tbuckley/cabot-search huggingface dataset:
Constitutive short chromosome-specific telomere length of 17p and 12q, but not XpYp, 11q and 2p is associated with increased esophageal cancer risk
Authors: Jinliang Xing, Jaffer A Ajani, Meng Chen, Julie Izzo, Xifeng Wu
Journal: Clinical Cancer Research (2007)

A10   Telomere length plays a very critical role in the maintenance of genome integrity. The shortening of telomeres may cause genetic instability and thus promote cancer development. Previous studies mainly shaded light on the overall telomere shortening. However, the association between the chromosome-specific telomere shortening and tumorigenesis of a certain type of cancer has yet to be established. Therefore, in the present study, we measured both the overall telomere length and individual telomere lengths of XpYp, 17p,2p, 11q and 12q with quantitative real-time PCR in peripheral blood lymphocytes (PBLs) from an esophageal cancer case-control study consisting of 92 cases and 92 controls matched on age (±1 year), gender and ethnicity. The results showed that, compared with matched controls, EC patients had significantly shorter overall telomere length [case  vs.  control (mean ± standard deviation): 1.19±0.39  vs.  1.36±0.42; p=0.001] and individual telomere lengths of 17p (case  vs.  control: 1.08±0.27  vs.  1.23±0.38; p=0.018) and 12 q (case  vs.  control: 1.44±0.99  vs.  2.14±2.08; p=0.008). No significant differences of the individual telomere length were observed between cases and controls for chromosome XpYp (case  vs.  control: 0.91±0.31  vs.  0.85±0.23; p=0.08), 2p (case  vs.  control: 1.20±0.58  vs.  1.20±0.54; p=0.988) and 11q (case  vs.  control: 0.77±0.83  vs.  0.75±0.68; p=0.834). We further categorized the overall telomere lengths using the 50% value in the controls as cutoff points and found that short overall telomere length was associated with significantly increased EC risks [adjusted odds ration (OR) = 4.72; 95% confidence interval (CI) = 1.85-12.05]. In a tertile analysis, a dose response association was noted between the short overall telomere length and increased EC risk (p for trend = 0.004).The joint effect on EC risk between telomere length and smoking status was also identified. Using never smokers with long telomere length as the reference group, we found that ever smokers with long telomere length, never smokers with short telomere length and ever smokers with short telomere length exhibited significantly increased EC risk with ORs (95% CI) of 3.83 (1.06-13.85), 4.93 (1.21- 20.14), and 10.65 (2.94-38.56), respectively. Our findings provide the first evidence linking short overall and individual telomere lengths of 17p and 12q in PBLs to elevated EC risk, which warrants further investigation in large-size studies.
Fertility preservation: A novel method to improve fertility discussion and documentation.
Authors: Nalini Hasija, Rana Fawzi Hawamdeh, Lakshmikanth Katragadda, Jessica Marie Schmit, Karen Colleen Daily, Alice Rhoton-Vlasak
Journal: Journal of Clinical Oncology (2016)

e18152 Background: American Society of Clinical Oncology (ASCO) published guidelines in 2006 to address discussions regarding infertility and fertility preservation options, and referrals to fertility specialists. We proposed the incorporation of a fertility specific template into our established note template to document discussions and thus provide a new method to improve ASCO’s Quality Oncology Practice Initiative (QOPI) standards for cancer care. Methods: A template was incorporated into the electronic medical record including the questions: (1) Is this patient 13 to 44 years old? (2) Is this patient being considered for chemotherapy, brain radiation and/or pelvic radiation? (3) If #1 and #2 were yes, was the risk of infertility and fertility preservation discussed; if no, then document why; (4) Was a referral made to reproductive endocrinology and infertility specialists. A retrospective review was performed prior to and following initiation of the template. Only new female breast cancer patients were studied for this pilot. Results: 112 patient charts were reviewed, 56 prior to and 56 following the template initiation. Patient characteristics are listed in the table below. 9 patients (8%) were between 13 to 44 years old. Documentation of fertility preservation was 7% (4 of 56) prior to and 91% (51 of 56) following the template implementation. In the target population, fertility discussion improved from 40% (2 of 5) to 100% (4 of 4) (p < 0001). Conclusions: The addition of a short template improved fertility documentation. Although easy to use, there was reluctance to additional question prompts. The template can be easily implemented in other high-risk cancer populations. There is a need for additional education covering the options for fertility preservation. Patient Characteristics Pre-implementation Post-implementation Total number (n) 56 56 Age 13-44 5 4 45-55 17 17 56-65 18 17 66-75 12 14 76-85 4 4 Number of Children 0 9 6 1 9 11 2 16 18 3 8 9 4 4 4 5 0 3 unknown 7 3 Race Caucasian 48 45 African-American 6 9 Hispanic 1 2 Other 1 0
Prevalence of chemopreventive agent use among hospitalized women at high risk for breast cancer.
Authors: Waseem Khaliq, Danijela Jelovac, Scott M Wright
Journal: Journal of Clinical Oncology (2016)

e13050 Background: Preventing breast cancer would be highly valued by all women. Recent attention about risk stratification for breast cancer in women stems from opportunities for risk reduction using chemopreventive agents like tamoxifen and raloxifen. Effectiveness of primary prevention for women at highest risk for breast cancer has resulted in strategies for implementing chemoprevention guidelines. The purpose of the current study was to characterize the current utilization of chemoprevention agents among hospitalized women who are at higher risk for breast cancer. Methods: A cross sectional bedside survey of 250 women aged 50-75 years hospitalized to a general medicine service was conducted. Reproductive history, family history for breast cancer, chemopreventive agents use, and medical comorbidities data was collected for all patients. Chi square and t-tests were utilized to analyze population characteristics. Results: Mean age for the study population was 61.5 years (SD 7.5), and mean 5-year Gail risk score was 1.67 (SD 0.88). A third of study population was at high risk for breast cancer (5-year Gail risk score ≥ 1.7). None of the high-risk women (0%) were taking chemoprevention for breast cancer risk reduction, and 7% were at very high risk with 5-year Gail score ≥ 3%. These women were not recognized as being high risk by their hospital providers and none were referred to the high risk breast cancer clinics following discharge. Conclusions: Many hospitalized women are at high risk for breast cancer and we could not identify even a single woman who was using chemoprevention for risk reduction. Current chemoprevention guidelines may be falling short in their dissemination and implementation. Because women at high risk for breast cancer may only interface with the healthcare system at select points, all healthcare providers must be willing and able to do risk assessment. For those identified to be at high risk, providers must then either engage in chemopreventive counseling or refer patients to providers who are more comfortable working with patients on this critical decision.
“War of liberation” needed to fight battle against AIDS
Authors: Zosia Kmietowicz
Journal: BMJ (2000)

Many young people living in countries where HIV is prevalent are still ignorant about how the virus is transmitted and how to protect themselves from infection, according to a report from the United Nation's Children's Fund.

If they are to defeat AIDS, these countries need to organise themselves as though they were fighting “a full blown war of liberation” with all resources ploughed into preventative strategies and young people leading the way, said Carol Bellamy, Executive Director of UNICEF.

Speaking at the International …
Abstract 14926: What’s Missing? LVAD Patient and Caregiver Experiences With End-of-Life Planning
Authors: Lisa Kitko, Judith E Hupcey, Barbara Birriel, Windy Alonso
Journal: Circulation (2016)

Introduction:  The use of left ventricular assist devices (LVADs) continues to increase in patients with advanced heart disease. LVADs can extend and improve quality of life; nevertheless, some patients will ultimately die with the device in place. End-of-life (EOL) planning should begin before implantation and include specific plans related to device deactivation and EOL services such as palliative care (PC) or hospice. Poor device management at EOL may contribute to a decreased quality of death for patients and distress for family members.   Purpose:  The purpose of this study was to examine the post-implantation experiences of patients with LVADs and their caregivers including: conversations about device deactivation, use of hospice services, and whether device deactivation occurred prior to death.   Methods:  Patient-caregiver dyads (n=35) participated in a longitudinal study on the EOL needs of advanced heart failure patients living with an LVAD. During qualitative interviews, dyads were asked about their knowledge of device deactivation as part of advance care planning and their experiences with EOL services. After patients died, caregivers (n=6) were interviewed about device deactivation and EOL services prior to death. Chart reviews were conducted to determine use of EOL services.   Results:  The majority of patients and caregivers had no discussions with health care providers concerning device deactivation at the time of implantation, throughout the illness trajectory, or as patients were actively dying. Only 60% of the patients (21/35) received a PC consult prior to implantation. Of the 6 LVAD patients who died, two were deactivated prior to death and three had PC or hospice only during the terminal admission (days to hours prior to death). Only one patient had ongoing PC and hospice support throughout the EOL.   Conclusions:  Discussions concerning device deactivation should ideally occur at the time of implantation and continue through the EOL. PC services should be available throughout the trajectory. EOL services should transition with patients and caregivers across episodes of care. Current practice is less than optimal. By achieving these goals, healthcare providers can improve the quality of the death experience for patients and caregivers.
Virtual brain tumor histopathology and immunohistochemistry with stimulated raman scattering microscopy.
Authors: Spencer B Lewis, Balaji Pandian, Todd Hollon, Yashar Niknafs, Mia Garrard, Sandra Camelo-Piragua, Daniel A Orringer
Journal: Journal of Clinical Oncology (2017)

e13511 Background: Stimulated Raman scattering (SRS) microscopy is a label-free optical technique which uses the chemical composition of fresh tissue to generate image contrast. Prior work has demonstrated exceptional correlation between SRS images and H&amp;E microscopy for detecting brain tumor infiltration ex vivo. However, SRS has not previously been suitable for a clinical environment. Further, SRS has utilized structural, rather than chemical, diagnostic features. We present the first clinical validation of SRS, as well as our work towards mutation-targeted SRS imaging. Methods: Implementation of SRS with a fiber laser source allowed sufficient stability for clinical deployment. Unprocessed specimens from 200 neurosurgical cases were imaged at the CH2 and CH3 vibrational modes, then processed to mimic the appearance of H&amp;E staining. 30 cases were trialed in a simulated intraoperative consultation to assess concordance between SRS and cryosection microscopy. A multi-layer perceptron (MLP) model was then used to predict brain tumor diagnosis based on quantified image attributes. To explore the potential for chemically specific SRS, isogenic lines of normal human astrocyte were prepared, differing by the presence or absence of the R132H mutation in the isocitrate dehydrogenase 1 (IDH1) gene. IDH1 R132H cells accumulate high concentrations of the oncometabolite 2-hydroxyglutarate and display predictably altered metabolism. 200 Raman spectra were collected from 50 wild type (WT) and 50 R132H cells with the aim of detecting these changes. Each cell line was then submitted for targeted metabolomic analysis. Results: Excellent concordance was observed between SRS and frozen section histology ( κ &gt;0.89). The MLP diagnosed brain tumor subtype with 90% accuracy. A robust spectral difference was observed between wild type and R132H cells, which showed concordance with metabolomic data. Conclusions: The diagnostic capability, ease of use and speed of SRS make it well-suited for integration into the operative workflow. Further, because SRS amplifies the Raman signal with no resonant background, the spectral differences observed may allow rapid differentiation of IDH1 WT and R132H cells with SRS.
Circulating tumor DNA sequencing to reveal the genomic complexity of advanced EGFR-mutant lung adenocarcinoma.
Authors: Collin M. Blakely, Kimberly C. Banks, Richard Burnham Lanman, Jonathan Riess, Philip C. Mack, Trever Grant Bivona
Journal: Journal of Clinical Oncology (2016)

e23079 Background: Lung adenocarcinoma (LUAD)patients (pts)whose tumors harbor activating EGFR mutations (mt) respond initially to EGFR TKIs but responses are typically incomplete and acquired resistance (AR) occurs. EGFR T790M resistance mt are thought to drive AR in 60% of cases, yet responses to 3rd generation EGFR TKIs that can target this mt are also incomplete and transient. Additional concurrent genomic alterations may underlie EGFR TKI resistance. Methods: We performed next-generation sequencing (NGS) on circulating cell-free DNA (cfDNA) from 546 consecutive advanced LUAD pts with detectable EGFR mt. The analysis included pts prior to and during EGFR TKI therapy, and at TKI resistance. Using a 68-gene panel of cancer-related genes, we determined the frequency of mt in common oncogenic pathways concurrent with EGFR mt. Results: The most common mt co-occurring with EGFR were in TP53 (54%) and EGFR T790M (39%). Genetic alterations in > 1 cancer-relevant pathway were detected in 23% of T790M mt and 15% of T790wt cases (p = 0.06). Mt or copy number amplification (CNA) within genes involved in cell cycle control (CDKN2A, RB1, CDK4/6, CCNE1) were more common in samples that harbored T790M mt (20% vs. 12%, p = 0.02), as were mt in Wnt pathway genes (CTNNB1 and APC) (9.4% vs. 4.8%, p = 0.05). Mt in genes involved in MAPK (KRAS, NRAS, BRAF, NF1, GNAS) (14% vs. 17%), or PI3K signaling (PIK3CA and PTEN) (11% vs. 11%) were equivalent in T790M vs. wt cases. CNAs in pathways previously implicated in EGFR TKI acquired resistance were identified in T790M mt samples including MET (6.9%), and ERBB2 (3.9%). 3 pts with T790M were identified with co-occurring oncogene fusions (2 ALK, 1 NTRK1) at lower mt allele fractions. Cases in which serial samples from individual pts were analyzed will be presented. Conclusions: Both T790M and T790wt EGFR-mt LUAD can harbor additional mt in oncogenic pathways detectable in circulating cfDNA. Cases with detectable T790M mt were more likely to harbor mts in multiple oncogenic pathways. This may in part explain why treatment with EGFR TKI monotherapy results in only partial and temporary disease control across different classes of EGFR TKIs.
Scanner des occlusions du grêle: apports du signe du feces
Authors: I Boulay-Coletta, M Zins, J Boutboul, B Bessoud, L Mallet, JL Berrod
Journal: Endoscopy (2006)

Un nouveau signe TDM dans les occlusions du grêle a été décrit par Mayo- Smith en 1995, le „signe du feces“ (SF): il s'agit de la visualisation de bulles d'air associées à un agrégat de matières fécales dans une anse grêle dilatée de diamètre supérieur à 2,5cm. Les données de la littérature sur la prévalence et la signification du SF sont contradictoires. Le but de notre étude était d'étudier l'apport du SF 1) en déterminant sa prévalence et les circonstances cliniques favorisant sa survenue, 2) en précisant son aide diagnostique dans la localisation de la zone de transition, 3) en précisant sa reproductibilité interobservateur et 4) en déterminant si la présence de ce signe traduit une souffrance du grêle.
Evolution de la prévalence de la maladie ulcéreuse gastroduodénale:Expérience d'un centre d'endoscopie sur 10 ans
Authors: MN Abdelli, F Houissa, N Ben Mustapha, H Ben Abdallah, MR Bouali, MF Khediri
Journal: Endoscopy (2006)

Apprécier l'évolution de la fréquence de la maladie ulcéreuse gastroduodénale non compliquée à travers l'activité d'une unité d'endoscopie durant la dernière decennie.
Absinthe: what's your poison?
Authors: J. Strang, W. N Arnold, T. Peters
Journal: BMJ (1999)

Absinthe, the emerald green liqueur associated with excess, is back in business. Having been banned in many countries in the early 20th century, its newly fashionable image, combined with global purchasing opportunities through the internet, has brought its revival. Since 1998 several varieties of absinthe have again been available in Britain—from bars, stores, and mail order. But is absinthe a special problem or simply part of a general concern about excessive alcohol consumption?

Originally formulated in Switzerland, absinthe became most popular in 19th century France. Between 1875 and 1913 French consumption of the liquor increased 15-fold.1 It became an icon of “la vie de boheme,” and in fin-de-siecle Paris l'heure verte (the green [cocktail] hour) was a daily event. Although never as popular in Britain, the fashion of mixed drinks with a “spot” or “kick” of absinthe was reported in London as late as 1930.2

Many creative artists had their lives touched by absinthe (Toulouse-Lautrec, Oscar Wilde, Picasso).3 The illness of Vincent van Gogh was certainly exacerbated by excessive drinking of absinthe,4 and one of his six major crises was precipitated by drinking.3 Van Gogh probably had acute intermittent porphyria—a working hypothesis5 compatible with the documented porphyrogenicity of the terpenoids in absinthe as well …
The value of tamoxifen and trastuzumab in breast cancer treatment: A study based on uptake and use in Sweden.
Authors: Nils Erik Wilking, Adam Lundqvist, Ulf Gerdtham, Ulf Persson, Katarina Steen-Carlsson, Bengt Jönsson
Journal: Journal of Clinical Oncology (2014)

589 Background: Early breast cancer (EBC) and metastatic breast cancer (MBC) represents major health problems. Tamoxifen has since the late 1970s been a backbone in the treatment of hormone receptor positive (HR+) MBC and EBC, and lately also for primary prevention. Trastuzumab has since 2000 in the EU been the drug of choice for HER2+ MBC and from 2005 also in EBC. Methods: Sweden had in the end of the 1970s around 4500 and at present around 8000 new cases of EBC. Mortality has been stable over time with about 1500 patients dying annually. Tamoxifen was first introduced in the 1970s in the treatment of MBC. From 1985 and onwards it has been used extensively in EBC with adjuvant treatment times starting with a 1 year treatment period, which in the mid-1990ies was extended to 5 years. Trastuzumab was introduced in MBC in 2000 and became standard in the adjuvant setting in 2005-2006. We have calculated the value of the use of the two drugs from a societal perspective for two periods; 1979-2004 for tamoxifen (time of introduction of aromatase inhibitors as adjuvant treatment for EBC) and 2001-2011 for trastuzumab. We used outcomes from pivotal clinical trials and real world data on use of drugs from the National Pharmacy registry and the National Board of Health and Welfare. The value was estimated as the gains in QALYs and increased production net of costs for drugs and increased consumption in added years of life. Results: The gain from tamoxifen in EBC and MBC during 1979-2004 was 39 billion SEK; 32 from gains in QALY and 7 from added production. The cost was 1.1 billion SEK for drugs and 18 billion SEK for added consumption from improved survival. The gain from trastuzumab in EBC and MBC during 2001-2011 was 4.3-6.1 billion SEK from QALY gains and 5.3-7.2 billion SEK from added production. The cost was 2.0 billion SEK for drugs and 1.4 billion SEK for added consumption. (1 USD= 6.60 SEK). Conclusions: Tamoxifen and trastuzumab represent major gains in survival, quality of life and productivity of patients with breast cancer. Data showed a major surplus from a societal perspective for each SEK invested: for tamoxifen there was a return of 18 SEK from gains in QALYs and production; for trastuzumab the return was 3.2-5.0 SEK.
Managing adults with diabetes in hospital during an acute illness
Authors: Tahseen A Chowdhury, Hannah Cheston, Anne Claydon
Journal: BMJ (2017)

#### What you need to know

Diabetes is common and becoming commoner. Data from the UK National In-patient Diabetes Audit (NADia) suggests that around 1 in 5 inpatient beds are occupied by a person with diabetes and that diabetes can often be poorly managed in hospital, with around 1 in 10 in patients developing a severe hypoglycaemic episode and around 1 in 4 inpatient charts showing medication management errors in the preceding seven days.1 This article highlights the principles of managing adult patients in hospital with diabetes who are acutely unwell and is aimed at non-specialists.

#### Sources and selection criteria

We searched Pubmed, Google Scholar, CINAHL, and the Cochrane Database using the terms “management of diabetes/hyperglycaemia in hospital” and “management of diabetes during acute illness.” We reviewed guidelines from the Joint British Diabetes Societies, National Institute for Health and Clinical Excellence, European Association for the Study of Diabetes, and American Diabetes Association.

Poorly managed hyperglycaemia in patients who are acutely unwell can lead to adverse outcomes in terms of morbidity, mortality, and longer hospital stay.2 There is, however, no randomised trial evidence to demonstrate that tight management of glucose control in inpatients can improve outcomes, and such evidence is urgently required. Hyperglycaemia may be encountered in patients with known diabetes, patients newly presenting with diabetes, or patients with transient hyperglycaemia related to illness, medication (such as corticosteroids), or enteral feeding. Careful assessment and …