tbuckley/cabot-search huggingface dataset:
Outcomes for patients managed by Redo Craniotomy or Bevacizumab for pseudo-progression or true progression occurring within six months of adjuvant RT for glioblastoma
Authors: Prof Michael Back, Dr Dasantha Jayamanne
Journal: Neuro-Oncology (2018)

Minimal evidence exists to support decision-making that occurs at the time of symptomatic steroid refractory pseudo-progression or true progression occurring within six months of IMRT for GBM. This study aimed to audit the survival outcome of patients with managed with either redo craniotomy (Re-doSx) or Bevacizumab (BEV). Patients with GBM managed with IMRT and temozolomide between 2007 and 2017 as per the EORTC-NCIC (Stupp) Protocol were entered into a prospective ethics approved database. Eligible patients were those with GBM requiring either Re-doSx or BEV within 6 months of completion of IMRT because of symptomatic steroid refractory mass effect. For the primary endpoint of median overall survival (OS) data post intervention, outcome was analysed in regards to potential prognostic factors. 348 patients were managed with Stupp Protocol, and 59 required an intervention for true progression or pseudo-progression (38 with Re-doSx and 21 with BEV) within 6 months post-IMRT. Of 38 patients managed with Re-doSx, 14 were subsequently salvaged with BEV. Patients managed with Re-doSx or BEV had median OS of 6 months (95%CI:3.0–9.0) and 9 months (95%CI:7.6–10.4) respectively (p=0.19). Age (p=0.21), time from IMRT (p=0.37) and ECOG (p=0.31) also were not associated with survival. However for Re-doSx patients, subsequent BEV salvage was associated with improved survival (8 months vs 4 months, p=0.02).The histopathology of 38 patients at Re-doSx was pure necrosis (7patients); residual glioma cells (18patients), and gross tumour (13patients). Presence of residual glioma cells did not correlate with survival. However immunohistochemical features were predictive of survival including Ki-67 level of <10% (p<0.01); >50% reduction in Ki-67 (p<0.01); and >80% tumour necrosis (p=0.01). At symptomatic steroid refractory true or pseudo-progression following IMRT for GBM, BEV was equivalent to Re-doSx in terms of overall survival. Additionally, in those undergoing Re-doSx, subsequent BEV was associated with improved survival.
Hydroxypropyl-β-cyclodextrin protects from kidney disease in experimental Alport syndrome and focal segmental glomerulosclerosis
Authors: Alla Mitrofanova, Judith Molina, Javier Varona Santos, Johanna Guzman, Ximena A. Morales, G. Michelle Ducasa, Jonathan Bryn, Alexis Sloan, Ion Volosenco, Jin-Ju Kim, Mengyuan Ge, Shamroop K. Mallela, Matthias Kretzler, Sean Eddy, Sebastian Martini, Patricia Wahl, Santiago Pastori, Armando J. Mendez, George W. Burke, Sandra Merscher, Alessia Fornoni
Journal: Kidney International (2018)
Abstract 13743: Urinary N-terminal Fragment of Titin Predicts Mortality in Dilated Cardiomyopathy
Authors: Yu Sato, Akiomi Yoshihisa, Takatoyo Kiko, Yusuke Kimishima, Shunsuke Watanabe, Yuki Kanno, Makiko Tatsumi, Satoshi Abe, Takamasa Sato, Satoshi Suzuki, Masayoshi Oikawa, Atsushi Kobayashi, Takayoshi Yamaki, Hiroyuki Kunii, Kazuhiko Nakazato, Shu-ichi Saitoh, Takafumi Ishida, Yasuchika Takeishi
Journal: Circulation (2017)

Background: Titin, a giant sarcomeric protein, functions as a scaffold in striated muscle. Titin is involved in myocardial passive tension and viscoelasticity, and associated with myocardial stiffness and hypertrophy. Mutations in titin gene have been identified in cardiac myopathies such as dilated cardiomyopathy (DCM). It has been recently reported that in damaged muscle, the N-terminal fragment of titin (Titin-N) is cleaved by calpain-3, and the resulting fragments are excreted into the urine via glomerular filtration. We aimed to investigate the impact of urinary Titin-N on prognosis of DCM. Methods and Results: We measured urinary levels of Titin-N/creatinine (U-TN/Cr; pmol/mg/dl) in 102 DCM patients, and followed up all the patients (mean 1167 days). These patients were divided into 3 groups based on the U-TN/Cr: 1st (U-TN/Cr <3.35, n=34), 2nd (3.35≤ U-TN/Cr <7.26, n=34) and 3rd (7.26≤ U-TN/Cr, n=34) tertiles. Left ventricular ejection fraction (LVEF) and right ventricular fractional area change did...
Wnt/β-catenin target genes are differentially expressed within colorectal cancer
Authors: Falk Hlubek, Thomas Brabletz, Jan Budczies, Sabine Pfeiffer, Andreas Jung, Thomas Kirchner
Journal: Cancer Research (2007)

2152   Invasion of common colorectal adenocarcinomas is coupled with a transient loss of epithelial differentiation of tumor cells.  Previously we have shown that dedifferentiated tumor cells at the invasive front accumulate the transcriptional activator β-catenin in the nucleus, in contrast to cells of the tumor center. In order to characterize the cells of these two morphogenic tumor areas, gene expression profiling was performed. Our study demonstrates that intratumorous heterogeneity in colorectal cancer correlates with differential expression of 510 genes between the central tumor region (TC) and the invasive front (IF). Many genes differentially expressed at the IF are involved in cellular invasion processes like cell motility, cell adhesion and extracellular matrix interaction. This  in vivo  analysis shows overexpression of known Wnt/β-catenin target genes either in the entire tumor tissue (compared to normal mucosa) or specifically at the IF. Thus, even though all tumor cells overexpress β-catenin, the existence of at least two groups of Wnt/β-catenin target genes selectively activated in different tumor regions is suggested. The concomitant high expression of inflammation- and tissue repair-related genes at the invasive front supports the hypothesis that an inflammation-activated microenvironment may trigger selective Wnt/β-catenin target gene expression. Taken together, the gene expression analysis based on the intratumorous heterogeneity of colorectal carcinoma reveals a selective activation of Wnt/β-catenin target gene expression within the tumor. In conjuction with an inflammation-activated microenvironment at the invasion front this might contribute to the malignant progression of colorectal cancer  in vivo .
Complement Component C3 Is Highly Expressed in Human Pancreatic Islets and Prevents β Cell Death via ATG16L1 Interaction and Autophagy Regulation
Authors: Ben C. King, Klaudia Kulak, Ulrika Krus, Rebecca Rosberg, Ewelina Golec, Katarzyna Wozniak, Maria F. Gomez, Enming Zhang, David J. O'Connell, Erik Renström, Anna M. Blom
Journal: Cell Metabolism (2018)
Chinese expert consensus on echelons treatment of thoracic injury in modern warfare
Authors: Zhao-Wen Zong, Zhi-Nong Wang, Si-Xu Chen, Hao Qin, Lian-Yang Zhang, Yue Shen, Lei Yang, Wen-Qiong Du, Can Chen, Xin Zhong, Lin Zhang, Jiang-Tao Huo, Li-Ping Kuai, Li-Xin Shu, Guo-Fu Du, Yu-Feng Zhao
Journal: Military Medical Research (2018)

The emergency treatment of thoracic injuries varies of general conditions and modern warfare. However, there are no unified battlefield treatment guidelines for thoracic injuries in the Chinese People's Liberation Army (PLA). An expert consensus has been reached based on the epidemiology of thoracic injuries and the concept of battlefield treatment combined with the existing levels of military medical care in modern warfare. Since there are no differences in the specialized treatment for thoracic injuries between general conditions and modern warfare, first aid, emergency treatment, and early treatment of thoracic injuries are introduced separately in three levels in this consensus. At Level I facilities, tension pneumothorax and open pneumothorax are recommended for initial assessment during the first aid stage. Re-evaluation and further treatment for hemothorax, flail chest, and pericardial tamponade are recommended at Level II facilities. At Level III facilities, simple surgical operations such as emergency thoracotomy and debridement surgery for open pneumothorax are recommended. The grading standard for evidence evaluation and recommendation was used to reach this expert consensus.
Adoptive transfer of tumor-infiltrating lymphocytes in melanoma: a viable treatment option
Authors: Maartje W. Rohaan, Joost H. van den Berg, Pia Kvistborg, John B. A. G. Haanen
Journal: Journal for ImmunoTherapy of Cancer (2018)

The treatment of metastatic melanoma patients with autologous tumor-infiltrating lymphocytes (TIL) shows robust, reproducible, clinical responses in clinical trials executed in several specialized centers over the world. Even in the era of targeted therapy and immune checkpoint inhibition, TIL therapy can be an additional and clinically relevant treatment line. This review provides an overview of the clinical experiences with TIL therapy thus far, including lymphodepleting regimens, the use of interleukin-2 (IL-2) and the associated toxicity. Characteristics of the TIL products and the antigen recognition pattern will be discussed, as well as the current and upcoming production strategies, including the selective expansion of specific fractions from the cell product. In addition, the future potential of TIL therapy in melanoma and other tumor types will be covered.
Performance of Doppler-based resistive index and semi-quantitative renal perfusion in predicting persistent AKI: results of a prospective multicenter study
Authors: Michael Darmon, Aurelie Bourmaud, Marie Reynaud, Stéphane Rouleau, Ferhat Meziani, Alexandra Boivin, Mourad Benyamina, François Vincent, Alexandre Lautrette, Christophe Leroy, Yves Cohen, Matthieu Legrand, Jérôme Morel, Jeremy Terreaux, David Schnell
Journal: Intensive Care Medicine (2018)
Sonodynamic therapy-induced foam cells apoptosis activates the phagocytic PPARγ-LXRα-ABCA1/ABCG1 pathway and promotes cholesterol efflux in advanced plaque
Authors: Huan Wang, Yang Yang, Xin Sun, Fang Tian, Shuyuan Guo, Wei Wang, Zhen Tian, Hong Jin, Zhiguo Zhang, Ye Tian
Journal: Theranostics (2018)

In advanced atherosclerotic plaques, defective efferocytosis of apoptotic foam cells and decreased cholesterol efflux contribute to lesion progression. In our previous study, we demonstrated that 5-aminolevulinic acid (ALA)-mediated sonodynamic therapy (SDT) could induce foam cells apoptosis via the mitochondrial-caspase pathway. In the current research, we sought to explore ALA-SDT-induced apoptosis of phagocytes and the effects of cholesterol efflux and efferocytosis in advanced apoE-/- mice plaque. Methods: apoE-/- mice fed western diet were treated with ALA-SDT and sacrificed at day 1, day 3, day 7 and day 28 post treatment. THP-1 macrophage-derived foam cells were treated with ALA-SDT. 5 hours later, the supernatant was collected and added to fresh foam cells (phagocytes). Then, the lipid area, efferocytosis, cholesterol efflux, anti-inflammatory reactions and PPARγ-LXRα-ABCA1/ABCG1 pathway were detected in plaque in vivo and in phagocytes in vitro. Results: We found that ALA-SDT induced foam cells apoptosis coupled with efferocytosis and upregulation of Mer tyrosine kinase (MerTK) both in vivo and in vitro. The lipid content in plaque decreased as early as 1 day after ALA-SDT and this tendency persisted until 28 days. The enhancement of phagocytes cholesterol efflux was accompanied by an approximately 40% decrease in free cholesterol and a 24% decrease in total cholesterol in vitro. More importantly, anti-inflammatory factors such as TGFβ and IL-10 were upregulated by ALA-SDT treatment. Finally, we found that PPARγ-LXRα-ABCA1/ABCG1 pathway was activated both in vivo and in vitro by ALA-SDT, which could be blocked by PPARγ siRNA. Conclusions: Activation of PPARγ-LXRα-ABCA1/ABCG1 pathway induced by ALA-SDT treatment engages a virtuous cycle that enhances efferocytosis, cholesterol efflux and anti-inflammatory reactions in advanced plaque in vivo and in phagocytes in vitro.
Cancer-Related Cognitive Outcomes Among Older Breast Cancer Survivors in the Thinking and Living With Cancer Study
Authors: Jeanne S. Mandelblatt, Brent J. Small, Gheorghe Luta, Arti Hurria, Heather Jim, Brenna C. McDonald, Deena Graham, Xingtao Zhou, Jonathan Clapp, Wanting Zhai, Elizabeth Breen, Judith E. Carroll, Neelima Denduluri, Asma Dilawari, Martine Extermann, Claudine Isaacs, Paul B. Jacobsen, Lindsay C. Kobayashi, Kelly Holohan Nudelman, James Root, Robert A. Stern, Danielle Tometich, Raymond Turner, John W. VanMeter, Andrew J. Saykin, Tim Ahles
Journal: Journal of Clinical Oncology (2018)

To determine treatment and aging-related effects on longitudinal cognitive function in older breast cancer survivors.
Outbreak of <i>Salmonella</i> Chailey Infections Linked To Precut Coconut Pieces — United States and Canada, 2017
Authors: Sarah Luna, Marsha Taylor, Eleni Galanis, Rod Asplin, Jasmine Huffman, Darlene Wagner, Linda Hoang, Ana Paccagnella, Susan Shelton, Stephen Ladd-Wilson, Sharon Seelman, Brooke Whitney, Elisa Elliot, Robin Atkinson, Katherine Marshall, Colin Basler
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Foodborne salmonellosis causes an estimated 1 million illnesses and 400 deaths annually in the United States (1). In recent years, salmonellosis outbreaks have been caused by foods not typically associated with Salmonella. On May 2, 2017, PulseNet, CDC's national molecular subtyping network for foodborne disease surveillance, identified a cluster of 14 Salmonella Chailey isolates with a rare pulsed-field gel electrophoresis (PFGE) pattern. On May 29, Canadian health officials informed CDC that they were also investigating a cluster of five Salmonella Chailey infections in British Columbia with the same PFGE pattern. Nineteen cases were identified and investigated by CDC, U.S. state health departments, the Public Health Agency of Canada, and the British Columbia Centre for Disease Control. Isolates from all cases were highly related by whole genome sequencing (WGS). Illness onset dates ranged from March 10 to May 7, 2017. Initial interviews revealed that infected persons consumed various fresh foods and shopped at grocery chain A; focused questionnaires identified precut coconut pieces from grocery chain A as a common vehicle. The Canadian Food Inspection Agency (CFIA) and the U.S. Food and Drug Administration (FDA) conducted a traceback investigation that implicated a single lot of frozen, precut coconut as the outbreak source. Grocery chain A voluntarily removed precut coconut pieces from their stores. This action likely limited the size and scope of this outbreak.
Evolving Changes of the Use of Oral Anticoagulants and Outcomes in Patients With Newly Diagnosed Atrial Fibrillation in Taiwan
Authors: Tze-Fan Chao, Chern-En Chiang, Yenn-Jiang Lin, Shih-Lin Chang, Li-Wei Lo, Yu-Feng Hu, Ta-Chuan Tuan, Jo-Nan Liao, Fa-Po Chung, Tzeng-Ji Chen, Gregory Y.H. Lip, Shih-Ann Chen
Journal: Circulation (2018)
Abstract B17: ADGRB3 is a novel tumor suppressor epigenetically silenced in WNT medulloblastoma
Authors: Debanjan Bhattacharya, Dan Zhu, Narra Devi, Erwin G. Van Meir
Journal: Cancer Research (2018)

Abstract Medulloblastoma (MB) is the most aggressive primary malignant brain tumor in children and arises from neural progenitor cells in the developing cerebellum. Although some subtypes of MB show a favorable prognosis with treatment, still one third of patients succumb to this disease and the children who survive suffer from long-term side effects of the aggressive treatments. ADGRB3 (formerly called BAI3) is a member of the ADGRB1-3 subfamily of adhesion GPCR transmembrane proteins, which are highly expressed in the brain specially in cerebellum and hippocampal neurons. The ADGRB3 gene was recently found to undergo somatic mutations in several cancers, but nothing is known about the functional role of ADGRB3 in medulloblastoma. Our recent findings based on analysis of a published microarray dataset and RT-PCR experiments showed that ADGRB3 mRNA expression was selectively repressed in WNT-MB tumor tissue compared to other three molecular subgroups and normal human cerebellar tissue. Using bisulfite sequencing we have detected hypermethylation of the ADGRB3 promoter exclusively in WNT-MB subgroup of human MB tissue but not in the other three molecular subgroups and normal human cerebellar tissue. These results clearly indicate that ADGRB3 is epigenetically silenced in WNT-MB via promoter hypermethylation. In vitro experiments showed that restoration of ADGRB3 expression in ADGRB3-silenced MB cell lines slows cell growth and inhibits WNT signaling targets. We further analyzed whether methyl CpG binding proteins and histone modifications modulate transcriptional repression of ADGRB3 in WNT-MB. ChIP assays revealed enrichment of repressive MBD2 protein in the ADGRB3 promoter region. siRNA mediated knockdown of ADGRB3 in ADGRB3-silent MB cell line (UW288-1) was found to reactivate ADGRB3 expression. We found that in vitro treatment with KCC-07, a recently discovered MBD2 inhibitor, reactivates ADGRB3 mRNA expression in ADGRB3-silent but not expressing MB cells. We are currently investigating whether ADGRB3 can negatively regulate the WNT/beta-catenin pathway or acts via an independent pathway that synergizes with it to facilitate transformation. Altogether, our findings define an epigenetic mechanism for ADGRB3 silencing in WNT-MB and indicate a novel role of ADGRB3 as a potent suppressor of oncogenic cerebellar transformation. Our findings also highlight the potential of epigenetic reactivation of ADGRB3 as a less toxic therapeutic intervention for the children suffering from WNT-MB. Citation Format: Debanjan Bhattacharya, Dan Zhu, Narra Devi, Erwin G. Van Meir. ADGRB3 is a novel tumor suppressor epigenetically silenced in WNT medulloblastoma [abstract]. In: Proceedings of the AACR Special Conference: Pediatric Cancer Research: From Basic Science to the Clinic; 2017 Dec 3-6; Atlanta, Georgia. Philadelphia (PA): AACR; Cancer Res 2018;78(19 Suppl):Abstract nr B17.
Leading US cancer hospital alters conflict of interest rules after controversies
Authors: Owen Dyer
Journal: BMJ (2018)

One of the US’s leading cancer hospitals has banned its board members from investing in start-up companies that originate within the institution after recent negative headlines related to staff conflicts of interest.

The Memorial Sloan Kettering (MSK) Cancer Center in Manhattan, New York, also announced that its vice president Gregory Raskin, a physician, will turn over to his employer nearly $1.4m (£1.1m; €1.2m) of a windfall stake in a biotech company called Y-mAbs Therapeutics, which specialises in children’s cancer treatments derived from research conducted at the institution.

The developments follow a series of unflattering headlines regarding the centre. Last month an investigation by the New York Times and the watchdog group ProPublica found that the hospital’s chief medical officer, Jose Baselga, had published dozens of articles in major journals without mentioning extensive and often relevant industry …
Temporal trends and regional variation in the rate of arthroscopic knee surgery in England: analysis of over 1.7 million procedures between 1997 and 2017. Has practice changed in response to new evidence?
Authors: Simon G F Abram, Andrew Judge, David J Beard, Hannah A Wilson, Andrew J Price
Journal: British Journal of Sports Medicine (2018)

Objectives We investigated trends and regional variation in the rate of arthroscopic knee surgery performed in England from 1997–1998 to 2016–2017. Design Cross-sectional study of the national hospital episode statistics (HES) for England. Methods All hospital episodes for patients undergoing a knee arthroscopy between 1 April 1997 and 31 March 2017 were extracted from HES by procedure code. Age and sex-standardised rates of surgery were calculated using Office for National Statistic population data as the denominator. Trends in the rate of surgery were analysed by procedure both nationally and by Clinical Commissioning Group (CCG). Results A total of 1 088 872 arthroscopic partial meniscectomies (APMs), 326 600 diagnostic arthroscopies, 308 618 knee washouts and 252 885 chondroplasties were identified (1 759 467 hospital admissions; 1 447 142 patients). The rate of APM increased from a low of 51/100 000 population (95% CI 51 to 52) in 1997–1998 to a peak at 149/100 000 (95% CI 148 to 150) in 2013–2014; then, after 2014–2015, rates declined to 120/100 000 (95% CI 119 to 121) in 2016–2017. Rates of arthroscopic knee washout and diagnostic arthroscopy declined steadily from 50/100 000 (95% CI 49 to 50) and 47/100 000 (95% CI 46 to 47) respectively in 1997–1998, to 4.8/100 000 (95% CI 4.6 to 5.0) and 8.1/100 000 (95% CI 7.9 to 8.3) in 2016–2017. Rates of chondroplasty have increased from a low of 3.2/100 000 (95% CI 3.0 to 3.3) in 1997–1998 to 51/100 000 (95% CI 50.6 to 51.7) in 2016–2017. Substantial regional and age–group variation in practice was detected. In 2016–2017, between 11% (22/207) and 16% (34/207) of CCGs performed at least double the national average rate of each procedure. Conclusions Over the last 20 years, and likely in response to new evidence, rates of arthroscopic knee washout and diagnostic arthroscopy have declined by up to 90%. APM rates increased about 130% overall but have declined recently. Rates of chondroplasty increased about 15-fold. There is significant variation in practice, but the appropriate population intervention rate for these procedures remains unknown.
Persistence and Drivers of High-Cost Status Among Dual-Eligible Medicare and Medicaid Beneficiaries
Authors: Jose F. Figueroa, Zoe Lyon, Xiner Zhou, David C. Grabowski, Ashish K. Jha
Journal: Annals of Internal Medicine (2018)

Little is known about the persistence of high-cost status among dual-eligible Medicare and Medicaid beneficiaries, who account for a substantial proportion of expenditures in both programs.To determine what proportion of this population has persistently high costs.Observational study.Medicare-Medicaid Linked Enrollee Analytic Data Source data for 2008 to 2010.1 928 340 dual-eligible Medicare and Medicaid beneficiaries who were alive all 3 years.Medicare and Medicaid payments for these beneficiaries were calculated for each year. Beneficiaries were categorized as high-cost for a given year if their spending was in the top 10% for that year. Differences in spending were then examined for those who were persistently high-cost (all 3 years) versus those who were transiently high-cost (2008 but not 2009 or 2010) and those who were non-high-cost in all 3 years.In the first year, 192 835 patients were high-cost. More than half (54.8%) remained high-cost across all 3 years. These patients were younger than transiently high-cost patients, with fewer medical comorbidities and greater intellectual impairment. Persistently high-cost patients spent $161 224 per year compared with $86 333 per year for transiently high-cost patients and $22 352 per year for non-high-cost patients. Most of the spending among persistently high-cost patients (68.8%) was related to long-term care, and very little (<1%) was related to potentially preventable hospitalizations for ambulatory care-sensitive conditions.Potential misclassification of preventable spending and lack of detailed clinical data in administrative claims.A substantial majority of high-cost dual-eligible beneficiaries had persistently high costs over 3 years, with most of the cost related to long-term care and very little related to potentially preventable hospitalizations.Peterson Center on Healthcare.