) Immunization of Patients (Pts) with Epithelial Ovarian(Eoc), Fallopian Tube, or Peritoneal Cancer in First Remission
Authors: R.E. O'Cearbhaill, A. Iasonos, G. Ragupathi, S. Danishefsky, P. Sabbatini
Journal: Annals of Oncology (2014)
Efficacy and safety of XELIRI plus cetuximab versus XELOX plus cetuximab in first-line treatment of metastatic colorectal cancer (mCRC).
Authors: J. Ocvirk, M. Boc, M. Rebersek, T. Mesti, M. Ebert
Journal: Journal of Clinical Oncology (2011)

e14122 Background: FOLFIRI, FOLFOX, XELOX and XELIRI in combination with biologics are standard options in mCRC. The primary endpoint was to compare the overall response rate of XELIRI+cetuximab (C) vs. XELOX+C. The secondary endpoints were progression free survival (PFS), overall survival (OS) and evaluation of side effects (SE). Methods: Patients (pts) with previously untreated KRAS wt mCRC, > 18 years, ECOG PS 0-2 and adequate organ function were treated with irinotecan 250 mg/m2 day 1, C initial dose 400 mg/m2 then 250 mg/m2 days 1, 8, 15, capecitabine (X) 1,000 mg/m2 twice daily 1–14 (XELIRI+C); or oxaliplatin 130 mg/m2 day 1, C initial dose 400 mg/m2 then 250 mg/m2 days 1, 8 and 15, X 1,000 mg/m2 twice daily, 1–14 (XELOX+C). The cycle was repeated every 3 weeks. Prophylactic vitamin K1 cream was used. Results: From October 2008 to October 2010, 82 pts with mCRC were included. Median age was 59.5 years (27-76), M/F = 61%/39%. 33 pts were treated with XELIRI+C and 49 pts with XELOX+C. The most frequent site of metastases was liver (65.9%). At the time of analysis of results, 77 out of 82 pts were available for response evaluation. RR for XELIRI+C was as follows CR 28.6%, PR 23.8%, SD 28.6%, PD 19% in and CR 18.2 %, PR 39.4 %, SD 27.3%, PD 15.1% for XELOX+C. Median PFS was 15.0 months (95% CI: 10.8- 19.3) in XELIRI+C and 14.8 months (95% CI: 8.3- 21.3) in XELOX+C (p=0.420). Median OS was 26.7 months (95% CI: 1.1- 52.3) for XELIRI+C and not yet reached in XELOX+C (p=0.037). In pts with only liver metastases R0 resection rate was 16.3% (8 pts) in XELOX+C and 6.2% (2 pts) in XELIRI+C. Of hematological SE, G3/4 neutropenia was only observed in 5 pts in both groups. One pt in XELIRI+C had febrile neutropenia. Of non-hematological SE, G3/4 diarrhea was observed in 4 pts in XELIRI+C. One pt experienced G3 infusion reaction of C, any others G3/4 SE of C were not observed. No pts died because of SE. Conclusions: XELIRI+C and XELOX+C are of comparable efficacy. The results of efficacy are comparable with the results from previous phase III studies in first-line treatment of Cht+ C. Median OS was longer in XELOX+C than XELIRI+C. The observed SE of both regimens were of lower grades than previously reported in mCRC due to supportive treatment and were manageable.
Allogeneic T Cells That Express an Anti-CD19 Chimeric Antigen Receptor Induce Remissions of B-Cell Malignancies That Progress After Allogeneic Hematopoietic Stem-Cell Transplantation Without Causing Graft-Versus-Host Disease
Authors: Jennifer N. Brudno, Robert P.T. Somerville, Victoria Shi, Jeremy J. Rose, David C. Halverson, Daniel H. Fowler, Juan C. Gea-Banacloche, Steven Z. Pavletic, Dennis D. Hickstein, Tangying L. Lu, Steven A. Feldman, Alexander T. Iwamoto, Roger Kurlander, Irina Maric, Andre Goy, Brenna G. Hansen, Jennifer S. Wilder, Bazetta Blacklock-Schuver, Frances T. Hakim, Steven A. Rosenberg, Ronald E. Gress, James N. Kochenderfer
Journal: Journal of Clinical Oncology (2016)

Progressive malignancy is the leading cause of death after allogeneic hematopoietic stem-cell transplantation (alloHSCT). After alloHSCT, B-cell malignancies often are treated with unmanipulated donor lymphocyte infusions (DLIs) from the transplant donor. DLIs frequently are not effective at eradicating malignancy and often cause graft-versus-host disease, a potentially lethal immune response against normal recipient tissues.
Medical education in the United States 1979-1980
Journal: JAMA (1980)

These authors intend to provide a brief history of the medical educational system in the United States of America (USA), the educational structure, the current topics and challenges facing medical educators.     The structure of medical education in the USA differs from most countries. In the USA it is not possible for a student to start medical studies after the completion of high school at the undergraduate level. A student must first complete a four-year undergraduate 'pre-medical' program at a college or university and obtain a Bachelor's degree before entering medical school. Upon successful completion of four years of study at medical school, the medical doctor (M.D.) degree is conferred after which physicians take three to seven years of residency training. The whole process can take from 11 to 15 years.
Prognostic significance of the endoluminal ultrasound defined lymph node metastasis count in esophageal cancer
Authors: C. Twine, C. Rawlinson, X. Escofet, G. Blackshaw, T. Crosby, A. Roberts, W. Lewis
Journal: Journal of Clinical Oncology (2009)

4558 Background: TNM histopathological staging system for esophageal cancer is controversial, and will soon be revised to account for the relative burden of the number of lymph node metastases. The aim of this study was to assess the prognostic significance of endoluminal ultrasound (EUS) defined lymph node metastasis count (eLNMC) in patients with esophageal cancer. Methods: Two hundred and sixty-seven consecutive patients (median age 63 yr, 187 m) underwent EUS followed by stage directed multidisciplinary treatment [183 esophagectomy (92 neoadjuvant chemotherapy), 79 definitive chemoradiotherapy, and 5 palliative therapy]. The eLMNC was subdivided into four groups (0, 1, 2 to 4, &gt;4) and the primary measure of outcome was survival. Results: Survival was related to EUS T stage (p&lt;0.0001), EUS N stage (p&lt;0.0001), EUS tumour length (p&lt;0.0001), and the eLNMC (p&lt;0.0001). Multivariable analysis revealed EUS tumour length (HR 1.071, 95% CI 1.008 to 1.138, p=0.027) and eLNMC (HR 1.302, 95% CI 1.133 to 1.496, p&lt;0.0001) to be significantly and independently associated with survival. Median and 2 year survival for patients with 0, 1, 2 to 4, and &gt;4 lymph node metastases were: 44 months and 71%; 36 months and 59%; 24 months and 50%; and 17 months and 32% respectively. Conclusions: The eLNMC was an important and significant prognostic indicator in patients with esophageal cancer, which should in future be reported and used to revise the perceived radiological stage, in order to inform stage directed multimodal therapy. No significant financial relationships to disclose.