tbuckley/cabot-search huggingface dataset:
Patient-reported adverse events after colonoscopy in Norway
Authors: Geir Hoff, Thomas de Lange, Michael Bretthauer, Magne Buset, Stein Dahler, Fred-Arne Halvorsen, Jörg Halwe, Mathis Heibert, Ole Høie, Øystein Kjellevold, Volker Moritz, Per Sandvei, Birgitte Seip, Lars Aabakken, Øyvind Holme
Journal: Endoscopy (2017)

Abstract Background and aims Patient-reported outcome measures are increasingly important in healthcare. European guidelines have recommended inclusion of patient feedback to capture adverse events due to colonoscopy, but this is rarely implemented. Methods The Norwegian Quality Assurance network for endoscopy (Gastronet) collects patient-reported outcome for colonoscopies. Free-text comments on patient reports from January to December 2015 were characterized as positive or negative. All negative free-text comments were scrutinized for information that might suggest colonoscopy-related adverse events. We identified severe adverse events with and without admission to hospital. Results We included 16 552 outpatient colonoscopies performed at 21 hospitals. A total of 11 248 procedures (68 %) were accompanied by a patient feedback report, of which 2628 (23 %) had free-text comments (2196 [20 %] characterized as positive and 432 [3.8 %] as negative). These negative free texts on patient reports revealed 15 post-colonoscopy hospital admissions due to adverse events that had not been registered in the colonoscopy report. This increased the number of hospital admissions caused by adverse events from 3 (0.03 %) to 18 (0.16 %). In addition, there were 14 patient reports of severe events without hospital admission. Therefore, a total of 29 severe adverse events reported by patients were missed by conventional documentation in the colonoscopy form. Conclusion It is feasible to implement patient feedback as routine reporting to capture the full picture of colonoscopy-related adverse events. Some patients experience significant complications that are not recorded through any registries. Patient feedback forms should be tailored to capture adverse events after colonoscopy that are otherwise not easily disclosed.
Abstract 68: Endostatin Promotes Proliferation and Migration of Rat Myofibroblasts Isolated From the Infarcted Area After Myocardial Infarction
Authors: Muneyoshi Okada, Yuka Hirano, Hideyuki Yamawaki
Journal: Circulation Research (2015)

Background: Endostatin, a 20 kDa non-collagenous fragment of type XVIII collagen, is known as an endogenous anti-angiogenic factor. In the heart tissues of experimental heart failure models, such as cardiac hypertrophy and myocardial infarction, the expression levels of endostatin increase. Proliferation, migration and collagen synthesis of myofibroblasts are important processes during the tissue remodeling in injury sites after myocardial infarction. However, the effects of endostatin on cardiac myofibroblasts have not been clarified. We investigated the effect of endostatin on the functions of myofibroblasts isolated from infarcted myocardial tissues of rat. Methods and Results: Left ventricular myocardial infarction was induced by ligation the left anterior descending coronary artery of male Wistar rats. The infarcted myocardial tissues were harvested 2 weeks after the operation and placed on the culture plate with serum-containing medium. Migrated cells from the tissues were isolated and used as myofibroblasts. High expression of α-smooth muscle actin, vimentin and type I collagen in these cells were confirmed by immunofluorescence staining. Cell counting assay was performed to determine a cell proliferation. Endostatin (100-3000 ng/ml, 48 h) increased the proliferation of myofibroblasts. Boyden chamber assay was performed to measure a cell migration. Endostatin (300-3000 ng/ml, 24 h) stimulated the migration of myofibroblasts. Western blotting was performed to measure a secretion of type I collagen. Endostatin (100-3000 ng/ml, 24 h) had no influence on it. Conclusions: These data suggest that endostatin might promote scar formation after myocardial infarction through the activation of proliferation and migration of myofibroblasts.
Use of First or Second Generation TKI for CML after Allogeneic Stem Cell Transplantation: a Study By the CMWP of the EBMT
Authors: Yves Chalandon, Simona Iacobelli, Jennifer Hoek, Linda Koster, Liisa Volin, Jürgen Finke, Jan J. Cornelissen, Ibrahim Yakoub-Agha, Charles Craddock, Mahmoud Aljurf, Arnon Nagler, Jakob Passweg, Ellen Meijer, Charles Crawley, Ann Elizabeth Hunter, Boris Afanasyev, Christian Koenecke, Nicolaas P.M. Schaap, Marco R De Groot, Michael Schleuning, Eduardo Olavarria, Nicolaus Kröger
Journal: Blood (2016)
P08.26 ATP depletion induced by dual inhibition of ALDH and mitochondrial complex I make therapeutic response in glioblastoma
Authors: J. Park, J. Shim, J. Kang, J. Kang, J. Chang, S. Kim, S. Kang
Journal: Neuro-Oncology (2017)

Introduction: Deprivation of energy metabolism has been emerged as an effective therapeutic approach for various tumors. Cancer cells prefer cytosolic NADH supplied by aldehyde dehydrogenase (ALDH) for ATP production through oxidative phosphorylation (OxPhos). Dual inhibition of ALDH using KN817 and OxPhos using phenformin successfully induced ATP depletion and subsequent cell growth arrest in lung cancer. However, it remains to be elucidated how ATP depletion causes cell growth arrest. This study is aimed to evaluate therapeutic responses and working mechanisms of dual inhibition of ALDH and OxPhos in glioblastoma (GBM). Materials and Methods: Effect of combined treatment of KN817 and phenformin on GBM tumorspheres (TSs) were evaluated by functional and molecular studies. Results: We found that combined treatment of gossypol and phenformin also reduces ATP level and cell viability in GBM TSs. Gossypol treatment alone or in combination with phenformin significantly reduced expression of stemness factors such as Nestin, Sox2, PDPN, and Oct3/4, and mesenchymal transition- or invasiveness-associated genes including β-catenin, Snail, and Zeb1 in GBM TSs. Functional studies revealed that stemness and invasion were also reduced by combined treatment of gossypol and phenformin. Malate treatment reversed and knockdown of ALDH isoforms mimics these results, suggesting that disruption of ALDH-mediated ATP production is a key working mechanism. In vivo efficacy was examined in an orthotopic mouse xenograft model. Preclinical mouse model confirmed a remarkable therapeutic response to the combined treatment of gossypol and phenformin. CONCLUSION: Our approach demonstrates dual inhibition of tumor bioenergetics, proposing a novel strategy for the treatment of GBM.
Association of US Centers for Medicare and Medicaid Services Hospital 30-Day Risk-Standardized Readmission Metric With Care Quality and Outcomes After Acute Myocardial Infarction
Authors: Ambarish Pandey, Harsh Golwala, Hurst M. Hall, Tracy Y. Wang, Di Lu, Ying Xian, Karen Chiswell, Karen E. Joynt, Abhinav Goyal, Sandeep R. Das, Dharam Kumbhani, Howard Julien, Gregg C. Fonarow, James A. de Lemos
Journal: JAMA Cardiology (2017)

<h3>Importance</h3> The US Centers for Medicare and Medicaid Services Hospital Readmissions Reduction Program penalizes hospitals with higher-than-expected risk-adjusted 30-day readmission rates (excess readmission ratio [ERR] &gt; 1) after acute myocardial infarction (MI). However, the association of ERR with MI care processes and outcomes are not well established. <h3>Objective</h3> To evaluate the association between ERR for MI with in-hospital process of care measures and 1-year clinical outcomes. <h3>Design, Setting, and Participants</h3> Observational analysis of hospitalized patients with MI from National Cardiovascular Data Registry/Acute Coronary Treatment and Intervention Outcomes Network Registry–Get With the Guidelines centers subject to the first cycle of the Hospital Readmissions Reduction Program between July 1, 2008, and June 30, 2011. <h3>Exposures</h3> The ERR for MI (MI-ERR) in 2011. <h3>Main Outcomes and Measures</h3> Adherence to process of care measures during index hospitalization in the overall study population and risk of the composite outcome of mortality or all-cause readmission within 1 year of discharge and its individual components among participants with available Centers for Medicare and Medicaid Services–linked data. <h3>Results</h3> The median ages of patients in the MI-ERR greater than 1 and tertiles 1, 2, and 3 of the MI-ERR greater than 1 groups were 64, 63, 64, and 63 years, respectively. Among 380 hospitals that treated a total of 176 644 patients with MI during the study period, 43% had MI-ERR greater than 1. The proportions of patients of black race, those with heart failure signs at admission, and bleeding complications increased with higher MI-ERR. There was no significant association between adherence to MI performance measures and MI-ERR (adjusted odds ratio, 0.94; 95% CI, 0.81-1.08, per 0.1-unit increase in MI-ERR for overall defect-free care). Among the 51 453 patients with 1-year outcomes data available, higher MI-ERR was associated with higher adjusted risk of the composite outcome and all-cause readmission within 1 year of discharge. This association was largely driven by readmissions early after discharge and was not significant in landmark analyses beginning 30 days after discharge. The MI-ERR was not associated with risk for mortality within 1 year of discharge in the overall and 30-day landmark analyses. <h3>Conclusions and Relevance</h3> During the first cycle of the Hospital Readmissions Reduction Program, participating hospitals' risk-adjusted 30-day readmission rates following MI were not associated with in-hospital quality of MI care or clinical outcomes occurring after the first 30 days after discharge.
P03.01 Expression analysis and prognostic/predictive significance of a panel of microRNAs (miR-124a, miR-381, miR-637) in primary IDH-wildtype glioblastoma
Authors: L. Bertero, G. Mancuso, F. Callipo, L. Traballi, P. Cassoni, R. Senetta, R. Rudà, J. Antona, E. Trisolini, R. Boldorini
Journal: Neuro-Oncology (2017)

Background: MicroRNAs (miRNAs) are small non-coding RNA molecules regulating mRNAs translation. Significant differences in miRNAs expression have been found in glioblastoma compared to normal brain tissue. MiR-124a, miR-381 and miR-637 are involved in regulation of pathways which are commonly deregulated in glioblastoma (MAPK/ERK, WNT/β-catenin and AKT pathways, respectively). AIM: To investigate the expression profile and prognostic/predictive role of miR-124a, miR-381 and miR-637 in primary IDH-wildtype glioblastoma. Materials and Methods: Inclusion criteria were: pathological diagnosis of primary IDH-wildtype glioblastoma (according to WHO 2016 criteria), partial/total surgical resection followed by at least one line of postoperative adjuvant treatment, ≥ 6-months follow-up after diagnosis, Caucasian ethnicity. Histological revision was performed independently by two pathologists to confirm diagnosis. IDH1/IDH2 status was assessed by Sanger sequencing according to standard protocols. Total RNA was extracted using miRNeasy FFPE (QIAGEN), miRNAs were amplified with TaqMan MicroRNA Assays (ThermoFisher) and RNU6B was used as endogenous control, while ten normal brain areas were selected as external controls. Relative quantification miRNA expression values (RQ) were calculated using the ΔΔCt method. X-tile plots and Stata (StataCorp LP) were used to calculate RQ cut-off values and for statistical analyses, respectively. Informed consent was obtained according to local regulations. Results: Here we present preliminary results based on 49 patients, 30 males (61%). Median age was 59 years (range 38–75), median KPS before surgery 80 (range 70–90). Partial resection was achieved in 27/49 (55%), total in 22/49 (45%). Median progression-free survival (PFS) was 9.4 months (range 3.5–26), median overall survival (OS) 16 months (range 3.5–42.7). Total resection and adjuvant treatment according to Stupp regimen were both associated with a better outcome as expected. Glioblastoma samples showed a reduced expression of all three miRNAs compared to normal brain. Significantly better PFS (9.9 vs 6.0 months, p=0.002) was found in patients with up-regulated miR-637 (RQ cut-off: 0.248), whereas OS difference was not significant (16.9 vs 15.6, p=0.161). A specific RQ range of miR-381 (RQ 0.104–0.287) was associated with better PFS (9.8 vs 7.4, p=0.0183), but not with OS (16.4 vs 15.8, p=0.782). No significant associations were found between miR-124a and outcome. Conclusions: A better PFS was significantly associated with miR-637 up-regulation, a finding consistent with its reported inhibitory effect on the AKT pathway. Interestingly, the favorable role of miR-381 seems to be limited to a specific range of RQ comprising the cut-off value. These preliminary findings need to be assessed in a larger series and the study is ongoing.
Protein tyrosine phosphatase conjugated with a novel transdermal delivery peptide, astrotactin 1–derived peptide recombinant protein tyrosine phosphatase (AP-rPTP), alleviates both atopic dermatitis–like and psoriasis-like dermatitis
Authors: Won-Ju Kim, Ja-Hyun Koo, Hyun-Jung Cho, Jae-Ung Lee, Ji Yun Kim, Hong-Gyun Lee, Sohee Lee, Jong Hoon Kim, Mi Seon Oh, Minah Suh, Eui-Cheol Shin, Joo Yeon Ko, Myung Hyun Sohn, Je-Min Choi
Journal: Journal of Allergy and Clinical Immunology (2017)
Abstract 118: Adipose Inflammation Is Critically Involved in the Progression of Heart Failure During Pressure Overload
Authors: Ippei Shimizu, Tohru Minamino, Yohko Yoshida, Taro Katsuno, Issei Komuro, Yoshio Kobayashi
Journal: Circulation Research (2012)

Several clinical studies have shown that insulin resistance is prevalent among patients with impaired cardiac function and that systemic insulin resistance is the risk factor for the development of heart failure; however, underlying mechanisms have not been fully elucidated. We have previously reported that increased p53 level in adipose tissue is crucially involved in adipose inflammation and insulin resistance during pressure overload. Here we show that . Pressure overload increased sympathetic activity and promoted lipolysis in adipose tissue. Accelerated lipolysis resulted in increases of reactive oxygen species and DNA damage, leading to up-regulation of adipose p53. This up-regulation activated the NF-kappaB pathway and induced adipose inflammation and insulin resistance. Genetic disruption of adipose p53 markedly attenuated adipose inflammation and metabolic abnormalities associated with heart failure. We also observed that cardiac function and survival in the chronic phase of heart failure were significantly better in adipose tissue p53-deficient mice than control littermates. Pharmacological inhibition of adipose p53 after imposing pressure overload also improved cardiac dysfunction as well as insulin resistance in the chronic phase of heart failure. These results suggest that inhibition of adipose inflammation is a potential target for treating metabolic abnormalities and systolic dysfunction in patients with heart failure.
High Risk Multiple Myeloma: Better Outcomes with Upfront Tandem Autologous- Non-Myelo Ablative Allogeneic Stem Cell Transplantation Compared to Upfront Autologous Stem Cell Transplantation
Authors: Anish Puliyayil Nair, Cindy Lee, Anna Kalff, Patricia A. Walker, Krystal Bergin, Jay Hocking, Sue Morgan, Daniela Klarica, Jenny Muirhead, Andrew Spencer, Oi Lin Lee, Noemi Horvath
Journal: Blood (2016)
P01.27 Repressive histone marks (H3K27me3) and DNA hypermethylation suggests epigenetic regulation of miR-379/miR-410 (C14MC) cluster in oligodendrogliomas
Authors: A. Kumar, S. Nayak, P. Pathak, S. Purkait, V. Suri, M. C. Sharma, A. Mukhopadhyay, A. Suri, C. Sarkar
Journal: Neuro-Oncology (2017)

MicroRNAs(miRNAs) are often grouped into clusters in the genome and dysregulation of miRNA clusters has been shown in various cancers. miR-379/miR-656 cluster(C14MC) is one of the largest miRNA clusters located within an imprinted chromosomal region, Dlk1-Dio3 locus. Downregulation of miRNAs from C14MC has been observed in several CNS tumors, including GBM. However, status of expression of entire C14MC miRNA cluster and its clinicopathological significance in Oligodendrogliomas(ODGs) remains unexplored. Expression profile of C14MC miRNAs was performed on 44 ODGs using TaqMan low-density array (TLDA). Majority of C14MC miRNAs were observed to be significantly down-regulated in ODGs which was further validated on larger sample size using TCGA datasets. 17 miRNAs of C14MC were significantly dysregulated between grade II and III of ODGs in TLDA data, however TCGA dataset did not show any dysregulated miRNAs between the grades in ODGs. MEF2 has been reported as key transcription regulator for C14MC in rat neurons and muscle cell. Hence ChIP was performed for MEF2 binding in HS683 ODG cell line and we observed binding of MEF2A upstream of C14MC. Down-regulation of MEF2A was noted in both in-house and REMBRANDT dataset in ODGs. As per the TCGA methylation analysis of genomic region encompassing C14MC, we noted hypermethylation of this region in ODG. Treatment with the demethylating drug 5-AZA-cytidine resulted in re-expression of several miRNAs from C14MC in HS683 cells, thus suggesting the role of DNA methylation in regulation of C14MC. Further MEG3, a long noncoding gene located upstream of this cluster, showed downregulation in ODG (both in-house data and REMBRANDT) and also correlated with decrease in C14MC miRNA expression. Treatment of HS683 cell line with 5-aza-dC did not significantly induce MEG3 expression, further supporting contention that MEG3 region acquires a repressive chromatin state in ODGs. ChIP analyses revealed the predominance of H3K27me3 at the MEG3 DMR in the HS683 cell line suggesting a strong shift towards repressive histone modifications across major regulatory regions in MEG3. This further suggests involvement of epigenetic regulation of MEG3 expression in ODGs. Survival analysis of TCGA dataset demonstrated 59% prognostic correlation with C14MC miRNAs in ODGs. To conclude, this is the first report demonstrating the silencing of the second largest microRNA cluster in ODGs, implicating its tumor-suppressive role in their pathogenesis. Dysregulation of the transcription factor, particularly MEF2, along with epigenetic machinery involving DNA methylation and repressive histone modifications H3K27 mediated MEG3 downregulation could be the possible mechanism for C14MC downregulation, acting independently or in synergy. Further prognostic significance of this cluster is also highlighted.
Survival Following Allogeneic Hematopoietic Cell Transplantation in Older High-Risk Acute Myeloid Leukemia Patients Initially Treated with CPX-351 Liposome Injection Versus Standard Cytarabine and Daunorubicin: Subgroup Analysis of a Large Phase III Trial
Authors: Jeffrey E. Lancet, Antje Hoering, Geoffrey L. Uy, Jorge E. Cortes, Laura F Newell, Tara L. Lin, Ellen K. Ritchie, Robert K. Stuart, Stephen A. Strickland, Donna Hogge, Scott R. Solomon, Richard M. Stone, Dale L. Bixby, Jonathan E. Kolitz, Gary J. Schiller, Matthew J. Wieduwilt, Daniel H. Ryan, Michael T. Chiarella, Arthur C. Louie, Bruno C. Medeiros
Journal: Blood (2016)
Pneumocystis Pneumonia
Authors: Charles F. Thomas, Andrew H. Limper
Journal: New England Journal of Medicine (2004)

Pneumocystis pneumonia remains the most prevalent opportunistic infection in patients infected with the human immunodeficiency virus. Molecular techniques have provided new insights into the complex cell biology of this fungus. The authors summarize advances that have resulted from studies of the cell biology, biochemistry, and genetics of pneumocystis in the past several years and provide recommendations for the diagnosis of pneumocystis pneumonia and for prophylaxis and treatment.
P16.03 Is navigated ultrasound the most efficient intraoperative imaging technique?
Authors: C. de Quintana Schmidt, A. Leidinger, O. Gallego, B. Gomez, J. Craven, L. Salgado, M. Rico, J. Aibar, J. Molet
Journal: Neuro-Oncology (2017)

Introduction: Since its introduction to modern neurosurgery, neuronavigation has aided the surgeon during presurgical planning. However, this technique loses power throughout the surgical intervention due to brain shifting, thus not being reliable to assess whether the optimal resection rate has been achieved. One possible solution to this is the acquisition of intraoperative neuroimaging. In this original study, we evaluate the efficiency of navigated ultrasound as a potential tool for acquiring intraoperative real time imaging. Materials and Methods: Prospective study including all intracerebral tumors operated with navigated ultrasound at Sant Pau Hospital. Follow up started in July 2015 until present day. Results: N = 70 patients. 38 (54,3%) female and 32 (45,7%) male. Mean age 56,3 (19-79) years. Tumors by histology: glioblastoma 22 (31,4%), metastases 18 (25,7%), low-grade glioma 7 (10%), anaplasic glioma 6 (8,5%), anaplasic oligodendroglioma 5 (7,1%), oligodendroglioma 4 (5,7%), gliosarcoma 2 (2,8%), cavernoma 2 (2,8%), lymphoma 1 (1,4%), pilocytic astrocitoma 1 (1,4%), nonspecific inflammation 1 (1,4%) and demyelinating disease 1 (3%). All lesions were classified according to the ultrasonographic visibility scale, described in the literature: Grade 3: Lesion clearly identifiable and clear border with normal tissue, Grade 2: Lesion clearly identifiable but no clear border with normal tissue, Grade 1: Lesion difficult to visualize and no clear border with normal tissue and Grade 0: Lesion not visible. Of all included cases, 51 (72,8%) where Grade 3 tumors, 16 (22,8%) Grade 2, 2 (2,8%) Grade 1 and 1 (1,4%) Grade 0. Interestingly, the most frequently operated intracranial lesions (metastases and glioblastoma) present a high degree of adequate intraoperative visualization with a mean 94,4% Grade 3 for metastases and 77,2% for glioblastoma. Despite being regularly visualized, low-grade gliomas tend to show blurred margins, presenting on our series with a 54,5% Grade 3 and 57,1% grade 2. We need to consider the infiltrative nature of low-grade gliomas when interpreting these results. On 11 (15,7%) of all cases, the navigated ultrasound provided imaging information to lead to further tumor resection. On 5 (7,1%) of all cases, a Doppler study was performed to assess vascular permeability. There were no complications associated to the use of navigated ultrasound. Conclusions: Navigated ultrasound is an effective, economic and secure technique that provides good quality real-time intraoperative images.
Achievement of Minimal Residual Disease Negativity By Multiparameter Flow Cytometry Is an Important Therapeutic Endpoint in Patients with Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia Receiving Salvage Treatment
Authors: Nicholas J. Short, Hagop M. Kantarjian, Jeffrey L. Jorgensen, Farhad Ravandi, Musa Yilmaz, Maria R. Khouri, Sa Wang, Deborah A Thomas, Joseph D Khoury, Richard E. Champlin, Issa F. Khouri, Partow Kebriaei, David Marin, Susan M. O'Brien, Guillermo Garcia-Manero, Jorge E. Cortes, Koji Sasaki, Courtney D DiNardo, Tapan M. Kadia, Nitin Jain, Marina Konopleva, Rebecca Garris, Elias J. Jabbour
Journal: Blood (2016)
UK spent 9.9% of GDP on healthcare last year, official figures show
Authors: Gareth Iacobucci
Journal: BMJ (2017)

The UK spent 9.9% of its gross domestic product (GDP) on healthcare expenditure in 2015, official figures have shown.

The UK ranked 13th out of 35 Organisation for Economic Co-operation and Development states in terms of health spending, but sixth lowest out of the G7 nations, with only Italy (9.1%) investing less.

The UK’s standing on the …
Stabilizing the Mixed Lineage Leukemia Protein
Authors: Jolanta Grembecka, Tomasz Cierpicki
Journal: New England Journal of Medicine (2017)

The translocation of the gene encoding mixed lineage leukemia with other genes results in chimeric, oncogenic proteins. A recent study shows that stabilization of wild-type MLL (encoded by the untranslocated allele) is an experimental approach to treating leukemia.