tbuckley/cabot-search huggingface dataset:
Second-line chemotherapy for gallbladder cancer.
Authors: Nicha Wongjarupong, Mohamed Abdelrahim Muddathir Hassan, Cristobal T. Sanhueza, Mindy L. Hartgers, Fatima Hassan, Lewis R. Roberts, Amit Mahipal
Journal: Journal of Clinical Oncology (2018)

450 Background: The standard treatment for patients with gallbladder cancer is a combination of gemcitabine and cisplatin based on ABC-02 trial. However, there are no guidelines regarding treatment after first-line therapy. We retrospectively analyzed the efficacy and overall survival of different second-line regimens. Methods: We identified 203 patients with advanced gallbladder cancer who received palliative treatment between January 2000 and December 2015 at Mayo Clinic, Rochester. RECIST criteria was used to assess response. Results: 68 patients received second-line chemotherapy. Median age was 63 years (range: 32-86) and majority were males (60.6%). The median time from the diagnosis to the start of the second line chemotherapy was 8 (1-120) months. The most common used second-line chemotherapy were FOLFOX (14), gemcitabine alone (10), single agent fluoropyrimidine (11), gemcitabine with capecitabine (5), and capecitabine with oxaliplatin (4). There were 30 patients that received 5-fluorouracil based regimens, 20 patients received gemcitabine-based regimen, 3 patients received taxane-based regimen, and 15 patients received other types of chemotherapy. Median progression free survival and overall survival was 2.1 (1.8-2.7) and 16.7 (13.2-21.3) months respectively. There were 10 (52%), 11 (37%), 2 (67%), 5 (33%) with partial response and stable disease in 5-fluorouracil-based, gemcitabine-based, taxane-based, and others, respectively. There were no difference in PFS, with median PFS of 2.5, 2.0, 2.8 and 2.3 months, respectively (p=0.43). The overall survival were 15.7 (8.9-40.2), 15.0 (10.7-21.3), 40.3 (22.0-47.0), and 20.4 (9.2-30.7) months, respectively (p=0.83). There were 27 patients that received single agent chemotherapy and 41 patients that received combined regimen. There were 17 (42%) patients and 13 (48%) patients with partial response or stable disease in single and combined regimen. There were no differences in progression free survival and overall survival between single and multi agent chemotherapy. Conclusions: In this largest single institution study, second-line chemotherapy regimens for gallbladder cancer provided benefit in select patients and there is an urgent need to develop more active therapeutic regimens.
Response to Comment on Bress et al. Effect of Intensive Versus Standard Blood Pressure Treatment According to Baseline Prediabetes Status: A Post Hoc Analysis of a Randomized Trial. Diabetes Care 2017;40:1401–1408
Authors: Adam P. Bress, Vasilios Papademetriou, Mark N. Feinglos
Journal: Diabetes Care (2018)

We thank Neves et al. (1) for their comments on our article (2). They agree with our findings that results from the Systolic Blood Pressure Intervention Trial (SPRINT) demonstrate that the beneficial effects of intensive systolic blood pressure control are consistent among those with prediabetes and normoglycemia. We found no attenuation of effect of intensive systolic blood pressure control at higher fasting serum glucose levels, including patients with fasting serum glucose levels approaching the diabetic range (i.e., >126 mg/dL) (2). Although this analysis was not a prespecified subgroup analysis in SPRINT, we determined the need for this particular analysis based on considerations external …
Daily Rhythms of TNFα Expression and Food Intake Regulate Synchrony of Plasmodium Stages with the Host Circadian Cycle
Authors: Isabella Cristina Hirako, Patrícia Aparecida Assis, Natália Satchiko Hojo-Souza, George Reed, Helder Nakaya, Douglas Taylor Golenbock, Roney Santos Coimbra, Ricardo Tostes Gazzinelli
Journal: Cell Host & Microbe (2018)
Functional role of endothelial CXCL16/CXCR6-platelet–leucocyte axis in angiotensin II-associated metabolic disorders
Authors: Aida Collado, Patrice Marques, Paula Escudero, Cristina Rius, Elena Domingo, Sergio Martinez-Hervás, José T Real, Juan F Ascaso, Laura Piqueras, Maria-Jesus Sanz
Journal: Cardiovascular Research (2018)

Angiotensin-II (Ang-II) is the main effector peptide of the renin-angiotensin system (RAS) and promotes leucocyte adhesion to the stimulated endothelium. Because RAS activation and Ang-II signalling are implicated in metabolic syndrome (MS) and abdominal aortic aneurysm (AAA), we investigated the effect of Ang-II on CXCL16 arterial expression, the underlying mechanisms, and the functional role of the CXCL16/CXCR6 axis in these cardiometabolic disorders.Results from in vitro chamber assays revealed that CXCL16 neutralization significantly inhibited mononuclear leucocyte adhesion to arterial but not to venous endothelial cells. Flow cytometry and immunofluorescence studies confirmed that Ang-II induced enhanced endothelial CXCL16 expression, which was dependent on Nox5 up-regulation and subsequent RhoA/p38-MAPK/NFκB activation. Flow cytometry analysis further showed that MS patients had higher levels of platelet activation and a higher percentage of circulating CXCR6-expressing platelets, CXCR6-expressing-platelet-bound neutrophils, monocytes, and CD8+ lymphocytes than age-matched controls, leading to enhanced CXCR6/CXCL16-dependent adhesion to the dysfunctional (Ang-II- and TNFα-stimulated) arterial endothelium. Ang-II-challenged apolipoprotein E-deficient (apoE-/-) mice had a higher incidence of AAA, macrophage, CD3+, and CXCR6+ cell infiltration and neovascularization than unchallenged animals, which was accompanied by greater CCL2, CXCL16, and VEGF mRNA expression within the lesion together with elevated levels of circulating soluble CXCL16. Significant reductions in these parameters were found in animals co-treated with the AT1 receptor antagonist losartan or in apoE-/- mice lacking functional CXCR6 receptor (CXCR6GFP/GFP).CXCR6 expression on platelet-bound monocytes and CD8+ lymphocytes may constitute a new membrane-associated biomarker for adverse cardiovascular events. Moreover, pharmacological modulation of this axis may positively affect cardiovascular outcome in metabolic disorders linked to Ang-II.
Potential Association of Anti-CCR4 Antibody Mogamulizumab and Graft-vs-Host Disease in Patients With Mycosis Fungoides and Sézary Syndrome
Authors: Julia Dai, Timothy H. Almazan, Eric K. Hong, Michael S. Khodadoust, Sally Arai, Wen-Kai Weng, Youn H. Kim
Journal: JAMA Dermatology (2018)

This case series describes the occurrence of graft-vs-host-disease (GVHD) in patients with cutaneous T-cell lymphomas (CTCLs) treated with the CC chemokine receptor 4 (CCR4) antibody mogalizumab prior to allogeneic hematopoietic stem cell transplantation (HSCT).
The prognostic value of a modified tumor regression grade after neoadjuvant chemoradiotherapy and resection of esophageal carcinoma.
Authors: Maarten CJ Anderegg, Sjoerd M Lagarde, Wernard A Borstlap, Suzanne S Gisbertz, Sybren L. Meijer, Maarten Hulshof, Jacques Bergman, Olivier R.C. Busch, Hanneke W.M. Van Laarhoven, Mark I van Berge Henegouwen
Journal: Journal of Clinical Oncology (2015)

4066 Background: The tumor regression grade (TRG) is used to define the response to preoperative chemoradiotherapy for esophageal carcinoma. The aim of this study was to determine whether inclusion of the postoperative pathological nodal status could improve the prognostic value of TRG. Methods: All patients who underwent an esophagectomy after chemoradiotherapy between 2003 and 2013 were included in this retrospective study. Patients were classified according to a modified TRG consisting of the TRG by Mandard et al (TRG 1 = complete response in the esophagus; TRG > 1 = incomplete response) and the postoperative node category (N0 = no lymph node metastases; N+ = at least 1 lymph node metastasis). Based on the TRG by Mandard and this modified TRG Kaplan-Meier survival analyses were performed and compared. Results: 411 patients underwent neoadjuvant chemoradiotherapy followed by esophagectomy. After exclusion due to non-specific histology (n = 2), unknown TRG (n = 3), intraoperative detection of distant metastases (n = 3), salvage procedures (n = 17) and in-hospital mortality (n = 15) 371 patients were analysed (289 adenocarcinoma, 82 squamous cell carcinoma). A significantly improved median disease free survival was observed in patients with TRG 1 compared to patients with TRG > 1 (90.3 vs. 30.8 months, P = 0.004). After implementation of the modified TRG significant differences in median disease free survival were found between the four categories: TRG 1-N0 (n = 76) 90.3 months; TRG 1-N+ (n = 10) 20.8 months; TRG > 1-N0 (n = 146) 81.3 months; TRG > 1-N+ (n = 139) 18.1 months (P < 0.001). Conclusions: The TRG, determined in the primary tumor, provides insufficient information about the prognosis after chemoradiotherapy followed by resection of esophageal cancer. It is advisable to use a modified classification in which the postoperative pathological nodal status is considered.
Abstract B35: An innovative in vivo model of metastasizing prostate cancer using orthotopic xenografts
Authors: Johannes Linxweiler, Christina Körbel, Andreas Müller, Markus Hammer, Michael Stöckle, Kerstin Junker, Michael D. Menger
Journal: Cancer Research (2018)

Abstract Introduction: In this study, we aimed to develop a versatile in vivo model of prostate cancer using orthotopic xenografts, which adequately represents intraprostatic tumor growth as well as the natural routes of metastatic spread. Materials and Methods: 5x105 VCaP-, LuCaP136-, and LuCaP147 cells were injected into the prostate of male CB17-SCID mice (n=8 for each cell line; VCaP cultured as monolayer, LuCaP136 and LuCaP147 as three-dimensional spheroid culture). During 12 weeks of follow-up, orthotopic tumor growth and the development of metastases was monitored by repetitive serum-PSA measurements and imaging studies (ultrasonography, CT, MRI). At autopsy, primary tumors and metastases were harvested and examined by conventional histology (H&amp;E) and immunohistochemistry (CK5, CK8, AMACR, AR, Ki67, ERG, PSA). From the results of the imaging studies and PSA measurements, tumor volume doubling time, tumor-specific growth rate, and PSA-density were calculated for each cell line. Results: All 24 mice developed orthotopic tumors, whose growth could be reliably monitored by ultrasonography, CT, MRI, and serum-PSA measurements. 4 animals died during follow-up (1 in the VCaP group, 1 in the LuCaP136 group, 2 in the LuCaP147 group). Mean PSA-density was 433.9 ng/ml per ml tumor in the VCaP group, 6.5 ng/ml per ml tumor in the LuCaP136 group, and 11.2 ng/ml per ml tumor in the LuCaP147 group. Tumor-specific growth rate and tumor volume doubling time were 3.87% per day and 21.24 days in the VCaP group, 3.11% and 27.57 days in the LuCaP136 group, and 4.47% and 16.2 days in the LuCaP147 group, respectively. In up to 100% of animals, lymph node metastases could be detected after 12 weeks (5/7 in the VCaP group, 6/7 in the LuCaP136 group, 6/6 in the LuCaP147 group). These could also be visualized by ultrasonography and MRI. Immunohistochemistry showed positive CK8, AR, and AMACR as well as negative CK5 reactions in all tumors. ERG-straining was positive in VCaP and negative in both LuCaP tumors, Ki67 proliferation indices were &amp;gt;90% in all groups. Conclusions: By using different monolayer as well as 3D spheroid cell cultures in an orthotopic xenograft model, we could establish an innovative, versatile in vivo model of prostate cancer, which enables the study of both intraprostatic tumor growth as well as metastatic spread to regional lymph nodes. Citation Format: Johannes Linxweiler, Christina Körbel, Andreas Müller, Markus Hammer, Michael Stöckle, Kerstin Junker, Michael D. Menger. An innovative in vivo model of metastasizing prostate cancer using orthotopic xenografts [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr B35.
Outbreaks Associated with Untreated Recreational Water — United States, 2000–2014
Authors: Daniel S. Graciaa, Jennifer R. Cope, Virginia A. Roberts, Bryanna L. Cikesh, Amy M. Kahler, Marissa Vigar, Elizabeth D. Hilborn, Timothy J. Wade, Lorraine C. Backer, Susan P. Montgomery, W. Evan Secor, Vincent R. Hill, Michael J. Beach, Kathleen E. Fullerton, Jonathan S. Yoder, Michele C. Hlavsa
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Untreated recreational water is water that has not undergone a disinfection or treatment process to maintain good microbiological quality for recreation.recreational water or to pathogens, toxins, or chemicals aerosolized or volatilized from recreational water into the surrounding air.Public health officials in the 50 states, the District of Columbia, U.S. territories, and Freely Associated States † can voluntarily report recreational water-associated outbreaks to CDC.This report focuses on data on two groups of untreated recreational water-associated outbreaks: 1) those that began during 2000-2012 and were previously reported (1), and † Includes Federated States of Micronesia, Marshall Islands, and Palau.
Fast Forward — Neoadjuvant Cancer Immunotherapy
Authors: Thomas F Gajewski
Journal: New England Journal of Medicine (2018)

Immunotherapies that are based on blocking the axis of the programmed death 1 (PD-1) pathway are having a transformational effect in cancer medicine. To date, the Food and Drug Administration has approved PD-1 pathway inhibitors for 10 types of cancer, with continued clinical study under way. The therapeutic efficacy of these drugs relies on endogenous tumor-antigen–specific T cells that are functionally held in check by negative signaling through PD-1. Preclinical models and human correlative biomarker data indicate that efficacy depends on antitumor CD8+ T cells that are recruited into the tumor microenvironment and that are functionally restrained. Treatment with PD-1 . . .
HIPAA and Protecting Health Information in the 21st Century
Authors: I. Glenn Cohen, Michelle M. Mello
Journal: JAMA (2018)

HIPAA and Protecting Health Information in the 21st CenturyIn March 2018, the Trump administration announced a new initiative, MyHealthEData, to give patients greater access to their electronic health record and insurance claims information. 1 The Centers for Medicare & Medicaid Services will connect Medicare beneficiaries with their claims data and increase pressure on health plans and health care organizations to use systems that allow patients to access and send their health information where they like.MyHealthEData is part of a broader movement to make greater use of patient data to improve care and health.The movement seeks to make information available wherever patients receive care and allow patients to share information with apps and other online services that may help them manage their health.At the population level, this approach may help identify optimal treatments andwaysofdeliveringthemandalsoconnectpatientswith healthservicesandproductsthatmaybenefitthem.Analysis of deidentified patient information has long been the foundation of evidence-based care improvement, but the 21st century has brought new opportunities.With developmentsininformationtechnologyandcomputationalsciencethatsupporttheanalysisofmassivedatasets,the"big data" era has come to health services research.For all its promise, the big data era carries with it substantialconcernsandpotentialthreats.Partofwhatenables individuals to live full lives is the knowledge that certain personal information is not on view unless that person decides to share it, but that supposition is becoming illusory.The increasing availability and exchange of healthrelated information will support advances in health care and public health but will also facilitate invasive marketing and discriminatory practices that evade current antidiscrimination laws. 2 As the recent scandal involving Facebook and Cambridge Analytica shows, a further risk is that private information may be used in ways that have notbeenauthorizedandmaybeconsideredobjectionable.Reinforcing such concerns is the stunning report that Facebook has been approaching health care organizations to try to obtain deidentified patient data to link those data to individual Facebook users using "hashing" techniques. 3iven these concerns, it is timely to reexamine the adequacy of the Health Insurance Portability and Accountability Act (HIPAA), the nation's most important legal safeguard against unauthorized disclosure and use of health information.Is HIPAA up to the task of protecting health information in the 21st century?
Solitary chemosensory cells are a primary epithelial source of IL-25 in patients with chronic rhinosinusitis with nasal polyps
Authors: Michael A. Kohanski, Alan D. Workman, Neil N. Patel, Li-Yin Hung, Julie P. Shtraks, Bei Chen, Mariel Blasetti, Laurel Doghramji, David W. Kennedy, Nithin D. Adappa, James N. Palmer, De'Broski R. Herbert, Noam A. Cohen
Journal: Journal of Allergy and Clinical Immunology (2018)
Creating space for quality improvement
Authors: Dominique Allwood, Rebecca Fisher, Will Warburton, Jennifer Dixon
Journal: BMJ (2018)

Today The BMJ and the Health Foundation are launching a joint series of papers exploring how to improve the delivery of healthcare (https://www.bmj.com/quality-improvement). 1 2 The series aims to discuss the evidence for systematic quality improvement, provide knowledge and support to clinicians, and ultimately to help improve care for patients.Stories of a disordered system abound in healthcare: the notes or test results that don't arrive, the overbooked clinic, the frail patient who wastes hours travelling to and from an appointment that the hospital had rescheduled but failed to communicate.At the front line the problems frustrate, waste time, and add avoidable risk; at national level, they add up to slow progress on quality, wasted resource, and severely dented staff enthusiasm and public trust in the NHS.
Abstract 13623: T-Axis Deviation on 12-leads Electrocardiography Can Predict Left Ventricular Dysfunction in Patients With Complete Left Bundle Branch Block
Authors: Masato Shimizu, Munehiro Iiya, Mari Ohmori, Yuta Taomoto, Toshio Kaneda, Yosuke Yamakami, Yoshikazu Sato, Hiroshi Shimada, Tomoko Manno, Hiroyuki Fujii, Makoto Suzuki, Noriyoshi Yamawake, Mitsuhiro Nishizaki, Harumizu Sakurada, Masayasu Hiraoka
Journal: Circulation (2017)

Introduction: The patients with complete left bundle branch block (CLBBB) and low left ventricular (LV) ejection fraction (EF) are often treated by cardiac resynchronization therapy (CRT). However,...
Optimizing Adjuvant Therapy for Localized Colon Cancer and Treatment Selection in Advanced Colorectal Cancer
Authors: Axel Grothey, Alan P. Venook
Journal: Journal of the National Comprehensive Cancer Network (2018)

<section class="abstract"><p id="P1">Results from the pivotal IDEA trial, which evaluated 3 versus 6 months of adjuvant oxaliplatin-based chemotherapy, are incorporated into the NCCN Guidelines for Colon Cancer. The guidelines recommend that for patients with low-risk stage III disease, the preferred regimen is CAPEOX for 3 months or FOLFOX for 3 to 6 months. For patients with high-risk stage III disease, the preferred regimen is CAPEOX for 3 to 6 months or FOLFOX for 6 months. In metastatic disease, tumor sidedness should be a consideration when choosing a biologic. For <em>BRAF</em>-mutated disease, several triplets are now recommended options. Importantly, for a subset of patients with metastatic disease, new to the NCCN Guidelines is the incorporation of nivolumab and pembrolizumab as subsequent therapy for those with microsatellite instability–high or mismatch repair–deficient tumors. </section>
Pulmonary function after treatment for embryonal brain tumors on SJMB03 that included craniospinal irradiation.
Authors: Daniel M. Green, Thomas E. Merchant, Catherine A Billups, Dennis C Stokes, Alberto Broniscer, Ashok Srinivasan, Murali M. Chintagumpala, Timothy E Hassall, Eric Bouffet, Sridharan Gururangan, Stewart J Kellie, David M Ashley, Richard J Cohn, Michael J. Fisher, Amar J. Gajjar
Journal: Journal of Clinical Oncology (2013)

10021 Background: Treatment of children with embryonal brain tumors (EBT) includes craniospinal irradiation. There are limited data regarding the effect of radiation therapy (RT) on pulmonary function. Methods: Protocol SJMB03 enrolled patients 3 to 21 years of age with EBT. Pulmonary function tests (PFTs) [forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) by spirometry, total lung capacity (TLC) by plethysmography and diffusing capacity of the lung for carbon monoxide (DLCO)] were obtained following completion of RT, prior to each of four courses of high-dose chemotherapy (cumulative cyclophosphamide dose, 16 g/m 2 ), and 24 months after completion of treatment (ACT). Differences between PFTs obtained following the completion of RT and 24 months ACT were compared using exact Wilcoxon signed rank tests. Results: 303 eligible patients were enrolled between June 24, 2003 and March 1, 2010, 258 of whom had at least one PFT. Median age at diagnosis - 8.9 years (range, 3.1 to 20.4 years). Median spinal RT dose - 23.4 Gy (range, 23.4 to 50.4 Gy). Median cyclophosphamide dose was 16.24 g (range, 0 to 34.38 g). 24 months ACT, DLCO was &lt; 75% predicted in 23% (27/115 evaluated), FEV1 was &lt; 80% predicted in 21% (32/150 evaluated), FVC was &lt; 80% predicted in 27% (46/168 evaluated) and TLC was &lt; 80% predicted in 18% (24/135 evaluated) of patients. DLCO was significantly decreased 24 months ACT compared to the end of RT (median difference (MD) in % predicted, - 3.00%; p = 0.035). Race and cumulative cyclophosphamide dose were not significant predictors of DLCO. DLCO was significantly higher among males (p = 0.037) than females in a model that included time point, sex, RT dose group, RT dose*time interaction and age at diagnosis. The differences in FEV1 ((MD, - 1.00%), FVC (MD, 0.00%) and TLC (MD, -2.00%) were not statistically significant. Conclusions: Among patients with EBT treated with spinal RT, DLCO was significantly decreased 24 months after completion of treatment compared to immediately post-RT. TLC was decreased 24 months ACT, suggesting that a significant minority of patients have restrictive lung disease. Continued monitoring of this cohort to five years ACT is planned. Clinical trial information: NCT00085202.