tbuckley/cabot-search huggingface dataset:
Differentiation of overall survival by breast cancer tumor subtype following stereotactic radiosurgery for brain metastasis.
Authors: Eunpi Cho, Lena Rubinstein, Mary Weber Redman, Jason Rockhill, Lia Moriguchi Halasz, Michael Gensheimer, Mark Phillips, Hannah M. Linden, Vijayakrishna K. Gadi
Journal: Journal of Clinical Oncology (2014)

e11584 Background: Brain metastases occur late in the course of metastatic breast cancer and the median survival from time of brain metastases has historically been ~4 months. Stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT) are two nonsurgical techniques used to manage brain lesions. We report our institutional experience of SRS for brain metastases in breast cancer patients to address questions regarding outcomes of treatment based on primary tumor biology and the benefit of retreatment with SRS for metachronous brain metastases. Methods: One hundred twenty-two consecutive breast cancer patients treated with SRS for brain metastases from 2001-2013 were included in this retrospective study. Forty-five patients received first SRS after WBRT (4 as planned boost, 41 as salvage) and 13 patients received WBRT as salvage after SRS. Primary tumor biologies were classified as ER+Her2- (n=41), ER+Her2+(n=31), ER-Her2+ (n=23), ER-Her2- (n=28). Median survival from time of SRS (OS) and hazard ratio (HR) by receptor status were calculated. Results: Median age at treatment was 50 and median time from primary cancer diagnosis to brain metastasis was 51 months. The median number of SRS sessions received was 1 (range 1-5), and the median number of lesions treated with the first session was 3 (1-22). For the entire cohort, OS was 15.7 months (95% CI 11.8-20.9), with poorer survival in ER-Her2-patients (Table). For patients treated with multiple SRS sessions for metachronous lesions, each additional SRS treatment was associated with HR benefit of 0.53 (p<0.001). Conclusions: In our series, SRS was associated with improved survival compared to historical outcomes achieved with WBRT. Primary tumor biology may help identify those most likely to benefit from SRS. SRS may be beneficial over a broad range of number of sessions and number of treated lesions. Survival following SRS. Median months OS (range) HR (95% CI) P value ER+ Her2+ 26(16-40) 0.75(0.42-1.33) 0.32 Her2- 16(11-29) ER- Her2- 7(4-11) 4.69(2.42-9.08) <0.0001 Her2+ 23(19-++) HER2+ ER- 23(19-++) 0.89(0.45-1.73) 0.72 ER+ 26(16-40) HER2- ER- 7(4-11) 3.09(1.78-5.38) <0.0001 ER+ 16(11-29)
Sugar makes neutrophils RAGE: linking diabetes-associated hyperglycemia to thrombocytosis and platelet reactivity
Authors: Robert H. Lee, Wolfgang Bergmeier
Journal: Journal of Clinical Investigation (2017)

Diabetes mellitus is associated with an increased risk for cardiovascular disease, but the link between hyperglycemia and atherothrombotic disease is not completely understood. Patients with diabetes often show hyporesponsiveness to antiplatelet therapies, and it has been suggested that hyperreactive reticulated platelets underlie this altered therapeutic response. In this issue of the JCI, Kraakman et al. uncover a previously unknown link between hyperglycemia and enhanced platelet production and reactivity. The authors demonstrate that high blood glucose levels trigger neutrophil release of S100 calcium-binding protein A8/A9 (S100A8/A9), which binds to the receptor for advanced glycation end products (RAGE) on Kupffer cells, ultimately leading to increased thrombopoietin (TPO) production in the liver. TPO causes megakaryocyte proliferation and increased platelet production. This study demonstrates the importance of glycemic control and identifies potential therapeutic targets in the normalization of platelet numbers and function in diabetes.
“Weekend effect” is due to patient differences rather than staffing levels, study concludes
Authors: Jacqui Wise
Journal: BMJ (2017)

The “weekend effect” on mortality arises from patient level differences at admission rather than reduced hospital staffing or services, research published in the Lancet concludes.1

Substantial medical and media attention has been paid to the weekend effect—namely, that patients admitted to hospital at a weekend have greater mortality than patients admitted on weekdays.

In 2015 the health secretary, Jeremy Hunt, claimed that 6000 avoidable deaths occurred each year and that a lack of weekend cover by consultants was a key factor. He cited various studies to support the government’s push to improve hospital services on Saturdays and Sundays and to justify imposing new contracts on junior doctors.234

Sarah Walker, of the Oxford Biomedical Research Centre, and colleagues analysed unselected emergency admissions …
Characterisation of resistance associated substitutions in direct acting antivirals treatment naive patients with genotype 3 hepatitis C virus
Authors: D.A. Smith, A. Magri, D. Bonsall, M.A. Ansari, C. Ip, A. Trebes, A. Brown, P. Piazza, R. Bowden, P. Klenerman, P. Simmonds, E. Barnes
Journal: Journal of Hepatology (2017)
Metaplastic breast cancer: Is it really rare or underdiagnosed?
Authors: Carina Meira Abrahao, Andrea Malta Ferrian, Jessica Ribeiro Gomes, Giselle Almeida, Aline Rocha Lino, Tercia Tarciane Souza, Marcelo Rocha Cruz
Journal: Journal of Clinical Oncology (2014)

e12032 Background: Metaplastic breast cancer (MBC) is a malignancy characterized by the histologic presence of two or more cellular types. MBC is rare relative to invasive ductal carcinoma (IDC), representing less than 1% of all breast cancers. However, since it presents a “triple-negative” (TN) immunohistochemistry feature, MBC may be mistakenly reported as IDC, which may have important consequences on management and outcomes. Methods: A retrospective analysis of patients with final diagnosis of MBC was conducted. The aim was to compare the initial diagnosis, usually from community pathology services, with the final pathology report from certified pathology service. Results: From January 2008 to January 2014, there were 17 consecutive female patients diagnosed with MBC. Median age was 49 years-old (range 26-80), and 47% were above 50 years-old. About 52.9% had a tumor size less than 3 cm, and 35.2% from 3.1 cm to 6 cm. Immunohistochemistry for Ki67 was > 14% in 100% of tissue samples. Most patients had no axillary lymphadenopathy at diagnosis (76.4%), and none of them had distant metastases at presentation. Seven patients (40%) had initial diagnosis of triple-negative IDC from community pathology services. Interestingly, 3 out of 5 patients that were initially treated with neoadjuvant chemotherapy for IDC presented major disease progression during the first cycles and pathology review was requested changing the diagnosis to MBC. Conclusions: Due to the triple-negative histopathologic features, metaplastic breast cancer has been underdiagnosed by community pathology services and may not be as rare as reported. Since triple-negative IDC patients that undergo neoadjuvant chemotherapy usually present high response rates, in cases of no response or disease progression MBC diagnosis should be considered and pathology report must be reviewed.
Retrospective analysis of glioblastoma patients treated with bevacizumab who presented with multifocal disease at diagnosis.
Authors: Jethro Lisien Hu, Kristin Nosova, Miriam Nuno, Anthony Yi, Adam Elramsisy, Debraj Mukherjee, Jeremy Rudnick, Surasak Phuphanich, Serguei I. Bannykh, John Yu, Keith L. Black, Chirag Patil
Journal: Journal of Clinical Oncology (2012)

2080 Background: Glioblastoma patients who present with multifocal disease have an extremely poor prognosis – a recent analysis at our institution demonstrated a median survival of 6 months, versus 11 months for a cohort of unifocal glioblastoma patients matched for age, extent of resection, and KPS. Bevacizumab is frequently used to treat patients with recurrent or progressive glioblastoma. However, its benefit in the setting of multifocal disease is unproven, particularly in light of the concern that antiangiogenic treatment may promote a more invasive, multifocal, and potentially treatment-resistant phenotype. Methods: Between 2004 to 2010, 368 patients were diagnosed with glioblastoma at our institution. We identified 46 patients with multifocal disease on initial presentation, and retrospectively reviewed their clinical course and treatment history. Kaplan-Meier estimates and Wilcoxon tests were used to assess survival distribution. Results: Of the 46 patients with multifocal disease, 12 were treated with bevacizumab (7 upfront and 5 at first recurrence). All 12 bevacizumab-treated patients received external beam radiation therapy, and 11 received temozolomide. In the bevacizumab-treated cohort, median age at the time of surgery was 59 years, and median KPS was 80. For the 34 patients with multifocal disease who did not receive bevacizumab, median age was 69 years, and median KPS was 75. Median survival for the bevacizumab-treated patients was 12.9 months, with 12-month survival of 58.3%. By comparison, median survival for patients with multifocal disease who did not receive bevacizumab was 5.8 months, with 12-month survival of 20.6%. The difference in survival between the two groups was statistically significant, with p-value of 0.045 by the Wilcoxon test. Conclusions: This single-institution retrospective analysis suggests that bevacizumab treatment is associated with a survival benefit for glioblastoma patients who present with multifocal disease. One can infer that the clinical benefit of bevacizumab in this setting outweighs any potential concerns regarding the ability of bevacizumab to promote an invasive, treatment-resistant tumor phenotype.
Haemodynamically proven pulmonary hypertension in a patient with GATA2 deficiency-associated pulmonary alveolar proteinosis and fibrosis
Authors: Stéphane Jouneau, Alice Ballerie, Mallorie Kerjouan, Xavier Demant, Elodie Blanchard, Mathieu Lederlin
Journal: European Respiratory Journal (2017)

Over the past few years, genetics has significantly improved the understanding of interstitial lung diseases (ILD). For example, in idiopathic pulmonary fibrosis, telomerase complex mutations have been shown to drive a specific phenotype including haematological, liver and cutaneous abnormalities [1]. Recently, GATA2 deficiency has been associated with a broad phenotype including haematological, vascular, infectious and pulmonary diseases [2–4]. GATA2 is a zinc finger transcription factor essential for differentiation of immature haematopoietic cells. Among many other functions, GATA2 regulates the phagocytosis of alveolar macrophages. Therefore, alveolar macrophage dysfunction is thought to be the pathophysiological basis for the occurrence of pulmonary alveolar proteinosis, the main lung condition in GATA2 deficiency [4]. However, pulmonary alveolar proteinosis associated with GATA2 deficiency does not share the same clinical, biological or radiological features as autoimmune pulmonary alveolar proteinosis. In all cases of GATA2 deficiency-associated pulmonary alveolar proteinosis reported in the literature, granulocyte–macrophage colony-stimulating factor (GM-CSF) antibodies were absent [2, 4]. Moreover, other pulmonary diseases such as fibrosis or pulmonary hypertension (PH) have been reported to occur in GATA2 deficiency [4], suggesting that the precise pathophysiological mechanisms are not fully understood. Pulmonary fibrosis may be more prevalent in adults with GATA2 deficiency due to a longer duration of the disease <http://ow.ly/WHnu30aCZ4S>
Risk of hepatocellular carcinoma development in patients with cirrhosis of viral etiology assessed by protein induced by vitamin k absence or antagonist II
Authors: G.P. Caviglia, M.L. Abate, C. Bosco, S. Gaia, A. Olivero, C. Rosso, P. Canicci, A. Ciancio, E. Bugianesi, G.M. Saracco, A. Smedile
Journal: Journal of Hepatology (2017)
Validation of novel eligibility criteria by integrating ALBI grade and progression pattern for sorafenib-failed hepatocellular carcinoma
Authors: P.-C. Lee, Y.-T. Chen, Y. Chao, T.-I. Huo, C.-P. Li, C.-W. Su, M.-H. Lee, M.-C. Hou, F.-Y. Lee, H.-C. Lin, Y.-H. Huang
Journal: Journal of Hepatology (2017)
High sustained virological response rates in hepatitis C genotypes 1a and 4 patients treated with elbasvir and grazoprevir and basal viremia &gt;800.000 UI/mL
Authors: A. Olveira, M. Montes, A.L. Navas, J. García-Samaniego, L. Martín-Carbonero, J.R. Larrubia, P. Castillo, A. Madejón, M. Romero, A. García, J.C. Erdozain, J. González
Journal: Journal of Hepatology (2017)
Hair ethyl glucuronide is a highly accurate and objective biomarker of continued alcohol use in patients with alcoholic cirrhosis
Authors: J. Verbeek, C.L. Crunelle, P. Michielsen, M. De Doncker, T. Roskams, S. Van der Merwe, D. Cassiman, H. Neels, F. Nevens
Journal: Journal of Hepatology (2017)
Improved prediction of survival by a risk factor-integrated inflammatory score in Sorafenib treated hepatocellular carcinoma
Authors: M.F. Sprinzl, S. Koch, M.L. Seib, J. Weinmann-Menke, H. Lang, D. Zöller, J.U. Marquardt, M.-A. Wörns, P.R. Galle, A. Weinmann
Journal: Journal of Hepatology (2017)
Abstract B11: Oncogenic KRAS regulates 4E-BP1, a repressor of cap-dependent translation, independently of growth factor activity
Authors: Jillian M. Silva, Rachel K. Bagni, Davide Ruggero, Frank McCormick
Journal: Cancer Research (2017)

Abstract Oncogenic mutations in K-Ras often occur at high frequencies in human cancer resulting in the sustained activation of the ERK1/2 mitogen-activated protein kinase (MAPK) signaling pathway. However, the unique dependencies on upstream or downstream oncogenic signaling amongst the mutant K-Ras proteins remains elusive and often masked by the remaining wild-type allele, other Ras isoforms, or additional secondary genetic alterations. Thus, we employed an isogenic mouse embryonic fibroblast (MEFs) system devoid of H-, N-, and K-Ras alleles and reconstituted with a single Ras isoform to examine the dependencies of growth factors on K-Ras mediated control of translational regulation. Although oncogenic K-Ras G12D and G12V mutant MEF lines proliferated at twice the rate of K-Ras4b wild-type MEF cells, growth factor deprivation led to a cytostatic effect on the proliferation of all MEF lines. Analysis of signaling downstream of K-Ras revealed that phosphorylation of 4E-BP1, eIF4E, and ERK1/2 occurred in a growth factor-independent manner, which stood in contrast to the substantive effects of growth factor inhibition on AKT, p70S6K, and ribosomal protein S6 phosphorylation. Moreover, growth factor deprivation resulted in a marginal decrease of global protein synthesis with negligible effects on cap-dependent translation initiation in all K-Ras MEF cell lines. Taken together, these data suggest that oncogenic K-Ras signaling regulates 4E-BP1 phosphorylation independently of growth factor and mTORC1/2 effects. Citation Format: Jillian M. Silva, Rachel K. Bagni, Davide Ruggero, Frank McCormick. Oncogenic KRAS regulates 4E-BP1, a repressor of cap-dependent translation, independently of growth factor activity. [abstract]. In: Proceedings of the AACR Special Conference on Translational Control of Cancer: A New Frontier in Cancer Biology and Therapy; 2016 Oct 27-30; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2017;77(6 Suppl):Abstract nr B11.
HAMSTRING/QUADRICEPS RATIO IN ACL INJURY PREDICTION IN ELITE FOOTBALL PLAYERS
Authors: Monika Grygorowicz, Martyna Michalowska, Tomasz Walczak, Jakub Grabski, Andrzej Pyda, Tomasz Piontek
Journal: British Journal of Sports Medicine (2017)

Background Hamstring/quadriceps conventional ratio (H/Q) has been widely used in the prediction of anterior cruciate ligament (ACL) injury; however there is still no consensus on the values that are really predictive for ACL injury in elite male football players. Objective To verify the value of H/Q predictive for ACL injury in elite male footballers. Design Retrospective study, analysing ACL injury occurrence in footballers and H/Q value from isokinetic tests. Setting Male football elite division. Patients (or Participants) Records of 74 professional male footballers who played at least one season between 2010–2016 have been analysed. Interventions (or Assessment of Risk Factors) All players were monitored and treated by one clinic, thus medical history of each player was documented. ACL injury was confirmed in USG examination. Players were dichotomously categorized as injured or uninjured for data analysis. The same clinic was responsible for conducting isokinetic assessment using Biodex System 3 Pro. Retrospective footballer's records were reviewed between May 2006 and April 2016. Receiver operating characteristic (ROC) curves were used to evaluate the possibility of using the H/Q value to predict ACL injury. Level of significance was set at p&lt;0.05 and Statistica v.12.5 software was used. Main Outcome Measurements Area under the curve (AUC); number of ACL injuries and values of H/Q were also analysed. Results Total 331 knee isokinetic tests of 74 elite male football players were reviewed, and data of 8 ACL injuries were analysed. Cut-off value of H/Q ratio was calculated at 0.63±0.11. The ROC analyses showed an area under the curve of 0.67 (95% CI 0.49–0.84; p=0.0598). Conclusions Although it occurred to be insignificant we observed a tendency towards H/Q values at 0.63±0.11, that may be useful in future studies in multifactorial analysis of ACL injury prediction. However, studies on bigger sample should be performed to verify these results.
Monocytes exhibit an immune and metabolic reprogramming during acute-on-chronic-liver-failure
Authors: H. Korf, J. Du Plessis, J. van Pelt, L. Langouche, M. Mekeirele, D. Cassiman, P. Meersseman, G. van den Berghe, A. Wilmer, W. Laleman, T. Gustot, G. Mehta, R. Jalan, F. Nevens, S. Van Der Merwe
Journal: Journal of Hepatology (2017)
Predictive value of KRAS mutation and skin rash in Korean colorectal cancer patients treated with cetuximab
Authors: Byeong Seok Sohn, Tae-Won Kim, Jae-Lyun Lee, Min-Hee Ryu, Heung Moon Chang, Yoon-Koo Kang, Hyoungnam Lee, Young-Soon Na, Se Jin Jang, Jin Cheon Kim, Jeong Shin Lee
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

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BACKGROUND : There has been many candidate for predicting the clinical outcome of metastatic colorectal cancer (mCRC) treated with cetuximab. Skin rash correlates with tumor response after cetuximab. Recently, The KRAS mutation state of the tumor has been proposed as a promising marker of response to cetuximab. The aim of this study was to determine the clinical relevance of combined analysis of KRAS mutational status and skin rash in Korean mCRC patients treated with cetuximab.    METHODS : We included 45 irinotecan refractory mCRC patients treated with cetuximab plus irinotecan-based chemotherapy. Tumors were screened for KRAS mutation using direct sequencing. Clinical response was evaluated according to RECIST.    RESULTS : A KRAS mutation was detected in 20 out of 45 (43.5%) tumors and skin rash was observed in 25 out of 45 (55.6%) patients. The response rate (RR) for this treatment was 26.1%. The RR in patients with KRAS mutation was 15.8% (3/19), in contrast to 36.0% (9/25) in patients without mutation (P= 0.181). The RR in patients with skin rash after cetuximab was higher than those in patients without skin rash (40.0% vs 10.0%, p=0.040) Patients with wild KRAS /skin rash (+) group showed a significant improved efficacy compared with other groups. (RR: 50.0% vs 14.3% [p=0.012], PFS: 28.0 wk vs 7 wk [p=0.002])    [Table is here]    CONCLUSION : Patients with wild KRAS /skin rash (+) group showed good clinical efficacy to cetuximab. However, clinical outcome in patients with wild KRAS /skin rash (-) group was as poor as in patients with KRAS mutant. Dose escalation trial of cetuximab may be considered in patients with wild KRAS /skin rash (-) group.    Keywords : cetuximab, metastatic colorectal cancer, KRAS , skin rash, biomarker    

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Prevalence and risk factors for hepatitis B infection in the adult population of Georgia: a nationwide survey
Authors: A. Kasradze, G. Kuchukhidze, D. Baliashvili, S. Salyer, A. Gamkrelidze, M. Tsereteli, N. Chitadze, M. Alkhazashvili, K. Zakhashvili, J. Drobeniuc, C. Blanton, S. Russell, P. Imnadze, J. Morgan, F. Averhoff, L. Hagan
Journal: Journal of Hepatology (2017)
Peripheral Blood Cytokine Levels After Acute Myocardial Infarction
Authors: Mahan Shahrivari, Elizabeth Wise, Micheline Resende, Jonathan J. Shuster, Jingnan Zhang, Roberto Bolli, John P. Cooke, Joshua M. Hare, Timothy D. Henry, Aisha Khan, Doris A. Taylor, Jay H. Traverse, Phillip C. Yang, Carl J. Pepine, Christopher R. Cogle
Journal: Circulation Research (2017)

Intracoronary infusion of bone marrow (BM) mononuclear cells after acute myocardial infarction (AMI) has led to limited improvement in left ventricular function. Although experimental AMI models have implicated cytokine-related impairment of progenitor cell function, this response has not been investigated in humans.To test the hypothesis that peripheral blood (PB) cytokines predict BM endothelial progenitor cell colony outgrowth and cardiac function after AMI.BM and PB samples were collected from 87 participants 14 to 21 days after AMI and BM from healthy donors was used as a reference. Correlations between cytokine concentrations and cell phenotypes, cell functions, and post-AMI cardiac function were determined. PB interleukin-6 (IL-6) negatively correlated with endothelial colony-forming cell colony maximum in the BM of patients with AMI (estimate±SE, -0.13±0.05; P=0.007). BM from healthy individuals showed a dose-dependent decrease in endothelial colony-forming cell colony outgrowth in the presence of exogenous IL-1β or IL-6 (P<0.05). Blocking the IL-1R or IL-6R reversed cytokine impairment. In AMI study participants, the angiogenic cytokine platelet-derived growth factor BB glycoprotein correlated positively with BM-derived colony-forming unit-endothelial colony maximum (estimate±SE, 0.01±0.002; P<0.001), multipotent mesenchymal stromal cell colony maximum (estimate±SE, 0.01±0.002; P=0.002) in BM, and mesenchymal stromal cell colony maximum in PB (estimate±SE, 0.02±0.005; P<0.001).Two weeks after AMI, increased PB platelet-derived growth factor BB glycoprotein was associated with increased BM function, whereas increased IL-6 was associated with BM impairment. Validation studies confirmed inflammatory cytokine impairment of BM that could be reversed by blocking IL-1R or IL-6R. Together, these studies suggest that blocking IL-1 or IL-6 receptors may improve the regenerative capacity of BM cells after AMI.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00684060.
Egr2 and 3 control adaptive immune responses by temporally uncoupling expansion from T cell differentiation
Authors: Tizong Miao, Alistair L.J. Symonds, Randeep Singh, Janine D. Symonds, Ane Ogbe, Becky Omodho, Bo Zhu, Suling Li, Ping Wang
Journal: The Journal of Experimental Medicine (2017)

Egr2 and 3 are important for maintaining immune homeostasis. Here we define a fundamental function of Egr2 and 3 operating as a checkpoint that controls the transition between clonal expansion and differentiation of effector T cells. Egr2 and 3 deficiency resulted in defective clonal expansion but hyperactivation and excessive differentiation of T cells in response to viral infection. Conversely, sustained Egr2 expression enhanced expansion but severely impaired effector differentiation. Egr2 bound to and controlled the expression of genes regulating proliferation (Myc and Myb) and differentiation repressors (Bcl6, Id3), while repressing transcription factors required for effector function (Zeb2, RORa, RORc, and Bhlhe40). Egr2 and 3 expression in T cells was regulated reciprocally by antigen and IFNγ, providing a mechanism for adjusting proliferation and differentiation of individual T cells. Thus, Egr2 and 3 are upstream regulators of effector CD4 and CD8 T cells that are essential for optimal responses with limited immunopathology.