tbuckley/cabot-search huggingface dataset:
Shining a Light on the Dark Side
Authors: Shafik Dharamsi
Journal: Annals of Internal Medicine (2016)

Letters5 January 2016Shining a Light on the Dark SideShafik Dharamsi, BEd, MSc, PhDShafik Dharamsi, BEd, MSc, PhDFrom University of the Incarnate Word School of Osteopathic Medicine, San Antonio, Texas.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L16-0011 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I read the anonymous essay (1) and Laine and colleagues' editorial (2) with interest. Not long ago, my colleagues and I published an editorial on the use of cynical humor in medical practice and the related implications for professionalism, empathy, and the development of humanistic qualities in medicine (3). We observed that health workers are almost always overworked, tired, and overwhelmed with the demands and stresses of their profession. Indeed, they are not immune to the numbing effect of the day-to-day clinical grind. Some turn to derogatory humor as a coping mechanism.We acknowledged that laughter can ...References1. Anonymous. Our family secrets. Ann Intern Med. 2015;163:321. [PMID: 26280420]. doi:10.7326/M14-2168 LinkGoogle Scholar2. Laine C, Taichman DB, LaCombe MA. On being a doctor: shining a light on the dark side [Editorial]. Ann Intern Med. 2015;163:320. [PMID: 26280419]. doi:10.7326/M15-1144 LinkGoogle Scholar3. Dharamsi S, Whiteman M, Woollard R. The use of cynical humor by medical staff: implications for professionalism and the development of humanistic qualities in medicine [Editorial]. Educ Health (Abingdon). 2010;23:533. [PMID: 21290366] MedlineGoogle Scholar4. Boyer E. Scholarship Reconsidered: Priorities of the Professoriate. Princeton: Carnegie Foundation for the Advancement of Teaching; 1990. Google Scholar Author, Article, and Disclosure InformationAffiliations: From University of the Incarnate Word School of Osteopathic Medicine, San Antonio, Texas.Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOf InterestForms.do?msNum=L15-0517. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoOn Being a Doctor: Shining a Light on the Dark Side Christine Laine , Darren B. Taichman , and Michael A. LaCombe Shining a Light on the Dark Side Linda Ray Shining a Light on the Dark Side Gaetan Sgro , Mark T. Gladwin , Alexander Teng , Akshata Moghe , and Shanta M. Zimmer Shining a Light on the Dark Side Jordan Cohen and Richard I. Levin Shining a Light on the Dark Side Elizabeth Allemann Shining a Light on the Dark Side Christine Laine , Darren B. Taichman , and Michael A. LaCombe Shining a Light on the Dark Side Alvaro F. Vargas Pelaez Metrics 5 January 2016Volume 164, Issue 1Page: 68KeywordsConflicts of interestDisclosureForecastingMedical education ePublished: 5 January 2016 Issue Published: 5 January 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Predicting survival with health-related quality of life scores in locally advanced breast cancer: Results from an international randomized controlled trial
Authors: F. Efficace, P. Therasse, M. Piccart, C. Coens, K. Van Steen, M. Welnicka-Jaskiewicz, T. Cufer, M. Lichinitser, L. Shepherd, A. Bottomley
Journal: Journal of Clinical Oncology (2004)

618 Background: Whilst evidence suggests that baseline health related quality of life (HRQOL) scores predict survival in metastatic cancer patients, few trials have examined prognostic HRQOL factors in non-metastatic cancer patients. In this international phase III randomized controlled trial (RCT), we address these issues and retrospectively explore if baseline HRQOL scores predict survival in locally advanced breast cancer (LABC) patients. Methods: 435 LABC patients were enrolled over a period of three years randomized to receive in arm A: F (500 mg/m2 IV d1, 8 q 28 d x 6), E (60 mg/m2 IV d1, 8) and C (75 mg/m2 p.o. d1–14) versus E (120 mg/m2 IV d 1), C (830 mg/m2 IV d 1) and G-CSF (5 ug/kg/d s.c. d 2–13) q 14 d x 6 in arm B. HRQOL was assessed using the EORTC QLQ-C30 with baseline assessments being conducted before randomization. The Cox proportional hazards regression model was used for both univariate and multivariate analyses of survival. In addition, a bootstrap re-sampling technique was used to assess the stability of the outcomes. In this prognostic factor analysis, 359 (82.5%) of the 435 patients had a HRQOL assessment available at baseline and were then evaluated. Age, TNM stage, ER status as well as pre-selected HRQOL variables from the EORTC QLQ-C30 were analyzed for prognostic factor analyses in predicting overall survival (OS). Results: Diagnosis of inflammatory breast cancer (T4d, any N, M0) significantly predicted poor survival with a hazard ratio (HR) 1.375 (95% CI 1.027 –1.840, p=0.0323). However, no HRQOL scores at baseline showed up as prognostic indicators of OS, either in the univariate or multivariate analysis. A confirmatory analysis using a model-averaging technique, based on repeated forward Cox PH model-building on bootstrap generated data-sets were applied and confirmed the previous results. Conclusions: This is the first HRQOL prognostic factor analysis (PFA) study in LABC, and overall one of the largest HRQOL PFA using a robust methodology carried out in a homogenous cancer population. Our results indicate that HRQOL scores have no prognostic value in LABC patients. No significant financial relationships to disclose.
O028 : Cross-talk between IL13 and Hedgehog pathways contributes to schistosomiasis mansoni fibrosis
Authors: T. De Almeida Pereira, L. Borthwick, G. Xie, P. Vidigal, M. Machado, I. Voieta, V. Resende, A. Cheever, Z. Andrade, J. Lambertucci, T. Wynn, A.M. Diehl
Journal: Journal of Hepatology (2015)
Clinical impact and follow-up of taste disturbances following myeloablative or nonmyeloablative chemotherapy and stem cell transplantation
Authors: F. Mayer, J. Weidmann, B. Federmann, S. Schwarz, J. T. Hartmann, L. Kanz, W. Bethge
Journal: Journal of Clinical Oncology (2009)

e20609 Background: Stem cell transplantation (SCT) after myeloablative (MA) or non-myeloablative (NMA) chemotherapy is a successful treatment option for a variety of diseases. Although alterations of taste and smell are frequently encountered after these modalities, no systematic evaluation is available so far. Methods: A questionaire was developed covering aspects of the dietary pattern and changes in the perception of taste and smell. Clinical data were gathered from the charts. The study was approved by the institutional review board. Data of the first 100 of 200 planned patients’ (pts) are presented. Results: pts were surveyed after a median of 22 months from SCT (range 1–292), their age ranged from 20–76 years. Indications for SCT included acute leukemia (n=38), myeloproliferative disease (n=20), lymphoma (n=13), and others (n=29). Pts received an allogeneic graft after MA (n=48) or NMA (n=32) conditioning, 20 pts received an autologous one. 75% of pts reported moderate to severe changes in taste perception on a semiquantitative visual analogue scale during the acute phase of SCT with no differences between the three groups (73%, 79%, 75%). 28% of the pts reported a complete regression at the time of survey, 25% still suffered from moderate to severe changes. This finding was more prevalent after allogeneic SCT (30% after MA conditioning, 28% after NMA) compared to pts with autologous grafts (10%). Whereas pts without persisting changes in taste perception lost a median of 3 kg of body weight, pts suffering from severe changes lost 15 kg. Conclusions: Taste disturbances are a common after SCT. Symptoms are persistant in one third of the pts. In the allogeneic setting, no differences exist between MA and NMA conditioning. The lower incidence of persiting changes in taste perception after autologous SCT might be attributed to the absence of graft versus host disease or the dispensability of immunosuppression. Changes in taste perception correlate with weight loss. No significant financial relationships to disclose.
Predictors of early relapse in high risk prostate cancer patients treated with neoadjuvant mitoxantrone and docetaxel
Authors: C. A. O’Brien, M. Garzotto, C. S. Higano, E. M. Wersinger, V. Kaimaktchiev, C. L. Corless, P. H. Lange, C. W. Ryan, L. D. True, T. M. Beer
Journal: Journal of Clinical Oncology (2005)

4640 Background: The addition of chemotherapy (CTX) to primary treatment is being evaluated in clinical trials to improve outcomes in high-risk prostate cancer. Factors that predict relapse after combined treatment with CTX and radical prostatectomy (RP) are not known. Understanding which clinical and pathologic factors affect outcome can facilitate the design of studies of combined modality treatment of high-risk prostate cancer. Methods: Using the Kaplan-Meier method and log-rank test for univariate analyses and Cox’s proportional hazards regression for the multivariate analysis, we examined the relationship between progression-free survival (PFS, defined as time to serum PSA ≥ 0.4 ng/mL) and a series of variables in men with high risk prostate cancer (cT2b or T3a or PSA ≥ 15 ng/mL or Gleason score (GS) ≥ 4+3) who received 4 cycles of docetaxel (35 mg/m2) and mitoxantrone (2–5 mg/m2) weekly for 3 of every 4 weeks prior to RP. Pre-CTX variables were PSA, PSA density (PSAD), age, biopsy GS, and cT stage. Post-treatment variables were: CTX doses delivered, %PSA change, surgical GS, pT stage, pN stage, margin status, Ki-67 index (% Ki-67 staining cells/total cancer cells from a tissue microarray), and presence of intraductal carcinoma (IDC). Results: 48 patients received at least 1 cycle of CTX and were evaluable for efficacy endpoints. Median follow-up is 18.6 months. Estimated PFS at 2 years is 70±14%. In univariate analyses PSA ≥ 15 ng/dL (p=0.02), presence of IDC (p=0.003), and lymph node metastases (+LN) (p<0.001) were associated with shorter PFS. In a multivariate analysis of pre-treatment factors, PSAD (HR 1.25 per 0.1 ng/ml/cc, 95%CI 1.03–1.5, p=0.03) was the only factor significantly associated with shorter PFS. When both pre- and post-treatment factors were included, PSAD (HR 1.3 per 0.1 ng/ml/cc, 95%CI 1.05–1.6, p=0.02) and +LN (HR 27, 95% CI 6–125, p<0.001) were independent predictors of shorter PFS. There was a trend for biopsy GS 8–10 (HR 3.9, 95%CI 0.9–16.9, p=0.068). Conclusions: Our early results show that in high risk prostate cancer treated with neoadjuvant chemotherapy followed by radical prostatectomy, PSAD and persistent nodal disease are significantly associated with early relapse. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis, OSI
Maternal Phenylketonuria
Authors: C. Charlton Mabry, Joseph C. Denniston, Thomas L. Nelson, Choon D. Son
Journal: New England Journal of Medicine (1963)

IT has been demonstrated that excessive phenylalanine, or its products, can damage the developing brain of an otherwise normal young animal or human infant, and clinical studies suggest that the phenylketonuric infant's neurologic damage is acquired. There have been no animal experiments concerning the effect of an abnormally elevated maternal serum phenylalanine level on a developing fetal brain. Furthermore, it is generally considered that persons with phenylketonuria seldom reproduce because of their severe mental retardation. Thus, there have been almost no observations on their offspring.We have recently found 3 elderly phenylketonuric mothers who have had 1, 5 and 8 . . .
THU0426 Dietary Sodium Increases the Risk for Rheumatoid Arthritis among Smokers
Authors: B. Sundström, I. Johansson, S. Rantapää-Dahlqvist
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Studies in animal models and on human cells have suggested that sodium chloride may affect autoimmunity by the induction of pathogenic Th17 cells mediated through salt-sensing kinase-1. Since Th17 cells may play a role in the early stages of disease development of rheumatoid arthritis (RA), the dietary intake of sodium is of interest to analyse as a risk factor for the development of RA. <h3>Objectives</h3> To investigate if sodium intake is associated with increased risk for developing RA. <h3>Methods</h3> A nested case–control study was performed using the population based prospective data from the Västerbotten Intervention Programme (VIP). The study included 386 individuals (271 women, 115 men) who had stated their dietary habits as part of a community intervention programme before the onset of symptoms of RA. Sodium intake was assessed on basis of food frequency questions and analysed as tertiles adjusted by total energy intake. For comparison, 1886 matched controls were identified from the same database and co-analysed. Data were analysed for the outcome of rheumatoid factor (RF) and/or antibodies against cyclic citrullinated peptides (anti-CCP) or human leukocyte antigen shared epitope (HLA-SE) positive RA. <h3>Results</h3> In analysis of all cases as a homogeneous group no significant associations between sodium intake and the risk of developing RA could be seen. In stratified analyses for smoking status at the time of the survey (smokers and non-smokers), smokers within the highest tertile of sodium intake had more than double the risk for developing RA compared to smokers within the lowest tertile of sodium consumption (OR=2.26, 95% CI 1.06–4.81). This was not seen in non–smokers. Furthermore, smokers with low sodium consumption revealed no significantly increased risk for developing RA compared to non-smokers. Interaction analysis of smoking and sodium intake revealed that among cases with the highest tertile of sodium intake, 54% of the attributable proportion (AP) of developing RA from these exposures was due to interaction (AP=0.54, 95% CI 0.26-0.82). The corresponding relative excess risk of the interaction (RERI) between smoking and highest sodium intake was also significant (RERI=1.34, 95% CI 0.37 to 2.32). These associations was further increased with the outcome of anti-CCP positive or HLA-SE positive RA disease (OR=2.42, 95% CI 1.07-5.49; and OR=3.28, 95% CI 1.24-8.67, respectively). <h3>Conclusions</h3> A higher sodium consumption among smokers was associated with an increased risk for developing RA. This interaction between sodium intake and smoking can provide new insights into the pathogenesis of RA. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1590
Relation of tumor pathologic and molecular features to outcome after surgical resection of localized primary gastrointestinal stromal tumor (GIST): Results of the intergroup phase III trial ACOSOG Z9001.
Authors: C. L. Corless, K. V. Ballman, C. Antonescu, C. D. Blanke, M. E. Blackstein, G. D. Demetri, M. von Mehren, R. G. Maki, P. W. Pisters, R. P. DeMatteo
Journal: Journal of Clinical Oncology (2010)

10006 Background: Adjuvant therapy with imatinib mesylate increases recurrence-free survival (RFS) in primary GIST (Lancet 2009). However, the effect of tumor pathologic and molecular factors on outcome in patients treated with or without adjuvant imatinib is uncertain. Methods: 713 patients with a KIT-expressing, ≥3 cm, primary GIST were randomized postoperatively in a double-blind manner to 1 year of 400 mg imatinib or placebo daily. Patients underwent serial (q3 months x8 then q6 months x6) cross-sectional imaging. Mitotic rate (mitoses per 50 high power fields) and KIT and PDGFRA mutation status were determined by central pathologic analyses. Tumor mitotic rate, size, location, and mutation status were available in 513 patients. Results: Tumor size was <5 cm in 41% of patients, 5-10 cm in 34%, and ≥10 cm in 25%. Tumor location was stomach (65%), small bowel (31%), rectum (1%), or other (3%). Mitotic rate was high (≥5) in 39% of patients. The most common (68%) mutation occurred in KIT exon 11. At a median follow-up of 20 months, 2 year RFS was 74% in the placebo arm vs. 91% in the imatinib arm. On multivariate analysis of the placebo arm, RFS was worse with high mitotic rate (p<0.0001, HR 17.1), tumor size (p<0.01, HR 1.7), small bowel location (p<0.05, HR 2.1), and KIT exon 11 mutation (p<0.05, HR 3.0). On multivariate analysis of the imatinib arm, RFS was worse with high mitotic rate (p<0.001, HR 7.4), tumor size (p<0.01, HR 2.9), and small bowel (p<0.05, HR 3.1) or rectal (p<0.05, HR 5.4) location. In the placebo and imatinib arms respectively, 2 yr RFS was 65 vs. 91% (p<0.0001) for KIT exon 11 mutation and 76 vs. 100% (p<0.01) for PDGFRA mutation. Notably, there was only 1 event in the 28 total patients with a PDGFRA D842V mutation. Patients with a KIT exon 9 mutation assigned to placebo (n=13) had a 1 yr RFS of 80% vs. 100% on the imatinib arm (n=22), but overall RFS was not different. There was no statistical difference in RFS between arms in the 64 patients with wild-type KIT and PDGFRA. Conclusions: Tumor pathologic features and mutation status are both prognostic and predictive for RFS after surgical resection of primary GIST. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis, Pfizer Novartis, Pfizer Novartis, Pfizer Pfizer
Abstract 19220: Potential of Human Cardiac Progenitor Cells from Young versus Old Donor Hearts in Cardiac Protection against Ischemic Left Ventricular Dysfunction and Late Remodeling
Authors: Ann Sophie Walravens, Ellen Caluwé, Sander Trenson, Hilde Gillijns, Nina Vanden Driessche, Manu Beerens, Ming Wu, Aernout Luttun, Stefan Janssens
Journal: Circulation (2014)

Introduction: Recent discovery of c-Kit + resident cardiac progenitor cells (CPC) has demonstrated cardiac regenerative capacity, which is lost upon increasing age in mice. Accordingly, we hypothesized that c-KIT + -selected CPC from young human hearts (yCPC) have a greater myocardial repair potential after myocardial infarction (MI) than CPC from old patients (oCPC). Methods: After Ethics Committee approval, cardiac biopsies from young (1-15y old) and old (58-80y old) patients, undergoing corrective or valve surgery were obtained. After collagenase-based digestion, cells were culture-expanded for 2 passages prior to c-KIT + selection using magnetic beads. Purity was confirmed using qRT-PCR for c-KIT, GATA4, CD90, CD105, DDR2, CD31 and MYH11 expression levels. To trace transplanted cells, CPC were lentivirally tagged with GFP. After permanent LAD coronary artery ligation in immunodeficient mice, 250,000 CPCs were injected in the infarct border zone (4x 62,500 cells/2.5 μl; yCPC, n =8; oCPC, n =6; or PBS, n =6). Cardiac ultrasound (VisualSonics, 3D 30 MHz probe) was performed at baseline, 1 and 35 days after MI. At 35 days post-MI, infarct remodeling and cell survival was evaluated using Sirius red and CPC engraftment by anti-GFP staining. Results: In contrast to low MYH11 and CD31 expression levels, c-KIT and GATA4 were markedly and equally expressed in yCPC and oCPC, whereas transcript levels of DDR2, CD105 and CD90 were 89, 109 and 56% higher in oCPC compared to yCPC. Systolic function was better preserved in yCPC than in oCPC and PBS-treated mice 24h after MI (LVEF from baseline - D1: 53±1 - 38±3 vs. 52±3 - 30±5 vs. 50±3 - 27±4%; ESVi from baseline - D1: 3.7±0.2 - 5.1±0.4 vs. 3.8±0.5 - 6.2±0.7 vs. 3.9±0.5 - 6.5±0.6ml/mm 2 ). Moreover, after 35 days, the dilatory response was reduced in yCPC compared to oCPC and PBS-treated mice (EDVi from D1 - D35: 8.3±0.5 - 13.5±1.3 vs. 8.8±0.5 - 16.7±1.8 vs. 8.5±0.5 - 16.6±1.3ml/mm 2 ). Improved remodeling was consistent with a markedly greater rim of surviving myocardium while anti-GFP staining showed only rarely retained CPC. Conclusions: In summary, these findings suggest enhanced protection by c-KIT + CPC isolated from young donor hearts against acute systolic left ventricular dysfunction and late remodeling after MI.
SWOG S0727: A randomized phase II trial of combination gemcitabine plus erlotinib plus IMC-A12 (cixutumumab) versus gemcitabine plus erlotinib as first-line treatment in patients (pts) with metastatic pancreatic cancer.
Authors: P. A. Philip, B. H. Goldman, R. K. Ramanathan, H. Lenz, A. M. Lowy, R. P. Whitehead, S. Iqbal, V. M. Chung, J. K. Benedetti, C. D. Blanke
Journal: Journal of Clinical Oncology (2010)

TPS223 Background: A multitargeted approach in treating pancreatic cancer is rationalized by the multiple genetic abnormalities in this disease. In addition, evidence so far indicates that a single targeted treatment is unlikely to be effective. Insulin-like growth factor-1 receptor (IGF-1R) overexpression is observed and implicated in proliferation, survival, angiogenesis, and invasion. There is preclinical evidence of a cross talk between epidermal growth factor receptor (EGFR) and IGF-1R signaling pathways that may explain the acquired resistance to anti-EGFR drugs. SWOG reported a phase I evaluation of the combination of gemcitabine (1,000 mg/m2 i.v. days 1, 8, 15), erlotinib (100 mg po daily), and cixutumumab (6 mg/kg iv days 1, 8, 15, 22) of each 28-day cycle in chemonaive pts with metastatic pancreatic cancer. Ten pts were enrolled and assessed for toxicity. There was no apparent worsening of gemcitabine or erlotinib related toxicities by the addition of cixutumumab (Philip et al., GI Symposium 2010). Methods: The recommended phase II dose of cixutumumab 6 mg/kg/week in combination with standard dose and schedule of gemcitabine and erlotinib carried forward to the randomized phase II portion of the study, which has enrolled 38 pts to date. The primary endpoint for the phase II portion of this trial is progression-free survival (PFS). Pts are randomized to either Arm 1 (erlotinib + gemcitabine + cixutumumab) or Arm 2 (erlotinib + gemcitabine). Major inclusion criteria include metastatic disease, PS of 0-1, measurable or evaluable disease, and no prior gemcitabine. Major exclusions are AST/ALT > 2.5 × ULN, abnormal bilirubin, ANC < 1,500, or platelet < 100,000. Based on a type 1 error of 10% and 90% power and approximately 1.5 years of accrual and 1 year of follow-up, a planned sample size of 106 pts would be needed to detect an improvement in PFS from 2-3.3 months. Once 50% of the expected events in the control arm have occurred, an interim analysis of the primary endpoint will be performed with the intent of testing the alternative hypothesis (e.g., terminate early if a 1.65 hazard ratio is deemed highly unlikely [p< 0.005]). Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer, Bristol-Myers Squibb, Curis, Nektar Therapeutics, OSI, Roche, sanofi-aventis OXiGENE Amgen, Bayer, Onyx, Roche, sanofi-aventis Bristol-Myers Squibb, Chugai Pharma, Genentech, Genvec, GlaxoSmithKline, ImClone Systems, Novartis, OSI, sanofi-aventis