tbuckley/cabot-search huggingface dataset:
PWE-145 Contemporary uk experience with preoperative chemoradiotherapy and surgery for oesophageal cancer
Authors: F Noble, J Ponichtera, D Sharland, J Byrne, J Kelly, A Jackson, A Bateman, T Underwood
Journal: Gut (2015)

<h3>Introduction</h3> The optimal neoadjuvant therapy regime for cancers of the oesophagus and OGJ remains controversial. In the UK preoperative chemotherapy is the standard of care, and we have been slow to adopt chemoradiotherapy (CRT) fearing increased surgical morbidity and under-treatment of systemic disease. The CROSS trial has led to a renewed interest in the use of CRT in the UK. We present our recent experience of patients treated with CRT and surgery for oesophageal carcinoma. <h3>Method</h3> All patients planned for CRT and surgery in a single UK institution were included. CRT consisted of carboplatin (AUC2) and paclitaxel (50 mg/m<sup>2</sup>) weekly x 5 with concurrent radiotherapy (41.4Gray in 23 fractions, n = 25 (CROSS regime); 45Gray in 25 fractions, n = 4) for 29 patients and 2 patients had Oxaliplatin, Capecitabine (OxCap) and RT (45Gray in 25 fractions). In 5 CRT was preceded by 2 cycles of OxCap chemotherapy. <h3>Results</h3> Radiotherapy 31 patients (median age 66 years; male 21 (68%): female 10 (22%)) with 13 adenocarcinomas (AC) and with 17 squamous cell carcinomas (SCC) underwent CRT. One patient (3%) died during CRT after oesophageal perforation at OGD. 3 patients (9.7%) were admitted to hospital (neutropenic sepsis 1; non-neutropenic sepsis 2). The median time between CRT and surgery was 10 weeks (range 5.7–14.1). 8 patients are awaiting resection. Surgery 22 patients have completed CRT and surgery. All patients underwent an oesophagectomy (minimally invasive: 15 (62.2%); Ivor Lewis: 7 (30.4%); Mckeown: 1 (4.3%)) with median length of stay: 10 days (range 6–45). There were no deaths. Complications according to Clavien-Dindo were Grade 1: 1 (4.5%); Grade 2: 10 (45.5%); Grade 3: 1 (4.5%); Grade 4: 1 (4.5%) with no complications in 9 (40.9%) patients. One (4.5%) patient had an anastomotic leak and this required reoperation and oesophageal exteriorisation with subsequent colonic interposition. 6 (27%) patients experienced a post-operative cardiac arrhythmia. There were 6 (27%) respiratory complications and no chyle leaks. Pathology 21 pathology reports were available with one under analysis. Complete pathological response (47.6%) was observed in 8 (72.7%) SCCs and 2 (20%) ACs (Tumour regression grade (TRG)1: 10 (47.6%); 2: 6 (28:6%); 3: 3 (14.3%); 4: 2 (9.5%); 5: 0). 20 (95.2%) patients had complete (R0) resection. Median nodal yield was 22 (range 8–65). <h3>Conclusion</h3> In a single centre UK series, CRT and surgery for oesophageal cancer is safe and effective in the short term. This may in part be explained by increasing the time between the CRT and surgery from 6 to 10 weeks without compromising tumour pathology. <h3>Disclosure of interest</h3> None Declared.
Species-specific properties of the glomerular mesangium.
Authors: J D Sraer, C Adida, M N Peraldi, E Rondeau, A Kanfer
Journal: Journal of the American Society of Nephrology (1993)

Mesangial cells play a central role in the physiology and pathophysiology of the glomerulus. To date, most of the in vitro studies have been performed in cultured rat mesangial cells, with only 10% of them performed in human mesangial cells. In this article, the major differences between results obtained with these two types of cultured cells will be reviewed. In rats and in humans, most of the mesangial cells appear to be of smooth muscle origin. In the rat, some of the cultured cells also express a phenotype suggesting a monocyte/macrophage origin. Phagocytosis and synthesis of cytokines or proinflammatory proteins that have been described in cultured rat cells seem mostly linked to this monocyte/macrophage subtype of resident mesangial cells. In humans, macrophages are only detected in pathologic conditions, suggesting that they are not resident but rather infiltrating cells. Mesangial receptors, most notably angiotensin II receptors, are clearly present on mesangial cell membranes and are linked to prostaglandin E2 synthesis and to cell contraction. In humans, spontaneous prostanoid synthesis is low and is increased by the induction of cyclooxygenase by sodium butyrate in the medium. Even so, the amount of prostaglandin E2 synthesized by human mesangial cells is quantitatively low comparatively with that in rats. In rats, accordingly, mesangial cells play a role in the regulation of single-nephron GFR. In humans, angiotensin II also exerts a control on GFR but it is more difficult to demonstrate its contractile effect on human than on rat mesangial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Determinants of therapeutic delays and their impact on axillary node involvement in operable invasive breast cancer (BC) patients (pts)
Authors: D. Dionysopoulos, N. Berrada, J. Chevalier, F. Rimareix, M. Mathieu, C. Balleyguier, S. Gouy, F. André, P. Vielh, S. Delaloge, S. Delaloge
Journal: Journal of Clinical Oncology (2009)

615 Background: International guidelines recommend rapid diagnostic and therapeutic procedures for suspect breast lesions. However, the impact of the interval between screening and treatment (trt) (STI) on the severity of the disease remains unclear. We explored the potential impact of STI on a surrogate of survival, axillary nodal involvement (N+), among 1,000 recently diagnosed BC pts, as well as the causes of potential delays. Methods: We collected complete data of prospectively recorded community BC cases in a single regional cancer center between January 1, 2005, and October 10, 2007. Pts were eligible if they i. had a final diagnosis of invasive BC ii. were operated as first trt for BC, iii. had no history of other previous malignancy within the past 5 year period. Logistic regression analyses (SAS) were used to determine factors predictive of N+ and those influencing intervals between first description of the lesion and first therapeutic surgery (STI). Candidate factors included socio-economic variables (marital status, occupation, county of living, country of birth), personal and familial medical history parameters, as well as BC characteristics. Results: 990 pts met the inclusion criteria and had full data available. Med age: 59 years, BI-RAD ACR3/4/5: 2/41/55%, med pathological tumor size (pT): 16 mm (2–100), N+: 41%, med delay between first description of the lesion and surgery: 67 days. Factors predicting longer STI were: Birad ACR&lt;5 vs 5 (p = 0.0004), not palpable lesion vs palpable (p = 0.01), microcalcifications vs solid lesion (p = 0.0008), presence of important comorbidities (p=.04), single life vs couple (p = 0.001). However, STI had no effect on N+: med STI was 68 days in N- vs 66 days in N+ pts. Factors predictive of N+ were lymphovascular invasion (LVI) (p=.0001) and pT (p = 0.0001), while age, social conditions, screening mode, per-cutaneous biopsy vs FNAC, grade, HR and HER-2 status, had no effect. Among pts with grade III BC, LVI (p = 0.0001) and pT (p = 0.02) were the sole predictors of N+ as well. Conclusions: This study identifies for the first time factors able to negatively influence STI of women with invasive BC. However, longer STI does not appear to influence axillary nodal invasion, even in pts with high grade BC. No significant financial relationships to disclose.
MD Anderson’s Oncology Expert Advisor powered by IBM Watson: A Web-based cognitive clinical decision support tool.
Authors: Koichi Takahashi, Hagop M. Kantarjian, Guillermo Garcia-Manero, Rick J Stevens, Courtney Denton Dinardo, Joshua Allen, Emily Hardeman, Scott Carrier, Cynthia Powers, Pat Keane, Sherry Pierce, Mark Routbort, Thai Nguyen, Brett Smith, Jeffery Frey, Keith Perry, John C. Frenzel, Rob High, Andrew Futreal, Lynda Chin
Journal: Journal of Clinical Oncology (2014)

6506 Background: Application of cognitive computing technology in cancer has potential to democratize expert knowledge and enable personalized evidenced based oncology care. Methods: We developed a web based prototype of MD Anderson’s Oncology Expert Advisor (OEA), a cognitive clinical decision support tool powered by IBM Watson. The Watson technology is IBM’s third generation cognitive computing system based on its unique capabilities in natural language processing and deep QA (question-answer). OEA is built with four core capabilities: 1) Patient Evaluation through interpretation of structured and unstructured clinical data to create a dynamic case summary with longitudinal view of the pertinent events 2) Treatment and Management suggestions based on patient profile weighed against consensus guidelines, relevant literature, and MD Anderson expertise, which will include approved therapies, genomic based therapies as well as automatic matching to eligibility criteria of clinical trials at MD Anderson, 3) Care Pathway Advisory that supports management of patients by alerting adverse events and/or suggesting proactive care support, and 4) Patient-oriented Research functionalities for identification of patient cohorts and generation of hypothesis. Results: We trained OEA by loading 400 cases of historical patient cases and assessed the accuracy of OEA treatment suggestions using MD Anderson’s physicians’ decisions as benchmark. False positive result was defined when OEA recommends a non-correct answer with high confidence, whereas false negative was defined when OEA recommends a correct answer with low confidence. When 200 leukemia cases were tested to assess accuracy of standard-of-care (SOC) treatment recommendation, false positive rate was 2.9%, whereas false negative rate was 0.4%. Overall accuracy of SOC treatment recommendation by OEA was 82.6%. Conclusions: OEA is able to generate dynamic patient case summary by interpreting structured and unstructured clinical data and suggest personalized treatment options with reasonably high accuracy. Live system evaluation of OEA is ongoing and application of OEA in clinical practice is expected to be piloted at our institution.
Cystometry in the Evaluation of Nerve Root Compression in the Lumbar Spine
Authors: H L ROSOMOFF, J D JOHNSTON, A E GALLO, M LUDMER, F T GIVENS, F T CARNEY, C A KUEHN
Journal: JAMA (1963)

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Drug Therapy in Cardiac Arrhythmias
Authors: A Dietz, M Manz
Journal: New England Journal of Medicine (1960)

Current antiarrhythmic drug therapy is employed in strict compliance with the proper indication, which is itself limited by the side effects of the available drugs, and modified by the increasing success of such non-drug options as electrical ablation and implantable cardioverters/defibrillators. Drug treatment is restricted to 3 major indications, regular paroxysmal supraventricular tachycardias, atrial flutter and fibrillation, and ventricular tachycardias. Class IA and IC agents are used only to treat supraventricular and ventricular arrhythmias with no structural heart disease. Class III drugs, e.g. sotalol and in particular amiodarone are used preferentially to treat the pre-damaged heart, in particular left-ventricular functional impairment and in coronary heart disease in consideration of their side effects. In the case of the most common treatment-requiring arrhythmia-atrial fibrillation-anticoagulation alone may be indicated. For the prevention of sudden death, beta-blockers continue to be the drugs of first choice.
Travellers returning to Sweden as sentinels for comparative disease incidence in other European countries, campylobacter and giardia infection as examples
Authors: K Ekdahl, J Giesecke
Journal: Eurosurveillance (2004)

Comparable figures on disease incidence between countries are difficult to attain. We therefore compared risk of infection for Swedes going to other European countries. We took as the numerator the number of imported cases from European countries of campylobacter and giardia infection in the national Swedish surveillance database, and as the denominator, the number of visitors to each country from a commercial database on foreign travel. Risk of infection in tourists was also compared to national incidence figures for a selection of countries.
AG-221, an Oral, Selective, First-in-Class, Potent IDH2-R140Q Mutant Inhibitor, Induces Differentiation in a Xenotransplant Model
Authors: Cyril Quivoron, Muriel David, Kim Straley, Jeremy Travins, Hyeryun Kim, Yue Chen, Dongwei Zhu, Véronique Saada, Olivia Bawa, Paule Opolon, Mélanie Polrot, Jean-Baptiste Micol, Christophe Willekens, Olivier Bernard, Hua Yang, Sam Agresta, Stéphane de Botton, Katharine Yen, Virginie Penard-Lacronique
Journal: Blood (2014)
Impaired eye tracking in undergraduates with schizotypal personality disorder
Authors: T Lencz, A Raine, A Scerbo, M Redmon, S Brodish, L Holt, L Bird
Journal: American Journal of Psychiatry (1993)

Qualitative ratings of smooth pursuit eye movements were significantly worse for 14 undergraduates with DSM-III-R schizotypal personality disorder than for 18 comparison subjects. The groups did not differ on IQ, indicating that deficits in smooth pursuit eye movements in schizotypal personality disorder are not a function of cognitive deficits.
Ordering of mutations in acute myeloid leukemia with partial tandem duplication of MLL (MLL-PTD)
Authors: Q-Y Sun, L-W Ding, K-T Tan, W Chien, A Mayakonda, D-C Lin, X-Y Loh, J-F Xiao, M Meggendorfer, T Alpermann, M Garg, S-L Lim, V Madan, N Hattori, Y Nagata, S Miyano, A E J Yeoh, H-A Hou, Y-Y Jiang, S Takao, L-Z Liu, S-Z Tan, M Lill, M Hayashi, A Kinoshita, H M Kantarjian, S M Kornblau, S Ogawa, T Haferlach, H Yang, H P Koeffler
Journal: Leukemia (2016)

Partial tandem duplication of MLL (MLL-PTD) characterizes acute myeloid leukemia (AML) patients often with a poor prognosis. To understand the order of occurrence of MLL-PTD in relation to other major AML mutations and to identify novel mutations that may be present in this unique AML molecular subtype, exome and targeted sequencing was performed on 85 MLL-PTD AML samples using HiSeq-2000. Genes involved in the cohesin complex (STAG2), a splicing factor (U2AF1) and a poorly studied gene, MGA were recurrently mutated, whereas NPM1, one of the most frequently mutated AML gene, was not mutated in MLL-PTD patients. Interestingly, clonality analysis suggests that IDH2/1, DNMT3A, U2AF1 and TET2 mutations are clonal and occur early, and MLL-PTD likely arises after these initial mutations. Conversely, proliferative mutations (FLT3, RAS), typically appear later, are largely subclonal and tend to be unstable. This study provides important insights for understanding the relative importance of different mutations for defining a targeted therapeutic strategy for MLL-PTD AML patients.
General hospital psychiatry: overview from a sociological perspective
Authors: L L Bachrach
Journal: American Journal of Psychiatry (1981)

The role of the general hospital within the psychiatric service delivery network has undergone profound changes in recent years. Current issues in general hospital psychiatry revolve around questions concerning boundaries, target populations, appropriate services, structural characteristics, and deinstitutionalization. Decisions in general hospital psychiatry derive from a series of influences that originate at varing distances from day-to-day hospital operations. Planning should ideally be filtered through the hospital's internal decision-making process in order to ensure a "bottom-up" rather than a "top-down" emphasis in service policy.
Patient Outcomes By Prior Therapies and Depth Of Response: Analysis Of MM-003, a Phase 3 Study Comparing Pomalidomide + Low-Dose Dexamethasone (POM + LoDEX) Vs High-Dose Dexamethasone (HiDEX) In Relapsed/Refractory Multiple Myeloma (RRMM)
Authors: Jesús F. San Miguel, Katja Weisel, Kevin W. Song, Michel Delforge, Lionel Karlin, Hartmut Goldschmidt, Philippe Moreau, Anne Banos, Albert Oriol, Laurent Garderet, Michele Cavo, Valentina Ivanova, Adrian Alegre, Joaquin Martinez-Lopez, Christine I. Chen, Christoph Renner, Nizar J. Bahlis, Xin Yu, Terri Teasdale, Lars Sternas, Christian Jacques, Mohamed H. Zaki, Meletios A. Dimopoulos
Journal: Blood (2013)
Untitled
Authors: Thomas B. Cole
Journal: JAMA (2013)

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Authors: Stuart C Gordon, Eduardo Bruno Martins, Leland J. Yee
Journal: Hepatology (2013)

We thank Dr. Lo for his insightful comments. We agree that the finding of greater hepatitis B surface antigen (HBsAg) loss among patients with high baseline viral load (HVL) than those with non-HVL is of interest. In a previous report of this cohort, the 23 individuals who achieved HBsAg loss by week 192 of therapy were exclusively hepatitis B e antigen (HBeAg)+ at baseline.1 In addition, those individuals who achieved HBsAg loss had higher hepatitis B virus (HBV)-DNA levels at baseline, compared to HBeAg+ subjects who did not achieve HBsAg loss (median, 9.31 vs. 8.82 log10 copies/mL, respectively).1 The viral genotype distribution among the 23 subjects with HBsAg loss was genotype (gt)-A: 14, gt-B: 1, gt-D: 7, and gt-F: 1, whereas among HBeAg+ individuals who did not experience HBsAg loss, distribution was gt-A: 46, gt-B: 32, gt-C: 69, gt-D: 79, gt-E: 5, and gt-F: 7.1 Among the 23 subjects who lost HBsAg, 7 were in the adefovir arm and all experienced HBsAg loss after the addition of tenofovir.1 We also examined surface antigen levels and found that the median levels of HBsAg at baseline were 5.07 log10 IU/mL among those who lost HBsAg, compared to 4.51 among those who did not achieve HBsAg loss. Patients who experienced HBsAg loss had rapid, continuous declines of HBsAg, with the decline at week 12 >0.5 log10 IU/mL. No Asian patient achieved HBsAg loss.1 In multivariable analysis, having had a diagnosis of HBV for ≤4 years was associated with HBsAg loss, compared to those who had their HBV diagnosed 5 years or longer (odds ratio: 6.9; P = 0.0375).1 Therefore, Dr. Lo raises several intriguing questions that will require additional studies to better understand, including potential differences between spontaneous versus therapy-mediated HBsAg loss. Stuart C. Gordon, M.D.1Leland J. Yee, Ph.D., MPH2Eduardo Bruno Martins, M.D., D.Phil.2 1Henry Ford Hospital, Detroit, MI 2Gilead Sciences, Foster City, CA
AB0393 Rates and Characteristics of Post-Arthroplasty Flare in Rheumatoid Arthritis: A Prospective Cohort Study
Authors: S.M. Goodman, R. Friedlander, C. Figgie, A. Pernis, R. Khianey Maharaj, C. Rozo, E. DiCarlo, M. Figgie, V.P. Bykerk
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Medication withdrawal for RA patients undergoing total hip (THA) and knee (THA) arthroplasty balances risk of infection with risk of flare, yet little is known about post-op flare. <h3>Objectives</h3> To describe rates, characteristics and molecular profile of flare within 6 weeks of THA/TKA. <h3>Methods</h3> Baseline (BL) sociodemographic, RA characteristics and tissue/blood samples for molecular profile, BL and 6 week DAS-28, and weekly flare &amp; function questions (MDHAQ, HOOS ADL) were collected in RA patients undergoing THA/TKA. Patient-MD concordant flarers were identified using patient report of flare ("yes" to "Are you in a flare?"), flare intensity/duration combined with MD agreement by review of records. Medication management was standard of care: biologic DMARDs were stopped pre-op; steroids and MTX were continued. Measures of immune activation include Rho associated kinases (ROCKs) pathways, which act via phosphorylation of ezrin-radixin-moesin (pERM) protein substrates. <h3>Results</h3> Included are results of the first 24 of 50 RA subjects; 20 THA and 4 TKA. 18/24 (75%) met RA 2010 classification criteria. Patients were (median (IQR)) 54 (18) yrs old with 14.5 (23) yrs of disease; 74% were female, 84% white, 88% college educated; 65% ACPA/RF positive. Median (IQR) time to flare was reported at 3.0 (3.0) wks in 14/24 (63%) of patients (flare intensity of 5 (4), duration &gt;4 days in 79%; 1 already flared by BL. More flarers had stopped biologic DMARDs (67 vs 22%). All but 2 stopping biologics flared. More flarers were on steroids (6 vs 1), and MTX (11 vs 5). At BL, DAS-28 was not different (3.8 (1.5) vs 3.9 (1.3), p=.44) but flarers had higher ESR 14 (41) vs 2.5 (7), CRP 1.1 (4.3) vs 0.68 (0.9), and HAQ 4.7 (2) vs 2.0 (2.4). HOOS ADL was worse 34.6 (28.8) vs 44.2 (37.2). Trend for baseline lymphocyte associated pERM was higher in a subset of 5 flarers. <h3>Conclusions</h3> Flares are frequent and severe in RA patients undergoing THA/TKA, more after discontinuing biologics. Work to identify clinical and novel molecular signatures to predict flare are needed to optimize perioperative management. Activation of the ROCK pathway may signal and play a role in flare. <h3>Disclosure of Interest</h3> S. Goodman: None declared, R. Friedlander: None declared, C. Figgie: None declared, A. Pernis Grant/research support from: Kadmon Pharmaceuticals, R. Khianey Maharaj: None declared, C. Rozo: None declared, E. DiCarlo: None declared, M. Figgie: None declared, V. Bykerk: None declared
High Numbers Of Memory T Cells Are Associated With Higher Risk Of Grade II-IV Acute Gvhd After Human Allogeneic Transplantation
Authors: Michael Loschi, Régis Peffault de Latour, Raphael Porcher, Valerie Vanneaux, Marie Robin, Alienor Xhaard, Jerome Larghero, Gérard Socié
Journal: Blood (2013)