tbuckley/cabot-search huggingface dataset:
Chemotherapy for Colorectal Cancer
Authors: Alastair J.J. Wood, Charles G. Moertel
Journal: New England Journal of Medicine (1994)

Carcinoma of the large bowel, which will afflict over 150,000 Americans this year, is second only to lung cancer as a cause of death from cancer1. Although most patients present with surgically resectable disease, almost half die of the cancer. Radiation therapy has a largely palliative role. In the past, chemotherapy resulted in only infrequent and usually transient shrinkage of the tumor, scarcely justifying the discomforts and costs of the treatment. In recent years, however, there have been some advances. In the discussion that follows, credence is given only to therapeutic claims validated by controlled trials with sufficiently long . . .
Expansion and Activation of CD103+ Dendritic Cell Progenitors at the Tumor Site Enhances Tumor Responses to Therapeutic PD-L1 and BRAF Inhibition
Authors: Hélène Salmon, Juliana Idoyaga, Adeeb Rahman, Marylène Leboeuf, Romain Remark, Stefan Jordan, Maria Casanova-Acebes, Makhzuna Khudoynazarova, Judith Agudo, Navpreet Tung, Svetoslav Chakarov, Christina Rivera, Brandon Hogstad, Marcus Bosenberg, Daigo Hashimoto, Sacha Gnjatic, Nina Bhardwaj, Anna Karolina Palucka, Brian D. Brown, Joshua Brody, Florent Ginhoux, Miriam Merad
Journal: Immunity (2016)
National Variability and Appropriateness of Surgical Antibiotic Prophylaxis in US Children’s Hospitals
Authors: Thomas J. Sandora, Monica Fung, Patrice Melvin, Dionne A. Graham, Shawn J. Rangel
Journal: JAMA Pediatrics (2016)

Appropriate use of surgical antibiotic prophylaxis (AP) reduces surgical site infection rates, but prior data suggest variability in use patterns.To assess national variability and appropriateness of AP in pediatric surgical patients.Retrospective cohort study of 31 freestanding children's hospitals in the United States using administrative data from 2010-2013. The study included 603 734 children younger than 18 years who underwent one of the 45 most commonly performed operations.Receipt of surgical AP.Primary outcomes included procedure- and hospital-specific rates of AP use and appropriateness of use based on clinical guidelines and consensus statements. We also assessed rates of Clostridium difficile infection and potential allergic reactions (using epinephrine administration as a surrogate event) after AP receipt.Of the 603 734 eligible patients, the mean (SD) patient age was 4.8 (4.4) years and 384 571 (63.7%) were boys. For the 671 255 operations evaluated, AP was administered for 348 119 (52%) of procedures. Intrahospital variation in AP use by procedure ranged from 11.5% to 100% (median, 78.1%). Overall, AP use was considered appropriate for 64.6% of cases. Appropriate use of AP by hospital varied from 47.3% to 84.4% with large variability by procedure within each hospital. For procedures for which AP was indicated, the median rate of appropriate use by hospital was 93.8%; however, for procedures for which AP was not indicated, the median rate of appropriate use by hospital was 52.0%. The odds of C difficile infection and epinephrine administration were significantly higher among children who received AP (odds ratio, 3.34; 95% CI, 1.66-6.73 and odds ratio 1.97; 95% CI, 1.92-2.02; respectively).There is substantial national variability in the overall and appropriate use of AP for the most commonly performed operations in children both at a procedure and hospital level. A high proportion of AP use is inappropriate, potentially exposing many children to avoidable adverse events. Urgent attention should be directed to efforts to standardize the use of surgical AP in pediatrics.
Urinary Excretion of Radiovitamin B<sub>12</sub>in Carriers of<i>Diphyllobothrium latum</i>
Authors: Wolmar Nyberg, Ralph Gräsbeck, Äinö Sippola
Journal: New England Journal of Medicine (1958)

USING the fecal-excretion test, Nyberg1 found that nonanemic carriers of the fish tapeworm, Diphyllobothrium latum, absorb on the average 55 per cent less radiovitamin B12 than normal subjects. Though the fecal-excretion test appears to be at present the most accurate method for the assay of radiovitamin B12 absorption, it cannot be considered an ideal method for routine purposes and for the study of a large number of subjects. Therefore, we have considered it desirable to check the earlier results by performing an absorption study using Schilling's urinary radioactivity test.2 Since this test is commonly used in the . . .
Prevention of delayed nausea and vomiting (D-CINV): Carryover effect analysis of pooled data from 2 phase III studies of palonosetron (PALO)
Authors: S. M. Grunberg, J. A. Vanden Burgt, S. Berry, E. B. Rubenstein, D. Berry
Journal: Journal of Clinical Oncology (2004)

8051 Background: Control of acute chemotherapy-induced nausea and vomiting (A-CINV) is a positive predictor of control of D-CINV. First-generation 5-HT3 receptor antagonists (RA) are highly effective in preventing A-CINV but less so in preventing D-CINV. PALO is a pharmacologically distinct 5-HT3 RA with a 30+ fold higher binding affinity, a 40 hr plasma half-life, and has greater efficacy than ondansetron (OND) and dolasetron (DOL) in preventing both A-CINV and D-CINV in patients receiving moderately emetogenic chemotherapy (Aapro, ASCO '03, Rubenstein ASCO '03). Methods: Establishing whether this efficacy benefit in control of D-CINV is strictly a carryover effect from better control of A-CINV was analyzed using pooled data from 2 identically designed phase III trials where 754 patients received either a single IV dose of 0.25 mg PALO or 32 mg OND (study 1) or 100 mg DOL (study 2). Two methods for evaluating the carryover effect were conducted: evaluating control of D-CINV in all patients with or without A-CINV (Grunberg, ASCO '03) and hierarchical models evaluating treatment effects adjusting for risk factors over time. Results: Of the 500 pts across all groups with no A-CINV, 376 (75%) had no D-CINV. Of these pts controlled for A-CINV, more pts (218/272; 80%) receiving PALO had no D-CINV compared with those receiving OND or DOL (158/228; 69%) [P = 0.005]. A similar benefit was also seen among the 254 pts who did have A-CINV. 24/106 (23%) receiving PALO had no D-CINV while 18/148 (12%) receiving OND or DOL had no D-CINV [P = 0.027]. Conclusions: The same magnitude of improved prevention of D-CINV with PALO in patients with or without A-CINV provides evidence that this greater efficacy in preventing D-CINV is a true pharmacologic effect rather than carryover from better prevention of A-CINV. Complete results utilizing a hierarchical (random-effects) model accounting for risk factors and trial heterogeneity will also be presented. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration MGI Pharma Helsinn; MGI Pharma MGI Pharma Merck; MGI Pharma MGI Pharma Helsinn
MP versus MPT for previously untreated elderly patients with multiple myeloma: A meta-analysis of 1,682 individual patient data from six randomized clinical trials.
Authors: A. Waage, A. P. Palumbo, P. Fayers, M. Beksac, C. Hulin, J. Mary, S. Bringhen, P. Sonneveld, P. Wijermans, T. Facon
Journal: Journal of Clinical Oncology (2010)

8130 Background: Randomized clinical trials including previously untreated patients were initiated in Italy, France (2), Netherlands/Belgium, and Nordic countries in 2000-2002 and in Turkey in 2006. These groups have agreed on a common analysis of their individual-patient data. Characteristics of the studies are shown in the Table. Methods: An electronic search for publications, abstracts, and presentations about MP versus MPT in multiple myeloma found no trial additional to the 6 presented here. The GIMEMA and 2 French studies have been published as articles, the 3 other as abstracts, and full publications are underway. The protocol for the common analyses was finalized after discussions with participants from all groups. All patients from the original studies have been entered into a common data base. Results: We analyzed 1,682 patients, 868 in the MP arm and 814 in the MPT arm. Median OS was 32.7 (95 % CI 30.4-36.5) months in the MP arm and 39.3 (35.6-39.0) months in the MPT arm. Median PFS was 14.9 (14.0-16.6) months in the MP arm and 20.4 (18.8-21.6) months in the MPT arm. Overall hazard ratio of MPT compared to MP was 0.82 (0.66-1.02) for OS and 0.67 (0.55-0.80) for PFS when a random effects model was used. Test of heterogeneity between the studies was statistically significant for OS (p = 0.26) and for PFS (p = 0.23). More complete analyses will be presented at the meeting. Conclusions: The meta-analysis demonstrates a significant effect on progression-free survival and is consistent with the observed difference in OS when thalidomide is added to melphalan and prednisone in first-line treatment to elderly patients with multiple myeloma. GIMEMA IFM I IFM II NMSG HOVON TMSG Age, years >65 65-74 >75 >65 >65 >55 No. of pts 331 321 229 354 333 114 Inclusion 2002-2005 2002-2005 2002-2006 2002- 2007 2002-2007 2006-2009 Placebo No No Yes Yes No No MelPred 4 mg/sqm 40 mg/sqmd 1-7 0.25 mg/kg2 mg/kgd 1-4 0.20 mg/kg2 mg/kgd 1-4 0.2 5mg/kg 100 mgd 1-4 0.25 mg/kg 1 mg/kgd1-5 9 mg/sqm 60 mg/sqmd1-4 No. of cycles/interval, weeks 6/4 12/6 12/6 Until plateau/6 At least 8/4 8/6 Thal mg/d Duration 100 Until relapse 200-400 12 cycles 100 12 cycles 400-200 Until relapse 200 4 w after last cycle 100 8 cycles Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene, Janssen-Cilag, Ortho Biotech, Pharmion Celgene, Janssen-Cilag, Johnson & Johnson, Millennium, Ortho Biotech, Pharmion Celgene, Janssen-Cilag
Case 49-1964
Authors: Herbert Mescon, Wallace H. Clark
Journal: New England Journal of Medicine (1964)

Presentation of CaseA forty-nine-year-old woman entered the hospital because of a skin rash.Five months previously she began to experience mild fatigue and weakness. Four months later a rash over the exposed area of the neck appeared and spread to the scalp and hands, accompanied by swelling and stiffness of the hands in the morning and by swelling of the face and eyelids. Several weeks before admission the shoulder muscles became sore, and mild exertional dyspnea occurred. During the five months before admission there was a weight gain of 15 pounds.Arthritis of the interphalangeal joints of both hands . . .
A Few Good Words
Authors: Christopher Moriates
Journal: Annals of Internal Medicine (2016)

On Being a Doctor19 April 2016A Few Good WordsChristopher Moriates, MDChristopher Moriates, MDFrom University of California, San Francisco, San Francisco, California.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M15-2198 Audio Reading - “A Few Good Words” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "A Few Good Words," by C. Moriates. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail “Do you have any questions?” I asked. My team of residents and medical students standing around the bed began to slump a bit. We had 10 more patients to see this morning, and we were already falling behind. As I asked the question, my brain immediately began chanting, “Please don't, please don't, please don't.” I thought the chant was quiet enough that only I could hear it, but my patient seemed to read my mind. She was an elderly woman with cancer, admitted with shortness of breath due to fluid that had built up around her lung. This stubbornly progressive ... Author, Article, and Disclosure InformationAffiliations: From University of California, San Francisco, San Francisco, California.Corresponding Author: Christopher Moriates, MD, University of California, San Francisco, 505 Parnassus Avenue, M1287, San Francisco, CA 94143-0131; e-mail, [email protected]ucsf.edu. PreviousarticleNextarticle Advertisement Audio Reading - “A Few Good Words” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "A Few Good Words," by C. Moriates. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics Cited byTrust-Based Partnerships Are Essential — and Achievable — in Health Care ServiceRole of Kindness in Cancer CareWhen Patients and Their Families Feel Like Hostages to Health CareWhat Adult Cancer Care Can Learn From Pediatrics 19 April 2016Volume 164, Issue 8Page: 566-567KeywordsArmed forcesBrainDyspneaElderlyHabitsLung and intrathoracic tumorsPatientsPerceptionPleural effusionShoulders ePublished: 19 April 2016 Issue Published: 19 April 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Growth Suppression of Subcutaneously Inoculated Hepatic Tumors After Iniection of Syngeneic Liver Cells Into the Subcutaneous Tissue of Rats2
Authors: Hideo Kamei, Tatsuhei Kondo, Tomoyoshi Momoi, Keisuke Terabe, Kazuyoshi Sugimoto
Journal: JNCI Journal of the National Cancer Institute (1976)

One week after the sc injection of minced tissues of the livers, kidneys, or spleens of W, Donryu, and MP rats into the left back of syngeneic rats, ascites-type tumor cells derived from rat hepatoma (AH 130) or Walker carcinosarcoma cells derived from rat breast tumor were inoculated sc into the right back. Ascites hepatoma cell growth was slowest in the group given the liver preparation, whereas no significant difference was noted in the growth of Walker carcinosarcoma in all groups. The results were similar in all strains.
Rapid Detection and Quantitation of Human Cytomegalovirus in Urine through DNA Hybridization
Authors: Sunwen Chou, Thomas C. Merigan
Journal: New England Journal of Medicine (1983)

We detected cytomegalovirus DNA in clinical urine specimens after immobilization on nitrocellulose filters and hybridization with a radioactively labeled, cloned fragment of cytomegalovirus DNA. We accomplished the specific detection and quantitation of viral DNA within 24 hours with 39 urine specimens from nine patients with cytomegalovirus viruria, mostly at a tissue-culture infective titer of 103 per milliliter or higher. None of 57 urine specimens from 21 patients that were culture-negative for cytomegalovirus gave false-positive results. Analysis of specimens from patients with cytomegalovirus viruria showed a correlation of the infective titer with the intensity of DNA hybridization (r = 0.77). Hybridization of sequential urine specimens from a patient undergoing treatment with interferon for cytomegalovirus retinitis revealed quantitative variations in hybridizable viral DNA over a period that correlated with clinical findings. This assay can be useful in the selection of patients for antiviral therapy and for the assessment of its efficacy. (N Engl J Med 1983; 308: 921–5.)
Abstract 16108: Right Ventricular Strain is a More Sensitive Marker of Right Ventricular Dysfunction Than Right Ventricular Ejection Fraction in a Cohort of Patients With Idiopathic Pulmonary Arterial Hypertension
Authors: Julia Grapsa, Timothy C Tan, David Dawson, Petros Nihoyannopoulos
Journal: Circulation (2014)

Introduction: Strain has been shown to be more sensitive that ejection fraction in detecting subclinical dysfunction in the left ventricle. A number of echocardiographic parameters associated with right heart size and function have been shown to be impaired in idiopathic pulmonary arterial hypertension (IPAH) but there is minimal data on which may be the most sensitive. Aim: To characterize the changes in functional and echocardiographic indices of right ventricular (RV) size and function, in a cohort of IPAH patients followed serially to determine if strain is a more sensitive measure of RV dysfunction than RVEF. Methods: Thirty patients (24 women, mean age 46.8 ± 5.3 years) with newly diagnosed IPAH were prospectively recruited and followed with serial transthoracic echocardiograms (TTE; Philips Medical Systems, Andover, MA) 6 monthly for up to 18 months. A range of 2D and 3D echocardiographic measures of right ventricular dimensions and function, including right ventricular ejection fraction (RVEF) and systolic longitudinal strain (LS), was assessed at each time point after commencing treatment using vendor independent software (TomTec, Germany). Functional status was assessed at18 months. Statistical analyses were performed using JMP statistical package (SAS Institute In. Cary, NC) Results: 3D RV volumes, ejection fraction, mass, 2D global strain and 2D free wall strain all show significant changes over 18 months (p-value &lt; 0.05; ANOVA of repeated measures) although peak tricuspid regurgitant velocity, RV systolic pressure and stroke volume do not. However, RV global strain and RV free wall strain showed significant changes within 6 months after diagnosis but not RVEF, peak TR velocity or RVSP. The degree of change in the RV free wall strain change at 18 months but not RVSP, RV mass or RVEF, was also associated with an abnormal 6 min walk test (18 months change, p=0.03). Conclusion: RV global and free wall strain demonstrate significant decreases prior to RVEF, peak TR velocity and RVSP hence may be more more sensitive measures of RV dysfunction in patients with IPAH. These results may help guide treatment decisions and highlight the potential value of echocardiography in detecting subacute cardiac pathology.
The Risk of Transfusion-Transmitted Viral Infections
Authors: George B. Schreiber, Michael P. Busch, Steven H. Kleinman, James J. Korelitz
Journal: New England Journal of Medicine (1996)

Accurate estimates of the risk of transfusion-transmitted infectious disease are essential for monitoring the safety of the blood supply and evaluating the potential effect of new screening tests. We estimated the risk of transmitting the human immunodeficiency virus (HIV), the human T-cell lymphotropic virus (HTLV), the hepatitis C virus (HCV), and the hepatitis B virus (HBV) from screened blood units donated during the window period following a recent, undetected infection.
A phase I study of intra-arterial (IA) cisplatin (C) and accelerated fractionation (AF) radiotherapy (RT) for locally advanced head and neck squamous cell carcinoma (HNSCC)
Authors: K. Yu, S. C. Yu, A. C. Vlantis, M. K. Kam, E. P. Hui, A. King, R. K. Tsang, G. M. Tse, F. Mo, A. T. Chan
Journal: Journal of Clinical Oncology (2007)

16512 Background: Concurrent IAC and conventional fractionation (CF) RT is an effective treatment for locally advanced HNSCC. AF RT with 2 late concurrent IAC doses may be equally effective since AF RT produces better local tumor control compared with CF RT and late chemotherapy boost may counteract accelerated repopulation of tumor cells. The maximum-tolerated dose (MTD) of IAC given concurrently with AF RT is not known. Methods: A phase I study was conducted in patients with locally advanced stage III/IV HNSCC to determine the MTD of C that was given as 2 selective IA infusions 1 week apart during the last 2 weeks of AF RT (70 Gy/35 fractions/6 weeks) using 6 fractions/week. IV sodium thiosulfate was used to neutralize the systemic toxicity of C. Starting at 100 mg/m 2 , cohorts of 3 to 6 patients were treated with escalating doses of IAC, in 25 mg/m 2 increments, up to the highest level of 200 mg/m 2 per infusion. Dose-limiting toxicity (DLT) was defined as the occurrence in 2 patients at a dose level of grade 3 acute mucositis or skin reactions lasting more than 8 weeks after completion of treatment; grade 4 hematologic, infective, metabolic or hearing toxicity; or grade 3 renal, hepatic or neurological toxicity. The MTD was defined as the dose level immediately lower than that resulting in DLT. Results: Ten patients were recruited with a mean age of 56 years. Two patients had stage III; 1, stage IVa; and 7, stage IVb disease. The T-stages were T1 (n = 2), T2 (n = 1), T3 (n = 2), and T4 (n = 5). The N-stages were N0 (n = 2), N1 (n = 1), N2 (n = 4), and N3 (n = 3). Three patients received IAC at a dose level of 100 mg/m 2 , 3 at 125 mg/m 2 , and 4 at 150 mg/m 2 . All patients had the 2 planned doses except one in the lowest dose level who developed grade 3 hyponatremia after the first dose. There was no treatment-related mortality. DLT occurred in 2 patients at the 150 mg/m 2 dose level. One of them had grade 4 leukopenia, and the other had grade 3 acute skin reactions lasting 9 weeks after RT. Thus, MTD was 125 mg/m 2 . At a median follow-up of 24 months, 6 patients remained alive and disease-free. Conclusions: In patients with locally advanced HNSCC, AF RT with 2 doses of late IAC boost was feasible. The MTD of IAC was 125 mg/m 2 . No significant financial relationships to disclose.
Phase I/II trial of BAY 43-9006, carboplatin (C) and paclitaxel (P) demonstrates preliminary antitumor activity in the expansion cohort of patients with metastatic melanoma
Authors: K. T. Flaherty, M. Brose, L. Schuchter, D. Tuveson, R. Lee, B. Schwartz, C. Lathia, B. Weber, P. O'Dwyer
Journal: Journal of Clinical Oncology (2004)

7507 Background: BAY 43-9006 (BAY) is a novel signal transduction inhibitor that prevents tumor cell proliferation and angiogenesis through blockade of the Raf/MEK/ERK pathway at the level of Raf kinase and the receptor tyrosine kinases VEGFR-2 and PDGFR-β. BAY inhibits CRAF and BRAF (wild type/V599E mutant) and inhibits growth of melanoma xenografts. This phase I/II study was initiated to define safety, pharmacokinetics (PK), and efficacy of oral BAY administered in combination with C and P. Methods: BAY was given from day 2 to 19 of a 21 day cycle at 3 dose levels (DL): DL 1, 100 mg bid; DL 2, 200 mg bid; and DL 3, 400 mg bid. C (AUC 6) and P (225 mg/m2) were each administered on day 1. PK data were collected on days 1, 2, 22, and 23. Tumor samples were obtained pretreatment for BRAF mutation analysis. Based on responses during the dose escalation phase, melanoma pts were accrued in the expansion phase. Results: 35 melanoma patients (pts) (median age 47, PS 0–1) have been treated for at least 6 weeks and 32 are evaluable for response. Twenty-one (60%) pts received ≥ 1 prior therapy, and 68% had AJCC M1c disease. Early data shows this combination is well tolerated with no unexpected adverse events. Responses using RECIST criteria demonstrated 11 partial responses; 10 are ongoing at 3–16 months (response rate 31%). Median time to response is 3 months. Nineteen pts have stable disease as best response, and 12 remain on study for ≥3 months since entry. Median time to progression has not been reached at a median follow-up of 5 months. Preliminary PK shows lack of interaction between BAY, P, and C. There was no change in the preliminary PK values of P, the 6-OH metabolite, total platinum, or free platinum from Cycle 1 to Cycle 2. Conclusions: The combination of BAY with C and P has demonstrated activity in melanoma with a favorable safety profile and no apparent PK interaction. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer Health Care; Bayer Pharmaceuticals Bayer AG; Bayer Pharmaceuticals