tbuckley/cabot-search huggingface dataset:
PTU-081 Use of the enhanced liverpool liver abdominal ratio (elaar) to predict outcome in patients assessed for transjugular intrahepatic porto-systemic shunt (tips)
Authors: M Swaminathan, L Smith, N Kibriya, P Kumar, T Cross
Journal: Gut (2017)

Introduction  TIPS is an effective treatment for patients with refractory variceal bleeding and diuretic resistant ascites. Patient selection is a vital component to the success of TIPs. Liver volume may be a determinant in TIPs outcome, as it may indicate liver reserve. A previous study using the liver to abdominal area ratio (LAAR), has been shown and validated to be effective at determining prognosis in patients with end stage liver disease. The utility of this tool in the setting of TIPs has not been previously evaluated.  Aims  To assess the use of (eLAAR) in determining outcome following TIPS.  Method  Retrospective-prospective study of TIPs patients in Liverpool, UK (Aintree University Hospital, Royal Liverpool Hospital) January 2010 to September 2016. Only patients undergoing TIPS were included. Parameters collected included: gender, disease aetiology, albumin, bilirubin, platelets, prothrombin time, creatinine, sodium, and TIPs indication. Liver and abdominal areas were measured from cross-sectional imaging taken no more than three months prior to the procedure. Measurements will be taken by radiologists or clinicians trained in the measurement technique required. The primary outcome measure was death from date of TIPs.  Results  179 patients were identified, after exclusions 115 patients were in the final analysis. 86 (75%) were male. The indications for TIPs were: 108 variceal bleeding and 7 diuretic resistant ascites. The disease aetiology was ALD 77 (67%), NASH 14 (12.2%), hepatitis C 4 (3.5%), Autoimmune 2 (1.7%), mixed alcohol 12 (10.4%) and others 6 (5.2%). The median MELD score was 22.2 (IQR 20.8–24.4), and eLAAR score was 45.2 (IQR 38.1–50.55). Survival at 90 days, 1 and 2 years, and overrall post TIPs was 80.9%, 77.4%, 70.4% and 59% respectively. The median eLAAR between survivors and non survivors were 42.4 and 47.3. Bilirubin was significant in predicting death at 90 days, 1 year and 2 years (p=  Conclusion  Early death post TIPs was best predicted using MELD or bilirubin. Overall survival was best predicted with eLAAR and bilirubin. The higher eLAAR score than anticipated from previous studies may be a reflection of a higher proportion of alcoholic hepatitis patients. The use of eLAAR in severe liver disease warrants further study.  Disclosure of Interest  None Declared
A Novel Nonlinear Parameter Estimation Method of Soft Tissues
Authors: Qianqian Tong, Zhiyong Yuan, Mianlun Zheng, Xiangyun Liao, Weixu Zhu, Guian Zhang
Journal: Genomics Proteomics & Bioinformatics (2017)

Abstract The elastic parameters of soft tissues are important for medical diagnosis and virtual surgery simulation. In this study, we propose a novel nonlinear parameter estimation method for soft tissues. Firstly, an in-house data acquisition platform was used to obtain external forces and their corresponding deformation values. To provide highly precise data for estimating nonlinear parameters, the measured forces were corrected using the constructed weighted combination forecasting model based on a support vector machine (WCFM_SVM). Secondly, a tetrahedral finite element parameter estimation model was established to describe the physical characteristics of soft tissues, using the substitution parameters of Young’s modulus and Poisson’s ratio to avoid solving complicated nonlinear problems. To improve the robustness of our model and avoid poor local minima, the initial parameters solved by a linear finite element model were introduced into the parameter estimation model. Finally, a self-adapting Levenberg–Marquardt (LM) algorithm was presented, which is capable of adaptively adjusting iterative parameters to solve the established parameter estimation model. The maximum absolute error of our WCFM_SVM model was less than 0.03 Newton, resulting in more accurate forces in comparison with other correction models tested. The maximum absolute error between the calculated and measured nodal displacements was less than 1.5 mm, demonstrating that our nonlinear parameters are precise.
Imaging of Acquired Demyelinating Syndrome With 18F-FDG PET/CT
Authors: Caroline Malo-Pion, Raymond Lambert, Jean-Claude Décarie, Sophie Turpin
Journal: Clinical Nuclear Medicine (2017)

Abstract Acquired demyelinating syndromes include acute disseminated encephalomyelitis, transverse myelitis and may progress to multiple sclerosis (MS). Acute disseminated encephalomyelitis is characterized by impairment of level of consciousness and multifocal neurological deficits and transverse myelitis by back pain, weakness and sphincter dysfunction. Only a few cases of acquired demyelinating syndrome have been imaged with 18 F-FDG PET/CT. We present two such cases.
Abstract IA27: Current perspectives on the treatment of nasopharyngeal carcinoma (NPC)
Authors: Anthony T. C. Chan
Journal: Clinical Cancer Research (2017)

Abstract 70% of NPC patients present with UICC stages III and IV locoregionally advanced (LA) disease. A recently completed population screening study using plasma EBV DNA may change this picture. For LA NPC, despite a high locoregional control rate after concurrent cisplatin-IMRT, the rate of distant metastases remains around 30%. Recent phase III studies adding induction chemotherapy have reported conflicting results, while studies adding adjuvant chemotherapy in unselected population have been negative. HKNPC 0502 and NRG HN001 are studies attempting to risk-stratify adjuvant therapy using post-RT plasma EBV DNA levels. With the publication of exome and whole genome sequencing of NPC, precision targeted therapies and immunotherapies are being investigated. Early results using immune checkpoint inhibitors in patients with recurrent and metastatic disease are encouraging. Citation Format: Anthony T. C. Chan. Current perspectives on the treatment of nasopharyngeal carcinoma (NPC) [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr IA27.
Clinical next generation sequencing in lung cancer: Beyond personalized medicine.
Authors: Jane Jiang, Cheryl Eifert, Stephen Lyle, Alexei Protopopov, Ruobai Sun, Angeliki Pantazi, Joerg Heyer, Meaghan Russell
Journal: Journal of Clinical Oncology (2016)

e23128 Background: NSCLC adenocarcinoma is the most common subtype of NSCLC lung cancer occurring in 40% of these patients. Recently approved targeted treatment options show prolonged survival. Key drivers of NSCLC adenocarcinoma are well described, and several targeted therapies are either FDA approved or under clinical evaluation for patients with advanced cancers. Thus there is an increasing need to better molecularly characterize the tumor of each patient to apply appropriate therapy. Personalized medicine has become a reality with the availability of rapid and actionable clinical NGS-based genomic profiling, which is now strongly endorsed by the NCCN through its issued guidelines. Methods: 125 NSCLC adenocarcinoma patient tumors were analyzed by the CancerPlex test that includes targeted, full-gene sequencing of over 400 cancer genes for detection of SNVs, indels, structural abnormalities, also MSI markers, and an estimation of mutation load (performed at CLIA and CAP-certified KEW Group Inc. laboratory, Cambridge, MA). All sequencing has been done using clinical FFPE samples, with 500x depth, and at mean TAT of 8.1 days from sample receiving to reporting matching therapies. Results: As expected, the CancerPlex test has identified mutations in EGFR that predict response to FDA approved anti-EGFR therapies. Among 28% of patients, we found a number of KRAS mutations which are negative predictors of response to the EGFR TKIs, Erlotinib and Gefitinib. We found that the majority of patients have alterations in STK11 that is impacting the mTOR signaling. Predictably, several ALK-EML4 translocations have been detected. The EML4-ALK gene fusion is a strong, independent driver of NSCLC and as such these tumors are highly sensitive to ALK targeted inhibitors Crizotinib and Ceritinib. We also found a significant number of mutations in DNA repair enzymes that may sensitize these tumors to PARP inhibition. Lastly, there are 8.2% cases with high mutation burdens, which predicts likely positive response to immune-checkpoint inhibition therapies. Conclusions: Tumor specific sequencing analysis using the CancerPlex panel leads to appropriate and successful targeted treatment of lung cancers as supported by the literature.
World Wide Fingers will advance dementia prevention
Authors: Miia Kivipelto, Francesca Mangialasche, Tiia Ngandu, Eg, Jorge José Eg, Nuñez Martín, Miia Kivipelto, Tiia Ngandu, Hilkka Soininen, Jaakko Tuomilehto, Jaana Lindström, Alina Solomon, Fransesca Mangialasche, Shireen Sindi, Laura Baker, Rachel Whitmer, Mark Espeland, Yifeng Du, Yongxiang Wang, Chengxuan Qiu, Christopher Chen, Lefkos Middleton, Tobias Hartmann
Journal: The Lancet Neurology (2017)
Abstract 14311: Congestive Heart Failure Upregulates Volume-Dependent Chloride Currents in c-Kit+ Endogenous Cardiac Stem Cells
Authors: Patrick Vigneault, Patrice Naud, Darryl R Davis, Stanley Nattel
Journal: Circulation (2016)

Introduction: Adult hearts contain c-Kit+ endogenous cardiac stem cells (eCSCs) that are being studied for regenerative therapy. eCSCs express volume-dependent Cl- channels (ICl,vol) activated unde...
A double blind, randomised placebo controlled trial evaluating the effect of a pholyphenolic rich plant based nail bed balm on the severity of chemotherapy-induced onycholysis.
Authors: Robert J. Thomas, Madeleine M A Williams, Masoom Mutilib, Saul Berkovitz, Fawzi Attia, Michael Cauchi, Sarah Smith
Journal: Journal of Clinical Oncology (2017)

10103 Background: Nail damage is common amongst patients receiving chemotherapy, especially taxanes, causing pain, distress, disfigurement, infection and restricted daily activities. Cooling the nail beds helps but there has been no published evidence for the effectiveness of nail balms, despite their popular use. We investigated whether a topical nail bed balm containing bioactive polyphenolic rich African salvia officinalis, gaultheria procumbens in a natural base of olea europaea, butyrospermun parkii, cera alba and theobroma cacao protected the nail beds via their reported anti-inflammatory, analgesic, anti-oxidant and anti-microbial properties. Methods: 60 patients (23 male, 37 female) were randomized to apply to their nail bed (tds) the natural balm or a petroleum balm suitably scented for a placebo control. Demographics, type and number of chemotherapy cycles did not differ between the two groups, recruited between Sept 2016-Sept 2017. At baseline and at the end of chemotherapy both patients and physicians measured outcomes of nail health. Patients completed a Dermatology Life Quality questionnaire and a linear severity scale; physician completed a Nail Psoriasis Index (NPSI) and a linear severity scale based on clinical examination and photographs. Differences were analyzed using an unpaired t-test; significance level α = 0.05 at 95% confidence intervals (CI); probability (p). Results: The mean change in nail health outcomes over the course of chemotherapy were: (see table). Conclusions: The polyphenolics rich essential oils and plant-based waxes in this nail bed balm profoundly reduced chemotherapy related nail damage and improved nail related quality of life compared to a plain petroleum based balm. A future evaluation combining nail bed cooling and this natural balm is planned. Clinical trial information: 015-001866-24. [Table: see text]
Sixty seconds on . . . flu vaccine for health staff
Authors: Nigel Hawkes
Journal: BMJ (2017)

Not at all. Scarcely half of those in the NHS get an annual flu vaccination, despite repeated urging.

They don’t think they’re at risk; they’re afraid it will make them unwell; they think flu is a minor illness and, frankly, getting vaccinated is a bit too much trouble. Those are the commonest excuses. …
Chemokine receptor 2 (CCR2) antagonism with a small molecule enhances the effectiveness of checkpoint inhibition by altering the tumor microenvironment in mouse colorectal tumours: Reducing tumor size and increasing long term survival
Authors: J. Campbell, C. Janson, L. Ertl, C. Li, Z. Miao, V. Chhina, M. Vilalta, A. Kumamoto, T. Dang, S. Liu, S. Yao, P. Zhang, T.J. Schall, R. Singh
Journal: Annals of Oncology (2017)
Physical activity investments that work—Get Scotland walking: a National Walking Strategy for Scotland
Authors: Aileen Campbell, Catherine Calderwood, Graeme Hunter, Andrew Murray
Journal: British Journal of Sports Medicine (2017)

### Programme card

#### Country/coverage

#### Target population

#### What modes/types/domains of physical activity does the programme promote?

#### Which of the seven best investments does the programme address?

#### What sectors does it involve?

#### What is special about this programme?

#### Key contact

#### Programme website

The Scottish Government recognises that increasing physical activity is crucially important for the mental and physical health of our country. Big health gains come from getting inactive people more active, particularly in the outdoors. The argument is compelling, and our aim to get more people active, more often is clear.

The question we face in Scotland, and indeed worldwide, is ‘how do we achieve this’. We recognise no single intervention will work for all, and that cross-sectoral …
Acidosis and Deafness in Patients with Recessive Mutations in FOXI1
Authors: Sven Enerbäck, Daniel Nilsson, Noel Edwards, Mikael Heglind, Sumaya Alkanderi, Emma Ashton, Asma Deeb, Feras E.B. Kokash, Abdul R.A. Bakhsh, William van’t Hoff, Stephen B. Walsh, Felice D’Arco, Arezoo Daryadel, Soline Bourgeois, Carsten A. Wagner, Robert Kleta, Detlef Bockenhauer, John A. Sayer
Journal: Journal of the American Society of Nephrology (2017)

Maintenance of the composition of inner ear fluid and regulation of electrolytes and acid-base homeostasis in the collecting duct system of the kidney require an overlapping set of membrane transport proteins regulated by the forkhead transcription factor FOXI1. In two unrelated consanguineous families, we identified three patients with novel homozygous missense mutations in FOXI1 (p.L146F and p.R213P) predicted to affect the highly conserved DNA binding domain. Patients presented with early-onset sensorineural deafness and distal renal tubular acidosis. In cultured cells, the mutations reduced the DNA binding affinity of FOXI1, which hence, failed to adequately activate genes crucial for normal inner ear function and acid-base regulation in the kidney. A substantial proportion of patients with a clinical diagnosis of inherited distal renal tubular acidosis has no identified causative mutations in currently known disease genes. Our data suggest that recessive mutations in FOXI1 can explain the disease in a subset of these patients.
A study of ovarian cancer patients tested with a 25-gene panel of hereditary cancer genes.
Authors: Lucy R. Langer, Heidi McCoy, Kelsey Moyes, Jennifer Saam, Brian Abbott, Larry J. Geier
Journal: Journal of Clinical Oncology (2014)

1511 Background: With advances in next-generation sequencing, patients receiving hereditary cancer testing can be tested for more genes, more efficiently. Patients with ovarian cancer are at risk for several different hereditary cancer syndromes—Hereditary Breast and Ovarian Cancer (HBOC) and Lynch syndrome (LS) in particular. Methods: We queried a laboratory database for patients affected with ovarian cancer and tested with a 25-gene panel of hereditary cancer genes from September 4, 2013 through December 27, 2013. All patient data regarding clinical history was obtained by health care provider report on test requisition forms. Results: We identified 263 patients with a personal history of ovarian cancer who received genetic testing using a 25-gene hereditary cancer panel. Of these patients, 77.2% met NCCN guidelines for HBOC, 0.8% met for NCCN guidelines for LS and 22.1% met guidelines for both syndromes. Deleterious or suspected deleterious mutations were identified in at least one gene in 16.3% of ovarian cancer patients. These included mutations in BRCA1 or BRCA2 (11%) and ATM (3.4%). Positive mutations were also identified in APC (3 patients), BRIP1 (2 patients), and 1 patient each in RAD51C, MSH6, CHEK2, and NBN. We detected 137 variants of uncertain significance (VUS) in 263 patients with a range of 0 to 4 VUS identified per patient. No VUS were detected in the majority (61.6%) of patients. Conclusions: Testing patients using a 25-gene hereditary cancer panel increased the number of positive test results in ovarian cancer patients by 48% over BRCA1 and BRCA2 testing alone, showing the benefit of using a panel approach in this population.
Disorders of Immunoglobulin Metabolism
Authors: Thomas A. Waldmann
Journal: New England Journal of Medicine (1969)

SINCE the discovery of agammaglobulinemia in 1952 by Bruton, more than a score of diseases due to deficiencies of the immunologic system have been described. Clinical studies of patients with these disorders in conjunction with basic investigations in the laboratory have led to major insights into the sequence of biologic and chemical events involved in the immune response as well as the nature and metabolism of immunoglobulins. Two major forms of specific immune response have been considered: the delayed, or cellular, immune response; and the immediate, or antibody, response. The physiology of the cellular immune response and the genetic disorders . . .
Pathogen-Reduced Platelets for the Prevention of Bleeding in People of Any Age
Authors: Lise J. Estcourt, Reem Malouf, Michael F. Murphy
Journal: JAMA Oncology (2018)

Are pathogen-reduced platelets as effective as standard platelets for the prevention of bleeding in people of any age requiring platelet transfusions?In people with cancer who have a low platelet count due to their disease or its treatment, pathogen-reduced platelet transfusions increase risk of platelet refractoriness and platelet transfusion requirement (high-quality evidence) but probably do not effect all-cause mortality, risk of clinically significant or severe bleeding, or risk of a serious adverse event (moderate-quality evidence). There was insufficient evidence for people with other diagnoses.
Atherosclerosis is exacerbated by chitinase-3-like-1 in amyloid precursor protein transgenic mice
Authors: Yu Yeon Jung, Ki Cheon Kim, Mi Hee Park, Youngsik Seo, Heonyong Park, Min Hee Park, Jun Chang, Dae Youn Hwang, Sang Bae Han, Sanghyeon Kim, Dong Ju Son, Jin Tae Hong
Journal: Theranostics (2017)

Although the important role of amyloid precursor protein (APP) in vascular diseases associated with Alzheimer's disease (AD) has been demonstrated, the underlying molecular mechanisms and physiological consequences are unclear.We aimed to evaluate vascular inflammation and atherosclerosis in Swedish mutant of human APP transgenic (APPsw-Tg) and ApoE -/-/APPsw-Tg mice.We also aimed to explore the mechanisms underlying any changes observed in these mice compared with non-Tg controls.Methods: The transgenic and non-Tg mouse strains were subjected to partial ligation of the left carotid artery to induce atherosclerotic changes, which were measured using histological approaches, immunohistochemistry, quantitative polymerase chain reaction, and gene expression microarrays.Results: Our results showed increased vascular inflammation, arterial wall thickness, and atherosclerosis in APPsw-Tg and ApoE -/-/APPsw-Tg mice.We further found that the expression of chitinase-3-like-1 (Chi3l1) is increased in the APPsw-Tg mouse artery and Chi3l1 mediates endothelial cell (EC) inflammation and vascular smooth muscle cell (VSMC) activation, which in turn exacerbates atherosclerosis.In addition, using two publicly available microarray datasets from the dorsolateral prefrontal cortex of people with AD and unaffected controls as well as inflamed human umbilical vein endothelial cells, we found that Chi3l1 and associated inflammatory gene were significantly associated with AD, evaluated by co-expression network analysis and functional annotation.Knockdown of Chi3l1 in the arterial endothelium in vivo suppressed the development of atherosclerosis.We also show that microRNA 342-3p (miR-342-3p) inhibits EC inflammation and VSMC activation through directly targeting Chi3l1, and that APPsw increased Chi3l1 expression by reducing miR-342-3p expression in the arterial endothelium, promoting atherosclerosis.Conclusion: Our findings suggest that targeting Chi3l1 might provide new diagnostic and therapeutic strategies for vascular diseases in patients with AD.
The Reality of Long-term Follow-up of Bariatric/Metabolic Surgery Patients—A Conundrum
Authors: Kelvin D. Higa, Jacques Himpens
Journal: JAMA Surgery (2017)

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Prognostic value of cytokines in acute panvcreatitis
Authors: Davor Stimac, Elizabeta Fisic, Relja Peric
Journal: Gut (2002)

Several studies tried to define the proinflamatory and anti-inflamatory cytokine response in acute pancreatitis. In our prospective studywe focused on the role of IL-6, IL-8, and IL-10 in the prognosis of acute pancreatitis. One hundred and seventeen consecutive patients(65 males and 52 females) with diagnosis of acute pancreatitis were eligible for participation in the study. Conclusions: Pts with severe acute pancreatitis had elevated values of IL-6, IL-8 and IL-10. Because of its sensitivity, elevated IL-6 should be considered in the prediction of acute pancreatitis complications.