tbuckley/cabot-search huggingface dataset:
P4-02-06: Progesterone Receptor Expression Predicts Poor Outcome in Estrogen Receptor Positive, Lymph Node Negative Breast Cancer – A Population Based Study.
Authors: CA Purdie, P Quinlan, LB Jordan, A Ashfield, L Baker, JA Dewar, AM Thompson
Journal: Cancer Research (2011)

Abstract Background: Estrogen receptor (ER) positive, lymph node (LN) negative breast cancer usually carries a good prognosis; endocrine therapy is often the only adjuvant treatment. However, a small proportion of such patients do badly (possibly representing those with luminal B cancers identified by gene expression profiling). A clinically applicable method for identifying this subgroup of poor prognosis ER+, LN- patients is required to offer them more intensive adjuvant therapy. Material and methods: A consecutive, unselected series of 1072 new, operable breast cancer patients diagnosed between 2000 and 2004 was studied for ER and progesterone receptor (PR) expression, HER2 status and standard pathological and demographic parameters. ER and PR expression were scored on immunohistochemistry (IHC) on preoperative, diagnostic core biopsies using the “Quickscore” method. This ensured optimal fixation and tissue processing avoiding the variable fixation of resection specimens and the well-described sampling error of tissue micro-array (TMA) methodologies. PR expression is frequently heterogeneous resulting in false negative scores in at least 12% of cases by TMA analysis. HER2 status was assessed using IHC with dual color FISH for cases scoring 2+. Adjuvant therapy was prescribed using standard protocols; all patients with ER+ disease received adjuvant endocrine therapy. Follow up data were obtained from the oncology database, and the registrar of deaths for the date and cause of death. All deaths not attributable to breast cancer were censored at the date of death. Accordingly, the primary end-point was breast cancer-specific overall survival. Survival analysis was carried out by Kaplan-Meier survival curves analysed by the Log-Rank test. Multivariate analysis was carried out using Cox's regression. Results: Overall, PR- cancers had a worse prognosis than PR+ (p&amp;lt;10−12, Hazard Ratio 3.40), even in the ER+ (p=0.006, HR 1.86), LN- (p=10−8, HR=5.33) and LN+ (p=10−11, HR=3.26) sub-groups. In the ER+ LN- group, the absence of PR expression predicted worse prognosis (88% vs 96% 8 year survival, p=0.0003) with a hazard ratio of 3.75. This is considerably more significant than Ki67 IHC scoring reported for a similar group of patients in other studies (HR 2.22). Multivariate analysis demonstrated that PR expression was an independent prognostic variable second only to LN status and more powerful than ER. Discussion: Patients with ER+, LN-, PR- breast cancers have a significantly worse prognosis than those with ER+, LN-, PR+ cancers. Unlike Ki67, PR IHC uses a simple, cost effective, standard methodology (as for ER) and should identify patients who may require chemotherapy in addition to endocrine therapy in this group of otherwise good prognosis patients. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-02-06.
PWE-074 Factors that predict severe<i>Clostridium difficile</i>infection (CDI)
Authors: A Sugumaran, M Eisa, G Musiime, F Mendes, H Khan, C Cefai
Journal: Gut (2012)

<h3>Introduction</h3> <i>Clostridium difficile</i> is a well-recognised infective cause for increased morbidity and mortality especially in hospitalised patients.<sup>1</sup> “Severe” CDI as defined by Health Protection Agency (HPA) is infection with stool positive for toxin, with white cell count &gt;15×10<sup>9</sup>/l, or an acute rising serum creatinine (ie, &gt;50% increase above baseline), or a temperature of &gt;38.5°C, or evidence of severe colitis (abdominal or radiological signs). Increasing age, female sex, prolonged hospital stay, patient movement between wards, previous CDI, usage of proton pump inhibitors (PPI), histamine blockers (H2B) and antibiotics were reported to be associated with CD infection and colonisation,<sup>2 3</sup> but our aim was to check if the above factors predicted the severity of the infection. <h3>Methods</h3> Data were collected from 392 patients who were diagnosed with CDI between January 2010 and December 2011. The CDI team (one Consultant, two nurse practitioners, one pharmacist) normally review patients twice weekly in our district general hospital. Details on the above risk factors were noted to study the correlation with severity of infection. Results were analysed with Pearson correlation test. <h3>Results</h3> At the time of diagnosis, out of 392 patients, 206 were classified as “mild,” 76 “moderate,” 91 “severe” and 3 “life-threatening” infection (severity not documented in 16). Age distribution varied between 22 and 100 years, with 153 male and 239 female patients. 316 patients were on atleast one antibiotic when they developed CDI, chest infection being the commonest indication (36.8%). Amoxicillin was the most used antibiotic and the range of days on antibiotic varied between 1 day and long term usage (&gt;3 years). 46% of patients were taking PPI while only 7.8% were on H2Bs. There were upto maximum four ward transfers and average of 17.62 inpatient days before CDI. Pearson correlation test showed there is no significant association between severity and any of the identified risk factors, closest being previous CD infection (p=0.058). <h3>Conclusion</h3> Though there are definite risk factors associated with development of CDI, our study confirms that none correlate with the severity. More research is needed to clarify factors that will help identify hospitalised patients at risk of developing severe CDI. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Leffler DA</b>, Lamont JT. Editorial: not so nosocomial anymore: the growing threat of community-acquired Clostridium difficile. <i>Am J Gastroenterol</i> 2012;<b>107</b>:96–8. 2. <b>Johnson S</b>. Recurrent Clostridium difficile infection: a review of risk factors, treatments and outcomes. <i>J Infect</i> 2009;<b>58</b>:403–10. 3. <b>Loo VG</b>, Bourgault A, Poirier L, <i>et al.</i> Host and Pathogen factors for CD infection and colonization. <i>N Engl J Med</i> 2011;<b>365</b>:1693–703.
Intermittent Facial Flushing and Diarrhea
Authors: Orla Mc Cormack, John V Reynolds
Journal: New England Journal of Medicine (2014)

A 67-year-old man presented with a history of vague abdominal discomfort on the right side, intermittent diarrhea, and episodes of facial flushing every 2 to 3 days. He reported no history of ingestion of alcohol or other precipitants of flushing.
THU0425 Associations between radiographic and clinical osteoarthritis features and MRI-defined bone marrow lesions in the finger joints:
Authors: I.K. Haugen, P. Bøyesen, B. Slatkowsky-Christensen, S. Sesseng, D. van der Heijde, T.K. Kvien
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Bone marrow lesions (BMLs) are associated with pain in hand OA (1), but it is currently not known whether they are related to biomechanical or inflammatory processes. <h3>Objectives</h3> To explore whether radiographic OA features and inflammation are associated with BMLs in a cross-sectional study of hand OA patients. <h3>Methods</h3> We included 108 patients (98 women, mean (SD) age 68.8 (5.6) years) from the Oslo hand OA cohort with available MRIs (coronal/axial STIR images, 1.0T), radiographs (posteroanterior view) and clinical joint examination of soft tissue swelling of the 2nd-5th distal (DIP) and proximal interphalangeal (PIP) joints of the dominant hand. One reader read the STIR images for presence of BMLs according to the proposed Oslo hand OA MRI scoring system (2). The hand radiographs were scored for presence of radiographic osteophytes, joint space narrowing (JSN), erosions, cysts, sclerosis and malalignment according to the OARSI atlas. We examined whether radiographic hand OA features (markers of structural pathology) and clinical soft tissue swelling of the joints (marker of inflammation) were associated with presence of MRI-defined BMLs using logistic regression with Generalized Estimating Equations. Features that were associated (p&lt;0.25) with BMLs in univariate analyses (adjusted for age and sex) were included in a multivariate model. The multivariate model included features that were associated with BMLs (p&lt;0.10) after backward selection (adjusted for age and sex). <h3>Results</h3> Patients with hand OA had low prevalence MRI-defined BMLs in the DIP and PIP joints of the dominant hand; the median (interquartile range; IQR) number of joints with BMLs was 1 (0-2). Radiographic JSN (grade 1-3) were present in the majority of joints (median 7, IQR 6-8), and we therefore defined presence of JSN as grade 2-3. All features except sclerosis were associated with presence of BMLs in the adjusted univariate analyses and were included in the multivariate model (table). The final multivariate model included JSN, malalignment, clinical soft tissue swelling and cysts (table), of which the latter was borderline significant. <h3>Conclusions</h3> Radiographic JSN and malalignment and clinical soft tissue swelling were strongly associated with presence of MRI-defined BMLs in the DIP and PIP joints in this cross-sectional study. Whether BMLs in hand OA are caused by increased loading and bone trauma (as in knee OA) and/or inflammation needs to be proven in future longitudinal studies. <h3>References</h3> Haugen et al. ARD 2011 Nov 25 [Epub ahead of print]. Haugen et al. ARD 2011;70:1033. <h3>Disclosure of Interest</h3> None Declared
THE PROFESSIONAL LIFE OF CARDIOLOGISTS: INSIGHTS FROM THE THIRD AMERICAN COLLEGE OF CARDIOLOGY PROFESSIONAL LIFE SURVEY
Authors: Sandra J. Lewis, Laxmi Mehta, Pamela Douglas, Martha Gulati, Marian Limacher, Athena Poppas, Mary Walsh, Kelli Bohannon, Anne Rzeszut, Claire Duvernoy
Journal: Journal of the American College of Cardiology (2016)
GE-13 * A NOVEL ASSOCIATION OF PRIMARY CNS GERMINOMA IN A PATIENT WITH NAIL PATELLA SYNDROME
Authors: S. Hanmantgad, Y. Khakoo
Journal: Neuro-Oncology (2014)

Nail patella syndrome (NPS) is an autosomal dominant disorder with a prevalence of 1/50,000 characterized by developmental abnormalities of the nails, knees and elbows, as well as renal dysplasia and open angle glaucoma. NPS is caused by a mutation in the LMX1B gene, a transcription factor involved in ventral/dorsal patterning of the vertebrate limb. While malignancy is rare in patients with NPS, Ewing's sarcoma and colon cancer have been reported. Additionally, NPS has been described in a 5 generation family with neurofibromatosis type 1. We report a novel association of NPS with primary CNS germinoma. A 22-year-old male presented with a two-month history of diabetes insipidus (DI) and headaches. Physical examination revealed partial Parinaud's syndrome, dystrophic nails and surgical repair of left hypoplastic patella. Because the family history revealed numerous maternal family members with dystrophic nails and hypoplastic patellae, we subsequently made a formal clinical diagnosis of NPS. Contrast enhanced MRI of the brain revealed an enhancing cystic pineal mass and a Chiari I malformation; serum and CSF alpha-fetoprotein and beta-human chorionic gonadotropin were negative. Biopsy of the pineal mass was consistent with pure germinoma for which the patient received external beam radiation therapy via intensity modulated radiation therapy (IMRT) as follows: 1) 2520 cGy to the craniospinal axis; 2) 5040 cGy to the pineal region; 3) and 4620 cGy to the suprasellar region (for presumed tumor in the posterior pituitary given the history of DI). He remains in remission 9 years post-treatment. For the NPS, the patient declined referral to genetics due to insurance concerns but he and his family have been referred to appropriate services for screening of other abnormalities associated with the syndrome. This case report suggests that LMX1B may play a role in the development of CNS germinoma.
AB0454 EULAR-DAS28 versus RAPID3 for treatment monitoring in patients with rheumatoid arthritis receiving tnf inhibitors
Authors: C.M. Ancuta, E. Ancuta, C. Belibou, R. Chirieac
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> treat-to-target and tight control strategies are actually the two main paradigms in the treatment of rheumatoid arthritis (RA), aiming to improve patients outcome by achieving either remission or minimal disease activity status. There is actually no consensus regarding the right assessment tools for monitoring the magnitude of improvement and the absolute reached level in routine clinical practice. <h3>Objectives</h3> to compare EULAR-DAS28 with RAPID3 (a patient-reported outcome based on pain, patient global assessment of disease activity, and multidimensional HAQ)response criteria in patients with moderate to severe active RA treated with anti-TNF agents <h3>Methods</h3> retrospective observational study on 178 moderate to severe active RA (DAS28&gt;3.2) receiving anti-TNFs (etanercept, infliximab, adalimumab, golimumab). Response to treatment was appreciated after 12 months of biologics based on (i) EULAR-DAS28 response criteria, classified as EULAR good (decrease with 1.2 units), moderate (decrease of 0.6–1.2 units) or non-responder (decrease ≤0.6 units); and (ii) RAPID3 response categories defined as good (decrease with 3.6 units), moderate (decrease of 1.8–3.6 units) and poor (decrease ≤1.8 units). Statistical analysis was done in SPSS.16 (weighted kappa statistics, p&lt;0.05. <h3>Results</h3> up to 67% of RA (120) has been classified as good and moderate responders based on RAPID3, while about 60% (107) have been responders according to EULAR-DAS28 at 12 months; moreover, half of the RAPID3 good responders have also been categorized as moderate EULAR-DAS28 responders. Moderate agreement between the EULAR-DAS28 response criteria and RAPID3 has been demonstrated (p&lt;0.05). <h3>Conclusions</h3> Patient-centered tools such as RAPID3 allow more easily and quickly to quantify disease activity levels and patient responses to therapy, providing a more complex insight into the patient's perception of disease status. <h3>Disclosure of Interest</h3> None Declared
The Little Women of Loja — Growth Hormone–Receptor Deficiency in an Inbred Population of Southern Ecuador
Authors: Arlan L. Rosenbloom, Jaime Guevara Aguirre, Ron G. Rosenfeld, Paul J. Fielder
Journal: New England Journal of Medicine (1990)

Laron-type dwarfism, which is characterized by the clinical appearance of isolated growth hormone deficiency with elevated serum levels of growth hormone and decreased serum levels of insulin-like growth factor I (IGF-I), has been described in approximately 50 patients. This condition is caused by a deficiency of the cellular receptor for growth hormone, and it is transmitted as an autosomal recessive trait, as indicated by an equal sex distribution and a high rate of consanguinity in affected families. We studied 20 patients (19 females and 1 male, 2 to 49 years of age), from an inbred Spanish population in southern Ecuador, who had the clinical features of Laron-type dwarfism.
Hillary Clinton looks to an AIDS free generation
Authors: E. Davies
Journal: BMJ (2012)

Secretary of State Hillary Clinton has revealed her “blueprint” to wipe out HIV and “get ahead of the pandemic.”

Launching her report on 29 November for the President’s Emergency Plan for AIDS Relief (PEPFAR), she said that she believed that by improving treatment and prevention she had the plan to usher in an “AIDS free generation.”1

Clinton said in the report, “An AIDS-free generation is not just a rallying cry—it is a goal that is …
Abstract 2972: Intestinal p53 deletion leads to accumulation of chromosomal instability without promoting tumor formation
Authors: Yvonne Begus-Nahrmann, André Lechel, Lenhard Rudolph
Journal: Cancer Research (2010)

Abstract Background: Colorectal cancer is after lung cancer the second biggest cancer threat for humans and the tumor burden is rising steadily during human ageing. One important issue during human ageing is the accumulation of DNA damage inducing a p53 dependent response leading to p21-dependent senescence or apoptosis. It has been shown that deletion of DNA repair proteins as well as other components of the DNA damage pathway leads to tumor formation. Methods: In this approach we investigated the role of the tumor suppressor p53 with and without telomere dysfunction in intestinal tumor formation. Late generation of iG4 mTerc−/−; p53lox/lox and iF1 mTerc+/− p53lox/lox mice were crossed to Villin-Cre-ERT2 transgenic mouse model. In 1 month old mice Tamoxifen was injected on 5 consecutive days leading to functional deletion of the Trp53 gene. Results: In aging IF1 Terc+/− p53 deletion did not induce an obvious intestinal phenotype including tumor formation until 24 months. In contrast to p21 deletion the deletion of p53 significantly shortened the lifespan of iG4 Terc−/− Trp53−/− animals compared to iG4 Terc−/− Trp53+/+. This reduction correlated with earlier appearance of crypt atrophy and weight loss but was not associated with tumor formation. Deletion of the Trp53 gene resulted in an abrogation of the p21-dependent senescence and accumulation of DNA damage in the intestinal epithelium of both p53 deleted cohorts. Moreover this correlated with an accumulation of intestinal stem cells carrying high levels of DNA damage. On contrary to p21 deletion the deletion of p53 impaired the depletion of chromosomal instable intestinal stem cells in aging telomere dysfunctional mice. Conclusion: These results provide first proof that deletion of p53 is not able to promote tumorigenesis in the intestinal epithelium of mice and that p53 induction has a protective role preventing accumulation of damaged intestinal stem cells in aging telomere dysfunctional mice. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2972.
Abstract 3015: DNA methylation biomarkers for lung cancer diagnostics: Validation in bronchial washings
Authors: Triantafillos Liloglou, George Nikolaidis, Olaide Raji, John Kirpatrick Field
Journal: Cancer Research (2011)

Abstract Epigenetic reprogramming is a characteristic of virtually of lung tumors. DNA methylation is unique for biomarker utilization in body fluids due to its chemical stability and the high frequency of abnormal hypermethylation in lung tumors. Despite the evidence from a wide range of studies in this field, very little is progressing to clinical exploitation, mainly due to the insufficient preclinical and clinical validation. In this study we have undertaken extensive preclinical validation of DNA methylation biomarkers in bronchial washings from 320 lung cancer cases and 320 age/sex matched controls organized in training (n=150 in each arm) and validation (n=170 in each arm) sets. Quantitative methylation specific PCR (qMSP) assays were developed and optimized through multiple sets of methylation standards. The hypermethylation detection threshold was set to 0.5% based on the reproducibility of signal detection. Among the promoters tested p16, RASSF1, WT1, RARbeta, TERT and CYGB proved to be highly discriminating between cases and controls while CDH13, TMEFF2, p73 and DAPK did not demonstrate a significant difference. Using a criterion of at least two positives from the discriminating markers in the validation set, this panel of six markers demonstrated an overall 70.5% sensitivity and 97.7% specificity. It is of note that when combining methylation biomarker with cytology, the positive detection rate was 81.5%. Regarding tumor histology, the detection sensitivity (combining training and validation sets) was higher in small cell carcinomas (95.1%) and squamous carcinomas (65.2%) than in adenocarcinomas (51.6%). Our results clearly demonstrate the clinical potential of DNA methylation in lung cancer diagnostics, although it is profound that this panel must be enriched by additional promoters. It also becomes apparent that combined multi-center studies of increased statistical power must be undertaken in order to promptly validate biomarker panels for clinical implementation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3015. doi:10.1158/1538-7445.AM2011-3015
Wireless pH capsule – yield in clinical practice
Authors: S. Roman, F. Mion, F. Zerbib, R. Benamouzig, J. Letard, S. Bruley des Varannes
Journal: Endoscopy (2012)

Wireless pH monitoring is one of the recent technologies that focus on improving the diagnosis of gastroesophageal reflux disease (GERD). The capsule, which is fixed within the esophagus, transmits data via telemetry to an external receiver. The capsule is usually inserted 6 cm above the squamocolumnar junction during an upper endoscopy. The standard recording duration is 48 hours but this can be extended to 96 hours. The wireless capsule has been shown to be at least as accurate as the conventional catheter for the monitoring of esophageal pH. Normal pH values have been established in three different series. The use of a wireless capsule provides an increased diagnostic yield for GERD compared with the conventional catheter. The increased yield is the result of higher sensitivity to detect both abnormal acid esophageal exposure and positive symptom – reflux association. This may be related both to the prolonged recording duration and to fewer dietary modifications and restrictions on activities. Several studies have shown that the pH capsule was better tolerated by patients than the conventional pH catheter. Mild-to-moderate chest pain represents the main side effect of the pH capsule: severe chest pain requiring endoscopic removal of the capsule is rare. The main indication for wireless capsule application is monitoring of distal esophageal pH for diagnostic purpose, particularly in patients with a normal endoscopic examination. The capsule technique has some limitations: costs are higher than conventional pH monitoring, misplacement may occur, and the sampling rate is lower. Finally, compared with pH-impedance monitoring, only acid reflux events can be evaluated.