tbuckley/cabot-search huggingface dataset:
A phase II randomized study of adjuvant imatinib versus high-dose interferon alpha-2b for resected high-risk c-kit mutated melanoma.
Authors: Lu Si, Xuan Wang, Yan Kong, Bin Lian, Zhi Hong Chi, Chuan Liang Cui, Xi Nan Sheng, Li Li Mao, Bi Xia Tang, Si Ming Li, Qiao Xie Yan, Jun Guo
Journal: Journal of Clinical Oncology (2013)

e20027 Background: Imatinib, a selective inhibitor targeting Abl as well as C-Kit and the platelet-derived growth factor receptor, has been tested for the efficacy and toxicities in metastatic melanoma patients harboring mutations in C-Kit gene. High-dose interferon for one year (HDI) is the FDA approved adjuvant therapy for patients (pts) with high-risk melanoma. This study (NCT01782508) aims to see whether imatinib is more effective than interferon alfa-2b in adjuvant therapy for patients with C-Kit mutated melanomas. Methods: This study enrolled C-Kit mutated(exon 9,11 or 13)pts who were high risk (stage IIB to stage IIIC) and randomized them to receive either imatinib (400mg daily for a year) or HDI (interferon a-2b 15X10 6 U/m 2 d 1–5 /wX4w + 9X10 6 U tiwX48w) in the absence of disease progression or unacceptable toxicity. 40 pts of each group were planned to enroll. Routine tests including blood tests, medical history updates, physical exams and Brain/Chest/Abdomen/Pelvic CT were performed every 2 months. The endpoints were recurrence-free survival (RFS) and overall survival. Results: Through Jan 2013,7 pts were recruited F3 in imatinib arm and 4 in HDI arm. The three pts received imatinib haven’t had recurrence or metastasis. The RFS were 6m+ (Exon 11: W577S), 5m+ (Exon 11: L576P), 5m+ (Exon 11: L576P) respectively. Two pts have already had lung or regional lymphnode at 4 months (Exon 13: K642E) and 5 months (Exon 11: V560D) in the HDI arm. The other two pts (both Exon 11: 579 insert) in the HDI arm were still disease free for 6 months. The toxicities were consistent with the usual reported studies. Conclusions: In the C-Kit mutated melanoma pts, it’s promising that imatinib may provide more beneficial effect than HDI for high-risk melanomas. (Supported by the National Natural Science Foundation of China (30973483, 81172196, 81102068.) Clinical trial information: NCT01782508.
Anticancer antibodies for lung cancer.
Authors: M J Kelley, J L Mulshine
Journal: Journal of Clinical Oncology (1994)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1994.12.11.2519 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 7818695 Anticancer antibodies for lung cancer. M J KelleyxM J KelleySearch for articles by this author , J L MulshinexJ L MulshineSearch for articles by this author https://doi.org/10.1200/JCO.1994.12.11.2519 PDF "Anticancer antibodies for lung cancer.." Journal of Clinical Oncology, 12(11), pp. 2519–2520© 1994 by American Society of Clinical Oncology
Infectious morbidity and defects of phagocytic function in end-stage renal disease
Authors: R Vanholder, S Ringoir
Journal: Journal of the American Society of Nephrology (1993)

Infectious diseases remain among the most morbid events and are an important cause of death in ESRD. These events are related to an acquired immunodeficiency that progresses during the development of uremic retention, as part of the broader spectrum, displayed by the "uremic syndrome". A central role in the hose defense against bacterial infection is played by the phagocytic polymorphonuclear white blood cells, which are characterized by the capacity to ingest bacteria (phagocytosis), which is followed by the destruction of those bacteria (killing capacity). This article reviews the mechanisms of development and the potential causes that have been held responsible for this aspect of the defective immune function. The observed changes are attributed to alterations in receptor expression, although more convincing evidence points in the direction of metabolic functional disturbances, especially in the NAD(P)H-oxidase-dependent production of oxygen free radicals. The most important causative factors are: uremic toxicity, iron overload, renal anemia, dialyzer bioincompatibility, and the type of renal replacement therapy. It is concluded that the phagocytic defect in ESRD is multifactorial and that each factor should be managed by specific therapeutic approaches.
Acute mesenteric ischemia following cardiovascular surgery – A nested case-control study
Authors: H. Mothes, J. Koeppen, O. Bayer, M. Richter, B. Kabisch, D. Schwarzkopf, H.A.T. Hein, J. Zanow, T. Doenst, U. Settmacher
Journal: International Journal of Surgery (2016)
WHO should commit to eradicating malaria by 2040, says Gates Foundation
Authors: Anne Gulland
Journal: BMJ (2015)

The World Health Organization has been urged to commit to eradicating malaria by 2040, building on recent progress that has cut the number of deaths from the disease.

A report by the Bill & Melinda Gates Foundation and Ray Chambers, the United Nations’ special envoy for malaria, laid out what it would take to eliminate malaria by 2040.1 It urged the World Health Assembly, WHO’s decision making body, to make a declaration on malaria eradication if certain key milestones are met.

Around …
Strava: challenge yourself to greater heights in physical activity/cycling and running
Authors: Liam Richard West
Journal: British Journal of Sports Medicine (2015)

Fitness.

iOS (iPhone 4 and above), Android (V. 2.3.3 and above), Google Glass and over 50 GPS devices (eg, Garmin) that then upload date onto the Strava website.

Free for the standard app, but the user can choose to pay £4.49/month or £44.99/year for the premium version that offers extended functionality.

Strava has been created for cyclists and runners to track their activities and offer analysis on their performance. It maps the route taken and tracks the pace achieved. Once a route is completed this data is uploaded onto the app and website with subsequent analysis of the activity; calories burned, average speed, maximum speed, speed over certain distances, and heart rate (if a compatible monitor was used during activity).

The reason that Strava has become so popular is its emphasis on competition. …
Cardiovascular abnormalities in children with autosomal dominant polycystic kidney disease.
Authors: D D Ivy, E M Shaffer, A M Johnson, W J Kimberling, A Dobin, P A Gabow
Journal: Journal of the American Society of Nephrology (1995)

It is known that adults with autosomal dominant polycystic kidney disease (ADPKD) have an increased incidence of cardiovascular abnormalities, including mitral valve prolapse. The cardiac manifestations of ADPKD in the pediatric population have not been well established. To determine the cardiac manifestations of children with ADPKD, echocardiography was performed in 154 children of 66 families in which one parent has ADPKD. Eighty-six affected children and 68 unaffected children were evaluated in a prospective, single-blinded manner by echocardiography. Affected children were defined as those with any cysts on a concurrent renal ultrasound or those predicted to be gene carriers by gene linkage analysis. A 12% incidence of mitral valve prolapse was found in the affected children compared with only 3% of the unaffected children (P < 0.05). ADPKD children, but not their unaffected siblings, demonstrate a significant correlation between left ventricular mass index and systolic blood pressure. Moreover, hypertensive ADPKD children have significantly larger left ventricular mass index than do normotensive ADPKD children. A 3.5% incidence of congenital heart disease was found in the affected group, whereas 2.9% of the unaffected children had congenital heart disease. It was concluded that systemic manifestations of ADPKD, particularly cardiovascular abnormalities, are present even in childhood and these warrant the clinician's attention.
Advisory Committee on Immunization Practices Recommended Immunization Schedules for Persons Aged 0 Through 18 Years — United States, 2016
Authors: Candice L. Robinson
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

Each year, the Advisory Committee on Immunization Practices (ACIP)* reviews the recommended immunization schedules for persons aged 0 through 18 years to ensure that the schedules reflect current recommendations for Food and Drug Administration-licensed vaccines. In October 2015, ACIP approved the recommended immunization schedules for persons aged 0 through 18 years for 2016; the 2016 schedules include several changes from the 2015 immunization schedules. For 2016, the figures, footnotes, and tables will be published on the CDC immunization schedule website (http://www.cdc.gov/vaccines/schedules/index.html). This provides readers electronic access to the most current version of the schedules and footnotes on the CDC website. Health care providers are advised to use figures, tables, and the combined footnotes together. Printable versions of the 2016 immunization schedules for persons aged 0 through 18 years in several formats (e.g., portrait, landscape, and pocket-sized versions) and ordering instructions for laminated versions and "parent-friendly" schedules are available at the immunization schedule website.
Clinical outcomes in patients with castrate-refractory prostate cancer (CRPC) metastatic to bone randomized in the factorial TRAPEZE trial to docetaxel (D) with strontium-89 (Sr89), zoledronic acid (ZA), neither, or both (ISRCTN 12808747).
Authors: Nicholas David James, Sarah Pirrie, Darren Barton, Janet Elizabeth Brown, Lucinda Billingham, Stuart I. Collins, Adam Daunton, Alison J. Birtle, Prabir Ranjan Chakraborti, Daniel Ford, Syed A. Hussain, Helen Jones, Ann Pope, Emilio Porfiri, John Martin Russell, Andrew Stanley, John Staffurth, Duncan McLaren, Chris Parker, James Wylie
Journal: Journal of Clinical Oncology (2013)

LBA5000 Background: Bony metastatic CRPC has a poor prognosis and high morbidity. TRAPEZE is a factorial RCT using three agents, D, ZA, and Sr89. All have palliative benefits and are used in bony metastatic CRPC to control bone symptoms and (for D) to prolong survival. ZA was approved on the basis of reducing skeletal related events (SRE). Sr89 was approved to control pain from metastases and to reduce the need for subsequent bone treatments. ZA is commonly combined with D in practice but evidence that the combination is effective is lacking and costs considerable. Sr89 is generally used as a palliative therapy in patients unfit for chemotherapy. Phase II analysis confirmed the safety and feasibility of combining these agents. TRAPEZE aimed to determine clinical and cost-effectiveness scheduling. Methods: Patients were randomised to receive 6 cycles of D plus prednisolone: alone; with ZA; with a single dose of Sr89 after cycle 6 or both. Primary outcomes were clinical progression-free survival (CPFS: pain progression, SRE or death) and cost-effectiveness. Secondary outcomes were SRE free interval (SREFI); total SREs, and overall survival (OS). The log rank test and Cox regression modelling were used to determine clinical effectiveness. Results: TRAPEZE randomised 757 patients; median age 68.7 yrs; ECOG 0: 40% 1: 52% 2: 8%; prior RT 45%; median PSA 144 (IQR 51, 354). Provisional stratified log rank analysis of CPFS did not reach statistical significance for either agent (Sr89 p=0.11, ZA p=0.45). Cox regression analysis adjusted for all stratification variables showed benefit of Sr89 on CPFS (HR=0.845; 95%CI 0.72, 0.99, p=0.036) and confirmed no effect of ZA (p=0.46). ZA did show a significant effect on SREFI (HR=0.76; 95%CI 0.63, 0.93, p=0.008). There was no effect of either agent on overall survival (Sr89 p=0.74, ZA p=0.91). Conclusions: Sr89 after six cycles of docetaxel improved CPFS but not OS. ZA did not improve CPFS or OS but did significantly improve median SREFI, mostly post progression, suggesting a role as post chemotherapy maintenance therapy. Further health economic and QoL analyses are pending. Clinical trial information: 12808747.
Continuity of care for cancer patients at the end of life (EoL).
Authors: R. Bascioni, B. Esperide, D. Iacopini, F. Basirat, F. Rastelli, L. Acito, R. Bisonni, L. Giustini, F. Giorgi
Journal: Journal of Clinical Oncology (2010)

6145 Background: The transition from curative to palliative care is a difficult phase in the illness trajectory of many oncologic patients (pts). Change of the health care professionals involved in EoL assistance may result in a sense of abandonment for pts and families. Methods: A semistructured telephone interview was conducted by two psychologists on relatives of pts who died between 01/2008 and 06/2009 (time from death ranged between 6 and 24 months). Research questions focused on the last month of life and included oncologist's involvement, sense of abandonment if the patient-oncologist relationship was lost, satisfaction with the quality of care (measured with a five-point scale: poor, fair, good, very good, excellent; and converted to a 0-to-100 scale) and oncologist's involvement in bereavement activities. A final open-ended question addressed suggestions for improvement. Results: Fifty-eight patient's relatives were contacted, 50 accepted the interview (32 spouses, 14 children, 3 in-laws, 1 nephew). Twenty-two pts had died at home, 28 in hospital. In 39 (78%) cases the oncologist-patient relationship was maintained in the last month of life, and this continuity was highly appreciated by the family. For the 11 pts (26%) who lost contact with their oncologist, a sense of abandonment was reported only in one case; in all other cases there was a closure of the patient-physician relationship that prevented feelings of abandonment. While the mean score of overall satisfaction relative to the quality of care in the last month of life was 61, this score dropped to 34 for pts who were no longer followed by their oncologist. Only in 13 (26 %) cases there was a post-mortem communication between the family and the oncologist, always on the family's initiative. Every relative interviewed expected at least a phone call from the oncologist. Conclusions: Continuity of care at the EoL is a priority issue for the families of cancer pts. The daily routine of palliative care and hospice facilities should involve the oncologist to improve the experience of care. Patients' families expect a commitment by the oncologist in bereavement activities. No significant financial relationships to disclose.
Initial results of a new clinical trial matching service to increase patient participation
Authors: T. Gansler, R. Comis, K. Sharpe, L. Tis, M. Jin, K. Dahlquist, J. Kepner, Y. Hao, G. Cressman, K. Naples
Journal: Journal of Clinical Oncology (2009)

e17504 Methods: Data from CTMS constituents and follow-up information describing enrollment status and barriers to trial participation are reviewed. Results: During 15 months of operation the CTMS provided information to 10,997 individuals; 7,521 (68.39%) used the website only, and 3,476 (31.61%) also contacted the ACS call center. Among 981 of the 3,476 (28.22% the basis of analyses below) who consented to and could be reached for follow-up and who answered the question on enrollment status, 119 (12.13%) enrolled in a CT. Trial phase was known for 74 enrollees (phase I: 17 [22.97%]; II: 36 [48.65%]; III: 21 [28.38%]; IV: 0 [0%]). Enrollment was negatively (p &lt; 0.05) associated with poor ECOG functional status and black race, and was positively related to disease stage. Among the 757 individuals with available disease site and enrollment information, those with stomach cancer accounted for the most enrollments (25, 24.75% of all enrollments); followed by melanoma (12, 11.88%) and kidney, renal pelvis, bladder, ureter and urethra (also 12, 11.88%), and breast cancer (11, 10.89%). The highest enrollment rates (% enrollees among individuals with available follow-up) were for multiple myeloma/plasma cell disorders (4/14, 28.57%), melanoma (12/49, 24.49%), primary CNS malignancy (5/31, 16.13%), and soft tissue sarcoma (6/45, 13.33%). The following barriers were significantly associated with non-enrollment: ‘I cannot travel to clinical trial site,‘ ‘I cannot find a clinical trial using the modality or treatment I want,‘ ‘My physical activity level is too low,‘ and ‘I do not have measurable disease or am cancer-free.‘ Conclusions: 12% of CTMS participants with available follow-up data for enrollment status participated in a CT. Several determinants of CT participation were identified. Strategies for eliminating racial disparities, facilitating transportation, and increasing participation among patients with earlier stage disease and more common tumor types must be developed and implemented. No significant financial relationships to disclose.
Abstract 13466: Adjusted Risk Survival Benefit Following Angiographic Complete Percutaneous Revascularization in the Era of Drug-Eluting Stents
Authors: Marco A Magalhaes, Sa`ar Minha, Israel M Barbash, Hironori Kitabata, Salem M Badr, Omar Alfazir, Joshua P Loh, Pendyala K Lakshmana, Hideaki Ota, Rebecca Torguson, Fang Chen, William O Suddath, Kenneth M Kent, Lowell F Satler, Augusto D Pichard, Ron Waksman
Journal: Circulation (2013)

Background: A conservative approach consisting of percutaneous intervention (PCI) of ischemic lesions has been associated with better outcomes; however, these findings are based on studies that pre...
A phase I pharmacokinetic, pharmacogenomic trial of weekly amonafide in patients (pts) with solid tumors
Authors: J. G. Kuhn, S. Jones, D. Hein, N. Willcutt, F. A. Greco, E. Raefsky, D. Thompson, A. Meluch, D. Brown, H. Burris
Journal: Journal of Clinical Oncology (2004)

2023 Background: Amonafide (AMF) is a topoisomerase II inhibitor previously tested in clinical trials, predominantly with a daily x 5 administration schedule. AMF is extensively metabolized by N-acetyltransferase 2 to N-acetylamonafide (AAMF), an active metabolite which demonstrates nearly equipotent activity to the parent compound. Previous trials indicated a relationship between AMF related neutropenia and acetylator phenotype. Methods: Dose escalation was initiated at 400 mg/m2 IV on days 1, 8, and 15 every 28 days. Blood samples were obtained for acetylator genotyping, but initially the results were not prospectively determined. Due to dose-limiting toxicities (DLT) encountered at 500 mg/m2, genotype results were obtained prospectively and subsequent pts were dosed by genotype (slow [S] vs intermediate/rapid [I/R]). Blood and urine samples for pharmacokinetics (PK) were obtained with the first dose of AMF. Results: 26 pts (14F/12M; median age 65, range 32–74; median PS 1;acetylator status: S =11; I/R = 15; common tumor types: ovarian [5], prostate [3], breast [3], colon [3]) have been enrolled at doses of 400 and 500 mg/m2. Myelosuppression consisting of ANC and platelet nadirs preventing Day 15 dosing has been the DLT. Non-hematologic toxicities include nausea/vomiting, phlebitis, and infusion-related symptoms. PK analyses confirm the marked difference in drug exposure between S and I/R acetylators as determined by genotype. The mean AAMF/AMF AUC ratio for S vs I/R acetylators is 0.66 (range 0.28 - 1.31) vs 2.75 (range 1.2 - 5.98) [p = 0.00008]. Percent change of ANC for I/R at the 400 mg/m2 dose level was 78% vs 55% for S at 500 mg/m2 (p = 0.02). Antitumor activity has been noted in prostate cancer (declining PSA; 400 mg/m2; S), ovarian cancer (declining CA125; 400 mg/m2; I/R), and GIST (decreased lymph nodes; 500 mg/m2; S). Conclusions: Determination of pt acetylator status via genotyping allows pts to receive amonafide doses that are tailored to their drug metabolism. Weekly amonafide is well tolerated in S acetylators, and the recommended phase II dose is 500 mg/m2 weekly x 3 q4weeks. Enrollment for I/R acetylators continues at 320 mg/m2. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ChemGenex Bristol-Myers Squibb; Chemgenex; GlaxoSmithKline; ILEX GlaxoSmithKline; ILEX Aventis; Bristol-Myers Squibb; GlaxoSmithKline ChemGenex
Veno-Occlusive Disease After Haematopoietic Stem Cell Transplantation for β Thalassaemia Major Is Predicted by the Severity of Hepatic Fibrosis and Ameliorated by Defibrotide
Authors: Prashant Hiwarkar, Farah O'Boyle, Leena Karnik, Helen New, Richard Szydlo, Irene Roberts, Josu de la Fuente
Journal: Blood (2010)
Assessment of Host Immune Status During Progressive Growth and After Excision of DNA Virus (Simian Virus 40) Tumors in Hamsters: Comparison of Tumor-Specific and Tumor-Unrelated Parameters of Immune Responsiveness2
Authors: Karen J. Houston, John W. Blasecki
Journal: JNCI Journal of the National Cancer Institute (1979)

The kinetics of cell-mediated immunity to simian virus 40 (SV40) tumor-specific transplantation antigen (TSTA) were compared to the kinetics of tumor-unrelated parameters of immune responsiveness in the assessment of the immune statuses of inbred MHA/SsLAK hamsters during the course of progressive syngeneic SV40 tumor growth and after tumor excision. With the use of the tumor cell neutralization test in vivo and the macrophage migration inhibition assay in vitro, specific cellular immunity to SV40 TSTA was detected by 4 days after tumor cell inoculation, when the tumor was small. This tumor-specific immune response was no longer detected at 7 days after tumor cell inoculation, when the tumor had reached a mean diameter of 12.5 mm, but it returned by 14 days after surgical excision of the tumor. The patterns of host responsiveness to mitogens in spleen cells derived from tumor-bearing animals or from tumor-excised animals generally showed little or no correlation with the kinetics of tumor-specific cellular immunity. The kinetics of the humoral immune response to murine erythrocytes, as determined by hemagglutination assays, correlated much more closely with the kinetics of tumor-specific immunity than did the responses to mitogens. IgG antibody (T-dependent) responses were more affected by progressive tumor growth than were IgM antibody (T-independent) responses. The data suggest that results of tests with the use of tumor-unrelated parameters of immune responsiveness for the assessment of the immune status of cancer patients should be interpreted with caution.
Pooled Normal Human Polyspecific IgM Contains Neutralizing Anti-Idiotypes to IgG Autoantibodies of Autoimmune Patients and Protects From Experimental Autoimmune Disease
Authors: Vincent Hurez, Michel D. Kazatchkine, Tchavdar Vassilev, Sheela Ramanathan, Anastas Pashov, Bertrand Basuyaux, Yvonne de Kozak, Blanche Bellon, Srini V. Kaveri
Journal: Blood (1997)