tbuckley/cabot-search huggingface dataset:
Dual Inhibition of EGFR with Afatinib and Cetuximab in Kinase Inhibitor–Resistant <i>EGFR</i>-Mutant Lung Cancer with and without T790M Mutations
Authors: Yelena Y. Janjigian, Egbert F. Smit, Harry J.M. Groen, Leora Horn, Scott Gettinger, D. Ross Camidge, Gregory J. Riely, Bushi Wang, Yali Fu, Vikram K. Chand, Vincent A. Miller, William Pao
Journal: Cancer Discovery (2014)

EGFR-mutant lung cancers responsive to reversible EGFR inhibitors (gefitinib/erlotinib) develop acquired resistance, mediated by second-site EGFR T790M mutation in >50% of cases. Preclinically, afatinib (irreversible ErbB family blocker) plus cetuximab (anti-EGFR monoclonal antibody) overcomes T790M-mediated resistance. This phase Ib study combining afatinib and cetuximab enrolled heavily pretreated patients with advanced EGFR-mutant lung cancer and acquired resistance to erlotinib/gefitinib. Patients provided post-acquired-resistance tumor samples for profiling EGFR mutations. Among 126 patients, objective response rate (overall 29%) was comparable in T790M-positive and T790M-negative tumors (32% vs. 25%; P = 0.341). Median progression-free survival was 4.7 months (95% confidence interval, 4.3-6.4), and the median duration of confirmed objective response was 5.7 months (range, 1.8-24.4). Therapy-related grade 3/4 adverse events occurred in 44%/2% of patients. Afatinib-cetuximab demonstrated robust clinical activity and a manageable safety profile in EGFR-mutant lung cancers with acquired resistance to gefitinib or erlotinib, both with and without T790M mutations, warranting further investigation.This article reports the results of a trial combining afatinib and cetuximab in patients with acquired resistance and details the first clinical proof-of-concept for the preclinical hypothesis that a significant proportion of tumors in patients with acquired resistance to gefitinib/erlotinib remain dependent on EGFR signaling for survival.
Lectin-like, oxidized low-density lipoprotein receptor-1 (LOX-1): A critical player in the development of atherosclerosis and related disorders
Authors: J MEHTA, J CHEN, P HERMONAT, F ROMEO, G NOVELLI
Journal: Cardiovascular Research (2005)

LOX-1, a lectin-like 52-kD receptor for oxidized low-density lipoproteins (ox-LDL), is present primarily on endothelial cells. This receptor is upregulated by ox-LDL itself and by angiotensin II, endothelin, cytokines, and shear stress, all participants in atherosclerosis. This receptor is upregulated in the arteries of hypertensive, dyslipidemic, and diabetic animals. Upregulation of LOX-1 has been identified in atherosclerotic arteries of several animal species and humans, not only on the endothelial lining, but also in the neovasculature of the atherosclerotic plaque, and this receptor is often co-localized with apoptotic cells. Recent studies show upregulation of LOX-1 in the ischemic-reperfused myocardium. LOX-1 inhibition is associated with attenuation of atherosclerosis and associated ischemic injury. LOX-1 may be a novel, exciting target for drug therapy.
The impact of early goal-directed fluid management on survival in an experimental model of severe acute pancreatitis
Authors: Constantin J. C. Trepte, Kai A. Bachmann, Jan H. Stork, Till J. Friedheim, Andrea Hinsch, Matthias S. Goepfert, Olliver Mann, Jakob R. Izbicki, Alwin E. Goetz, Daniel A. Reuter
Journal: Intensive Care Medicine (2013)
Early Revascularization and Long-term Survival in Cardiogenic Shock Complicating Acute Myocardial Infarction
Authors: Judith S. Hochman, Lynn A. Sleeper, John G. Webb, Vladimir Dzavik, Christopher E. Buller, Philip Aylward, Jacques Col, Harvey D. White, for the SHOCK Investigators
Journal: JAMA (2006)

Cardiogenic shock remains the major cause of death for patients hospitalized with acute myocardial infarction (MI). Although survival in patients with cardiogenic shock complicating acute MI has been shown to be significantly higher at 1 year in those receiving early revascularization vs initial medical stabilization, data demonstrating long-term survival are lacking.To determine if early revascularization affects long-term survival of patients with cardiogenic shock complicating acute MI.The Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock (SHOCK) trial, an international randomized clinical trial enrolling 302 patients from April 1993 through November 1998 with acute myocardial infarction complicated by cardiogenic shock (mean [SD] age at randomization, 66 [11] years); long-term follow-up of vital status, conducted annually until 2005, ranged from 1 to 11 years (median for survivors, 6 years).All-cause mortality during long-term follow-up.The group difference in survival of 13 absolute percentage points at 1 year favoring those assigned to early revascularization remained stable at 3 and 6 years (13.1% and 13.2%, respectively; hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.57-0.97; log-rank P = .03). At 6 years, overall survival rates were 32.8% and 19.6% in the early revascularization and initial medical stabilization groups, respectively. Among the 143 hospital survivors, a group difference in survival also was observed (HR, 0.59; 95% CI, 0.36-0.95; P = .03). The 6-year survival rates for the hospital survivors were 62.4% vs 44.4% for the early revascularization and initial medical stabilization groups, respectively, with annualized death rates of 8.3% vs 14.3% and, for the 1-year survivors, 8.0% vs 10.7%. There was no significant interaction between any subgroup and treatment effect.In this randomized trial, almost two thirds of hospital survivors with cardiogenic shock who were treated with early revascularization were alive 6 years later. A strategy of early revascularization resulted in a 13.2% absolute and a 67% relative improvement in 6-year survival compared with initial medical stabilization. Early revascularization should be used for patients with acute MI complicated by cardiogenic shock due to left ventricular failure.clinicaltrials.gov Identifier: NCT00000552.
Prevalence of allergic respiratory diseases in patients with RA
Authors: G Provenzano, G Donato, G Brai, F Rinaldi
Journal: Annals of the Rheumatic Diseases (2002)

Sonography as a replacement for sialography for the diagnosis of salivary glands affected by Sjögren's syndromeRecently, it has been suggested that sonographic evaluation of the salivary glands is useful
Congenital diaphragmatic hernia
Authors: S. Kotecha, A. Barbato, A. Bush, F. Claus, M. Davenport, C. Delacourt, J. Deprest, E. Eber, B. Frenckner, A. Greenough, A.G. Nicholson, J.L. Antón-Pacheco, F. Midulla
Journal: European Respiratory Journal (2011)

Infants with congenital diaphragmatic hernia (CDH) have significant mortality and long-term morbidity. Only 60–70% survive and usually those in high-volume centres. The current Task Force, therefore, has convened experts to evaluate the current literature and make recommendations on both the antenatal and post-natal management of CDH. The incidence of CDH varies from 1.7 to 5.7 per 10,000 live-born infants depending on the study population. Antenatal ultrasound scanning is routine and increasingly complemented by the use of magnetic resonance imaging. For isolated CDH, antenatal interventions should be considered, but the techniques need vigorous evaluation. After birth, management protocols are often used and have improved outcome in nonrandomised studies, but immediate intubation at birth and gentle ventilation are important. Pulmonary hypertension is common and its optimal management is crucial as its severity predicts the outcome. Usually, surgery is delayed to allow optimal medical stabilisation. The role of minimal invasive post-natal surgery remains to be further defined. There are differences in opinion about whether extracorporeal membrane oxygenation improves outcome. Survivors of CDH can have a high incidence of comorbidities; thus, multidisciplinary follow-up is recommended. Multicentre international trials are necessary to optimise the antenatal and post-natal management of CDH patients.
A Familial Aggregation of Pancreatic Cancer
Authors: B. Shannon Danes, Henry T. Lynch
Journal: JAMA (1982)

The incidence of pancreatic cancer has been increasing steadily in the United States and other industrialized nations. Its obscure etiology and difficult early diagnosis tend to hobble effective control programs. Innovative methods, such as biomarkers, might provide clues to its inevitable occurrence in high-risk individuals. We studied a family in which four individuals manifested pancreatic cancer verified through two generations. Cell cultures from split-thickness skin biopsy specimens were obtained for 24 members from three generations (17 bloodline relatives, seven family members by marriage) as well as ten nonfamily normal subjects, none with a family history of solid tumors. One of the constant features of human monolayer dermal cultures has been diploidy. Hyperdiploidy, other than tetraploidy, has been rarely observed in cultures from normal subjects without a family history of solid tumors. We observed increased in vitro hyperdiploidy in eight of 17 family members studied. (<i>JAMA</i>1982;247:2798-2802)
Physical Activity and Hemostatic and Inflammatory Variables in Elderly Men
Authors: S. Goya Wannamethee, Gordon D.O. Lowe, Peter H. Whincup, Ann Rumley, Mary Walker, Lucy Lennon
Journal: Circulation (2002)

Background — Physical activity is associated with lower risk of cardiovascular disease, but the mechanisms are uncertain. Hemostatic and inflammatory markers have been linked with risk of cardiovascular disease. We therefore examined the relationship between physical activity and hemostatic and inflammatory variables. Methods and Results — In 1998 to 2000, 20 years after the initial screening of 7735 men 40 to 59 years old from general practices in 24 British towns, 4252 subjects (77% of available survivors, now 60 to 79 old) attended for reexamination. A fasting blood sample was available in 4088 men. All men on warfarin (n=134) and men with incomplete data on physical activity (n=144) were excluded, leaving 3810 men for analysis. Physical activity showed a significant and inverse dose-response relationship with fibrinogen, plasma and blood viscosity, platelet count, coagulation factors VIII and IX, von Willebrand factor, fibrin d -dimer, tissue plasminogen activator antigen, C-reactive protein, and white cell count, even after adjustment for possible confounders. The effects were similar in men with and without prevalent cardiovascular disease. No relationship was seen with activated partial thromboplastin time, activated protein C resistance, hematocrit, or factor VII. An examination of changes in physical activity between baseline and 20 years later showed that inactive men who took up at least light physical activity had levels of blood variables approaching those who remained at least lightly active. Those who became inactive showed levels more similar to those who remained inactive. Conclusions — These data suggest that the benefit of physical activity on cardiovascular disease may be at least partly a result of effects on hemostasis and inflammation.
Prevalence and resistance of commensal Staphylococcus aureus, including meticillin-resistant S aureus, in nine European countries: a cross-sectional study
Authors: Casper DJ den Heijer, Evelien ME van Bijnen, W John Paget, Mike Pringle, Herman Goossens, Cathrien A Bruggeman, François G Schellevis, Ellen E Stobberingh
Journal: The Lancet Infectious Diseases (2013)
Eruptive Cherry Hemangiomatosis Associated With Multicentric Castleman Disease
Authors: David Fajgenbaum, Misha Rosenbach, Frits van Rhee, Adnan Nasir, Jason Reutter
Journal: JAMA Dermatology (2013)

Background: Eruptive cherry hemangiomatosis, which involves the sudden onset of multiple small vascular proliferations, has been rarely reported as a heralding sign of multicentric Castleman disease (MCD) and other lymphoproliferative diseases.We report a case wherein the rapid appearance of cherry hemangiomata is the presenting sign of MCD.Observations: A 25-year-old man with a 10-year history of benign vascular growths developed 23 cutaneous vascular proliferations and systemic symptoms 5 days prior to presentation.Biopsy of the cutaneous lesions revealed a polypoidal proliferation of vessels consistent with cherry hemangiomata.Laboratory studies disclosed systemic abnormalities, and the findings of a subsequent lymph node biopsy confirmed MCD.Combination chemotherapy was initiated, and the cutaneous proliferations improved in association with the systemic disease.Conclusions: There is a scarcity of literature describing the association between eruptive cherry hemangiomatosis and MCD.The likely underlying mechanism is hypersecretion of vascular endothelial growth factor secondary to an elevated interleukin 6 level.Failure to recognize this association may have led to diagnostic delays.The authors suggest careful evaluation and follow-up of all patients presenting with the sudden onset of cherry hemangiomata, particularly with systemic symptoms, lymphadenopathy, or other benign vascular endothelial growths, for the potential development of MCD and other lymphoproliferative diseases.
Clinical effectiveness of treatment with hyperbaric oxygen for neonatal hypoxic-ischaemic encephalopathy: systematic review of Chinese literature
Authors: Zulian Liu, Tengbin Xiong, Catherine Meads
Journal: BMJ (2006)

<h3>Abstract</h3> <b>Objectives</b> To investigate the clinical effectiveness of treatment with hyperbaric oxygen for neonates with hypoxic-ischaemic encephalopathy. This treatment is frequently used in China but much less often in the West. <b>Data sources</b> Western (Cochrane controlled trials register and database of systematic reviews, Medline, Embase, CINAHL, and HealthSTAR) and Chinese (China Hospital Digital Library, Chinese Medical Journal Network) databases and hand search of Chinese journals. No language restrictions. <b>Review methods</b> Randomised or quasi-randomised controlled trials of treatment with hyperbaric oxygen compared with "usual care" in term neonates with hypoxic-ischaemic encephalopathy. Outcomes included mortality and long term neurological sequelae. Standardised forms were used to extract and compare data. Criteria of York Centre for Reviews and Dissemination were used to assess quality. Analysis was mainly qualitative but included meta-analysis. <b>Results</b> 20 trials were found, mainly from Chinese sources. The reporting quality of trials was poor by Western (CONSORT) standards. Treatment with hyperbaric oxygen had better outcomes than the comparator in almost all trials. The odds ratios of the meta-analyses were 0.26 (95% confidence interval 0.14 to 0.46) for mortality and 0.41 (0.27 to 0.61) for neurological sequelae. <b>Conclusion</b> Treatment with hyperbaric oxygen possibly reduces mortality and neurological sequelae in term neonates with hypoxic-ischaemic encephalopathy. Because of the poor quality of reporting in all trials and the possibility of publication bias, an adequately powered, high quality randomised controlled trial is needed to investigate these findings. The Chinese medical literature may be a rich source of evidence to inform clinical practice and other systematic reviews.
Cardiogenic Genes Expressed in Cardiac Fibroblasts Contribute to Heart Development and Repair
Authors: Milena B. Furtado, Mauro W. Costa, Edward A. Pranoto, Ekaterina Salimova, Alexander R. Pinto, Nicholas T. Lam, Anthony Park, Paige Snider, Anjana Chandran, Richard P. Harvey, Richard Boyd, Simon J. Conway, James Pearson, David M. Kaye, Nadia A. Rosenthal
Journal: Circulation Research (2014)

Rationale: Cardiac fibroblasts are critical to proper heart function through multiple interactions with the myocardial compartment, but appreciation of their contribution has suffered from incomplete characterization and lack of cell-specific markers. Objective: To generate an unbiased comparative gene expression profile of the cardiac fibroblast pool, identify and characterize the role of key genes in cardiac fibroblast function, and determine their contribution to myocardial development and regeneration. Methods and Results: High-throughput cell surface and intracellular profiling of cardiac and tail fibroblasts identified canonical mesenchymal stem cell and a surprising number of cardiogenic genes, some expressed at higher levels than in whole heart. While genetically marked fibroblasts contributed heterogeneously to interstitial but not cardiomyocyte compartments in infarcted hearts, fibroblast-restricted depletion of one highly expressed cardiogenic marker, T-box 20, caused marked myocardial dysmorphology and perturbations in scar formation on myocardial infarction. Conclusions: The surprising transcriptional identity of cardiac fibroblasts, the adoption of cardiogenic gene programs, and direct contribution to cardiac development and repair provoke alternative interpretations for studies on more specialized cardiac progenitors, offering a novel perspective for reinterpreting cardiac regenerative therapies.
Epidermal Growth Factor Receptor and the Changing Face of Oropharyngeal Cancer
Authors: Duncan C. Gilbert, Richard Simcock, Andrew Schache, Richard Shaw
Journal: Journal of Clinical Oncology (2012)

Flushing Oral Oncology Drugs Down the Toilet," Ratain 1 provides an interesting opportunity to save a substantial amount of money by altering the circumstances of administration to increase the bioavailability of the drug abiraterone acetate.He points out that the development of the drug did not take advantage of the increased bioavailability obtained by administering the drug with a low-fat breakfast.If done as suggested by Ratain, the correct dose would be 250 mg once daily rather than 1,000 mg, as indicated.The essay assumes that had the clinical trials been done differently and the approved dose 250 mg, the price would be 75% lower.It would not.Drug pricing is not based on costs of manufacture, or research costs, or dosage size but rather on the highest cost the market will bear.In this regard, new drugs are no different than luxury automobiles.Cost of goods has little effect on price.A new drug with advantages over existing drugs will be priced at a premium to existing drugs, regardless of the actual dose or the cost of goods.Market research will attempt to identify a value for the treatment-generally, the full cost of a course of treatment.If the drug is taken daily for a year, then 365 doses is the course of treatment.If the drug is given by injection on alternate weeks for 6 months, then 13 doses is the course of treatment.A value is put on the course of
Modafinil for the Treatment of Fatigue in Lung Cancer: Results of a Placebo-Controlled, Double-Blind, Randomized Trial
Authors: Anna Spathis, Kate Fife, Fiona Blackhall, Susan Dutton, Ronja Bahadori, Rose Wharton, Mary O'Brien, Patrick Stone, Tim Benepal, Nick Bates, Bee Wee
Journal: Journal of Clinical Oncology (2014)

Fatigue is a distressing symptom occurring in more than 60% of patients with cancer. The CNS stimulants modafinil and methylphenidate are recommended for the treatment of cancer-related fatigue, despite a limited evidence base. We aimed to evaluate the efficacy and tolerability of modafinil in the management of fatigue in patients with non-small-cell lung cancer (NSCLC).
Phase I Study of Ixabepilone, Mitoxantrone, and Prednisone in Patients With Metastatic Castration-Resistant Prostate Cancer Previously Treated With Docetaxel-Based Therapy: A Study of the Department of Defense Prostate Cancer Clinical Trials Consortium
Authors: Jonathan E. Rosenberg, Charles J. Ryan, Vivian K. Weinberg, David C. Smith, Maha Hussain, Tomasz M. Beer, Christopher W. Ryan, Paul Mathew, Lance C. Pagliaro, Andrea L. Harzstark, Jeremy Sharib, Eric J. Small
Journal: Journal of Clinical Oncology (2009)

Purpose Mitoxantrone plus prednisone and ixabepilone each have modest activity as second-line chemotherapy in docetaxel-refractory castration-resistant prostate cancer (CRPC) patients. Clinical noncrossresistance was previously observed. Patients and Methods Metastatic CRPC patients progressing during or after taxane-based chemotherapy enrolled in a phase I multicenter study of ixabepilone and mitoxantrone administered every 21 days along with prednisone. Ixabepilone and mitoxantrone doses were alternately escalated in a standard 3 + 3 design. Patients were evaluated for toxicity and disease response. Dose-limiting toxicities (DLTs) were defined as treatment related, occurring during cycle 1, and included grade 4 prolonged or febrile neutropenia, thrombocytopenia (grade 4 or grade 3 with bleeding), or ≥ grade 3 nonhematologic toxicity. Results Thirty-six patients were treated; 59% of patients experienced grade 3/4 neutropenia. DLTs included grade 3 diarrhea (n = 1), prolonged grade 4 neutropenia (n = 4), and grade 5 neutropenic infection (n = 1). Due to prolonged neutropenia, the highest dose levels were repeated with pegfilgrastim on day 2 of each cycle. The maximum tolerated dose in combination with pegfilgrastim was not exceeded. The recommended phase II dose is mitoxantrone 12 mg/m 2 and ixabepilone 35 mg/m 2 every 21 days, pegfilgrastim 6 mg subcutaneously day 2, and continuous prednisone 5 mg twice per day. Thirty-one percent of patients have experienced ≥ 50% prostate-specific antigen (PSA) declines, and two experienced objective responses. Of 21 patients treated with mitoxantrone 12 mg/m 2 plus ixabepilone ≥ 30 mg/m 2 , nine (43%) experienced ≥ 50% PSA declines (95% CI, 22% to 66%). Conclusion These results suggest that the combination of ixabepilone and mitoxantrone is feasible and active in CRPC and requires dosing with pegfilgrastim.
Calcimimetic R-568 Decreases Extraosseous Calcifications in Uremic Rats Treated with Calcitriol
Authors: Ignacio Lopez, Escolastico Aguilera-Tejero, Francisco J. Mendoza, Yolanda Almaden, Jose Perez, David Martin, Mariano Rodriguez
Journal: Journal of the American Society of Nephrology (2006)

Calcimimetics decrease parathyroid hormone (PTH) levels in uremic patients with secondary hyperparathyroidism without increasing serum calcium (Ca). The aim of this study was to evaluate the effect of calcimimetic R-568 alone or in combination with calcitriol on vascular and other soft tissue calcifications in uremic rats with secondary hyperparathyroidism. Sham-operated and 5/6 nephrectomized Wistar rats were studied. 5/6 Nephrectomized rats were treated with vehicle, calcitriol (80 ng/kg every other day), R-568 (1.5 and 3 mg/kg per d), and both calcitriol and R-568 1.5 mg/kg, as above. Rats were killed after 14 or 56 d of treatment. Blood was drawn for biochemical measurements. Aortic, heart, kidney, lung, and stomach tissue samples were processed for histopathology and measurement of tissue Ca and phosphorus content. PTH concentrations were significantly reduced by all treatments. Treatment with calcitriol induced significant vascular calcification (aortic Ca increased to 4.2+/-1.2 mg/g at day 14 and to 11.4+/-0.7 mg/g at day 56; P<0.05 versus vehicle). Treatment with R-568 did not induce vascular calcification. Concurrent administration of R-568 with calcitriol reduced the aortic Ca (1.9+/-0.2 mg/g at day 14 and 7.5+/-1.4 mg/g at day 56) in relation to calcitriol alone. Soft tissue calcifications mirrored aortic mineralizations. Survival was significantly (P<0.001) reduced in calcitriol-treated rats, and mortality was attenuated (P=0.01) by concurrent treatment with R-568. In uremic rats, R-568 reduces elevated PTH levels without inducing vascular calcification, prevents calcitriol-induced vascular calcification, and decreases mortality.