tbuckley/cabot-search huggingface dataset:
PTU-169 Comparison between sphincteroplasty and sacral nerve stimulation for treat-ment of anal incontinence patients with sphincter injuries
Authors: FG Rodrigues, S Chadi, A Cracco, G Dasilva, DR Sands, SD Wexner
Journal: Gut (2015)

<h3>Introduction</h3> This study aimed to compare outcomes of patients with anal sphincter defects treated by sacral nerve stimulation (SNS) or sphincteroplasty (SP). <h3>Method</h3> After IRB approval, patients treated for FI with a sphincter defect were identified from a prospective database; treatment groups were matched and stratified by SNS or SP. Primary outcome was change in Wexner FI Score (FIS). Demographic variables, past medical history and complication rates were also reviewed. Sphincter defects were assessed by endoanal ultrasound and ranged from 45°–180°. Continuous variables were compared with independent t-tests or Mann-Whitney U tests based on evidence of Gaussian distribution. Categorical variables were compared with Chi-squared analyses. Paired within group analyses were performed with paired t-tests and Wilcoxon signed-rank test. In order to perform a paired assessment of the role of each intervention in affecting the FIS, an Analysis of Covariance (ANCOVA) was performed. <h3>Results</h3> 26 female patients were included, 13 each underwent sphincteroplasty or SNS. The groups were similar with regards to age (62.2 vs 57.2 years, p = 0.16), BMI (26.2 vs 26.5, p = 0.33), initial FIS (15.9 vs 16.8, p = 0.39) and follow-up (14 vs 10 months, p = 0.72). The groups were similar for &gt;1 vaginal delivery or rates of urinary incontinence (p = 1.00 and p = 0.62, respectively). Early postoperative complications included 1 patient in each group with wound infection. Within group analyses revealed a significant improvement of FIS in SNS patients (15.9 to 8.4; p = 0.003) but not observed in the SP group (16.9 to 12.9; p = 0.078). Between groups, a trend towards lower FIS was seen in the SNS group as compared to SP but was not significant (8.4 vs 12.9; p = 0.06). ANCOVA analysis did reveal either procedure as superior in reducing FIS. <h3>Conclusion</h3> This study demonstrates that within each group SNS is effective at reducing FI in patients with a sphincter defect. Larger sample sizes will be required to better compare the difference in scores and assess for superiority between procedures. <h3>Disclosure of interest</h3> None Declared.
Antitumor activity of the combination of cetuximab, an anti-EGFR blocking monoclonal antibody and ZD6474, an inhibitor of VEGFR and EGFR tyrosine kinases
Authors: M. P. Morelli, T. Cascone, T. Troiani, C. Tuccillo, R. Bianco, M. Romano, S. G. Eckhardt, S. De Pacido, G. Tortora, F. Ciardiello
Journal: Journal of Clinical Oncology (2006)

13170 Background: The epidermal growth factor receptor (EGFR) autocrine pathway plays an important role in cancer cell growth. Vascular endothelial growth factor A (VEGF-A) is a key regulator of tumor-induced endothelial cell proliferation and vascular permeability. ZD6474 (ZACTIMA™) is an orally available, small molecule inhibitor of VEGF receptor-2 (VEGFR-2), EGFR and RET tyrosine kinase activity. We investigated the activity of ZD6474 in combination with cetuximab, an anti-EGFR blocking monoclonal antibody, to determine the antitumor activity of EGFR blockade through the combined use of two agents targeting the receptor at different molecular sites in cancer cells and of VEGFR-2 blockade in endothelial cells. Methods: The antitumor activity in vitro and in vivo of ZD6474 and/or cetuximab was tested in human cancer cell lines with a functional EGFR autocrine pathway. Results: In vitro, the combination of ZD6474 and cetuximab produced synergistic growth inhibition in all cancer cell lines tested as assessed by the Chou and Talalay method. In vivo, 4 weeks of treatment with ZD6474 (75 mg/kg p.o., days 1–5 each week) or cetuximab (1 mg i.p., days 2 and 5 each week) produced a tumor growth delay of 21–28 days (P &lt; 0.001) in nude mice bearing established human colon carcinoma (GEO) or lung adenocarcinoma (A549) cancer xenografts compared with untreated controls. Combination treatment with ZD6474 and cetuximab for 4 weeks resulted in a more marked tumor growth delay of 120–140 days compared with controls, and this was significantly greater than with either single agent therapy (P &lt; 0.001). Following combination treatment, 3/10 A549 xenograft-bearing mice and 4/10 GEO xenograft-bearing mice had no histologic evidence of tumor at the end of the experiment. Immunohistochemical analysis of tumor samples obtained from mice treated with the two drugs in combination demonstrated a cooperative inhibition of cancer cell proliferation and an almost complete suppression of tumor angiogenesis. Conclusions: This study provides a rationale for evaluating in a clinical setting the double blockade of EGFR in combination with inhibition of VEGFR-2 signaling as cancer therapy. [Table: see text]
Antitumor Activity of Picolinic Acid in CBA/J Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: S W Leuthauser, L W Oberley, T D Oberley
Journal: JNCI Journal of the National Cancer Institute (1982)

The growth of a solid tumor induced by im implantation of Ehrlich ascites tumor cells in inbred CBA/J mice was retarded by treatment with an iron chelator, picolinic acid (PLA). Survival of the mice was also significantly increased after PLA treatment. However, the iron chelator deferoxamine had no such effects; tumor growth was slightly enhanced, and survival was decreased.
Expression of metastasis-associated gene products and liver metastases in pancreatic endocrine tumors
Authors: J. Helm, J. Strosberg, E. Henderson-Jackson, N. Hafez, A. Hakam, N. A. Nasir, D. Coppola, M. P. Malafa, K. K. Larry, A. Nasir
Journal: Journal of Clinical Oncology (2009)

11089 Background: Outcomes in well-differentiated pancreatic endocrine tumors can be difficult to predict using pathologic criteria. We recently identified a novel set of 3 metastasis-associated genes by microarray: Palladin, p21, RUNX1T1. Our aim was to evaluate the potential for these markers, individually or in combination, to predict liver metastases as an indicator of adverse outcome. Methods: Palladin, p21, and RUNX1T1 immunostains were done on a tissue microarray of 39 resected primary pancreatic endocrine neoplasms, 14 of which had hepatic metastases. The Allred score was determined as the sum of stain intensity (scored 0–3) and % cells stained (scored 0–5). Receiver operating characteristic (ROC) analysis was used to choose the cutpoint in Allred score (high vs low protein expression) to optimize sensitivity and specificity for predicting liver metastases. Results: Nearly all tumors with liver metastases showed high Palladin and p21 levels (Allred score &gt; 3 and &gt; 4, respectively), while protein expression was lower in the majority of non-metastatic tumors. In contrast, RUNX1T1 expression was low (Allred score &lt; 4) in most tumors with liver metastases, but higher in all except one of the non-metastatic tumors. Individual test sensitivities for predicting liver metastases were 100% for high Palladin, 93% for high p21 and 85% for low RUNX1T1, while corresponding specificities were 63%, 75%, and 96%. Tumors were correctly classified as being metastatic or not (predictive accuracy) by Palladin, p21, or RUNX1T1 expression in 76%, 76%, and 92% of cases, respectively. If abnormal expression of even one of 3 proteins is considered a positive test (parallel testing), then sensitivity of all 3 together for predicting liver metastases was 100%, specificity 48%, and predictive accuracy 68%. Conclusions: 1) High Palladin, high p21, or low RUNX1T1 expression have good sensitivity and specificity for predicting liver metastases in pancreatic endocrine tumors. 2) Parallel testing with all 3 markers achieved 100% sensitivity but at a cost of reduced specificity. 3) Differential expression of these biomarkers may predict aggressive tumor behavior that warrants more aggressive management. No significant financial relationships to disclose.
Interferon-γ facilitates hepatic antiviral T cell retention for the maintenance of liver-induced systemic tolerance
Authors: Zhutian Zeng, Lu Li, Yongyan Chen, Haiming Wei, Rui Sun, Zhigang Tian
Journal: The Journal of Experimental Medicine (2016)

Persistent exposure to liver pathogens leads to systemic antigen-specific tolerance, a major cause of chronicity during hepatotropic infection. The mechanism regarding how this systemic tolerance is maintained remains poorly elucidated. In a well established mouse model of hepatitis B virus (HBV) persistence–induced systemic tolerance, we observed that interferon-γ (IFN-γ) deficiency led to complete loss of tolerance, resulting in robust anti-HBV responses upon peripheral vaccination. The recovery of vaccine-induced anti-HBV responses was mainly caused by the retained antigen-specific CD4+ T cells rather than decreased functional inhibitory cells in the periphery. Mechanistically, HBV persistence induced sustained hepatic CD4+ T cell–derived IFN-γ production. IFN-γ was found to promote CXCL9 secretion from liver-resident macrophages. This T cell chemokine facilitated the retention of antiviral CD4+ T cells in the liver in a CXCR3-dependent manner. Hepatic sequestrated antiviral CD4+ T cells subsequently underwent local apoptotic elimination partially via cytotoxic T lymphocyte–associated protein 4 ligation. These findings reveal an unexpected tolerogenic role for IFN-γ during viral persistence in the liver, providing new mechanistic insights regarding the maintenance of systemic antigen-specific tolerance during HBV persistence.
Association between the Value-Based Purchasing pay for performance program and patient mortality in US hospitals: observational study
Authors: Jose F Figueroa, Yusuke Tsugawa, Jie Zheng, E John Orav, Ashish K Jha
Journal: BMJ (2016)

<b>Objective</b>&nbsp;To determine the impact of the Hospital Value-Based Purchasing (HVBP) program—the US pay for performance program introduced by Medicare to incentivize higher quality care—on 30 day mortality for three incentivized conditions: acute myocardial infarction, heart failure, and pneumonia. <b>Design</b>&nbsp;Observational study. <b>Setting</b>&nbsp;4267 acute care hospitals in the United States: 2919 participated in the HVBP program and 1348 were ineligible and used as controls (44 in general hospitals in Maryland and 1304 critical access hospitals across the United States). <b>Participants</b>&nbsp;2 430 618 patients admitted to US hospitals from 2008 through 2013. <b>Main outcome measures</b>&nbsp;30 day risk adjusted mortality for acute myocardial infarction, heart failure, and pneumonia using a patient level linear spline analysis to examine the association between the introduction of the HVBP program and 30 day mortality. Non-incentivized, medical conditions were the comparators. A secondary outcome measure was to determine whether the introduction of the HVBP program was particularly beneficial for a subgroup of hospital—poor performers at baseline—that may benefit the most. <b>Results</b>&nbsp;Mortality rates of incentivized conditions in hospitals participating in the HVBP program declined at −0.13% for each quarter during the preintervention period and −0.03% point difference for each quarter during the post-intervention period. For non-HVBP hospitals, mortality rates declined at −0.14% point difference for each quarter during the preintervention period and −0.01% point difference for each quarter during the post-intervention period. The difference in the mortality trends between the two groups was small and non-significant (difference in difference in trends −0.03% point difference for each quarter, 95% confidence interval −0.08% to 0.13% point difference, P=0.35). In no subgroups of hospitals was HVBP associated with better outcomes, including poor performers at baseline. <b>Conclusions</b>&nbsp;Evidence that HVBP has led to lower mortality rates is lacking. Nations considering similar pay for performance programs may want to consider alternative models to achieve improved patient outcomes.
Association Between Breast Cancer Recurrence and Immunosuppression in Rheumatoid Arthritis and Inflammatory Bowel Disease: A Cohort Study
Authors: Ronac Mamtani, Amy S. Clark, Frank I. Scott, Colleen M. Brensinger, Ben Boursi, Lang Chen, Fenglong Xie, Huifeng Yun, Mark T. Osterman, Jeffrey R. Curtis, James D. Lewis
Journal: Arthritis & Rheumatology (2016)

Objective Breast cancer recurrence may be promoted by immunosuppression due to decreased immune surveillance. The aim of this study was to examine the rates of breast cancer recurrence in patients with immune‐mediated disease and treated breast cancer who received therapy with methotrexate, thiopurines, or anti–tumor necrosis factor (anti‐TNF). Methods Three retrospective cohort studies within Medicare (2000–2012) included women with rheumatoid arthritis (RA) or inflammatory bowel disease (IBD) who underwent surgery for primary breast cancer. Recurrent or second primary breast cancers occurring more than 365 days after the initial surgery were identified. Separate Cox regression models were used to examine the risk of cancer recurrence in patients treated with methotrexate, thiopurines, or anti‐TNF agents after surgery, each compared with no use. Analyses were matched for type of breast surgery and receipt and type of adjuvant therapy. Results Across all medication groups, 107 women experienced breast cancer recurrence during 5,196 person‐years. The incidence rates were 20.3 and 19.6 per 1,000 person‐years in methotrexate users and nonusers, respectively, 32.3 and 17.6 in thiopurine users and nonusers, respectively, and 22.3 and 19.5 in anti‐TNF users and nonusers, respectively. There was no significantly increased risk of breast cancer recurrence with use of methotrexate (adjusted hazard ratio [HR] 1.07, 95% confidence interval [95% CI] 0.67–1.69), anti‐TNF therapy (HR 1.13, 95% CI 0.65–1.97), or thiopurines (HR 2.10, 95% CI 0.62–7.14). Conclusion The risk of breast cancer recurrence in patients who received methotrexate, thiopurine, or anti‐TNF therapy was not statistically significantly increased, although we cannot rule out a 2‐fold or greater increased risk in those treated with thiopurines. These data provide reassurance to clinicians choosing to start methotrexate or anti‐TNF therapy in RA or IBD patients with treated breast cancer.
Case 27-1986
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, G. William Dec, James F. Southern
Journal: New England Journal of Medicine (1986)

Presentation of CaseA 57-year-old woman was admitted to the hospital because of chest pain and dyspnea.She was well until eight months earlier, when progressive abdominal distention developed. Three months later she was first seen at this hospital, where examination showed a markedly distended abdomen, with a mass the size of a 40-week gestation, and ++ peripheral edema. X-ray films of the chest (Fig. 1) revealed elevation of both hemidiaphragms and small bilateral pleural effusions; numerous nodules, 1 to 1.5 cm, were observed diffusely throughout both lung fields; the heart was transversely oriented and was not grossly enlarged. An . . .
Mechanism of fat taste perception: Association with diet and obesity
Authors: Dongli Liu, Nicholas Archer, Konsta Duesing, Garry Hannan, Russell Keast
Journal: Progress in Lipid Research (2016)

Energy homeostasis plays a significant role in food consumption and body weight regulation with fat intake being an area of particular interest due to its palatability and high energy density. Increasing evidence from humans and animal studies indicate the existence of a taste modality responsive to fat via its breakdown product fatty acids. These studies implicate multiple candidate receptors and ion channels for fatty acid taste detection, indicating a complex peripheral physiology that is currently not well understood. Additionally, a limited number of studies suggest a reduced ability to detect fatty acids is associated with obesity and a diet high in fat reduces an individual's ability to detect fatty acids. To support this, genetic variants within candidate fatty acid receptors are also associated with obesity reduced ability to detect fatty acids. Understanding oral peripheral fatty acid transduction mechanisms and the association with fat consumption may provide the basis of novel approaches to control development of obesity.
Constitutive androstane receptor (Car)-driven regeneration protects liver from failure following tissue loss
Authors: Christoph Tschuor, Ekaterina Kachaylo, Përparim Limani, Dimitri A. Raptis, Michael Linecker, Yinghua Tian, Uli Herrmann, Kamile Grabliauskaite, Achim Weber, Amedeo Columbano, Rolf Graf, Bostjan Humar, Pierre-Alain Clavien
Journal: Journal of Hepatology (2016)
Doctors should continue to choose NHS care
Authors: L. Morrison
Journal: BMJ (1995)

Prescription of antibitics by general practitioners to patients with sore throat according to result of antigen detection test and cultureforgroup A streptococci Antibiotics prescribed Results on culturet Result of after test result No of patients Antibiotics prescribed before test* antigen detection test known (% of total) Positive Negative Yes Positive Yes 203 (15) 183 20 Yes Negative Yes 83 (6) 4 79 Yes Negative No 81(6)
Healthy approaches to rare conditions
Authors: Polly Moyer
Journal: BMJ (2016)

Healthy approaches to rare conditionsWhat do you do if your patient has a condition you've never come across before?Polly Moyer offers encouragement for doctors feeling overwhelmed Polly MoyerAbout one in 17 people will develop a rare condition at some point in their lives, 1 so you're going to encounter them in your clinics.Because most rare conditions are currently incurable, some general practitioners may feel defeated by them.There's no need to be.But it is worth being aware of some potential pitfalls and how to avoid them.
Virologic Studies in a Case of Transfusion-Associated AIDS
Authors: D J Salberg
Journal: New England Journal of Medicine (1985)

The authors evaluated the risk of transmission of human T-lymphotropic virus type III (HTLV-III) infection from hemophiliacs to household members.  The sample included 26 Danish hemophiliacs 9 female spouses or sexual partners 15 fathers 17 mothers 12 siblings and 11 children.  None of the 29 household members associated with the 12 seronegative subjects were seropositive.  However 1 of 35 household members associated with 14 seropositive hemophiliacs was positive.  She had had oral vaginal and anal sex with her partner approximately 3 times/month in the preceding year.  She had used oral contraceptives but no barrier method.  The seropositive subject did not belong to any risk groups for acquired immunodeficiency syndrome (AIDS).  Her partner had a history of cutaneous fungal infections and extensive lymphadenopathy.  Western blot serum analysis showed identical profiles for both including p15 p24 p41-p45 and p61-64.  Only 1 other couple studied had practiced anal intercourse and both members were seronegative.  This study suggests that heterosexual transmission of HTLV-III infection can occur between hemophiliacs and their sex partners and infectivity may be facilitated by anal intercourse.  On the other hand the risk for household members without sexual contact appears to be small.
Deletion of ADP Ribosylation Factor-Like GTPase 13B Leads to Kidney Cysts
Authors: Yuanyuan Li, Xin Tian, Ming Ma, Stephanie Jerman, Shanshan Kong, Stefan Somlo, Zhaoxia Sun
Journal: Journal of the American Society of Nephrology (2016)

The gene for ADP ribosylation factor–like GTPase 13B ( Arl13b ) encodes a small GTPase essential for cilia biogenesis in multiple model organisms. Inactivation of arl13b in zebrafish leads to a number of phenotypes indicative of defective cilia, including cystic kidneys. In mouse, null mutation in Arl13b results in severe patterning defects in the neural tube and defective Hedgehog signaling. Human mutations of ARL13B lead to Joubert syndrome, a ciliopathy. However, patients with mutated ARL13B do not develop kidney cysts. To investigate whether Arl13b has a role in ciliogenesis in mammalian kidney and whether loss of function of Arl13b leads to cystic kidneys in mammals, we generated a mouse model with kidney–specific conditional knockout of Arl13b . Deletion of Arl13b in the distal nephron at the perinatal stage led to a cilia biogenesis defect and rapid kidney cyst formation. Additionally, we detected misregulation of multiple pathways in the cystic kidneys of this model. Moreover, valproic acid, a histone deacetylase inhibitor that we previously showed slows cyst progression in a mouse cystic kidney model with neonatal inactivation of Pkd1 , inhibited the early rise of Wnt7a expression, ameliorated fibrosis, slowed cyst progression, and improved kidney function in the Arl13b mutant mouse. Finally, in rescue experiments in zebrafish, all ARL13B allele combinations identified in patients with Joubert syndrome provided residual Arl13b function, supporting the idea that the lack of cystic kidney phenotype in human patients with ARL13B mutations is explained by the hypomorphic nature of the mutations.
NIMG-28TREATMENT RESPONSE EVALUATION USING FET PET COMPARED TO STANDARD MRI IN GLIOBLASTOMA PATIENTS AT FIRST RECURRENCE TREATED WITH BEVACIZUMAB PLUS LOMUSTINE
Authors: Norbert Galldiks, Veronika Dunkl, Gabriele Stoffels, Christian Filss, Caroline Tscherpel, Garry Ceccon, Ian Law, Matthias Schmidt, Gereon Fink, Nadim Shah, Karl-Josef Langen
Journal: Neuro-Oncology (2015)

BACKGROUND: We compared prospectively MRI response assessment based on RANO criteria with metabolic O-(2-18F-fluoroethyl)-L-tyrosine (FET) PET response evaluation during bevacizumab plus lomustine (BEV/LOM) treatment in glioblastoma patients at first recurrence. METHODS: Patients at first recurrence of a primary glioblastoma after radiotherapy with concomitant and adjuvant temozolomide chemotherapy were treated accordingly to the BELOB trial with LOM 90 mg/m2 every 6 weeks and BEV 10 mg/kg every 2 weeks. Dynamic FET PET and standard MRI scans were performed at baseline and after 8-10 weeks. FET PET metabolic tumor volumes (MTV), maximum and mean tumor/brain ratios (TBRmax/mean) as well as dynamic FET PET parameters were obtained. The predictive ability of FET PET parameters and standard MRI on treatment response assessment was evaluated with regard to PFS and OS after starting of treatment. Using receiver-operating characteristic curve analyses, threshold values for FET PET parameter changes were obtained. MRI changes consistent with “Stable Disease”, “Partial Response” and “Complete Response” were considered as treatment response. Subsequently, Kaplan-Meier survival analyses were performed to assess their predictive power for survival. RESULTS: Nineteen patients were included. Fifteen of 19 patients (age range, 34-75 years; MGMT promoter not methylated, 87%; IDH wild type, 100%) were eligible for data evaluation. Treatment response as assessed by standard MRI based on RANO criteria was not predictive for a significant longer PFS (P = 0.23) and OS (P = 0.07), respectively. In contrast, FET PET changes predicted a longer PFS (MTV decrease > 25%, P = 0.01; TBRmax decrease > 12%, P = 0.02) and OS (MTV decrease > 10%, P = 0.04), respectively. Interestingly, absolute MTV at the first follow-up scan provides the most significant prediction for increased PFS (P = 0.006) as well as OS (P = 0.003). However, both TBRmean and dynamic FET PET parameters were not predictive for treatment response. CONCLUSIONS: FET PET appears to be helpful to identify treatment responders to BEV/LOM early after initiation of treatment.
Human STEAP3 mutations with no phenotypic red cell changes
Authors: Dun Liu, Sheng Yi, Xinhua Zhang, Ping Fang, Chenguang Zheng, Li Lin, Ren Cai, Yuhua Ye, Yuqiu Zhou, Yunhao Liang, Feng Cheng, Xuelian Zhang, Wanjun Zhou, Narla Mohandas, Xiuli An, Xiangmin Xu
Journal: Blood (2015)