tbuckley/cabot-search huggingface dataset:
P231 "Safety-net" for abnormal chest radiographs with a low index of suspicion for malignancy
Authors: C. Wall, P. Arora, P. M. Turkington, R. Chisholm, P. M. Turkington
Journal: Thorax (2011)

<h3>Introduction and Objectives</h3> Guidelines dictate that where a chest x-ray is incidentally suggestive of lung cancer, a copy of the radiologists report is sent to a designated member of the lung cancer multidisciplinary team. A similar system was implemented for abnormal chest radiographs demonstrating significant non-malignant changes or abnormalities with a low index of suspicion of malignancy. This was used to assess if abnormal chest radiographs are adequately followed-up by the requesting clinicians. <h3>Methods</h3> Reporting radiologists coded radiographs that warranted further action such as repeat imaging within a specified time frame. These were relayed to a designated coordinator. If action did not occur as suggested on the report, the requesting clinician was prompted on a weekly basis until the issue was resolved or else referred to a member of the chest team for further evaluation. At 6 months the cases were reviewed and information extracted including indication for further action, whether action occurred without coordinator intervention and outcome. <h3>Results</h3> All coded films over a 6-month period (n=331) were analysed. The most frequent indications for further action included the assessment of pneumonia resolution (n=167), further review of possible hilar pathology (n=25), small nodules (n=22) and other unexplained abnormalities. 143 cases (42.6%) required action by the coordinator. In total, 4% (n=13) of cases yielded significant diagnoses including eight malignancies, pulmonary embolism, cobalt induced fibrosis and asbestosis, of these one case required action by the coordinator. <h3>Conclusions</h3> This study suggests that a large proportion of abnormal chest radiographs are not followed-up as suggested by the reporting radiologist. Significant diagnoses may therefore be delayed unnecessarily. There is little reason to assume that similar practice is uncommon throughout the country. While the number of significant diagnoses detected by the “safety-net” system was perhaps lower than expected, some may consider a delay in 7.7% (1/13) unacceptably high. Further exploration of this area is needed to decide whether this is an effective use of resources.
Reduction of Serum Cholesterol with Sitostanol-Ester Margarine in a Mildly Hypercholesterolemic Population
Authors: Tatu A. Miettinen, Pekka Puska, Helena Gylling, Hannu Vanhanen, Erkki Vartiainen
Journal: New England Journal of Medicine (1995)

Dietary plant sterols, especially sitostanol, reduce serum cholesterol by inhibiting cholesterol absorption. Soluble sitostanol may be more effective than a less soluble preparation. We tested the tolerability and cholesterol-lowering effect of margarine containing sitostanol ester in a population with mild hypercholesterolemia.
PTU-145 A systematic review of the diagnostic yield of small-bowel capsule endoscopy in patients with iron deficiency anaemia
Authors: A Koulaouzidis, A Giannakou, E Rondonotti
Journal: Gut (2012)

<h3>Introduction</h3> Although current guidelines recommend Small-Bowel Capsule Endoscopy (SBCE) for the evaluation of patients with obscure gastrointestinal bleeding (OGIB), its role in investigating patients with iron deficiency anaemia (IDA) alone is still unclear. <h3>Aim</h3> To evaluate the diagnostic yield (DY) of SBCE in patients with IDA by means of a systematic review of studies reporting this data. <h3>Methods</h3> A recursive literature search (sources: Medline and Embase) of studies reporting DY of SBCE in patients with IDA was undertaken (November 2011). The search was restricted to fully reported papers in English, published between January 2001 and November 2011, including adult patients and clearly reporting DY for IDA patients. Studies were selected and evaluated separately by two of the authors. Data on DY were extracted, pooled, and analysed. Any discrepancy in papers selection or in data extraction was solved by consensus. The QUADAS tool was used to assess the study for methodological quality. Statistical analysis was performed with STATA version 12.0. <h3>Results</h3> A total of 27 (7 prospective, 20 retrospective; total of 1943 patients) studies was selected for final review and analysis. Five studies (including 316 patients) were specifically designed to evaluate only IDA patients; in the remaining 22 studies, the patients with IDA represented a subgroup of patients undergoing SBCE. Overall, the 27 studies were of poor to moderate quality. The overall pooled DY, estimated by applying the random effect model (I<sup>2</sup>: 77.7%), was 48.2% (95% CI 43.1 to 53.4%) while it was 53.4% (95% CI 34.7 to 72.0%) and 47.2 % (95% CI 42.1 to 52.2%) for studies focusing and not focusing on IDA patients, respectively. <h3>Conclusion</h3> Although the studies evaluating the DY of SBCE in IDA are of poor to moderate quality and heterogeneous, the estimated DY is about 50% and seems to be comparable with that observed in patients with OBIG. <h3>Competing interests</h3> None declared.
OPEN REPAIR OF PARAOESOPHAGEAL HERNIA–IS THERE STILL A ROLE?
Authors: N Burnside, P Mhandu, C d'Silva, J McGuigan, N McGonigle
Journal: Gut (2013)

<h3>Introduction</h3> Laparoscopy has become the standard repair in paraesophageal hernias as it is safe, with good symptomatic control. However several reports have demonstrated recurrence rates as high as 42%. This high recurrence rate has led us to question whether this procedure is more advantageous than the tradition open approach particularly in the elderly patient in whom reoperation at a later date may not be an option. <h3>Aims/Background</h3> The subgroup of multiple co-morbidity patients, present a specific problem, as many that might tolerate the laparoscopic approach would present significant risk when dealing with symptoms as a result of procedural failure. We questioned whether open gastropexy with or without antireflux procedure might be beneficial in these patients. <h3>Method</h3> This study looked at our recent experience with paraoesophageal hernia repair using a small upper midline laparotomy. Forty patients, 9 male and 31 female, underwent a reduction of hernia, crural repair, and either anterior gastropexy or antireflux procedure.We elected not to resect the peritoneal hernial sac. All patients were followed up for recurrence of their symptoms and hernia. <h3>Results</h3> Mean age of 63 years (27–82 years) 50%. All patients had significant co-morbidity and half of the patients (20/40) had a significantly limited exercise tolerance preoperatively, with one patient critically unwell and ventilated. Two patients developed a recurrence of their hernia (5%), one at day two post operatively and the other seven years post operatively following a road traffic collision. Operative mortality was 5% (2/40), the first patient was ventilator dependent in Intensive Care preoperatively and the procedure was performed to assist with ventilator weaning. The second patient died at home suddenly following discharge, post-mortem was non diagnostic. <h3>Conclusion</h3> Symptom control was excellent with only one patient (2.5%) developing recurrence of symptoms post operatively. The higher rate of recurrence demonstrated in laparoscopic surgery is not mirrored in open surgery. We believe these data demonstrate potentially superior results when performing open repair in higher risk patients.
714 LIVER STIFFNESS VALUES IN HEALTHY SUBJECTS WITHOUT EVIDENCE OF LIVER DISEASE PERFORMED IN A LARGE COMMUNITY-BASED POPULATION
Authors: F. Conti, A. Borghi, F.G. Foschi, M. Domenicali, P. Giacomoni, S. Savini, A.C. Dall'Aglio, G. Saini, M. Bernardi, G.F. Stefanini, P. Andreone
Journal: Journal of Hepatology (2013)
Abstract 3813: Recruitment of macrophages, NK cells, and dendritic cells with metronomic cyclophosphamide-induced regression of gliosarcoma xenografts
Authors: Joshua C. Doloff, David J. Waxman
Journal: Cancer Research (2010)

Abstract Metronomic chemotherapy displays improved therapeutic activity over conventional schedules for several malignancies in both preclinical and clinical studies. In particular, metronomic cyclophosphamide treatment (140 mg/kg BW every 6 days) induces dramatic, near-complete regression of established xenografts of human U251 and rat 9L gliosarcomas in s.c. scid mouse models, whereas maximum tolerated dose cyclophosphamide effects only moderate tumor growth delays. Furthermore, metronomic cyclophosphamide-induced regression of 9L tumors is accompanied by reduced microvessel density, induction of thrombospondin-1 (TSP1) and impaired drug uptake, all of which are consistent with the prevailing view that anti-angiogenesis is a major factor in the therapeutic effectiveness of metronomic chemotherapy. However, VEGF receptor inhibition induces substantially greater anti-angiogenesis in these tumor models but does not induce tumor regression. Therefore, we sought to investigate other non-anti-angiogenic mechanisms to explain the substantial regression and have found that it is strongly associated with recruitment of the host innate immune system. In regressing 9L and U251 tumors, host (mouse) PEDF (pigment epithelium-derived factor; Serpinf1) and PAI-1 (plasminogen activation inhibitor-1; Serpine1) expression is increased, with the levels of PEDF RNA being strongly correlated (r=0.89) with TSP1 RNA in large sets of 9L and U251 tumors isolated various times after initiation of metronomic cyclophosphamide therapy. Notably, PAI-1 and TSP1 are both expressed by tumor-associated macrophages. Metronomic cyclophosphamide also increased Fas, which stimulates macrophage activation, and the macrophage marker CD68, supporting the involvement of tumor-associated macrophages. Fas is also associated with cytotoxic lymphocytes, such as NK cells, and NK cell markers and cytotoxic effectors were dramatically increased in metronomic cyclophosphamide-treated tumors. Furthermore, dendritic cell markers important for cell-target interactions and antigen presentation were increased by metronomic cyclophosphamide treatment. Cytokines and chemokines were also up regulated in the metronomic cyclophosphamide-treated tumors, suggesting that chemokine and cytokine gradients help mobilize the host innate immune system in regressing 9L and U251 tumors. These findings highlight the ability of metronomic chemotherapy to induce macrophage, natural killer cell, and dendritic cell recruitment, thereby activating innate immunity leading to regression of established gliosarcomas and potentially other tumor types. Supported by NIH grant CA49248 (to DJW). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3813.
COMPARISON OF PSYCHOSOCIAL QUESTIONNAIRES BETWEEN SPONTANEOUS CORONARY ARTERY DISSECTION (SCAD) AND NON-SCAD POPULATIONS UNDERGOING CARDIAC REHABILITATION PROGRAM AFTER MYOCARDIAL INFARCTION
Authors: Jacqueline W.L. Saw, Andrew Starovoytov, Taira Birnie, Roshan Prakash, Milad Heydari-Kamjani, Saul Isserow, Carolyn Taylor, Sammy Chan, Andrew Ignaszewski
Journal: Journal of the American College of Cardiology (2016)
Infected hepatic hematoma 10 days after ERCP
Authors: Alexandre Oliveira Ferreira, Rui Tato Marinho, José Velosa
Journal: Endoscopy (2013)

An 84-year-old man with severe (GOLD-IV) chronic obstructive pulmonary disease (COPD) and a history of pulmonary thromboembolism and warfarin medication was admitted for elective endoscopic retrograde cholangiopancreatography (ERCP) for choledocholithiasis. He had stopped warfarin medication a week before (international normalized ratio [INR] 1.14), and was kept on low-molecular-weight heparin.
DNA repair protein biomarkers in triple negative breast cancer.
Authors: BM Alexander, K Sprott, X Wang, AD D'Andrea, SJ Schnitt, LC Collins, DT Weaver, JE Garber
Journal: Cancer Research (2009)

Abstract Abstract #1064 Introduction: Triple negative breast tumors form a distinct, aggressive, subgroup of breast cancers that exhibit a high degree of genomic instability and have many phenotypic similarities to BRCA1 deficient tumors. These observations suggest that aberrant DNA repair may be involved in triple negative tumor carcinogenesis. We profiled tumor DNA repair capacity using immunohistochemistry in order to develop prognostic biomarkers and suggest targets for novel therapies.&amp;#x2028; Methods: We identified 143 previously treated women with triple negative breast cancers and used their archived, formalin-fixed, paraffin-embedded primary excision biopsies to create a tissue microarray (TMA). The TMA was stained using antibodies against proteins in various DNA repair pathways including XPF, FANCD2, PAR, MLH1, and MK2. Stained tissue was evaluated using machine-based image analysis and scoring that represented both the intensity and quantity of positive tumor nuclei. Biomarker scores and clinical data were assessed for correlations with outcome. Patients were randomized into training and test cohorts for the development of a multiple marker model. A set of critical threshold marker values were determined that maximally separated the training samples into low and high risk recurrence groups. Training set thresholds and marker combinations were applied towards the test set. Kaplan-Meier and Cox proportional hazards were used to test time to recurrence.&amp;#x2028; Results: Clinical data for 115 patients with primary treatment data was available with a median follow up of 58 months. There were 37 recurrences: 18 were distant first, 12 were local first and 7 were simultaneous. Low XPF (p=0.002), pMK2 (p=0.02), MLH (p&amp;lt;0.001) and FANCD2 (p=0.05) were associated with shorter time to recurrence. In the training cohort, the high-risk group defined by a four marker model had a relative risk of recurrence of 3.0 (p&amp;lt;0.00001) and shorter median time to recurrence than the low risk group (13.1 months versus not reached). This was superior to single markers and to other markers such as P53 (p = 0.02) or Ki67 (p = 0.07). In the test set, the model produced similar results with a relative risk of 2.1 (p=0.029) for the high-risk group and shorter median time to recurrence (14.1 months versus not reached).&amp;#x2028; Conclusions: Triple negative breast cancers show variable expression of proteins involved in DNA repair. Levels of four DNA repair proteins correlated significantly with recurrence free survival, and were used to develop a DNA repair profile model in a training set which was prognostic in a test set. DNA repair biomarker panels may be useful as prognostic or predictive indicators as well as suggest possible targets for novel therapies such as PARP inhibition. Further study of the model in another validation set with other clinical variables is warranted. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1064.
Renin Sampling: Collection and Interpretation
Authors: E. Darracott Vaughan
Journal: New England Journal of Medicine (1974)

The report of Schambelan and his colleagues in this issue of the Journal demonstrates a refinement of differential renal-vein renin measurements useful in patients with segmental renal disease. In this study, renin concentrations were found to be higher in blood obtained selectively from venous segments draining underperfused areas than they were in the venous admixture collected from the main renal vein. These studies point to the increasing importance of renal-vein renin assays combined with an evaluation of the peripheral circulating renin level for identifying patients with potentially curable renovascular hypertension.Theoretically, hypersecretion of renin as a cause of the hypertension . . .
Preoperative Prediction of Reversible Myocardial Asynergy by Postexercise Radionuclide Ventriculography
Authors: Alan Rozanski, Daniel Berman, Richard Gray, George Diamond, Marjorie Raymond, JoAnn Prause, Jamshid Maddahi, H. J. C. Swan, Jack Matloff
Journal: New England Journal of Medicine (1982)

Myocardial asynergy is sometimes reversed by coronary bypass, and a noninvasive method of predicting which assess are reversible would be desirable. To assess whether changes in myocardial wall motion observed immediately after exercise can differentiate reversible from nonreversible myocardial asynergy, we evaluated 53 patients by radionuclide ventriculography before and after exercise and again at rest after coronary bypass surgery. Preoperative improvement in wall motion immediately after exercise was highly predictive of the surgical outcome (average chance-corrected agreement, 91 per cent). At surgery the asynergic segments that had improved after exercise were free of grossly apparent epicardial scarring. The accuracy of these predictions for postoperative improvement was significantly greater (P less than 0.01) than that of analysis of Q waves on resting electrocardiography (average chance-corrected agreement, 40 per cent). In contrast, preoperative changes in left ventricular ejection fraction after exercise were not predictive of postoperative resting ejection fraction. We conclude that postexercise radionuclide ventriculography can be used to identify reversible resting myocardial asynergy. This test should prove effective in predicting which patients with myocardial asynergy are most likely to benefit from aortocoronary revascularization.
House of care approach for patients with long term conditions works at the local level
Authors: S. Eaton, L. Oliver, S. Roberts
Journal: BMJ (2013)

As members of the Year of Care team that developed the “house of care” we welcome Watt’s editorial on the challenge of multimorbidity.1

Although he correctly states that the original Year of Care pilot programme focused on diabetes, this was simply a starting point. Subsequently, as intended, we have helped various health communities to extend the learning and experience to people with other …
Follicular Variant of Papillary Thyroid Carcinoma Presenting as a Toxic Nodule by I-123 Scintigraphy
Authors: Srinivas Bommireddipalli, Sumina Goel, Ramesh Gadiraju, Alberto Paniz-MondolFi, Ernest Gordon DePuey
Journal: Clinical Nuclear Medicine (2010)

The risk of malignancy in a "hot" thyroid nodule detected by radioiodine scintigraphy is rare. We report a case of a 63-year-old man with a hyperfunctioning nodule demonstrated by radioiodine scintigraphy and cytology suspicious for follicular variant of papillary thyroid carcinoma (FVPTC). There were no locoregional or distant metastases at initial diagnosis. Histopathologic examination following thyroidectomy confirmed the presence of an encapsulated FVPTC. A year into follow-up, his I-131 whole body scan performed following the withdrawal from exogenous thyroid hormone was negative, whereas his serum thyroglobulin (Tg) levels were intermediate. A subsequent PET/CT scan revealed a small, but stable, metabolically active pretracheal lymph node, which on biopsy was confirmed to be stage III FVPTC. In conclusion, the presence of hyperfunctioning thyroid nodule(s) does not preclude malignancy and, therefore, proper cytohistologic evaluation in such patients may help to exclude a coexistent thyroid carcinoma. Patients treated for localized PTC may benefit from serial PET/CT follow-up in the early detection and management of recurrence or distant metastases.
S62 Polyclonal free light chains: a potential biomarker for immune activation in alpha-1-antitrypsin deficiency (A1ATD) related chronic obstructive pulmonary disease: Abstract S62 Table 1.
Authors: JA Brebner, AM Turner, RA Stockley
Journal: Thorax (2013)

<h3>Introduction</h3> A1ATD is a hereditary condition associated with the premature onset of chronic obstructive pulmonary disease (COPD). In COPD, the immune response within the lung is known to involve cells of both the innate and adaptive immune systems. However, the antigenic stimulus to the adaptive immune response remains unknown. Bacterial colonisation of the lower airways is one potential factor. Alternatively this could reflect an autoimmune component. The production of antibodies by B-cells is a key element of the adaptive immune system. An excess of free light chains (FLCs) are produced as a by-product of antibody synthesis. The recent discovery of high polyclonal FLC levels in a number of autoimmune and inflammatory conditions has led to the assessment of their value as a biomarker of adaptive immune activation. Our aim was to investigate the use of serum FLCs as a marker of immune activation, phenotypic variation and disease severity in COPD related to A1ATD. <h3>Methods</h3> We measured FLC levels in 294 patients with A1ATD using the Freelite® serum FLC assay. We then compared combined (? &amp; ?) FLC levels (cFLC) in different subgroups defined by the presence of chronic bronchitis, CT findings, smoking status, subsequent mortality and colonisation status. In addition we determined any correlation with lung function parameters in a cross sectional analysis. <h3>Results</h3> Significantly higher cFLC levels were found to be associated with, subsequent mortality (p = 0.005), the presence of chronic bronchitis (p = 0.008) and chronic colonisation of the lower respiratory tract (p = 0.036) (Table 1). FLC levels are known to increase with age and reducing renal function. A partial correlation controlling for these factors revealed no relationship between cFLC levels and the severity of lung function impairment. <h3>Conclusions</h3> These results suggest that A1ATD patients with chronic bronchitis and chronically colonised airways have a greater adaptive immune response compared to those without. Whether this response is driven directly by microorganisms residing in the airways, or through an autoimmune phenomenon remains to be elucidated. Whether the use of FLCs in sub cohorts could have an impact on the clinical management of patients with COPD is yet to be determined.
A PEER-GROUP-BASED INTERVENTION ON CARDIOVASCULAR RISK FACTORS AND THE IMPACT ON QUALITY OF LIFE: THE FIFTY-FIFTY TRIAL
Authors: Ana Soto, Sameer Bansilal, Juan M. Fernández-Alvira, Ramona Martinez, Mercedes de Miguel, Jacqueline Latina, Rajesh Vedanthan, Emilia Gomez, Valentin Fuster
Journal: Journal of the American College of Cardiology (2016)
TM-05 * PTEN INDUCED KINASE1 (PINK1) NEGATIVELY REGULATES AEROBIC GLYCOLYSIS IN GLIOBLASTOMA
Authors: B. Golbourn, S. Agnihotri, M. Remke, R. Cairins, C. Smith, D. Mackenzie, G. Fuller, M. Taylor, C. Hawkins, G. Zadeh, J. Rutka
Journal: Neuro-Oncology (2014)

Aggressive cancer cells are characterized by high rates glycolysis and lactate production, a metabolic reprogramming event known as the Warburg effect. This ultimately provides tumor cells including GBM the most malignant and common primary brain tumor with intermediate metabolites for anabolic processes, cell proliferation and invasion. However, these biological processes generate oxidative stress that must be balanced through detoxification of reactive oxygen species (ROS). Using an unbiased retroviral loss of function screen in pre-disposed but non-transformed astrocytes, we demonstrate that PTEN Induced Kinase 1 (PINK1), a mitochondrial kinase is a crucial regulator of the Warburg effect. Mechanistically, loss of PINK1 mediates metabolic reprogramming in normal human astrocytes through ROS dependent hypoxia-inducible factor-1α (HIF1α) stabilization, a transcription factor that controls expression of several aerobic glycolysis genes. Overexpression of PINK1 in GBM cells suppresses ROS, HIF1a and the Warburg effect in vitro and in vivo. Surprisingly, loss of PINK1 in GBM cells that retain PINK1 expression increases oxidative stress and reduces cell viability suggesting ROS balance and maintenance is critical in tumor cells and can be therapeutically exploited. PINK1 loss was observed in GBM and correlated with poor patient survival. Collectively, we demonstrate that PINK1 is a negative regulator of the Warburg effect.