tbuckley/cabot-search huggingface dataset:
Risk of gastrointestinal and hepatic toxicities in patients with metastatic solid tumors treated with cabozantinib: A systematic review and meta-analysis of randomized controlled trials.
Authors: Myo Zaw, Kyaw Zin Thein, Myat M. Han, Henry Palangdao Igid, Fred L. Hardwicke, Lukman Tijani
Journal: Journal of Clinical Oncology (2017)

208 Background: The vascular endothelial growth factor (VEGF) signaling pathways and the proto-oncogenes MET, KIT and RET were implied in cancer development and progression. Cabozantinib is an oral inhibitor of multiple tyrosine kinases and hence employed in many solid tumors. We performed a systematic review and meta-analysis of randomized controlled trials (RCT) to determine the risk of gastrointestinal (GI) and hepatic toxicities among patients with metastatic solid tumors treated with cabozantinib. Methods: MEDLINE, EMBASE databases and meeting abstracts from inception to March 2017 were queried. Phase 3 RCTs that mention GI and elevation of liver enzymes as adverse effects were incorporated in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio with 95% confidence interval (CI). Random effects model was applied. Results: We included 3 RCTs with a total of 1999 patients treated with cabozantinib for various solid tumors. The study arm used cabozantinib while the control arm utilized everolimus, placebo or prednisone. The relative risks (RR) of all-grade side effects were as follows: diarrhea, 2.39 (95% CI: 2.01 – 2.85, P &lt; 0.0001); nausea, 1.86 (95% CI: 1.64 – 2.10, P &lt; 0.0001); vomiting, 2.53 (95% CI: 1.60 – 3.99, P &lt; 0.0001); stomatitis, 4.08 (95% CI: 0.55 – 30.01, P = 0.16); dysgeusia, 4.23 (95% CI: 2.30 – 7.76, P &lt; 0.0001); elevated AST, 2.04 (95% CI: 1.12 – 3.73, P = 0.02); and elevated ALT, 1.61 (95% CI: 0.67 – 3.88, P = 0.28). The RR of high-grade side effects were as follows: diarrhea, 5.93 (95% CI: 3.43 – 10.25, P &lt; 0.0001); nausea, 4.05 (95% CI: 1.99 – 8.23, P &lt; 0.0001); vomiting, 2.37 (95% CI: 1.26 – 4.44, P = 0.007); stomatitis, 3.36 (95% CI: 0.45 – 24.98, P = 0.23); dysgeusia, 1.52 (95% CI: 0.15 – 14.57, P = 0.71); elevated AST, 1.70 (95% CI: 0.72 – 4.01, P = 0.22); and elevated ALT, 3.00 (95% CI: 0.60 – 14.93, P = 0.17). Conclusions: The risk of developing all-grade and high-grade diarrhea, nausea and vomiting with cabozantinib is high. Moreover, it is associated with all-grade elevated AST and dysgeusia. Timely recognition and providing good supportive care will enhance patients’ quality of life.
Treatment options after sorafenib failure in patients with hepatocellular carcinoma
Authors: Imane El Dika, Ghassan K. Abou-Alfa
Journal: Clinical and Molecular Hepatology (2017)

Second line therapy after failure of sorafenib continues to be under study. Prognosis of hepatocellular carcinoma is measured in months, with median overall survival reaching 10.7 months with sorafenib. Because of the modest net benefit sorafenib has contributed, and rising incidence of hepatocellular carcinoma in the world, continued efforts are ongoing to look for efficient upfront, second line, or combination therapies. Herein we review the most relevant to date published literature on treatment options beyond sorafenib, reported studies, ongoing investigational efforts, and possibilities for future studies in advanced hepatocellular carcinoma. Keywords: Hepatocellular carcinoma; Antiangiogenic therapy; MET-inhibitors; Immunotherapy
miR-25 Tough Decoy Enhances Cardiac Function in Heart Failure
Authors: Dongtak Jeong, Jimeen Yoo, Philyoung Lee, Sacha V. Kepreotis, Ahyoung Lee, Christine Wahlquist, Brian D. Brown, Changwon Kho, Mark Mercola, Roger J. Hajjar
Journal: Molecular Therapy (2017)

MicroRNAs are promising therapeutic targets, because their inhibition has the potential to normalize gene expression in diseased states. Recently, our group found that miR-25 is a key SERCA2a regulating microRNA, and we showed that multiple injections of antagomirs against miR-25 enhance cardiac contractility and function through SERCA2a restoration in a murine heart failure model. However, for clinical application, a more stable suppressor of miR-25 would be desirable. Tough Decoy (TuD) inhibitors are emerging as a highly effective method for microRNA inhibition due to their resistance to endonucleolytic degradation, high miRNA binding affinity, and efficient delivery. We generated a miR-25 TuD inhibitor and subcloned it into a cardiotropic AAV9 vector to evaluate its efficacy. The AAV9 TuD showed selective inhibition of miR-25 in vitro cardiomyoblast culture. In vivo, AAV9-miR-25 TuD delivered to the murine pressure-overload heart failure model selectively decreased expression of miR-25, increased levels of SERCA2a protein, and ameliorated cardiac dysfunction and fibrosis. Our data indicate that miR-25 TuD is an effective long-term suppressor of miR-25 and a promising therapeutic candidate to treat heart failure.
Altered Activation of Endothelial Anti- and Proapoptotic Pathways by High-Density Lipoprotein from Patients with Coronary Artery Disease
Authors: Meliana Riwanto, Lucia Rohrer, Bernd Roschitzki, Christian Besler, Pavani Mocharla, Maja Mueller, Damir Perisa, Kathrin Heinrich, Lukas Altwegg, Arnold von Eckardstein, Thomas F. Lüscher, Ulf Landmesser
Journal: Circulation (2013)

Background— Endothelial dysfunction and injury are thought to play an important role in the progression of coronary artery disease (CAD). High-density lipoprotein from healthy subjects (HDL Healthy ) has been proposed to exert endothelial antiapoptotic effects that may represent an important antiatherogenic property of the lipoprotein. The present study therefore aimed to compare effects of HDL CAD and HDL Healthy on the activation of endothelial anti- and proapoptotic pathways and to determine which changes of the lipoprotein are relevant for these processes. Methods and Results— HDL was isolated from patients with stable CAD (HDL sCAD ), an acute coronary syndrome (HDL ACS ), and healthy subjects. HDL Healthy induced expression of the endothelial antiapoptotic Bcl-2 protein Bcl-xL and reduced endothelial cell apoptosis in vitro and in apolipoprotein E–deficient mice in vivo. In contrast, HDL sCAD and HDL ACS did not inhibit endothelial apoptosis, failed to activate endothelial Bcl-xL, and stimulated endothelial proapoptotic pathways, in particular, p38-mitogen-activated protein kinase–mediated activation of the proapoptotic Bcl-2 protein tBid. Endothelial antiapoptotic effects of HDL Healthy were observed after inhibition of endothelial nitric oxide synthase and after delipidation, but not completely mimicked by apolipoprotein A-I or reconstituted HDL, suggesting an important role of the HDL proteome. HDL proteomics analyses and subsequent validations and functional characterizations suggested a reduced clusterin and increased apolipoprotein C-III content of HDL sCAD and HDL ACS as mechanisms leading to altered effects on endothelial apoptosis. Conclusions— The present study demonstrates for the first time that HDL CAD does not activate endothelial antiapoptotic pathways, but rather stimulates potential endothelial proapoptotic pathways. HDL-proteome remodeling plays an important role for these altered functional properties of HDL. These findings provide novel insights into mechanisms leading to altered vascular effects of HDL in coronary disease.
Extensive virologic and immunologic characterization in an HIV-infected individual following allogeneic stem cell transplant and analytic cessation of antiretroviral therapy: A case study
Authors: Nathan W. Cummins, Stacey Rizza, Mark R. Litzow, Stephane Hua, Guinevere Q. Lee, Kevin Einkauf, Tae-Wook Chun, Frank Rhame, Jason V. Baker, Michael P. Busch, Nicolas Chomont, Patrick G. Dean, Rémi Fromentin, Ashley T. Haase, Dylan Hampton, Sheila M. Keating, Steven M. Lada, Tzong-Hae Lee, Sekar Natesampillai, Douglas D. Richman, Timothy W. Schacker, Stephen Wietgrefe, Xu G. Yu, Joseph D. Yao, John Zeuli, Mathias Lichterfeld, Andrew D. Badley
Journal: PLoS Medicine (2017)

Background Notwithstanding 1 documented case of HIV-1 cure following allogeneic stem cell transplantation (allo-SCT), several subsequent cases of allo-SCT in HIV-1 positive individuals have failed to cure HIV-1 infection. The aim of our study was to describe changes in the HIV reservoir in a single chronically HIV-infected patient on suppressive antiretroviral therapy who underwent allo-SCT for treatment of acute lymphoblastic leukemia. Methods and findings We prospectively collected peripheral blood mononuclear cells (PBMCs) by leukapheresis from a 55-year-old man with chronic HIV infection before and after allo-SCT to measure the size of the HIV-1 reservoir and characterize viral phylogeny and phenotypic changes in immune cells. At day 784 post-transplant, when HIV-1 was undetectable by multiple measures—including PCR measurements of both total and integrated HIV-1 DNA, replication-competent virus measurement by large cell input quantitative viral outgrowth assay, and in situ hybridization of colon tissue—the patient consented to an analytic treatment interruption (ATI) with frequent clinical monitoring. He remained aviremic off antiretroviral therapy until ATI day 288, when a low-level virus rebound of 60 HIV-1 copies/ml occurred, which increased to 1,640 HIV-1 copies/ml 5 days later, prompting reinitiation of ART. Rebounding plasma HIV-1 sequences were phylogenetically distinct from proviral HIV-1 DNA detected in circulating PBMCs before transplantation. The main limitations of this study are the insensitivity of reservoir measurements, and the fact that it describes a single case. Conclusions allo-SCT led to a significant reduction in the size of the HIV-1 reservoir and a >9-month-long ART-free remission from HIV-1 replication. Phylogenetic analyses suggest that the origin of rebound virus was distinct from the viruses identified pre-transplant in the PBMCs.
Collaborative Efforts With Opioid Users to Promote Competence and Voluntariness in Clinical Trials With Injectable Opioid Assisted Treatment
Authors: Kirsten Marchand, Daniel Steel, Eugenia Oviedo-Joekes
Journal: The American Journal of Bioethics (2017)

Our target article “Our Life Depends on this Drug: Competence, Inequity, and Voluntary Consent in Clinical Trials on Supervised Injectable Opioid Assisted Treatment” (Steel, Marchand, and Oveido-Jo...
Our Life Depends on This Drug: Competence, Inequity, and Voluntary Consent in Clinical Trials on Supervised Injectable Opioid Assisted Treatment
Authors: Daniel Steel, Kirsten Marchand, Eugenia Oviedo-Joekes
Journal: The American Journal of Bioethics (2017)

Supervised injectable opioid assisted treament (siOAT) prescribes injectable opioids to individuals for whom other forms of addiction treatment have been ineffective. In this article, we examine arguments that opioid-dependent people should be assumed incompetent to voluntarily consent to clinical research on siOAT unless proven otherwise. We agree that concerns about competence and voluntary consent deserve careful attention in this context. But we oppose framing the issue solely as a matter of the competence of opioid-dependent people and emphasize that it should be considered in the context of inequities in access to siOAT as a medical treatment. Consequently, we suggest that bioethics literature on nonexploitation, which focuses on clinical research in low-income countries, is helpful due to locating ethical issues within systemic social conditions. Finally, we consider the implications of our argument for the ethics of clinical research on siOAT.
THU0175 The celecoxib long-term arthritis safety study (class): celecoxib is associated with less renal toxicity compared to conventional nonsteroidal anti-inflammatory drugs (nsaids)
Authors: A Whelton
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> Conventional NSAIDs, which nonselectively inhibit cyclooxygenase (COX)-1 and COX-2, are associated with deleterious effects on renal function such as reductions in glomerular filtration rate and sodium retention. Celecoxib specifically inhibits COX-2. Such specific inhibition raises the possibility that the incidence of renal toxicity vs conventional NSAIDs may be reduced. <h3>Methods</h3> In a randomised, double-blind trial with exposures of up to 15 months, 7968 patients with osteoarthritis (OA) (n = 5746) or rheumatoid arthritis (RA) (n = 2183) were randomised to receive supratherapeutic doses of celecoxib (400 mg BID; n = 3,987) vs ordinary therapeutic doses of conventional NSAIDs: ibuprofen (800 mg TID; n = 1996) or diclofenac (75 mg BID; n = 1985). <h3>Results</h3> Fewer celecoxib-treated patients experienced renal toxicity compared to patients treated with NSAIDs (see Table 1; *p &lt; 0.05 vs celecoxib, **serum creatinine levels above 2 mg/dL and/or BUN values above 40 mg/dL). <h3>Conclusion</h3> Celecoxib at supratherapeutic doses was associated with a lower incidence of renal toxicity compared to conventional NSAIDs at ordinary therapeutic doses. Sponsored by Pharmacia Corporation and Pfizer, Inc.
Action sequences instead of representational levels
Authors: Ruth Kempson, Eleni Gregoromichelaki
Journal: Behavioral and Brain Sciences (2017)

Abstract Despite enthusiastic agreement that experimental data are directly relevant for determining grammar architecture, we present one main objection to the conclusions that the authors draw from their results: The data are perfectly compatible – in fact, much more in line – with an alternative that does not rely on syntactic representations. Instead, it is processing actions whose activation for comprehension/production explains intra-/inter-speaker priming.
Preoperative evaluation of older cancer patients: Why some patients did not proceed with planned surgery.
Authors: Taylor Raines Williams, Koshy Alexander, Beatriz Korc-Grodzicki, Saman Sarraf, Armin Shahrokni
Journal: Journal of Clinical Oncology (2017)

38 Background: Older cancer patients may need to make challenging treatment decisions at the time of preoperative evaluation. This study assesses the reasons and outcomes of older cancer patients who did not proceed with planned surgery. Methods: This is a retrospective analysis of a cohort of 1767 older cancer patients who presented to the Geriatrics clinic for preoperative evaluation between 1/2015 and 12/2016. Differences in Geriatric Assessment between those who proceeded and did not proceed with surgery were assessed within a month after preoperative evaluation. Charts of those who did not proceed with surgery were reviewed to identify the reasons, and outcomes of those patients. Results: In total, 114 out of 1767 (6.5%) did not proceed with surgery. Functional status played an important role in this decision. Among patients with Karnofsky Performance Scale (KPS) of 80+, 20% had their procedure in another institution; this was 0% for patients with KPS 70-. 61% of patients with KPS 50 opted for surveillance or supportive care, compared to 37% and 32% of those with KPS 60-70 and 80+, respectively. Reasons cited for not medically clearing the patients also differed. 60% and 69% of those with KPS 80+ and 60-70 were not cleared based on comorbid conditions, compared to 44% of those with KPS 50-. On the other hand, 44% of patients with KPS 50- had documented frailty as a reason for not getting clearance, compared to 15% and 23% of those with KPS 80+ and KPS 60-70. Conclusions: Geriatricians play an important role in helping patients reach proper medical decisions at the time of surgery. Future studies should look at various interventions that may assist older cancer patients/caregivers in their decision making at the time of surgery.
Abstract 20118: Current Smoking and Renal Dysfunction are Important Prognostic Factors following Successful De-novo Chronic Total Occlusion Intervention: 3-year Outcome Analysis
Authors: Yong Hoon Kim, Seung-Woon Rha, Ae-Young Her, Byoung Geol Choi, Se Yeon Choi, Jae Kyeong Byun, Yoonjee Park, Ahmed Mashaly, Won Young Jang, Woo Hyeun Kim, Eun Jin Park, Jah Yeon Choi, Jin Oh Na, Cheol Ung Choi, Hong Euy Lim, Eung Ju Kim, Chang Gyu Park, Hong Seog Seo, Dong Joo Oh
Journal: Circulation (2017)

Background:  Procedural success rates of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) has dramatically improved in recent years due to development of new devices and techniques. However, limited data are available for long-term prognostic clinical factors following successful PCI for de-novo coronary CTO lesions. We evaluated important prognostic factors in patients (pts) underwent successful de-novo CTO PCI during 3-year clinical follow up.   Method:  Between March 2004 and December 2012 total 266 consecutive pts who underwent successful PCI for de-novo coronary CTO lesions were enrolled; among them, 195 pts (73.3%) were male. The mean age was 62.2±23 years. Multi-vessel CTO and failed CTO PCI pts were excluded. Renal dysfunction was defined as eGFR 2 . Major adverse cardiovascular events (MACE) was defined as a composite of death, myocardial infarction (MI), target CTO lesion revascularization (TLR) and target CTO vessel revascularization (TVR). Independent predictors for MACE were evaluated up to 3 years.   Results:  At 3-year follow-up, current smoking (HR 3.567; 95% CI, 1.352-9.409; p = 0.010), and renal dysfunction (HR 5.297; 95% CI, 1.130-24.821; p = 0.034) were independent predictors of MACE following successful de-novo CTO PCI (Table).   Conclusion:  Current smoking and renal dysfunction are important prognostic factors following successful de-novo CTO PCI at 3 years.
Serum-Protein Changes in Malignant Disease. II. The Chronic Leukemias, Hodgkin's Disease, and Malignant Melanoma
Authors: Dane R. Boggs, M.D., John L. Fahey, M.D.
Journal: JNCI Journal of the National Cancer Institute (1960)

Four malignant neoplasms were investigated and each showed differing changes in the serum proteins. Uncomplicated chronic lymphocytic leukemia was characterized by hypogammaglobulinemia, chronic myelocytic leukemia by hypergammaglobulinemia, Hodgkin's disease by increased α-globulins and decreased albumin, and malignant melanoma by lowered serum-albumin levels. The changes with each malignant disease depend, in part at least, on the stage of disease activity. Hodgkin's disease strikingly displayed this fact where disease remission was associated with complete return of the serum-protein pattern to normal. Serum-albumin levels remained normal in most patients with uncomplicated chronic leukemia, even in the late stage of disease; the β-globulin level was little altered, even in the presence of marked changes in other serum proteins, and no characteristic pattern of serum-protein response could be found for all malignancy per se. Frequent complications of many malignant processes, such as infection, fever of undetermined etiology, or liver disease, produced further protein changes that were a reflection of the particular complication rather than of the primary type of neoplastic disease. Nitrogen mustard, tris(1-aziridinyl) phosphine sulfide (thio-TEPA), and adrenocortical steroids could not be shown to influence serum-protein levels directly.
Do hospitalized cancer patients requiring palliative care consultation discharged to subacute rehabilitation ever get anticancer therapy again?
Authors: Muhammad Azeem Khan, Clint S. Pettit, Hunter Groninger
Journal: Journal of Clinical Oncology (2017)

62 Background: Patients with advanced cancer inevitably experience a functional decline that is often associated with notable symptom burden and/or indications for clarification of goals. Palliative care (PC) services frequently engage such patients during hospital stays. For many of these patients, discharge plans to sub-acute rehabilitation facilities (SAR) in order to ‘gain strength’ for future cancer treatment is a common practice. We wished to examine if inpatients with advanced cancer receiving PC consultation who are discharged to SAR are ever able to follow up with their oncology team and receive anti-cancer therapy. Methods: A search was conducted in our institution’s electronic medical system for hospitalized patients with cancer who received inpatient PC consultation and were subsequently discharged to SAR. Patients were excluded if they did not follow with an oncologist at MWHC as an out patient prior to the admission being reviewed or if they had never received anti cancer therapy before. Results: From 2015-2017, 16 patients meeting our criteria were identified. For 14 (82.4%) patients Palliative Care was consulted to either discuss goals of care and/or assist with pain management.13 (76%) patients were discharged to SAR to ‘improve strength’. However only 7 (44%) patients saw their oncologist after discharge from SAR. Of those 7 only 3 (19%) received further anti cancer therapy. 4 of the 7 (57%) patients that saw their oncologist after SAR had an ECOG of 1 on admission, the other 3 had an ECOG of 2. No patient with an ECOG of 2 or greater ever received cancer treatment again. Exactly half of the 16 patients were eventually readmitted to our hospital. Conclusions: SAR may not be an appropriate discharge disposition for patients with cancer who have a decline in functional status. Less than half the patients with cancer discharged to SAR from our institute with the intention to gain strength for future chemotherapy saw their oncologist again and the overwhelming majority (particularly those with an ECOG performance score of 2 and greater) never received anti cancer therapy again. This data can be considered to make informed decisions when discussing goals of care.
Abstract 15368: Simple Interventions Improve Cardiopulmonary Resuscitation Quality Measures During Team-Based Training
Authors: Christopher Berry, Bo Zhu, Kenneth Glassford, Anthony Halupa, Eliza Reed, Thomas D Sallade, Chris Raup, Douglas F Kupas
Journal: Circulation (2017)

Introduction: High-quality CPR is essential to survival from cardiac arrest, yet the skill of resuscitation teams in delivering quality CPR is often poor. The purpose of this study was to evaluate ...
P1.06-045 Multiple Neoplasms Consist of Lung Cancer and Hematological Malignancies
Authors: Kazuhiko Natori, Daisuke Nagase, Susumu Ishihara, Yurika Mitsui, Akiko Sakai, Yasunobu Kuraishi, Haruka Izumi
Journal: Journal of Thoracic Oncology (2017)
Recomendações para a vigilância do VIH na Europa
Authors: F F Hamers
Journal: Eurosurveillance (1998)

A epidemia de VIH/SIDA na Europa esta actualmente num ponto importante da sua historia. Na Europa Ocidental, a incidencia da SIDA tem estado a diminuir desde 1996 em parte como resultado de novos e mais efectivos tratamentos das infeccoes pelo VIH. Como estes tratamentos atrasam a progressao da infeccao pelo VIH, as tendencias da SIDA sao significativamente afectadas e o numero de casos de SIDA ja nao reflecte o numero de pessoas com doenca grave provocada pelo VIH em necessidade de cuidados.
Gripa aviar y pandemia gripal – cinco preguntas para 2006
Authors: A Nicoll
Journal: Eurosurveillance (2005)

En Enero de este ano, se observo que 2005 iba a ser el ano del Gallo en el calendario chino, y que talvez eso seria un mal presagio para la gripe del pollo (aviar) y la pandemia gripal. Es cierto que la gripe ha sido la infeccion que domino la prensa popular en 2005, y asi, se puede decir que fue un muy “buen” ano para la gripe y los que la estudian. La enfermedad capto la atencion que merece en terminos de amenaza para los humanos.
Tackling the health burden of air pollution in South Asia
Authors: Bhargav Krishna, Kalpana Balakrishnan, Amna R Siddiqui, Bilkis A Begum, Damodar Bachani, Michael Brauer
Journal: BMJ (2017)

Bhargav Krishna and colleagues call for health driven, multisectoral policy making with defined air quality targets to curb the impact of air pollution exposure in South Asia