tbuckley/cabot-search huggingface dataset:
Late side effects of neoadjuvant chemotherapy in patients treated for osteosarcoma and Ewing's sarcoma: An Italian Sarcoma Group study.
Authors: A. Longhi, C. Ferrari, A. Tamburini, M. Berta, F. Fagioli, G. Bacci, M. Mercuri, S. Ferrari
Journal: Journal of Clinical Oncology (2010)

9551 Background: We report data of long term follow up of 883 patients with localized osteosarcoma of the extremity and 493 patients with localized Ewing's sarcoma treated with neoadjuvant chemotherapy from 1983 to 2007 to find out late side effects (second malignancies, cardiomyopathy, sterility). Methods: We reviewed our database and we interviewed by phone the missing patients. Data are updated to Dec 2009. Results: Osteosarcoma patients: 883 patients are evaluable. Median overall survival (OS) is 108 months (range 1-306), female/male: 370/403, alive 563, dead 320. 28 second malignant neoplasms (SMN) were reported for a cumulative risk at 10 yrs of 3.02 ±1.0 (SE): 9 hematologic malignancies (7 leukemia and 2 myelodysplastic syndrome) after a median of 36 ms and 19 solid tumor (6 breast ca, 3 parotid ca, 2 CNS tumor, 2 skin cancers, 2 soft tissue sarcomas, 1 Ewing's sarcoma, 1 kidney cancer, 1 colon cancer, 1 ovarian cancer) 2 patients had 2 SMN. 18 patients had adriamycin–cardiomyopathy. 46 male did sperm analysis with 28 azospermia and 11 oligospermia, 7 normospermia. 13 male and 20 female pts became parents. No abnormalities in offsprings were recorded. Ewing's sarcoma patients: 493patients. Median age was 16 yrs (1-40) female/male: 183/310. Median OS is 69 ms (4-302). 220 are dead, 273 alive. 44 pts received HDCT + PBSCR. Eleven SMN were reported: 2 AMLeukemia, 2 parotid gland carcinoma, 1 melanoma, 1 thyroid cancer and 5 radioinduced osteosarcoma. 10 yrs cumulative risk of SMN is 2.9 ± 1.1 (SE). Four patient had adriamycin–cardiomyopathy; 20 women experienced postTx amenorrea: 7 pts received RT in pelvic area, 9 did HDCT, 3 pts were over 30 yrs old. Conclusions: Cumulative risk of SMN increase with time from about 3% at 10 years to about 6% at 20 years. Breast cancer and salivary glands cancer are the most common solid SMN. Sterility is more common in males and it is related to alkylators doses. Cardiomyopathy is related to antracyclines doses. Updated data will be presented. No significant financial relationships to disclose.
PTU-308 Improving efficiency of gi out-patient service in partnership with primary care
Authors: KA Hill, C Davies, D Gritton, D Bush, A Smith, B McKaig
Journal: Gut (2015)

<h3>Introduction</h3> With increasing demand on outpatient (OP) services it is imperative to maximise efficiency to optimise patient management, reduce waiting times and DNA rates. Following an audit, the gastroenterology (GI) service felt that ∼30% of referrals did not require to be seen in a secondary care OP setting. In partnership with the CCG we developed a Clinical Assessment Service (CAS) to optimise patient care by ensuring that only the most clinically appropriate patients were seen by a Gastroenterologist, whilst other patients were triaged to a more appropriate managment pathway. <h3>Method</h3> From January 2014, Choose and Book Access for GPs for GI referrals was replaced by virtual CAS clinics. All referrals are triaged electronically to determine the most appropriate clinical pathway. The 4 options are: GI OP appointment; diagnostic test – followed by either OP appointment or discharge; refer back to GP with a management plan and advice; or return to GP as inappropriate referral for GI. <h3>Results</h3> The CAS service was implemented in Jan 2014 (3820 referrals to date) 14% of referrals have been referred back to the GP as inappropriate. 10% of referrals have been referred back to the GP with Primary Care Management plan. 26% of referrals are sent for a diagnostic test prior to attending an outpatient appointment or being discharged. DNA rates in outpatient clinics have fallen from 15% to 7.5%. CAS has saved the health economy ∼£8000 per month Patients now offered OP appt has reduced from 100% to 40% National targets in OP have been maintained without increased resource despite 17% increase in OP referrals from 2013/14 levels Patient and GP surveys have indicated high levels of satisfaction <h3>Conclusion</h3> Implementation of CAS has streamlined patient management pathways and has had a significant impact on OP efficiency whilst providing cost savings to the health economy. 50% of patients now referred to GI are directed to a more appropriate and timely management pathway as opposed to attending traditional OP appointment. This has alleviated pressure on outpatient services resulting in reduced waiting times. <h3>Disclosure of interest</h3> None Declared.
Serum Sex Hormone Levels Are Related to Breast Cancer Risk in Postmenopausal Women
Authors: Joanne F. Dorgan, Christopher Longcope, Hugh E. Stephenson, Roni T. Falk, Rosetta Miller, Charlene Franz, Lisa Kahle, William S. Campbell, Joseph A. Tangrea, Arthur Schatzkin
Journal: Environmental Health Perspectives (1997)

We conducted a nested case-control study to prospectively evaluate the relationship of serum estrogens and androgens to risk of breast cancer in postmenopausal women.From 1977 to 1987, 3375 postmenopausal women free of cancer and not taking replacement estrogens donated blood to the Breast Cancer Serum Bank in Columbia, Missouri.Of these, 72 were subsequently diagnosed with breast cancer.For each case, two controls matched on age and date and time of day of blood collection were selected using incidence density matching.The median age of subjects at blood collection was 62 years; the time from blood collection to diagnosis ranged from less than 1 to 9.5 years with a median of 2.9 years.Risk of breast cancer was positively and significantly associated with serum levels of estrogens and androgens.Compared to women in the lowest quartile, those in the highest quartile for non-sex hormone-binding globulin (non-SHBG) bound (bioavailable) estradiol had a relative risk of 5.2 (95% confidence interval [CII = 1.5-18.5)and those in the highest quartile for testosterone had a relative risk of 6.2 (95% Cl = 2.0-19.0).Our results lend considerable support to the hypothesis that serum concentrations of estrogens and androgens are related to the subsequent diagnosis of breast cancer in
CRISPR library designer (CLD): software for multispecies design of single guide RNA libraries
Authors: Florian Heigwer, Tianzuo Zhan, Marco Breinig, Jan Winter, Dirk Brügemann, Svenja Leible, Michael Boutros
Journal: Genome biology (2016)

Genetic screens using CRISPR/Cas9 are a powerful method for the functional analysis of genomes.
Psychiatric aspects of AIDS
Authors: M E Faulstich
Journal: American Journal of Psychiatry (1987)

AIDS is a multimorbid, severe and complex medical illness accompanied with psychiatric disorders and a strong stigma and discrimination of the people that are affected.Appearance of standard antiretroviral therapy and CART (combination antiretroviral therapy) reduced the morbidity rates of AIDS, but the incidence of AIDS is still on the rise.There are about 34 million people infected with AIDS worldwide.With the annual number of new AIDS cases less than 4 per million in the total population, Croatia is a country that has continuously had a very low incidence of the disease.Given that patients with AIDS live longer today, they are prone to psychological problems related to living with a chronic illness.Thus, psychiatric care is an essential part of a multidisciplinary treatment.
Metallothionein‐1G facilitates sorafenib resistance through inhibition of ferroptosis
Authors: Xiaofang Sun, Xiaohua Niu, Ruochan Chen, Wenyin He, De Chen, Rui Kang, Daolin Tang
Journal: Hepatology (2016)

Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide and currently has the fastest rising incidence of all cancers. Sorafenib was originally identified as an inhibitor of multiple oncogenic kinases and remains the only approved systemic therapy for advanced HCC. However, acquired resistance to sorafenib has been found in HCC patients, which results in poor prognosis. Here, we show that metallothionein (MT)-1G is a critical regulator and promising therapeutic target of sorafenib resistance in human HCC cells. The expression of MT-1G messenger RNA and protein is remarkably induced by sorafenib but not other clinically relevant kinase inhibitors (e.g., erlotinib, gefitinib, tivantinib, vemurafenib, selumetinib, imatinib, masitinib, and ponatinib). Activation of the transcription factor nuclear factor erythroid 2-related factor 2, but not p53 and hypoxia-inducible factor 1-alpha, is essential for induction of MT-1G expression following sorafenib treatment. Importantly, genetic and pharmacological inhibition of MT-1G enhances the anticancer activity of sorafenib in vitro and in tumor xenograft models. The molecular mechanisms underlying the action of MT-1G in sorafenib resistance involve the inhibition of ferroptosis, a novel form of regulated cell death. Knockdown of MT-1G by RNA interference increases glutathione depletion and lipid peroxidation, which contributes to sorafenib-induced ferroptosis.These findings demonstrate a novel molecular mechanism of sorafenib resistance and suggest that MT-1G is a new regulator of ferroptosis in HCC cells. (Hepatology 2016;64:488-500).
Depression and the reintegration phase of acute schizophrenia
Authors: P T Donlon, R T Rada, K K Arora
Journal: American Journal of Psychiatry (1976)

The authors found moderate to severe depression in 60% of a group of schizophrenic patients experiencing acute decompensations (N=30). The course of the depression was followed over an 8-week period8,during which patients were treated with depot fluphenazines. There was a statistically significant reduction in depression that closely paralleled the correction of the cognitive disorder. The authors discuss problems in identifying and quantifying depression during acute schizophrenic decompensation and suggest that the Hamilton scale anxiety/depression factor and the BRPS depression factor may be useful diagnositc tools.
Trainee who used escort while on call is suspended for 10 months
Authors: Clare Dyer
Journal: BMJ (2016)

A trainee anaesthetist who had sex with an escort in a hospital room, while on call at a maternity hospital, has been suspended from the UK medical register for 10 months.

Rupert Pemsel, 32, who arranged for the sex worker to visit him at the hospital in December 2013 after viewing internet porn, indulged in “deplorable and morally reprehensible” behaviour, a medical practitioners tribunal declared.

The tribunal considered striking the married father of two off the register but took into account that he was committed to continuing to practise medicine, “and it …
Paclitaxel and radiation-recall dermatitis.
Authors: T Shenkier, K Gelmon
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.1994.12.2.439 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 7906725 Paclitaxel and radiation-recall dermatitis. T ShenkierxT ShenkierSearch for articles by this author , K GelmonxK GelmonSearch for articles by this author https://doi.org/10.1200/JCO.1994.12.2.439 PDF "Paclitaxel and radiation-recall dermatitis.." Journal of Clinical Oncology, 12(2), p. 439© 1994 by American Society of Clinical Oncology
Abstract 10918: Increased Plasma Sphingosine-1-Phosphate (S1P) and Its Capacity to Increase Expression of Plasminogen Activator Inhibitor-1 In Adipocytes and Obese Subjects
Authors: Satoshi Fujii, Soichiro Iwaki, Shiori Ito, Ayako Nagasaki, Ryunosuke Ohkawa, Yutaka Yatomi, Tomoo Furumoto, Burton E Sobel
Journal: Circulation (2012)

Concentrations of plasminogen activator inhibitor type-1 (PAI-1), the physiologic inhibitor of fibrinolysis in blood, are increased in obese subjects. One source is adipocytes. Hypoxia is known to ...
MTR-18PREDICTIVE BIOMARKERS OF BEVACIZUMAB RESPONSE IN RECURRENT GLIOBLASTOMA PATIENTS
Authors: Thomas Urup, Signe Regner Michaelsen, Lars Rønn Olsen, Anders Toft, Ib Jarle Christensen, Kirsten Grunnet, Helle Broholm, Michael Kosteljanetz, Hans Skovgaard Poulsen, Ulrik Lassen
Journal: Neuro-Oncology (2015)

BACKGROUND: Bevacizumab (BEV) plus chemotherapy has shown activity in recurrent glioblastoma (GBM).However, the prognosis varies and only one third of patients have a durable clinical response to BEV combination therapy.Recent findings from a randomized phase-3 study (AVAglio) indicate that patients with the proneural GBM subtype have a survival benefit when treated with BEV in combination with standard treatment.However, no Overall survival
Normalization of cardiac substrate utilization and left ventricular hypertrophy precede functional recovery in heart failure regression
Authors: Nikole J. Byrne, Jody Levasseur, Miranda M. Sung, Grant Masson, Jamie Boisvenue, Martin E. Young, Jason R.B. Dyck
Journal: Cardiovascular Research (2016)

AimsImpaired cardiac substrate metabolism plays an important role in heart failure (HF) pathogenesis. Since many of these metabolic changes occur at the transcriptional level of metabolic enzymes, it is possible that this loss of metabolic flexibility is permanent and thus contributes to worsening cardiac function and/or prevents the full regression of HF upon treatment. However, despite the importance of cardiac energetics in HF, it remains unclear whether these metabolic changes can be normalized. In the current study, we investigated whether a reversal of an elevated aortic afterload in mice with severe HF would result in the recovery of cardiac function, substrate metabolism, and transcriptional reprogramming as well as determined the temporal relationship of these changes.
Low dose beta blockers are as effective as higher doses after myocardial infarction, study shows
Authors: Susan Mayor
Journal: BMJ (2015)

Patients who have had an acute myocardial infarction and are treated with a lower dose of beta blockers than used in clinical trials show similar or better survival than those given higher doses, a new study has found. 

The multicentre study, published in the Journal of the American College of Cardiology , enrolled 7057 consecutive patients with acute myocardial infarction at 26 centres in the United States and Canada.1 Researchers looked at the dose of beta blocker given …
Tumor CTR1 copper transporter modulation by decitabine (DAC) and relationship to global DNA methylation and time from prior therapy
Authors: D. J. Stewart, M. Nunez, J. Jelinek, Z. Guo, D. S. Hong, I. I. Wistuba, J. P. Issa, R. Kurzrock
Journal: Journal of Clinical Oncology (2008)

11088 Background: Impact of DAC on CTR1 (a copper transporter important in cell platinum uptake) was assessed by immunohistochemistry (IHC) in 31 patients with refractory solid tumors & lymphomas. A potentially DAC-reversible pleiotropic defect in drug accumulation has been noted in resistant cells (X Liang et al. J Inorg Biochem 2004) and CTR1 is down-regulated after platinum exposure (A. Holzer et al. Clin Cancer Res 2004). Methods: Cohorts 1–3 (≥ 6 patients/cohort) received DAC 2.5–10 mg/m2/day iv over 1 hr days 1–5 & 8–12, and cohorts 4 & 5 received 15 & 20 mg/m2/day days 1–5 only. Tumor biopsies pre day 1 & on day 12 were characterized histologically. CTR1, p16 & DNA methyltransferase 1 (DNMT1) were scored by IHC (staining intensity [0–4] × % tumor cells staining). Apoptosis was assessed by TUNEL & DNA methylation by LINE assay. Results: Patients starting DAC > 3 months (mo) past last prior targeted or chemotherapy had higher median pre DAC CTR1 scores than did patients ≤ 3 mo post prior therapy (285 vs 90, p=0.02). CTR1 scores did not correlate with necrosis, apoptosis, Ki67 or p16, but tended to be higher with more mitoses (r = 0.25, p = 0.095) and in non-epithelial than epithelial tumors (p=0.098). CTR1 correlated inversely with global DNA methylation (r= −0.46, p<0.002) and positively with DNMT1 score (r=0.43, p<0.003). DAC increased CTR1 in tumors with low pre-DAC scores and short times from last treatment. In paired comparisons, CTR1 scores were higher post DAC than pre DAC if pre DAC scores were <200 (p=0.025) (but not if pre DAC scores were >200) and in patients starting DAC < 3 mo vs ≥ 3 mo after last prior therapy (30 vs 0, p=0.025). Change in CTR1 with DAC did not correlate significantly with DAC dose, cohort, tumor type, or with change in DNA methylation, DNMT1, Ki67, p16, apoptosis, necrosis, response or time to progression with DAC. Assessments of other transporters, CTR1 gene methylation and autophagy are planned. Conclusions: Since CTR1 down-regulation may contribute to platinum resistance, we propose testing low dose DAC clinically as a method of reversing platinum resistance in recently treated patients or with low CTR1 tumor scores. Supported in part by NIH grant UO1 CA062461–10 & R21 CA112895–01A1. No significant financial relationships to disclose.
Welcome to the splice age: antisense oligonucleotide–mediated exon skipping gains wider applicability
Authors: Elizabeth M. McNally, Eugene J. Wyatt
Journal: Journal of Clinical Investigation (2016)

Exon skipping uses antisense oligonucleotides (ASOs) to alter transcript splicing for the purpose of rescuing or modulating protein expression. In this issue of the JCI, Lee and colleagues developed and evaluated an ASO-dependent method for treating certain molecularly defined diseases associated with alterations in lamin A/C (LMNA) splicing. Exon skipping by ASOs is gaining traction as a therapeutic strategy, and the use of ASOs is now being applied to bypass mutations and generate modified but functional proteins for an array of genetic disorders.
The microbiota-derived metabolite indole decreases mucosal inflammation and injury in a murine model of NSAID enteropathy
Authors: Canaan M. Whitfield-Cargile, Noah D. Cohen, Robert S. Chapkin, Brad R. Weeks, Laurie A. Davidson, Jennifer S. Goldsby, Carrie L. Hunt, Shelby H. Steinmeyer, Rani Menon, Jan S. Suchodolski, Arul Jayaraman, Robert C. Alaniz
Journal: Gut Microbes (2016)

Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most frequently used classes of medications in the world. Unfortunately, NSAIDs induce an enteropathy associated with high morbidity and mortality. Although the pathophysiology of this condition involves the interaction of the gut epithelium, microbiota, and NSAIDs, the precise mechanisms by which microbiota influence NSAID enteropathy are unclear. One possible mechanism is that the microbiota may attenuate the severity of disease by specific metabolite-mediated regulation of host inflammation and injury. The microbiota-derived tryptophan-metabolite indole is abundant in the healthy mammalian gut and positively influences intestinal health. We thus examined the effects of indole administration on NSAID enteropathy. Mice (n = 5 per group) were treated once daily for 7 days with an NSAID (indomethacin; 5 mg/kg), indole (20 mg/kg), indomethacin plus indole, or vehicle only (control). Outcomes compared among groups included: microscopic pathology; fecal calprotectin concentration; proportion of neutrophils in the spleen and mesenteric lymph nodes; fecal microbiota composition and diversity; small intestinal mucosal transcriptome; and, fecal tryptophan metabolites. Co-administration of indole with indomethacin: significantly reduced mucosal pathology scores, fecal calprotectin concentrations, and neutrophilic infiltration of the spleen and mesenteric lymph nodes induced by indomethacin; modulated NSAID-induced perturbation of the microbiota, fecal metabolites, and inferred metagenome; and, abrogated a pro-inflammatory gene expression profile in the small intestinal mucosa induced by indomethacin. The microbiota-derived metabolite indole attenuated multiple deleterious effects of NSAID enteropathy, including modulating inflammation mediated by innate immune responses and altering indomethacin-induced shift of the microbiota.
Reporting of symptoms in randomized controlled trials of atopic eczema treatments: a systematic review
Authors: L.A.A. Gerbens, J.R. Chalmers, N.K. Rogers, H. Nankervis, P.I. Spuls
Journal: British Journal of Dermatology (2016)

'Symptoms' is a core outcome domain for atopic eczema (AE) trials, agreed by consensus as part of the Harmonising Outcome Measures for Eczema (HOME) initiative. To standardize and validate the core domain symptoms and symptom instruments for AE trials the HOME roadmap is followed. Its first step is to establish if and how symptoms have been measured in published AE treatment trials. Therefore the Global Resource for Eczema Trials database was used to collect all randomized controlled trials (RCTs) of treatments for AE between January 2000 and April 2014. Study selection and data extraction were performed by three reviewers independently. We identified the use of symptoms in 295 of 378 trials (78%). Symptoms as a primary end point were applied by 147 RCTs (50%). Seventeen different symptoms were measured, but mostly itch and sleep loss. Symptoms were assessed by only 37% of trials by a stand-alone symptom measurement. Overall 63% of RCTs used a composite instrument, and 30 different instruments were identified. The Scoring Atopic Dermatitis (SCORAD) index was the most commonly applied, but only 23% of RCTs reported the SCORAD symptom score separately. This systematic review demonstrates that symptoms, most frequently itch and sleep loss, are commonly reported in AE treatment trials, but are measured using many different instruments. Often symptoms are evaluated as part of a composite instrument, and currently it is not possible to extract symptoms-only data from most published studies. Future trials should report symptom scores to permit meta-analysis of the core outcomes.
Practice Feedback Interventions: 15 Suggestions for Optimizing Effectiveness
Authors: Jamie C. Brehaut, Heather L. Colquhoun, Kevin W. Eva, Kelly Carroll, Anne Sales, Susan Michie, Noah Ivers, Jeremy M. Grimshaw
Journal: Annals of Internal Medicine (2016)

Electronic practice data are increasingly being used to provide feedback to encourage practice improvement. However, evidence suggests that despite decades of experience, the effects of such interventions vary greatly and are not improving over time. Guidance on providing more effective feedback does exist, but it is distributed across a wide range of disciplines and theoretical perspectives. Through expert interviews; systematic reviews; and experience with providing, evaluating, and receiving practice feedback, 15 suggestions that are believed to be associated with effective feedback interventions have been identified. These suggestions are intended to provide practical guidance to quality improvement professionals, information technology developers, educators, administrators, and practitioners who receive such interventions. Designing interventions with these suggestions in mind should improve their effect, and studying the mechanisms underlying these suggestions will advance a stagnant literature.
Gfi136N As a Novel Marker and Therapeutic Target of MDS and AML
Authors: Lars C. Michel, Lacramioara Botezatu, Judith Maria Hönes, Anna Marneth, Damien Grapton, Charles Vadnais, Ulrich Germing, Uwe Platzbecker, Thomas Schroeder, Rainer Haas, Bert A. van der Reijden, Gerhard Ehninger, Jaroslaw P. Maciejewski, Tomas Radivoyevitch, Andre Görgens, Bernd Giebel, Jan Fleckhaus, Hideki Makishima, Tarik Moroy, Ulrich Dührsen, Cyrus Khandanpour
Journal: Blood (2014)