tbuckley/cabot-search huggingface dataset:
MR lymphography of hepatic lymphatic system
Authors: Lionel Arrivé, Sanaâ El Mouhadi
Journal: Hepatology (2017)

Potential conflict of interest: Nothing to report. TO THE EDITOR: We read with great interest the article by Iwakiri in the September 2016 issue of Hepatology emphasizing the role of the lymphatic system in liver physiology.1 He indicated that the liver is the largest lymph‐producing organ of the body and that production of lymph markedly increases in cirrhosis with portal hypertension with likely implication of the lymphatic system in ascites formation.2 He also indicated that the study of the lymphatic vascular system is overlooked partly because of lack of established techniques for studying the lymphatic vasculature.1 We support the information provided by Iwakiri; however, we believe that the lymphatic vascular system may be analyzed by means of modern magnetic resonance (MR) techniques. Noncontrast heavily T2‐weighted three‐dimensional MR imaging, which was introduced in the early 1990s, is a completely noninvasive imaging technique that can accurately depict the morphological characteristics of the biliary and pancreatic ducts. Such sequences using very heavily T2‐weighted sequences may also be used to obtain a morphological evaluation of the lymphatic vascular system because of the high signal intensity of static or slow‐moving, fluid‐filled structures such as the lymphatic vessels, resulting in unique lymphatic vessel‐to‐background contrast.3 Given that MR cholangiopancreatography is very commonly performed in various liver diseases, we frequently observe dilated hepatic lymphatic vessels in patients with portal hypertension. Dilatation may affect both deep (Fig. 1A) and superficial (Fig. 1B) lymphatic systems, which are extensively interconnected. Iko et al. already demonstrated that cisterna chyli and thoracic duct were dilated in portal hypertension.4 We also commonly observe dilatation on hepatic lymphatic vessels in patients with long‐standing severe biliary stenosis, such as patients with severe primary sclerosing cholangitis (Fig. 1C). Dumont et al. demonstrated that after bile duct obstruction, bile was entirely regurgitated through the lymphatic vessels.5 They also demonstrated that bilirubin level was increased within thoracic duct in patients with obstructive jaundice.5 Therefore, we believe that with current improvement of MR techniques, noncontrast MR imaging may be useful to obtain an accurate anatomical evaluation of lymphatic vessels of the liver.Figure 1: Dilatation of hepatic lymphatic vessels demonstrated with noncontrast MR lymphography. (A) Dilatation of deep lymphatic vessels (arrows) in a patient with portal hypertension. Biliary ducts (arrowheads). (B) Dilatation of superficial lymphatic vessels (arrows) in a patient with portal hypertension. (C) Dilatation of deep lymphatic vessels (arrows) in a patient with severe primary sclerosing cholangitis. Dilated left biliary ducts (arrowheads).
Erratum: Hypermethylation of ASC/TMS1 is a sputum marker for late-stage lung cancer (Cancer Research (June 15, 2006) 66 (6210-6218))
Authors: E. O. Machida, M. V. Brock, C. M. Hooker, J. Nakayama, A. Ishida, J. Amano, Ma Picchi, S. A. Belinsky, J. G. Herman, S. Taniguchi, S. B. Baylin
Journal: Cancer Research (2007)
Genomic architecture and treatment outcome in pediatric acute myeloid leukemia: a Children’s Oncology Group report
Authors: Marijana Vujkovic, Edward F. Attiyeh, Rhonda E. Ries, Elizabeth K. Goodman, Yang Ding, Marko Kavcic, Todd A. Alonzo, Yi-Cheng Wang, Robert B. Gerbing, Lillian Sung, Betsy Hirsch, Susana Raimondi, Alan S. Gamis, Soheil Meshinchi, Richard Aplenc
Journal: Blood (2017)
Induction of apoptosis through down-regulation of AKT and activation of caspase-3 in human breast cancer MDA-MB-231 cells by aqueous extract of Codyceps militaris
Authors: jinwoo jeung, Cheng-Yun Jin, Mun-Ok Kim, Gi-Young Kim, Won Ho Lee, Yung Hyun Choi, Jae-Dong Lee
Journal: Clinical Cancer Research (2007)

A9  Cordyceps militaris is well known as a traditional herbal ingredient, which has been used for patients suffering from cancer in oriental medicine. In this study we have investigated the biochemical mechanisms of anti-proliferative effects by aqueous extract of C. militaris (AECM) in human breast cancer MDA-MB-231 cells. It was found that CME treatment induced chromatin condensation, mitochondrial energization, annexin V staining and sub-G1 phase DNA content. These indicators of apoptosis correlate with the mitochondrial dependent pathway, which results in the activation of caspase-3 activity. Both the cytotoxic effect by AECM treatment were significantly inhibited by z-DEVD-fmk, a caspase-3 inhibitor, demonstrating the important role of caspase-3 in the observed cytotoxic effect. Co-treatment of AECM and LY294002, resulted in significantly induction of apoptosis. These results indicate that caspase-3 is a key regulator of apoptosis in response to AECM in human breast cancer MDA-MB-231 through downregulation of Akt, and that the aqueous extract of C. militaris may therefore have therapeutic potential against human breast cancer.
Vascular adhesion protein-1 is elevated in primary sclerosing cholangitis, is predictive of clinical outcome and facilitates recruitment of gut-tropic lymphocytes to liver in a substrate-dependent manner
Authors: Palak J Trivedi, Joseph Tickle, Mette Nåmdal Vesterhus, Peter J Eddowes, Tony Bruns, Jani Vainio, Richard Parker, David Smith, Evaggelia Liaskou, Liv Wenche Thorbjørnsen, Gideon M Hirschfield, Kaisa Auvinen, Stefan G Hubscher, Marko Salmi, David H Adams, Chris J Weston
Journal: Gut (2017)

Objective Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of IBD. This clinical association is linked pathologically to the recruitment of mucosal T cells to the liver, via vascular adhesion protein (VAP)-1-dependent enzyme activity. Our aim was to examine the expression, function and enzymatic activation of the ectoenzyme VAP-1 in patients with PSC. Design We examined VAP-1 expression in patients with PSC, correlated levels with clinical characteristics and determined the functional consequences of enzyme activation by specific enzyme substrates on hepatic endothelium. Results The intrahepatic enzyme activity of VAP-1 was elevated in PSC versus immune-mediated disease controls and non-diseased liver (p&lt;0.001). The adhesion of gut-tropic α4β7 + lymphocytes to hepatic endothelial cells in vitro under flow was attenuated by 50% following administration of the VAP-1 inhibitor semicarbazide (p&lt;0.01). Of a number of natural VAP-1 substrates tested, cysteamine—which can be secreted by inflamed colonic epithelium and gut bacteria—was the most efficient (yielded the highest enzymatic rate) and efficacious in its ability to induce expression of functional mucosal addressin cell adhesion molecule-1 on hepatic endothelium. In a prospectively evaluated patient cohort with PSC, elevated serum soluble (s)VAP-1 levels predicted poorer transplant-free survival for patients, independently (HR: 3.85, p=0.003) and additively (HR: 2.02, p=0.012) of the presence of liver cirrhosis. Conclusions VAP-1 expression is increased in PSC, facilitates adhesion of gut-tropic lymphocytes to liver endothelium in a substrate-dependent manner, and elevated levels of its circulating form predict clinical outcome in patients.
Patients with chronic heart failure have “extreme” comorbidity, finds primary care study
Authors: Susan Mayor
Journal: BMJ (2017)

Patients with chronic heart failure often have “extreme” comorbidity and take multiple medicines, a UK primary care study has found.1

People with chronic disease often have multiple conditions, and comorbidity is common in heart failure, particularly among older patients. But previous studies of comorbidity in heart failure have analysed hospital records, so evidence from primary care, where patients with heart failure receive most of …
Effect of Deprenyl on the Progression of Disability in Early Parkinson's Disease
Journal: New England Journal of Medicine (1989)

In a clinical trial that is still in progress, we studied the ability of deprenyl and tocopherol, antioxidative agents that act through complementary mechanisms, to delay the onset of disability necessitating levodopa therapy (the primary end point) in patients with early, untreated Parkinson's disease. Eight hundred subjects were randomly assigned in a two-by-two factorial design to receive deprenyl, tocopherol, a combination of both drugs, or placebo, and were followed up to determine the frequency of development of the end point. The interim results of independent monitoring prompted a preliminary comparison of the 401 subjects assigned to tocopherol or placebo with the 399 subjects assigned to deprenyl, alone or with tocopherol. Only 97 subjects who received deprenyl reached the end point during an average 12 months of follow-up, as compared with 176 subjects who did not receive deprenyl (P<10-8). The risk of reaching the end point was reduced by 57 percent for the subjects who received deprenyl (Cox hazard ratio, 0.43; 95 percent confidence limits, 0.33 and 0.55; P<10-10). The subjects who received deprenyl also had a significant reduction in their risk of having to give up full-time employment (P = 0.01). We conclude from these preliminary results that the use of deprenyl (10 mg per day) delays the onset of disability associated with early, otherwise untreated cases of Parkinson's disease. (N Engl J Med 1989; 321: 1364–71.)
Vascular risk factors show link to development of Alzheimer’s
Authors: Jacqui Wise
Journal: BMJ (2017)

Middle aged people with a high number of vascular risk factors such as obesity, hypertension, diabetes, high cholesterol, and smoking are more likely to have elevated levels of brain amyloid in later life, a study published in JAMA has found. The researchers said their findings suggest that vascular disease has a role in the development of Alzheimer’s disease.1

The Atherosclerosis Risk in Communities (ARIC)-PET Amyloid Imaging Study included 322 adults …
From trial to practice: The Northern Ireland cancer center experience with abiraterone acetate in men with metastatic castration resistant prostate cancer.
Authors: Aya El-Helali, Prantik Das, Suneil Jain, Darren M. Mitchell, Lin Shum, David P. Stewart, Joe M. O'Sullivan
Journal: Journal of Clinical Oncology (2014)

e16101 Background: Treatment with Abiraterone acetate (AA) combined with prednisolone has proven benefit in overall survival compared with prednisolone alone in men with metastatic castration resistant prostate cancer (mCRPC) post Docetaxel. AA has been available in Northern Ireland since 2008. It is likely that previous exposure to other therapies such as corticosteroids may influence the ‘real world’ response rates to AA and hence we examined our own center’s early experience with the therapy. Methods: A retrospective electronic case note review was performed of all men with mCRPC who were commenced on Abiraterone Acetate, from December 2008 to January 2013. We documented patient demographics, PSA response, radiological response, overall survival, toxicities, as well as previous and subsequent prostate cancer therapies. Results: 48 patients were identified, with a median follow-up of 10months. The median age was 64 years. All patients received AA in the post docetaxel setting. Median duration of AA treatment was 6months (Range 19 (days)-24.8 Months). The median interval from completion of docetaxel to commencement of AA was 4.8months. After a median follow-up of 10 months, the median OS for our cohort was 10.1 months (95% CI 5.6 to 13.5). 63.26% of our cohort had received previous dexamethasone at a dose of 0.5-1.0 mg daily. We compared the median survival between patients who were corticosteroid naïve and those who had previous single agent corticosteroid therapy (13.5 versus 10 months, respectively. p-value=0.43). The PSA response rate (as defined by Prostate Cancer Working Group 2) was 26.6%. In patients with measurable disease, 55.9% had stable disease on CT. There were no unexpected toxicities identified in the cohort. Conclusions: Our retrospective review demonstrates favorable survival outcomes in a heavily pre-treated population of men with mCRPC treated with abiraterone acetate and prednisolone post docetaxel in Northern Ireland. Previous therapy with corticosteroid (as anti-tumor monotherapy treatment) may wellaffect the overall survival advantage of AA but further studies are required.
Abnormal levels of adipokines in adolescent offspring of women with type 1 diabetes – Results from the EPICOM study
Authors: Zuzana Lohse, Birgitte Bytoft, Sine Knorr, Tine D. Clausen, Rikke Beck Jensen, Henning Beck-Nielsen, Anne Pernille Hermann, Peter Oturai, Jan Frystyk, Peter Damm, Claus H. Gravholt, Kurt Højlund, Dorte M. Jensen
Journal: Metabolism (2017)
Image Gallery: Pemphigoid gestationis mimicking a gyrate erythema
Authors: C.H. Nam, S.P. Hong
Journal: British Journal of Dermatology (2017)

Funding sources: The present research was conducted by the research fund of Dankook University in 2015. Conflicts of interest: none declared. Dear Editor, A 31‐year‐old primigravida woman at 35 weeks' gestation presented with a 2‐month history of pruritic erythematous annular plaques on the trunk. The lesions began as intense pruritic erythematous urticarial plaques surrounding the umbilicus, which gradually spread to the abdomen (a). Skin examination revealed discrete, erythematous, polycyclic plaques with multiple tiny papulovesicles at the periphery (b). A biopsy specimen revealed epidermal spongiosis, with marked perivascular infiltration by lymphocytes, histiocytes and eosinophils in the superficial dermis (c, d). Direct immunofluorescence showed linear deposits of C3 along the basement membrane zone (e). Thus, the diagnosis of pemphigoid gestationis was made. The cutaneous lesions improved within 3 weeks after giving birth to a healthy baby.
Impact of sustained versus intermittent chemotherapy on rate of tumor repopulation in a xenograft model of human ovarian cancer
Authors: Vessela Vassileva, Micheline Piquette-Miller
Journal: Clinical Cancer Research (2007)

A3    Purpose:  Fractionated radiotherapy has been shown to cause increased rates of tumor repopulation, thereby limiting efficacy. As even longer intervals between cycles of chemotherapy exist, increasing rates of tumor repopulation likely negatively impact clinical outcomes. Thus sustained chemotherapy regimens may improve clinical response. We therefore investigated the impact of sustained versus intermittent administration of paclitaxel (PTX) on the  in vitro  and  in vivo  repopulation of ovarian tumor cells.  Methods:  The total number of proliferating and clonogenic cells was followed over 3 weeks  in vitro  in SKOV3 cells after equivalent exposure to intermittent and sustained levels of PTX.  In vivo , tumor repopulation rates were investigated in a murine intraperitoneal (IP) xenograft model of ovarian cancer throughout a 3 week treatment course. Tumor bearing mice (n=20/group) received PTX (60 mg/kg total dose) either as intermittent treatment (20 mg/kg weekly IP bolus doses) or sustained treatment (Alzet pumps implanted IP which provided sustained delivery of 20 mg/kg/week PTX). Treatment groups were also compared to non-treated controls (n=20). Tumour proliferation and apoptosis was evaluated at different intervals during the course of treatment using 5-bromo-2’-deoxyuridine (BrdU) uptake, TUNEL and Caspase3 immunoassays.  Results:   In vitro  results demonstrated a significant difference in the surviving fraction and number of colony forming SKOV3 cells between PTX treatment groups (ANOVA, p in vivo  tumour BrdU uptake was significantly different between the treatment groups (ANOVA, p Conclusions:  Intermittent administration of PTX resulted in an increase in both in vitro and in vivo tumor repopulation rates. On the other hand, sustained delivery decreased tumor survival and repopulation. By attenuating tumor repopulation, sustained administration of PTX may increase chemoresponsiveness and clinical response in ovarian cancer.
Observational study of treatment patterns among patients initiating first-line treatment for chronic lymphocytic leukemia in the U.S. community oncology setting.
Authors: Matthew J. Monberg, Arthur C. Houts, Mark S. Walker, Gaetano Bonifacio
Journal: Journal of Clinical Oncology (2014)

e18023 Background: For patients (pts) able to tolerate the combination, fludarabine, cyclophosphamide, and rituximab (FCR) is preferred in first-line chronic lymphocytic leukemia (CLL) (NCCN, 2014). However, other regimens are suggested for pts with advanced age and/or significant comorbidities. This study compared pts who received full-dose fludarabine (F, 25mg/m2) as part of their first-line treatment from those who did not in the US community oncology setting. Methods: This multicenter, retrospective study analyzed 404 pts who initiated CLL treatment between 1/1/2007 and 7/1/2013. Comparisons were made between demographic/clinical factors and treatment using t-tests or Fisher Exact Test, or a non-parametric equivalent. Results: F-containing regimens were used in 36% of the full cohort (147 of 404), and other common regimens contained/consisted of chlorambucil (21%, n=86), bendamustine (20%, n=79), or single-agent rituximab (17%, n=69). From 2007 to 2013, the percent receiving F declined from 41% to 20%. Among pts <70 yrs, 46% (112 of 242) received F. Conclusions: Advanced age and comorbidities, in particular cerebrovascular disease and myocardial infarction, were associated with reduced F use and greater use of other regimens. Full cohort N=404 Pts <70 yrs n=242 Received F n=147 Received Other Regimens n=257 P value Received F n=112 Received other regimens n=130 P value Median age, yrs 62.3 69.4 <.0001 - - - Male gender, % 67.3 56.6 0.03 72.7 64.4 0.21 Rai stage III or IV, % 13.6 10.1 0.41 14.5 8.3 0.26 Del 17p, % 10.1 5.6 0.41 9.0 3.9 0.49 Mean β2M, mg/L 3.3 4.5 0.74 3.3 3.3 0.15 Performance status ≥2, % 3.4 9.9 0.03 3.0 6.5 0.35 ≥2 Comorbidities, % 6.1 14.8 0.01 6.4 8.3 0.63 Comorbidities, % Cerebrovascular accident Chronic heart failure Diabetes Myocardial infarction Peripheral vascular disease - 0.0 2.2 24.7 1.1 0.0 - 10.6 3.1 26.9 8.8 2.5 - 0.0005 1.0 0.76 0.01 0.30 - 0.0 1.5 23.9 1.5 0.0 - 9.1 2.6 23.4 6.5 1.3 - 0.01 1.0 1.0 0.22 1.0 B symptoms, % Fever Sweats Night chills - 3.4 21.3 3.4 - 1.2 18.0 1.2 - 0.44 0.60 0.26 - 4.5 23.9 4.5 - 2.6 23.4 1.3 - 0.85 0.92 0.53
The Role of Spinal Manipulation in the Treatment of Low Back Pain
Authors: Richard A. Deyo
Journal: JAMA (2017)

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Novel Strategies to Reduce Femoropopliteal Restenosis
Authors: Andrew M. Goldsweig, Herbert D. Aronow
Journal: Circulation (2017)

Articles, see p 2218 and p 2227 

Peripheral artery disease affects >200 million individuals worldwide, and those with exertional leg discomfort, rest pain, and tissue or limb loss have significantly impaired functional status and quality of life. Despite their lower associated risk of repeat revascularization, open surgical procedures have been largely supplanted by endovascular intervention for symptomatic peripheral artery disease given the lower associated morbidity and mortality.1 Although standalone plain-old percutaneous transluminal angioplasty (PTA) was previously the standard endovascular strategy for these patients, high procedural failure and restenosis rates led to the development of new therapeutic technologies.2 Stent implantation improved procedural success,3 and a recent meta-analysis of randomized trials suggests that bare metal stenting (BMS) results in half as much restenosis as PTA. Nevertheless, restenosis after femoropopliteal BMS occurs in up to 37% of patients within 12 months,4 and observational data suggest that by 5 years, primary patency rates are roughly equivalent (41±4% for BMS versus 36±3% for PTA; P =0.31).5

Drug-coated balloons (DCBs) were developed as means to further reduce restenosis rates.6 Currently available DCBs carry the antiproliferative agent paclitaxel, which stabilizes microtubules, preventing mitotic spindle formation and ultimately resulting in reduced neointimal hyperplasia. Paclitaxel doses range from 2 to 3.5 μg/mm2 of balloon surface area, and carrier molecules (“excipients”) facilitate drug delivery to the vessel wall. LEVANT 2 (Lutonix Paclitaxel-Coated Balloon for the Prevention of Femoropopliteal Restenosis 2) demonstrated that in patients with intermittent claudication or rest pain due to femoropopliteal disease, a low-dose paclitaxel (2 μg/mm2) DCB with polysorbate/sorbitol excipient (Lutonix, Bard, Tempe, AZ) was superior to PTA for primary patency (65.2% versus 52.6%; P =0.02), equivalent to PTA for clinically driven target lesion revascularization (TLR; 12.3% versus16.8%; P =0.21), and noninferior to PTA on its primary safety end …
Sex Differences in Hospitalizations with Maintenance Hemodialysis
Authors: Scott V. Adams, Matthew Rivara, Elani Streja, Alfred K. Cheung, Onyebuchi A. Arah, Kamyar Kalantar-Zadeh, Rajnish Mehrotra
Journal: Journal of the American Society of Nephrology (2017)

Hospitalization is a major source of morbidity among patients with ESRD undergoing maintenance hemodialysis and is a significant contributor to health care costs. To identify subgroups at the highest risk of hospitalization, we analyzed by sex, age, and race, adjusting for demographic and clinical characteristics, the hospitalization rates, and 30-day readmissions for 333,756 hospitalizations among 111,653 patients undergoing maintenance hemodialysis in facilities operated by a large dialysis organization in the United States (2007–2011). The overall hospitalization rate was 1.85 hospitalizations per person-year and was much higher among women than among men (2.08 versus 1.68 hospitalizations per year for women versus men, P &lt;0.001). Age group–specific hospitalization rates were consistently higher for women than for men of the same race, and the differences were greatest in younger age groups (for example, women aged 18–34 years and ≥75 years had 54% [95% confidence interval, 42% to 67%] and 14% [95% confidence interval, 11% to 18%] higher hospitalization rates, respectively, than did men of respective ages). Women also had substantially higher risk for 30-day readmission, with the largest differences at younger ages. Women had a significantly lower serum albumin level than men, and stratification by serum albumin level attenuated sex differences in the age group–specific hospitalization and 30-day readmission rates. These findings suggest that women undergoing maintenance hemodialysis have substantially higher risks for hospitalization and 30-day readmission than men. In this cohort, the sex differences were greatest in the younger age groups and were attenuated by accounting for differences in health status reflected by serum albumin level.