tbuckley/cabot-search huggingface dataset:
Abstract 15784: Increased 20-HETE Signaling Contributes to Gender- and Mouse Strain-Specific Hypertension in the Setting of Impaired NO-sGC Signaling
Authors: Sara Vandenwijngaert, Ana C Dordea, Robert E Tainsh, Daniel I Nathan, Michael J Raher, Andrew Kirby, Christine Stevens, Mark J Daly, Peter Brouckaert, Michal L Schwartzman, Kenneth D Bloch, Emmanuel S Buys
Journal: Circulation (2014)

Introduction: Hypertension is a multifactorial disease affecting one in three adults in the US. Evidence suggests that dysregulated signaling of the vasodilator nitric oxide (NO) is involved in its pathogenesis. Previously, we reported that mice deficient in the α1 subunit of the NO receptor guanylate cyclase (sGCα1-/- mice), display gender- and strain-specific hypertension: male mice on an Sv129/J (S6) but not a C57BL6/J (B6) background are hypertensive.

Methods and Results: Via linkage analysis, we identified a quantitative trait locus (QTL) associated with elevated blood pressure in male sGCα1-/-S6 mice. This QTL encompasses the gene encoding CYP4a12a, a predominant synthase of the vasoconstrictor 20-hydroxyeicosatetraenoic acid (20-HETE) in murine kidneys. Renal CYP4a12a gene expression, assessed using qRT-PCR, was higher in male WT and sGCα1-/- S6 mice than in female S6 mice or male and female, WT and sGCα1-/- B6 mice. In addition, 20-HETE levels, measured via liquid chromatography-tandem mass spectrometry, were higher in renal preglomerular microvessels of male sGCα1-/-S6 than of male sGCα1-/-B6 mice (2.3±0.4 vs 1.6±0.4 ng/mg protein, respectively, n=5 and 3, P <0.05). Furthermore, treating male sGCα1-/-S6 mice with the 20-HETE synthesis inhibitor HET0016 (10 mg/kg/day IP for 14 days) reduced the mean arterial pressure (MAP; 130±13 mmHg in 6 HET0016-treated mice vs. 159±2 mmHg in 2 vehicle-treated mice). Similarly, administration of the 20-HETE antagonist, 20-6,15-HEDGE (20-HEDGE, 10 mg/kg IV) to male sGCα1-/-S6 mice lowered MAP in 20-HEDGE-treated but not in vehicle treated mice (delta MAP = -10±3 vs 1±2 mmHg, n=8 for both, P <0.05). Finally, the more significant impairment of acetylcholine-induced relaxation of renal interlobar arteries in male sGCα1-/-S6 than in sGCα1-/-B6 mice, was rescued by adding 20-HEDGE (10 μM).

Conclusions: Gender- and strain-specific hypertension in sGCα1-/-S6 mice is associated with elevated CYP4a12a gene expression and higher 20-HETE levels. Hypertension and vascular dysfunction in sGCα1-/-S6 mice is abrogated by 20-HETE inhibition. Our data identify CYP4a12a as a candidate blood pressure modifying gene in the context of deficient NO-sGC signaling.
Recurrence Score across the age spectrum: Is there an age discrimination?
Authors: Franz Omar Smith, Marie Catherine Lee, Geza Acs, William J. Fulp, Ji-Hyun Lee, Naznin Khakpour, John Kiluk, Christine Laronga
Journal: Journal of Clinical Oncology (2013)

27 Background: Treatment planning for early-stage estrogen receptor (ER) positive, lymph node negative breast cancer was based on prognostic factors with limited predictive power such as age. The Recurrence Score (RS) from the Oncotype DX assay (ODX) provides predictive power transcending age but is rarely applied to the elderly or young patients (pts). We examined our experience with RS along the age continuum. Methods: Retrospective review was conducted of prospectively gathered breast cancer pts having a RS obtained as part of their cancer care. Eligibility for performance of the ODX was based on NCCN guidelines or physician discretion. Comparisons on RS were made by age groups (young: &lt;45yrs; middle: &gt;45yrs -&lt;70yrs: elderly: &gt;70yrs) using general linear regression model and the exact Wilcoxon Rank Sum Test. Results: 677pts had 681 tumors with RS available (89 young, 476 middle and 112 elderly pts). Median RS for the study pts was 17 (range 0-85) and 16, 17, and 15 for the young, middle, and elderly respectively. Median age was 58yrs (range: 27-95); young, middle, and elderly was 42, 58, and 74yrs respectively. Age as a continuous or categorical variable was not predictive of RS (p value = 0.38, 0.58 respectively). No significant differences were seen between age cohorts for histology, mitotic rate, lymphovascular invasion (LVI), grade, nodal status, stage, or strength of ER positivity. Mastectomy rates were higher in the young (57.5%), compared to the middle (42.5%) and elderly (39.6%) (p=0.02). Median invasive tumor size was 1.6, 1.5, and 1.5cm for young, middle, and elderly. Larger tumor size, as a continuous variable, equaled higher RS (p=0.046). Other significant factors predicting higher RS were increased mitosis (p&lt;0.001), LVI (p=0.013), high grade (p&lt;0.001), and weak (&lt;10%) ER positivity (p&lt;0.001). Nodal status, stage, and histology did not affect RS. Conclusions: Age has limited predictive power for treatment planning for breast cancer. Age alone should not preclude recommendations for performance of ODX in estrogen receptor positive lymph node negative early stage breast cancer as the RS distribution across the spectrum of age is well matched.
Characteristics of 60 adult chronic hair pullers
Authors: G A Christenson, T B Mackenzie, J E Mitchell
Journal: American Journal of Psychiatry (1991)

This study was constructed to detail the demographic and phenomenological features of chronic hair pullers as well as to assess psychiatric comorbidity in a sizable study group.Subjects were drawn from an outpatient population of chronic hair pullers who had been referred to a trichotillomania clinic or had responded to a newspaper advertisement announcing a treatment study of adults who pull out their hair. Sixty adult chronic hair pullers completed a semistructured interview that focused on their hair-pulling behavior and demographic characteristics and that incorporated screening questions for DSM-III-R axis I disorders. The data were tabulated to derive a comprehensive picture of this group.The typical subject was a 34-year-old woman who had pulled hair from two or more sites for 21 years. All subjects described either tension before or relief/gratification after pulling hair from the primary site, but 17% (N = 10) failed to describe both of these characteristics and thus failed to fulfill the DMS-III-R criteria for trichotillomania. Forty-nine subjects (82%) qualified for past or current axis I diagnoses other than trichotillomania. Several characteristics of the study group suggested phenomenological differences between obsessive-compulsive disorder and trichotillomania.Adult trichotillomania is a chronic disorder, frequently involving multiple hair sites, and is associated with high rates of psychiatric comorbidity. Its relation to obsessive-compulsive disorder requires further clarification. The tension-reduction requirement in DSM-III-R for the diagnosis of trichotillomania may be overly restrictive.
Comparison of the clinical impact of endoscopic ultrasound-guided choledochoduodenostomy and hepaticogastrostomy for bile duct obstruction with duodenal obstruction
Authors: Takeshi Ogura, Yasutaka Chiba, Daisuke Masuda, Masayuki Kitano, Tatsushi Sano, Onda Saori, Kazuhiro Yamamoto, Hiroshi Imaoka, Akira Imoto, Toshihisa Takeuchi, Shinya Fukunishi, Kazuhide Higuchi
Journal: Endoscopy (2015)

<b>Background and study aim:</b> To date, only a few reports with small numbers of patients have described double stenting (biliary and duodenal), in particular endoscopic ultrasound (EUS)-guided biliary drainage, for patients with obstructive jaundice. In addition, no reports have sought to determine which EUS-guided biliary drainage route has better outcomes. The aim of the current study was to investigate adverse events and stent patency in patients who underwent EUS-guided biliary drainage and duodenal stenting. <b>Patients and methods:</b> Patients who were admitted to the Osaka Medical College with obstructive jaundice caused by lower biliary obstruction and duodenal obstruction due to malignant tumor between June 2012 and April 2014 were retrospectively enrolled in the study. <b>Results: </b>A total of 39 patients were enrolled in the study; 13 underwent EUS-guided choledochoduodenostomy (EUS-CDS), and 26 underwent EUS-guided hepaticogastrostomy (EUS-HGS). Adjusted analyses for covariates using propensity scores showed that the EUS-HGS group had significantly longer stent patency than the EUS-CDS group (duodenal stent patency: median 113 vs. 34 days; hazard ratio [HR] 0.415, 95 % confidence interval [CI] 0.175 – 0.984; <i>P</i> = 0.046; biliary stent patency: median 133 vs. 37 days; HR 0.391, 95 %CI 0.156 – 0.981; <i>P</i> = 0.045). On logistic regression analysis, only EUS-CDS was associated with adverse events, in particular reflux cholangitis (OR 10.285, 95 %CI 1.686 – 62.733; <i>P</i> = 0.012). <b>Conclusion:</b> In cases of obstructive jaundice with duodenal obstruction, EUS-HGS may be better than EUS-CDS, with longer stent patency and fewer adverse events.
Secondary surgery with intraoperative chemo-hyperthermia in recurrent ovarian adenocarcinoma. Prognostic factor analysis on 108 patients
Authors: J. Bereder, N. Sautot-Vial, B. Karimdjee, N. Mounier, J. Habre, E. Beniziri, J. Bernard, A. Rahili, D. Benchimol
Journal: Journal of Clinical Oncology (2008)

5548 Background: Optimal treatment of peritoneal recurrences in ovarian cancer is debating with second line chemotherapies. In this context we proposed the association of a secondary surgery with heated intraperitoneal per operative chemotherapy (HIPEC). The aim of study is to determine prognostic factors in a single center cohort. Methods: Patient eligibility criteria was peritoneal recurrence only and age up to 75 years. Peritoneal Cancer Index (PCI) assess tumor load and completeness cytoreductive score (CCS) was used to give quality of resection CC0 (no visible tumor), CC1 (persistent diffuse lesions < 2.5mm), CC2 (2.5mm <CC2< 25mm) and over CC3 status. Peritonectomies and organ resections are performed with HIPEC (cisplatine: 50 mg/m2 and Doxorubicin: 15 mg/m2) at 42°C. Endpoint was survival. Kaplan-Meier survival curve was fitted to the data. Cox's regression model was used for multivariate survival analysis. Results: We have operated on 120 procedures (HIPEC) in 108 consecutive patients from January 2000 to June 2007. The mean age was 57 years old range [28–75]. The median PCI was 14. After completion of resection the allocation of CCS was CC0=71, CC1=46, CC2=2 and CC3=1 anastomosis were protect by a digestive ostomy in 48%. Procedure related mortality was null and morbidity 21% The mean length of hospital stay was 17 days range [7–51]. 4 years overall and free survival were respectively 52 % and 25%. Median overall survival was 45 months and the median disease free survival was 30 months. A multivariate analysis using Cox model showed prognostic factors for survival. Peritoneal location was prognostic factor (mesentery and small bowel involvement HR = 2.44 IC 95% [1.32–4.48] and peritoneum of the epigastric area HR = 6.33 IC 95 % [1.17–34.11]). Conclusions: The chemo-hyperthermia is a standardized and reproducible feasible method. Less extensive disease and the quality of cytoreduction remain an independent factor of better outcome. Morbidity is acceptable. To date HIPEC allows to reach the longest median time survival in peritoneal recurrent ovarian cancer. In our knowledge this serie is the biggest sample size. No significant financial relationships to disclose.
Treating In-Hospital Stroke
Authors: Nada El Husseini, Larry B. Goldstein
Journal: JAMA Neurology (2015)

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Radiotherapy versus carboplatin for stage I seminoma: Updated analysis of the MRC/EORTC randomized trial (ISRCTN27163214)
Authors: R. T. Oliver, G. M. Mead, P. J. Fogarty, S. P. Stenning
Journal: Journal of Clinical Oncology (2008)

1 Background: At ASCO 2004 we reported a randomised trial (MRC TE19, EORTC 30982) comparing 1 course carboplatin (C) at AUC×7 with adjuvant radiotherapy (RT) for stage I seminoma. With median follow-up (FU) of 4 yrs, C was shown to be non-inferior for relapse free rate (1° outcome) and there was a reduction in contralateral testicular gem cell cancers (GCT). Because late relapses and 2nd GCT can occur beyond 5 and 10 yrs we have continued FU of these patients (pts). We report the updated results, and further analysis of C dose and outcome in relation to method of assessing renal function. Methods: The 1° randomisation was RT versus one injection of C dosed at 7× (GFR+25) based on EDTA(n=357) and 90% of this dose if based on creatinine clearance(n=202). The trial was powered to exclude absolute differences in the 2 yr relapse-free rates (RFR) of > 3%. RFR were determined by the Kaplan-Meier method, and hazard ratios (HR) from the Cox regression model; HR>1 favors RT. Results: Between 1996–2001, 1447 pts were randomised in a 3:5 ratio (C=573, RT=904). Median FU is now 6.5 yrs with documented minimum 5 yr FU on 1148 pts. RFRs at 5 yrs are 95% (C) and 96% (RT) (HR 1.25, 90% CI 0.83, 1.89); an increase in 5yr RFR of >3.6% can be excluded with 95% confidence. Only one death from seminoma (RT) has been reported. There was a significant difference in the rate of new GCTs (2 on C vs 15 on RT), giving a HR of 0.22 (95% CI 0.05, 0.95 p=0.03). High levels of pre-treatment FSH (>12 iu/L) were associated with an increased risk of developing a 2nd GCT (HR: 8.57 (95% CI 1.82 –40.38)) Analysing the variation in dose received in the C group, showed that those who received at least 99% of the 7AUC dose (n=347) ignoring GFR method had 5 yr RFR of 96.1% (95% CI 93.4–97.7) compared with 92.6% (88.0–95.5) in those who received lower doses (n=212, HR: 0.51 (0.24 - 1.07) p=0.08)). Analysis of the available data on pathological risk factors demonstrated that larger tumours (>4cm) had poorer RFR (HR: 3.68 (1.49 - 9.13)). Conclusion: With prolonged FU this trial confirms the non-inferiority of single dose C (AUC7) vs RT in terms of RFR but with a reduced risk of 2nd GCT in the C arm. The observation on the impact of C dosage, though not significant in its own right, reinforces the safety of adequately dosed C and may support studies of higher dose C. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Medical Research Council (non-commercial sponsor)
Lumen Measurements From Quantitative Coronary Angiography and IVUS: A PROSPECT Substudy
Authors: Kosaku Goto, Gary S. Mintz, Claire Litherland, Alexandra J. Lansky, Giora Weisz, John A. McPherson, Bernard De Bruyne, Patrick W. Serruys, Gregg W. Stone, Akiko Maehara
Journal: JACC. Cardiovascular imaging (2015)
Abstract P370: Cardiovascular Health Metrics, Lifetime Risks of Cardiovascular Disease and Chronic Disease Mortality, and Life Expectancy in Men and Women
Authors: Chong Lee
Journal: Circulation (2015)

Whether cardiovascular health metrics relates to lifetime risks of cardiovascular disease (CVD) and chronic disease mortality and life expectancy in U.S. population remains less explored. PURPOSE: We investigated the combined impact of 7 ideal cardiovascular health metrics on lifetime risks of CVD and chronic disease mortality and life expectancy in US men and women at 30 years of age. METHODS: Lifetime risks of CVD and chronic disease mortality to 80 years of age were estimated for men and women, with death free of chronic diseases as a competing event. We followed 11,341 men and women, aged 30 to 80 years, who participated in the Third National Health and Nutrition Examination Survey. All participants completed baseline lifestyle factors and lifestyle behavior questionnaires. The 7 ideal cardiovascular health metrics was defined as physically active, never smoking, a healthy diet, waist girth (&lt;102/88 cm), untreated blood pressure (&lt;120/80 mmHg), untreated total cholesterol (&lt;200 mg/dL), and untreated fasting glucose (&lt;100 mg/dL) defined by the American Heart Association Strategic Committee. They were further categorized as having 0, 1, 2, 3, 4, 5, 6 or 7 combined cardiovascular health metrics. RESULTS: During an average of 13.7 years of follow-up (155,726 person-years), there were a total of 1834 chronic disease deaths (945 CVD, 579 cancer, 217 respiratory disease, 93 diabetes mellitus). The lifetime risks of chronic disease mortality (at 30 years of age) across 0, 1, 2, 3, 4, 5, and 6 or 7 ideal health metrics were (95% CI) 46.2% (41.6, 50.7), 40.3% (36.9, 43.8), 33.1% (30, 36.1), 27.2% (23.9, 30.5), 25.8% (21, 30.5), 24.8% (16.8, 32.9), and 12.7% (1.2, 24.1), respectively. Men and women who had adopted increasing number ideal health metrics had a substantially lower lifetime risk of chronic disease mortality. The lifetime risks of CVD mortality across 7 ideal health metrics showed trends similar to chronic disease mortality. After adjustment for multiple risk factors, men and women with all 6 or 7 combined ideal health metrics had a 75% (95% CI: 51% to 88%) lower risk of chronic disease mortality and 93% (95% CI: 53% to 99%) lower risk of CVD mortality, respectively, when compared with men and women with zero ideal health metrics. Men and women with 0 compared with 6 or 7 combined ideal health metrics had a shorter life expectancy by 16 years (95% CI: 13 to 19.1 years). Approximately 63% (95% CI: 26% to 82%) of chronic disease deaths might have been avoided if men and women had maintained all 6 or 7 combined health factors and healthy lifestyle behaviors. CONCLUSION: Maintaining an ideal cardiovascular health metrics is associated with lower lifetime risks of CVD and chronic disease mortality in men and women.
Personal Immunization against Hepatitis B
Authors: N J Shanks, D F Rowlands
Journal: Journal of the Royal Society of Medicine (1993)

Doctors represent a high risk category for contracting hepatitis B virus. We report obstacles to our vaccination programme. Thirty per cent of the doctors (mainly Middle Eastern origin) were naturally immune to hepatitis, 29% received vaccination on completion of their pre-employment medical. However, 32% did not present for vaccination despite a total of 224 letters being dispatched, an average of 5.5 letters per doctor. Three medical staff were found to be HbsAg positive. More encouragement is required for those doctors who fail to attend for immunization. Measures such as: being a pre-requisite for employment, or withholding pay could be considered in high risk areas.
PALETTE: Final overall survival (OS) data and predictive factors for OS of EORTC 62072/GSK VEG110727, a randomized double-blind phase III trial of pazopanib versus placebo in advanced soft tissue sarcoma (STS) patients.
Authors: Winette T.A. Van Der Graaf, Jean-Yves Blay, Sant P. Chawla, Dong-Wan Kim, Binh Bui Nguyen, Paolo Giovanni Casali, Patrick Schoffski, Massimo Aglietta, Arthur P. Staddon, Yasuo Beppu, Axel Le Cesne, Hans Gelderblom, Ian Robert Judson, Nobuhito Araki, Monia Ouali, Sandrine Marreaud, Rachel Hodge, Mohamedraza Dewji, Angelo Paolo Dei Tos, Peter Hohenberger
Journal: Journal of Clinical Oncology (2012)

10009 Background: At ASCO 2011 we presented an increase in median progression-free survival (PFS) of pazopanib of 13 weeks (median 7 to 20 weeks; HR 0.31) in a randomized double-blind, placebo-controlled phase III trial in advanced non-adipocytic STS patients pretreated with chemotherapy. Now we present final OS data and predictive factors for OS, such as ethnicity, ancestry and well-known prognostic and predictive factors in STS patients treated with chemotherapy. Methods: At clinical cut-off median follow-up was 25 months. Comparison of both treatments for OS was performed using a two-sided log rank test stratified for number of prior lines of systemic therapy for advanced disease and WHO performance status (PS). HR was calculated with a 2-sided CI. A Kaplan-Meier OS curve was used. Baseline characteristics as potential predictive factors for OS were: PS (0 vs 1), number of lines of prior therapy for advanced disease (0-1 vs 2+), age (≤55 yrs vs &gt; 55 yrs), gender, ethnicity (Hispano or Latino vs other), geographic ancestry (White Caucasian, Asian, other), tumour grade (1-2 vs 3), histology (leiomyosarcoma vs synovial sarcoma vs other). A Cox model was fitted with the investigated factor, treatment arm and associated interaction factor. Data of all 369 randomized patients (123 placebo, 246 pazopanib) were used for the analyses. Results: Median OS (95% CI) was 10.7 (8.7-12.8) in the placebo versus 12.5 (10.6-14.8) months in the pazopanib group, HR: 0.86 (0.67-1.1). Post study protocol systemic treatment was administered in 63% of placebo, and in 49% of pazopanib treated patients. None of the investigated factors showed any statistical significant predictive value for OS. Conclusions: Although pazopanib demonstrated a statically significant increase in PFS compared to placebo, final OS analysis, which showed a trend in favor of pazopanib in patients with metastatic non-adipocytic STS, did not reach statistical significance. The factors studied were not predictive for OS.
Should NHS patients be allowed to pay extra for their care?
Authors: K. Sikora, H. Thornton, R. Osborne, T. Kilcoyne
Journal: BMJ (2002)

Promoting patient safety in primary care Honesty and openness may not be best policyEditor-We were both surprised by Wilson et al who, in their editorial, ask everybody to send in reports of their errors. 1Our concerns remain regardless of whether or not such accounts are published anonymously.After all, the police have used anonymous medical research data in their investigations.A conviction of culpable and reckless behaviour was secured against a man after he had sexual intercourse with his girlfriend without telling her he was infected with HIV.The scientific evidence that secured the conviction came from confidential research data that were obtained with a police warrant. 2 Furthermore, Wilson et all say that for doctors to report their errors, patient consent will be needed.This means that the patient will know that an account of his or her care is to be published and may read it.He or she may ask his lawyers to read it.The lawyers may then be able to substantiate this published account as a confession of guilt or negligence.Wherever and whoever we are, we must be careful as doctors what we say.For example, although we understand that no charges were brought, an incident last year highlights this point.Police are to hold a murder inquiry into the case of Peter Brand, a Member of Parliament for the Liberal Democrat Party for the Isle of Wight and a general practitioner, who mentioned during a parliamentary debate that he had withdrawn treatment from a two year old boy with leukaemia at the parents' request, to save him any more distress. 3This case had occurred in 1973, when he was a house officer.However regrettable, we do live in a culture of blame.To admit professional mistakes of a minor nature may be straightforwardly forgivable.The admission, however, of a serious offence or negligence by doctors may result in litigation against them.Before discussing such matters in public, doctors should seriously consider whether honesty and openness are the best policy.