tbuckley/cabot-search huggingface dataset:
Detecting Interval Metastases and Response Assessment Using 18F-FDG PET/CT After Neoadjuvant Chemoradiotherapy for Esophageal Cancer
Authors: Jurriën Stiekema, Daan Vermeulen, Erik Vegt, Francine E M Voncken, Berthe M P Aleman, Joyce Sanders, Henk Boot, Johanna W van Sandick
Journal: Clinical Nuclear Medicine (2014)

Aim The aim of this study is to evaluate the potential of FDG PET/CT for the detection of interval distant metastases after neoadjuvant chemoradiotherapy (CRT) and the prediction of the pathologic response to CRT in esophageal cancer patients. Patients and Methods In this retrospective study, all esophageal cancer patients for whom CRT followed by surgery was planned between January 2008 and April 2013 and in whom an FDG PET/CT was performed before and after CRT were included. For the response analyses, both FDG PET/CT scans had to be made on a similar scanner. Metabolic response of the primary tumor was assessed using the SUVmax, metabolic tumor volume (MTV), and total lesion glycolysis (TLG). These parameters were correlated with the pathologic response using the tumor regression grade (TRG) scale according to Mandard et al (Cancer. 1994;73:2680–2686). Results In 6 (8%) of 76 consecutively treated patients, new distant metastases were detected on FDG PET/CT after neoadjuvant CRT; these patients therefore did not undergo operation. Forty-eight (63%) of 76 patients were eligible for response analysis. The relative change in SUVmax, MTV, and TLG was significantly different between patients with a major (TRG, 1–2) and a minor response (TRG, 3–5) but not between patients with and without a pathologic complete response. The area under the curve of the receiver operating characteristic for predicting a major response was 0.70 (95% confidence interval, 0.65–0.92) for a relative decrease in SUVmax, compared with 0.73 (95% confidence interval, 0.58–0.88) both for MTV and TLG. A relative decrease in SUVmax of 60% or more had the highest positive predictive value (75%). Conclusions Futile surgery was prevented in 8% of our esophageal cancer patients because interval metastases were detected on an FDG PET/CT after neoadjuvant CRT. The accuracy for predicting a complete or major pathologic response was limited and does not support the use of FDG PET/CT for refraining from surgical treatment.
AB0517 Impaired Sexual Function in Women with Primary SjÖGren's Syndrome
Authors: J. van Nimwegen, S. Arends, G. van Zuiden, A. Vissink, F. Kroese, H. Bootsma
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Primary Sjögren9s syndrome (pSS) is a chronic and disabling disease, characterized by sicca symptoms of the eyes and mouth as well as fatigue. Besides these well-known symptoms, multiple studies have shown that women with pSS often experience complaints of vaginal dryness and dyspareunia. <h3>Objectives</h3> To compare sexual functioning and sexual distress between women with pSS and healthy controls, and to identify parameters that predict sexual dysfunctioning in women with pSS. <h3>Methods</h3> 46 women with pSS according to the AECG criteria (mean age 46.3±10.5) and 43 age-matched healthy controls (mean age 44.4±11.3) were included. Median disease duration of the patients was 7 years (interquartile range 4-14). Participants completed a self-administered questionnaire, which included the Female Sexual Function Index (FSFI), Female Sexual Distress Scale (FSDS), RAND-36 item health survey (RAND-36), Hospital Anxiety and Depression Scale (HADS), Multidimensional Fatigue Index (MFI) and Maudsley Marital Questionnaire (MMQ). In patients, disease activity was recorded with the EULAR Sjögren9s Syndrome Patient Reported Index (ESSPRI) and EULAR Sjögren9s Disease Activity Index (ESSDAI). <h3>Results</h3> Women with pSS had a significantly lower FSFI total score compared to healthy controls (median 20.6 vs. 30.3, p&lt;0.001), and experienced more sexual dysfunctioning in the domains of desire, arousal, orgasm, lubrication and pain (figure). Furthermore, pSS patients experienced more sexual distress according to the FSDS (median 7 vs. 4, p&lt;0.05) and reported more frequently that they had been sexually inactive in the past four weeks than healthy controls (24% vs. 7%, p&lt;0.05). In total, 67% of the patients never talked about sexual problems with their rheumatologist. Sexual dysfunctioning correlated significantly with depressive symptoms (HADS), higher ESSPRI score, more symptoms of fatigue (MFI), lower mental quality of life (RAND-36) and relationship dissatisfaction (MMQ). Furthermore, sexual dysfunctioning correlated significantly with higher ESSDAI score only in premenopausal patients. <h3>Conclusions</h3> Sexual dysfunctioning is an important symptom and leads to psychological distress in women with pSS. Symptoms of depression and higher disease activity are associated with sexual dysfunctioning. When treating pSS, this aspect of the disease should not be overlooked. More research is needed to obtain knowledge on the pathogenesis of vaginal sicca symptoms in pSS and the best treatment for this complaint. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1871
Intramuscular Lidocaine for Prevention of Lethal Arrhythmias in the Prehospitalization Phase of Acute Myocardial Infarction
Authors: Rudolph W. Koster, Arend J. Dunning
Journal: New England Journal of Medicine (1985)

In a randomized controlled study examining the value of an intramuscular injection of lidocaine in the prehospitalization phase of suspected acute myocardial infarction, paramedics used an automatic injector to administer 400 mg of the drug into the patient's deltoid muscle before transport to the hospital. In a 33-month period, 7026 patients with acute chest pain were seen. Of the 6024 patients randomized (2987 to the lidocaine group and 3037 to the control group), 1935 (32 per cent) proved to have an acute myocardial infarction. In the entire 60-minute period of observation by continuous electrocardiography, primary ventricular fibrillation was observed in 8 treated and 17 control patients (P = 0.08). However, from 15 minutes after randomization onward, when plasma lidocaine levels were in the therapeutic range, only 2 cases of ventricular fibrillation occurred in the treated group, as compared with 12 in the control group (P<0.01). Ventricular tachycardia terminated a mean of 10 minutes after injection in six of nine lidocaine-treated patients with acute myocardial infarction but in none of five control patients with infarction (P<0.02). Mean plasma lidocaine levels were 3 μg per milliliter 11 to 20 minutes after injection in 369 consecutive patients. In 65 patients, levels were below 2 μg per milliliter, and in 15 patients, levels were above 6 μg per milliliter. Side effects were rare and did not contribute to mortality. We conclude that intramuscular lidocaine may be useful if given by a paramedic, another person, or the patient himself when acute myocardial infarction is suspected outside the hospital. (N Engl J Med 1985; 313:1105–10.)
Democrat or Republican— Sailor or Landsman
Authors: Richard L. Pearse
Journal: JAMA (1965)

To the Editor:—  I think the main observation to be made about the charming Oslerian controversy ( 193 :223, 1965) started by the redoubtable chest surgeon, William Keith C. Morgan, (a Welshman, I am certain) is that regardless of our intellect we are entirely creatures of the brain stem or our emotions. Truly rational and sensible behavior eludes us all and I might add, thank goodness! This is what makes Democrats and Republicans, Catholics and Protestants, Conservatives and Liberals, sailors and landsmen and enables such institutions as horse racing to flourish. This makes understandable why one able scholar may draw one set of interpretations from the Dead Sea Scrolls and another equally erudite one makes diametrically opposed conclusions. We, all of us, are prone to see not the true situation as it exists, eg, Napoleon's misinterpretation of the arrival of Blucher on the field, but what we want to see. Napoleon
Abstract 5038: Non-cording microRNA hsa-miR-199a expression in hepatocellular carcinoma correlates with patient survival
Authors: Go Nakajima, Hidekazu Kuramochi, Yurin Kondo, Ryuji Okuyama, Masakazu Yamamoto, Toshinori Kanemura, Kazuhiko Hayashi
Journal: Cancer Research (2012)

Abstract [Aim] MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at a post-transcriptional level. Previous study from our group identified forty nine miRNAs that are expressed differentially by comparing 26 pair samples of hepatocellular carcinoma (HCC) tumor tissue and non-tumor liver tissue using next-generation sequencer system. In this study, the expression of hsa-miR-199a and hsa-miR-199b, one of the extracted targets from our study, were investigated by real-time PCR using validation set HCC samples, and were examined the correlation between the miRNA expression and clinical data. [Patients and Methods] Forty-eight patients diagnosed as HCC had undergone surgical removal from 1991 to 1997 at the Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Japan. The formalin-fixed paraffin embedded samples were prepared using the standard protocol. The paraffin blocks were cut into 10μm sections, and the tumor samples were collected using Laser-captured microdissection and total RNA including miRNA fraction were isolated. After synthesized cDNA using miRNA specific primer, real-time PCR was performed using miRNA specific primer/probe. [Results] The expression level of hsa-miR-199a and hsa-miR-199b were down-regulated in tumor compared to non-tumor (P&amp;lt;0.0001, P=0.0002, respectively). The patients were divided into two groups, higher/lower expression of each miRNA, the group of the higher hsa-miR-199a expression was significantly longer overall survival time compared to the lower expression group (P=0.0303). However, hsa-miR-199b was not significant difference (P=0.3801). [Conclusion] The hsa-miR-199a may be potential prognostic factor for HCC patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5038. doi:1538-7445.AM2012-5038
Selection of Indications for Pimasertib in Phase II Testing Based on Signals of Activity and Rational Choice of Target Disease
Authors: G. Massimini, B. Laffranchi, N. Rejeb, E. Asatiani, A. Milner, O. von Richter, G. Locatelli, J.A. Ogden, B. Osterwalder
Journal: Annals of Oncology (2013)
GE-07 * DNA METHYLATION IN MEDULLOBLASTOMA AND MOLECULAR DIAGNOSTICS OF BRAIN TUMORS
Authors: V. Hovestadt, D. Capper, M. Sill, S. Picelli, W. Wang, P. A. Northcott, M. Kool, M. Zapatka, B. Radlwimmer, A. von Deimling, S. M. Pfister, P. Lichter, D. T. W. Jones
Journal: Neuro-Oncology (2015)

We recently performed an in-depth analysis of the DNA methylation landscape of medulloblastoma, the most common malignant pediatric brain tumor (Hovestadt et al., 2014). By integrating whole-genome bisulfite sequencing and gene expression data of 50 primary human and murine samples, we identified profound differences between medulloblastoma subgroups. Most notable were extended regions of differential methylation downstream of the promoter of more than 1,000 genes that strongly correlated with gene expression (i.e. promoter downstream correlated regions, pdCRs). Enrichment of transcription factor binding motifs within focal lowly-methylated regions (LMRs) shed light on differential regulatory networks between subgroups. Some differences between subgroups were indicative of the cell-of-origin, while others were somatically acquired. Motivated by these findings, we expanded our study cohort to include an exhaustive set of more than 2,000 common and rare brain tumor samples from both pediatric and adult patients profiled by DNA methylation arrays. Unsupervised clustering refined histological entities into more than 70 molecular entities, often resulting in splitting or combining of morphology-based groups. To explore the diagnostic potential of DNA methylation profiling, we created a random forest-based classifier that is capable of predicting the molecular class of clinical specimens to complement histological diagnosis. Early clinical application frequently provided a refined diagnosis (e.g. molecular subtyping) or suggested re-classification, and was often associated with an expected benefit for patients.
Reversal by Levodopa of Cholinergic Hypersensitivity in Parkinson's Disease
Authors: Michael I. Weintraub, Melvin H. Van Woert
Journal: New England Journal of Medicine (1971)

The neurologic manifestations of Parkinson's disease may be derived from an imbalance of the dopaminergic and cholinergic pathways in the central nervous system. Levodopa was found to decrease or block completely the hypersensitivity to cholinergic stimulation in Parkinson's disease as measured by the physostigmine test. Levodopa-treated patients whose neurologic manifestations were no longer aggravated by intravenous physostigmine did not benefit by the addition of standard anticholinergic drugs. Cholinergic hyperactivity in Parkinson's disease may be secondary to decreased brain dopamine.
Abstract PD05-01: Next generation genomic sequencing (NGS) identifies molecular targets in inflammatory breast cancer (IBC)
Authors: M Cristofanilli, KR Alpaugh, J Ross, C Binghman, H Wu, P Stephens, D Lipson, G Palmer
Journal: Cancer Research (2012)

Abstract BACKGROUND: Inflammatory breast cancer (IBC) is the most aggressive form of invasive breast cancer and is associated with poor outcome in spite of optimal multidisciplinary management. The disease is associated poor response to neoadjuvant chemotherapy and a peculiar pattern of recurrence (chest wall, nodes, CNS). There currently few distinct molecular alterations for effective therapeutic targeting in the advance setting. The availability of comprehensive cancer genomic testing using Next-Generation Sequencing (NGS) technology may identify a number of genomic alterations not assessed by traditional methods and provide opportunities for more effective treatment selection particularly in aggressive and uncommon diseases such as IBC. METHODS: Twenty-three patients with refractory metastatic IBC were included in this analysis. All patients underwent confirmatory biopsy and/or tissue collection. Tissue from metastastic lesions of patients with recurrent IBC was submitted as slides or FFPE blocks. NGS was performed by Foundation Medicine, Cambridge, MA. The entire coding sequence of 182 cancer-related genes (3,230 exons) plus 37 introns from 14 genes often rearranged in cancer were sequenced to high depth (&amp;gt;500X) All classes of genomic alterations were detected. RESULTS: The site distribution and frequency of disease recurrence included: soft tissue (19) lung (4), bone and liver (3), and brain (2). The disease subtype classification based on the expression of ER, PR and HER-2 were as follow: ER−, PR−, Her-2−, Basal-like or TN (65%); ER+ and/or PR+, HER-2− (grade3) or HER-2+, Luminal B (22%); ER−, PR−, HER2+ (13%). Genomic alterations were identified in all patients with various frequencies. Genetic mutations included: P53 (DNA-binding domain, splice site), PI3KCA (H1047R, R441N, E545K, K111E,); RB1; PTEN (D107Y); EGFR (L858R); ERBB2 (V777L, S310F) in a patient with TN disease; ESR1 D538G. Gene amplifications included: MYC (26%); CCND1 (22%); ERBB2 (in a patient with TN disease), MLC-1, CCNE1, CK4, K-RAS. One patient had evidence of discordant genomic abnormalities in two simultaneous sites of recurrence (skin and pleura) suggesting disease heterogeneity. Three patients were effectively treated with genomic alterations-guided therapies. CONCLUSIONS: Genomic sequencing of advanced IBC is feasible, identifies potential therapeutic targets and can advance our understanding of the molecular alterations of this aggressive disease. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD05-01.
Central nervous system relapse in diffuse large B-cell lymphoma: analysis of risk factors and a new prognostic model
Authors: Yusuke Kanemasa, Tatsu Shimoyama, Yuki Sasaki, Sawada Takeshi, Eisaku Sasaki, Yasushi Omuro, Yoshiharu Maeda, Tsunekazu Hishima, Tsuneo Sasaki
Journal: Annals of Oncology (2015)
Abstract 407: Urinary C-reactive protein: A biomarker of metastatic kidney cancer.
Authors: Jeremiah Morrissey, Evan D. Kharasch
Journal: Cancer Research (2013)

Abstract Background: Approximately one-third of patients with kidney cancer who do not have detectable metastatic disease at the time of diagnosis and/or nephrectomy will nonetheless go on to develop metastasis. Presently, there is no method to predict which patients with kidney cancer and no evidence of metastases; will later develop metastatic disease. This investigation evaluated pre-nephrectomy urine C-reactive protein as an early diagnostic predictor of subsequent metastatic kidney cancer, and its use for tumor staging by molecular pathology to supplement conventional observational pathology. Methods: C-reactive protein was measured by a sensitive ELISA in the pre- and post-nephrectomy urine of 31 patients with a pathologic diagnosis of clear cell or papillary carcinoma (tumor size 1-11 cm) and in 23 surgical control patients matched for age and sex. C-reactive protein in the tumors was determined by immunohistochemistry. Results: By immunohistochemistry, kidney tumors synthesize C-reactive protein, thus making it available for potential excretion into the urine. The urine C-reactive protein of all control patients was 0.6 (0.2, 1.0) ng/ml (median, (1st and 3rd quintile)) while in the pre-nephrectomy urine of 31 patients with clear cell or papillary carcinoma was 3.9 (2, 11) ng/ml (P&amp;lt;0.0001, Wilcoxon rank sum test). The c-statistic for all controls and patients with kidney cancer was 0.89 (95% CI, 0.80 to 0.97) while the Spearman regression coefficient to tumor size was 0.72 (95% CI, 0.57-0.83). There was a significant 82% decrease in the urinary C-reactive protein concentration in the post-nephrectomy urine (P=0.0156, Wilcoxon test for paired samples). All stage 3 tumors and almost half of the stage 1 tumors excreted high amounts of biomarker. Four patients with stage 1 tumors and with concentrations of urine C-reactive protein significantly above the control range and no noted metastases at the time of partial nephrectomy subsequently developed clinical metastases over 32-34 months. Four patients with stage 1 tumors and urinary C-reactive protein concentrations equivalent to the controls had not developed metastatic disease in the same time frame. Conclusion: The measurement of C-reactive protein in the urine may be a non-invasive biopsy of the renal tumor indicating sub-clinical metastatic potential and may pre-surgically stage the tumor by molecular pathology. Citation Format: Jeremiah Morrissey, Evan D. Kharasch. Urinary C-reactive protein: A biomarker of metastatic kidney cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 407. doi:10.1158/1538-7445.AM2013-407
P97 Transition from a District General Hospital (DGH) Clinic to a Distant Adult Centre
Authors: SL Prudon, R Casans, F Hampton
Journal: Thorax (2012)

<h3>Background</h3> Transition between CF centres in the same town is well reported but there is less work on transition from large DGH clinics to distant adult centres. Our local paediatric unit provides total care for 60 patients. The majority will move on to the adult centre in a city 45 miles away. Until the last 2 years transition had been taking place very late because low staffing at the adult unit limited outreach support for the local patients who were thus reluctant to move on. The paediatric team felt that although transition was hampered by the lack of a local adult centre an increase in adult staffing was an opportunity to review current practiscs and identify areas for improvement. <h3>Aims</h3> To identify ways in which the transition process could be improved and to explore the need for the introduction of formal transition clinics. <h3>Methods</h3> Adolescents (13–18 years) within the paediatric clinic and young adults (18–26 years) who had completed transition to the adult centre in the last two years were surveyed using a proforma merging the standards of the CF trust and Department of Health. The CF nurses also completed questionnaires about these patients. <h3>Results</h3> 16/19 identified patients took part. CF nurse results showed that only 37% of patients started transition between ages 13 and 16 and only 50% had a key worker. Whilst the nurses felt that they offered most teenagers the opportunity to be seen alone only 14% of patients stated they were seen on their own and most said they would strongly prefer it. Discussions of careers, finance, higher education and fertility took place in up to 43%, but commonly after age 16. Patients reported wanting more information on these topics. Although 60% of patients marked the adult clinic was easy to reach and had appropriate facilities, the ‘free comments’ section revealed difficulties. <h3>Conclusions</h3> There are areas of practise that can be improved in the paediatric clinic independently of the setting up of transition clinics. More teenagers need to be seen on their own and cheque lists are needed to ensure all relevant areas are discussed.
Virologic and Immunologic Characterization of Long-Term Survivors of Human Immunodeficiency Virus Type 1 Infection
Authors: Yunzhen Cao, Limo Qin, Linqi Zhang, Jeffrey Safrit, David D. Ho
Journal: New England Journal of Medicine (1995)

In most subjects infected with human immunodeficiency virus type 1 (HIV-1), clinical or laboratory evidence of immunodeficiency develops within 10 years of seroconversion, but a few infected people remain healthy and immunologically normal for more than a decade. Studies of these subjects, termed long-term survivors, may yield important clues for the development of prophylactic and therapeutic interventions against the acquired immunodeficiency syndrome.
INCREASED ONE YEAR CARDIOVASCULAR EVENT RATE IN PATIENTS WITH CORONARY ARTERY DISEASE AND BILATERAL CAROTID ARTERY INFLAMMATION
Authors: Georgios Benetos, Konstantinos Toutouzas, Maria Drakopoulou, Charalampia Nikolaou, Pavlos Bounas, Iosif Koutagiar, Eumorfia Komatanou, Fotini Mitropoulou, Elias Siores, Dimitris Tousoulis
Journal: Journal of the American College of Cardiology (2015)
Whooping Cough in an Adult
Authors: Renee K Rutledge, Erica C Keen
Journal: New England Journal of Medicine (2012)

A 64-year-old man was admitted to the medical service with a presumed asthma exacerbation. His symptoms had worsened during the preceding 3 weeks despite treatment with oral glucocorticoids, leading him to present to the emergency department multiple times with a progressive cough.