tbuckley/cabot-search huggingface dataset:
Epidemiology and Mechanisms of Uremia-Related Cardiovascular Disease
Authors: Marcello Tonelli, S. Ananth Karumanchi, Ravi Thadhani
Journal: Circulation (2016)

Patients with chronic kidney disease and end-stage renal disease are at 5- to 10-fold higher risk for developing cardiovascular disease (CVD) than age-matched controls. Clinically, CVD in this population manifests as coronary artery disease, arrhythmias, stroke, or congestive heart failure. Beyond the traditional risk factors (eg, diabetes mellitus and hypertension), uremia-specific factors that arise from accumulating toxins also contribute to the pathogenesis of CVD. In this review, we summarize the literature on the epidemiology of both traditional and uremia-related CVD and focus on postulated mechanisms of the latter. In the context of current and emerging diagnostics and therapies for CVD, we highlight what we interpret as major gaps in the medical management of this growing population that need to be addressed with targeted epidemiological and translational research. Finally, we describe the global challenges associated with the recognition and management of uremia-related CVD in developed and developing nations.
Abstract 9312: Predictors of Survival in Primary Cardiac Amyloidosis
Authors: Abbas Bitar, Hussam Suradi, Mithilesh Das, Merrill Benson
Journal: Circulation (2012)

Background: Cardiac involvement in primary amyloidosis (AL) is associated with poor prognosis. We studied the prognostic significance of clinical, ECG and echocardiographic parameters of patients with primary cardiac amyloidosis. Methods: 60 patients with primary amyloidosis and cardiac involvement documented by endomyocardial tissue biopsy were studied. Results: 60 patients (mean age 57.94±10.22 years; 71.67% male and 86.67% Caucasian) were studied. The median survival was 12.23 (median) ±4.43 months, 50% of patients survived for more than 1 year. Congestive heart failure (NYHA II-IV) was present in 60% of patients. Low voltage, Q wave, conduction abnormalities, first degree AV block and abnormal QRS axis were present in 54.24%, 51.72%, 71.67%, 21.67% and 57.72% respectively. Echocardiogram revealed LVH, mitral regurgitation, left atrial enlargement, speckled appearance and pericardial effusion in 82.76%, 62%, 63.16%, 8.77% and 42.11% respectively. LVEF, RVSP, IVS and LVPW were 0.479±.129, 40.88±10.31 mmHg, 1.46±0.34 cm and 1.43±0.33cm respectively. CHF (NYHA II-IV), IVS, LVPW and LVEF were significant on univariate survival analysis (p&lt;0.05). Multivariate predictors of survival were CHF (NYHA II-IV) ( p=0.027, HR 3.04 [95% CI: 1.1-8.1]) and IVS&lt; 1.5cm (p=0.012, HR:3.51 [95% CI: 1.3-9.3]). Median survival of patients with CHF (NYHA II-IV) was 7.58±1.74 months contrary to those without CHF who had a median survival of 31.2±11.41 months. Conclusion: In patients with primary amyloidosis and cardiac involvement, lenght of survival is strongly associated with CHF (NYHA II-IV) and IVS thickness compared to other electrographic and echocardiographic parameters.
Phase II trial of bevacizumab and erlotinib in patients with metastatic renal carcinoma (RCC)
Authors: J. D. Hainsworth, J. A. Sosman, D. R. Spigel, R. C. Schwert, D. L. Carrell, F. Hubbard, F. A. Greco
Journal: Journal of Clinical Oncology (2004)

4502 Background: Treatment for advanced RCC remains poor, with meaningful responses in a small minority. Most pts with clear cell RCC have loss of VHL protein primarily due to gene mutation, resulting in impaired breakdown of HIF-1proportion and overexpression of HIF-1proportion regulated genes including VEGF, TGF-proportion, EGF, and PDGF. Bevacizumab (Avastin), an anti-VEGF antibody prolongs TTP in second-line therapy of advanced RCC versus placebo. Based on RCC biology, we hypothesized that combined VEGF and EGFR inhibition would enhance biological and clinical effects. Methods: In this phase II trial, we administered bevacizumab with erlotinib (Tarceva), an EGFR antagonist. Eligible pts had metastatic clear cell RCC, and 0 or 1 previous systemic regimens. Additional eligibility criteria: previous nephrectomy (if clinically appropriate); no previous anti-angiogenesis agents or EGFR inhibitors; ECOG PS 0 or 1; adequate organ function; no active CNS metastases; no bleeding abnormalities; no history of thromboembolic disease. All pts received bevacizumab 10mg/kg IV q 2 weeks, and erlotinib 150mg PO daily. Pts were evaluated for response after 8 weeks; treatment continued until tumor progression. Results: Between 2/03 and 11/03, 57 pts were treated: median age 60 years; male/female, 45/12; previous nephrectomy, 53; sites of metastases: lungs 41, liver 17, bone 15, adrenals 10, other 14; previous treatment: none 34, IL2 and/or IFN 18. 40 pts have been evaluated after 8 weeks of therapy. Current response rates: partial response, 10 pts (25%; 95% CI 13%–41%); minor response (20–30% decrease), 6 pts (15%); stable, 19 pts (47%); progression, 5 pts (12%). 27 pts continue treatment after median follow-up of 4.4 months. Actuarial PFS at 6 months is 71%. Treatment was well tolerated; 25 pts (63%) had no grade 3/4 toxicity. Grade 3/4 toxicity: hypertension 11%; diarrhea 9%; rash 7%; nausea/vomiting 7%; pruritus 4%; edema 2%. Conclusions: Bevacizumab/erlotinib treatment has substantial clinical activity in pts with metastatic RCC. The combination seems more active than either agent alone, and supports the concept of combined inhibition of critical pathways. Updated results on 60 pts will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech
Efficacy of chemotherapy after self-expanding metal stent placement for gastric outlet obstruction caused by an unresectable malignant tumor.
Authors: Taikan Yamamoto, Kouichirou Miyashita, Ken Shimada, Takashi Sekikawa, Yu Uto, Toshikazu Nunoue, Yasuhiro Kaga, Yu Kitahara, Yusuke Saito, Kouji Kobayashi, Eriko Kinugasa
Journal: Journal of Clinical Oncology (2015)

484 Background: Gastric outlet obstruction (GOO) is a late complication of advanced and metastatic malignant tumors. Self-expanding metal stent (SEMS) placement is a safe and effective palliative treatment for patients with GOO. In general, the median survival time after SEMS placement for GOO is approximately 90 days, and advanced chemotherapeutic treatment could further improve prognosis. Methods: This retrospective study aimed to analyze the efficacy of chemotherapy after SEMS placement on improvement of oral intake and survival time. Eight patients with symptomatic malignant GOO were treated by SEMS placement in our hospital. Surgical bypass could not be performed due to severe advanced malignant tumors. Patients were classified into two groups depending on whether they received chemotherapy after SEMS placement. Group A included five patients who were treated with palliative therapy alone (median age: 72 years; cases 1, 2, 3, and 4 with advanced gastric cancer, and case 5 with advanced pancreatic carcinoma). Group B included three patients who were treated with palliative therapy, followed by chemotherapy (median age: 68 years; case 6 with advanced pancreatic cancer treated with gemcitabine chemotherapy; case 7 with advanced gastric carcinoma treated with TS-1 and paclitaxel chemotherapy; and case 8 with duodenal stenosis due to advanced colonic carcinoma treated with irinotecan and cetuximab chemotherapy after SEMS placement). We estimated the gastric outlet obstruction scoring system (GOOSS ; no oral intake: 0; only liquids: 1; soft solids: 2; low-residue or full diet: 3) and survival time as the main outcomes. Results: SEMS placement using endoscopy was successful in all cases. No complications occurred after the procedure. Performance status did not change after SEMS placement. GOOSS improved from 0 to 1 in group A and from 0 to 2 in group B. Median survival time was 68 days in group A and 188 days in group B. We considered chemotherapy after SEMS contributed lifetime. Conclusions: Our study findings indicate that SEMS placement is a safe and effective method for managing malignant GOO and that chemotherapy after SEMS placement can improve diet intake and prognosis.
Differences in specificity and catalytic efficiency between allozymes of esterase-4 from Drosophila mojavensis.
Authors: J Pen, A Schipper, H A Rongen, J J Beintema
Journal: Molecular Biology and Evolution (1986)

A more than 10-fold difference in the specificity and catalytic efficiency for 1-naphthyl esters was measured between two allozymes of esterase-4 from Drosophila mojavensis. This difference is mainly caused by a difference in the affinity for the 1-naphthyl esters. The amino acid compositions of the allozymes are not significantly different, which means that the difference in primary structure is small. Small differences in primary structure generally do not result in such a large increase in catalytic efficiency and such a large shift in substrate specificity as was found in the present study.
Initial results from a phase II trial of motesanib diphosphate (AMG 706) in patients with differentiated thyroid cancer (DTC)
Authors: S. I. Sherman, M. J. Schlumberger, J. Droz, M. Hoffmann, L. Wirth, L. Bastholt, R. G. Martins, L. Licitra, Y. Shi, D. E. Stepan
Journal: Journal of Clinical Oncology (2007)

6017 Background: This phase 2 study evaluated the safety and efficacy of AMG 706, an oral, investigational multikinase (MKI) inhibitor with antiangiogenic and direct antitumor activity achieved by selectively targeting VEGF, PDGF, and Kit receptors and RET, in pts with advanced DTC or medullary thyroid cancer (MTC). Presented here are results from the DTC stratum. Methods: This was a multicenter, phase 2, open-label, single-arm study of pts with advanced thyroid cancer stratified by DTC or MTC (planned n=80 each). The primary endpoint was objective tumor response per modified RECIST by independent central review. Secondary DTC endpoints were duration of response and progression-free survival (PFS). Pts = 18 yrs with progressive, 131 I-resistant disease, ECOG 0–2, and no prior treatment with VEGFr MKIs received AMG 706 125mg QD until disease progression or unacceptable toxicity. Assessments included tumor response (q8w), pharmacokinetics (PK), and safety. Results: 93 pts with DTC were enrolled and received at least 1 dose of AMG 706. DTC subtypes were: papillary, 58%; Hürthle cell, 18%; follicular, 16%; other, 8%. Median (range) age was 62 (36–81) yrs. 20% of pts had prior chemotherapy; 96% had prior 131 I therapy. With median follow-up of 32 wks, objective tumor response (CR or PR) rate (95% CI) was 12% (6.1, 20.2); SD, n=64 (69%; durable SD =24 wks, 24%); PD, n=7 (8%). Median (95% CI) time to response was 103 (53, 161) days; median PFS was 276 (221, not estimable) days. 85% of pts were alive &gt;8 months after starting therapy. All pts (100%) had some treatment- emergent adverse events (AE): grade 3, 55%; grade 4, 10%; grade 5, 5% (all grade 5 were deemed unrelated to AMG 706). Common AEs included diarrhea (70%; 11% grade 3), fatigue (58%; 5% grade 3), hypertension (49%; 22% grade 3), headache (43%; 4% grade 3), nausea (40%; 2% grade 3), and hypothyroidism and/or increased TSH (17%; no grade 3); none of these were grade 4 or 5. 6% of pts had cholecystitis. PK results showed that AMG 706 PK at 125mg QD was comparable to data obtained in other monotherapy studies at the same dose level. Conclusions: In this study of pts with advanced 131 I-resistant DTC, AMG 706 showed encouraging antitumor activity and had tolerable and manageable toxicities. Further investigation is warranted. No significant financial relationships to disclose.
Mutations of conserved arginines in the membrane domain of erythroid band 3 lead to a decrease in membrane-associated band 3 and to the phenotype of hereditary spherocytosis
Authors: P Jarolim, HL Rubin, V Brabec, L Chrobak, AS Zolotarev, SL Alper, C Brugnara, H Wichterle, J Palek
Journal: Blood (1995)
Application of Sequencing, Liquid Biopsies, and Patient-Derived Xenografts for Personalized Medicine in Melanoma
Authors: Maria Romina Girotti, Gabriela Gremel, Rebecca Lee, Elena Galvani, Dominic Rothwell, Amaya Viros, Amit Kumar Mandal, Kok Haw Jonathan Lim, Grazia Saturno, Simon J. Furney, Franziska Baenke, Malin Pedersen, Jane Rogan, Jacqueline Swan, Matthew Smith, Alberto Fusi, Deemesh Oudit, Nathalie Dhomen, Ged Brady, Paul Lorigan, Caroline Dive, Richard Marais
Journal: Cancer Discovery (2015)

Targeted therapies and immunotherapies have transformed melanoma care, extending median survival from ∼9 to over 25 months, but nevertheless most patients still die of their disease. The aim of precision medicine is to tailor care for individual patients and improve outcomes. To this end, we developed protocols to facilitate individualized treatment decisions for patients with advanced melanoma, analyzing 364 samples from 214 patients. Whole exome sequencing (WES) and targeted sequencing of circulating tumor DNA (ctDNA) allowed us to monitor responses to therapy and to identify and then follow mechanisms of resistance. WES of tumors revealed potential hypothesis-driven therapeutic strategies for BRAF wild-type and inhibitor-resistant BRAF-mutant tumors, which were then validated in patient-derived xenografts (PDX). We also developed circulating tumor cell-derived xenografts (CDX) as an alternative to PDXs when tumors were inaccessible or difficult to biopsy. Thus, we describe a powerful technology platform for precision medicine in patients with melanoma.
The prevalence of COPD in Annaba, Algeria: Results of the BOLD study
Authors: Hamid Hacene Cherkaski, Foued Khalloufi, Feryal Atoui, Randa Yakoubi, Louisa Gnatiuc, Peter Burney, Rachid Benali
Journal: European Respiratory Journal (2014)

Introduction:  Chronic obstructive pulmonary disease (COPD) is an increasing health concern worldwide, particularly in developing countries which are experiencing an epidemiological and demographic transition, and where the burden of COPD is largely unknown.   Objective:  To assess the prevalence of spirometrically confirmed COPD in Annaba (Algeria).   Method:  We conducted a cross-sectional spirometric survey on a representative sample of adults of 40 years or more using the Burden Obstructive Lung Disease (BOLD) protocol. We collected information on exposure to risk factors, respiratory symptoms and medical history. Pre and post-bronchodilator spirometry were performed and quality controlled for inclusion in analyses. A post-bronchodilator FEV1/FVC below the lower limit of normal was defined as COPD. The severity of bronchial obstruction was further defined by post-bronchodilator FEV1   Results:  Among 917 participants, 97% performed acceptable post-bronchodilator spirometry that met the ERS/ATS criteria and 61% were never smokers. The overall population-prevalence of COPD in Elhadjar was estimated at 6.4%. It was more common in men than in women (8.2% vs 4.6%) and increased with age (from 4.5% in those aged 40-49 years to 11.7% in those aged 70 years or older). The overall population-prevalence of modified GOLD stage 2 or higher COPD was 5.5%. Only 1.9% responders reported a diagnosis of COPD.   Conclusion:  COPD is an under-diagnosed disease in Annaba. A wider use of spirometry would facilitate diagnosis of disease. These findings deserve the attention of the local medical community and policy makers.
Abstract 17472: Changes in the Vascular Properties, Not the Ventricular Properties, Predominantly Contributes to the Baroreflex Induced Arterial Pressure Regulation
Authors: Takafumi Sakamoto, Takamori Kakino, Keita Saku, Kazuo Sakamoto, Kenji Sunagawa
Journal: Circulation (2013)

Background: Baroreflex (BR) modulates both the ventricular and vascular properties, and feedback regulates arterial pressure (AP). However how changes in those mechanical properties quantitatively ...
Occurrence of Tumors Among Litters of BALB/c Female Mice
Authors: D W Gaylor, J J Chen, D L Greenman, C H Thompson
Journal: JNCI Journal of the National Cancer Institute (1985)

In the application of statistical techniques to tumor incidence data it is generally assumed that animals respond independently with regard to tumor occurrence, with littermates being no more alike than are animals from different litters. Data for nine different types of tumors from the large ED01 study conducted at the National Center for Toxicological Research were used to compare tumor prevalence rates among litters with the tumor rates expected under the assumption of homogeneity of tumor rates among litters. These data did not provide sufficient evidence to reject the assumption of homogeneity of tumor prevalence rates among litters of inbred female BALB/c mice for either spontaneously occurring tumors or bladder tumors produced by exposure to 2-acetylaminofluorene (CAS: 53-96-3). However, there does appear to be a difference in liver tumor prevalence rates among litters at 24 months of age. Thus litter effects are a factor that should be considered in the assignment of animals to treatment groups in carcinogenesis studies.
Exposure to Elevated Carbon Monoxide Levels at an Indoor Ice Arena — Wisconsin, 2014
Authors: Paul D. Creswell, Jon G. Meiman, Henry Nehls-Lowe, Christy Vogt, Ryan J. Wozniak, Mark A. Werner, Henry Anderson
Journal: MMWR Morbidity and Mortality Weekly Report (2015)

On December 13, 2014, the emergency management system in Lake Delton, Wisconsin, was notified when a male hockey player aged 20 years lost consciousness after participation in an indoor hockey tournament that included approximately 50 hockey players and 100 other attendees. Elevated levels of carbon monoxide (CO) (range = 45 ppm-165 ppm) were detected by the fire department inside the arena. The emergency management system encouraged all players and attendees to seek medical evaluation for possible CO poisoning. The Wisconsin Department of Health Services (WDHS) conducted an epidemiologic investigation to determine what caused the exposure and to recommend preventive strategies. Investigators abstracted medical records from area emergency departments (EDs) for patients who sought care for CO exposure during December 13-14, 2014, conducted a follow-up survey of ED patients approximately 2 months after the event, and conducted informant interviews. Ninety-two persons sought ED evaluation for possible CO exposure, all of whom were tested for CO poisoning. Seventy-four (80%) patients had blood carboxyhemoglobin (COHb) levels consistent with CO poisoning; 32 (43%) CO poisoning cases were among hockey players. On December 15, the CO emissions from the propane-fueled ice resurfacer were demonstrated to be 4.8% of total emissions when actively resurfacing and 2.3% when idling, both above the optimal range of 0.5%-1.0%. Incomplete fuel combustion by the ice resurfacer was the most likely source of elevated CO. CO poisonings in ice arenas can be prevented through regular maintenance of ice resurfacers, installation of CO detectors, and provision of adequate ventilation.
PWE-158 Non-selective non-steroidal antiinflammatory drugs, proton pump inhibitors, and the incidence of non-variceal upper gastrointestinal bleeding and<i>Clostridium difficile</i>infection: Abstract PWE-158 Table 1
Authors: A S Taha, C Kelly, C McCloskey, T Craigen, W J Angerson
Journal: Gut (2012)

<h3>Introduction</h3> It is not clear what impact the decline of COX-2 selective inhibitors has had on the use of non-selective non-steroidal anti-inflammatory drugs (ns-NSAIDs) or on the incidence of non-variceal upper gastrointestinal bleeding (NV-UGIB). Also, proton pump inhibitors (PPIs), recommended for NSAID-ulcer prophylaxis, have been linked to <i>Clostridium difficile</i> infection. <h3>Methods</h3> We aimed to measure the incidence [cases per 100 000 population per annum] of NV-UGIB and <i>C difficile</i> infection as well as the use of ns-NSAIDs and PPIs in a well-defined population served by a single centre. Data were collected over three calendar years, 2007–2009. Significance was assessed using the χ<sup>2</sup> test for trend. <h3>Results</h3> As shown in Abstract PWE-158 table 1, the use of COX-2 selective and newer NSAIDs continues to decline, while that of ns-NSAIDs continues to rise. This has been coupled with a steady rise in the use of PPIs. On the other hand, the incidence of both NV-UGIB and <i>C difficile</i> infection has been falling. <h3>Conclusion</h3> The incidence of NV-UGIB has been falling despite the increasing use of ns-NSAIDs. This could be, at least in part, due to the rise in PPI use. Also, the incidence of <i>C difficile</i> infection has been falling despite more PPIs being used: this might suggest a poor link between these two factors, or might reflect the outcome of other measures being deployed against this infection. While these falls appear promising, both NV-UGIB and <i>C difficile</i> infection continue to represent significant clinical challenges. <h3>Competing interests</h3> None declared.
Teratomas in Children: Epidemiologic Features
Authors: Joseph F. Fraumeni, Frederick P. Li, Nancy Dalager
Journal: JNCI Journal of the National Cancer Institute (1973)

In a search for etiologic clues, study was made of 369 death certificates for U.S. children who died from teratomas in 1960–68, and of 198 hospital charts of children with this tumor. Mortality rates for girls exceeded those for boys, as contrasted with the usual male preponderance for childhood neoplasia. There was a peak in deaths under age 3, primarily from sacrococcygeal tumors in girls. Arising trend in mortality developed after age 6 for ovarian tumors and after age 14 for testicular tumors. Although the cellular basis for teratomas remains unsettled, the female predominance at various sites is consistent with the concept of a common origin: Pluripotential germ cells which account for gonadal teratomas in older children may, if ectopic early in fetal life, give rise in infancy to sacrococ-cygeal and possibly other extragonadal teratomas. Furthermore, a high .frequency of children with sacrococcygeal teratomas had congenital anomalies involving the lower vertebrae, genitourinary system, and anorectum. The array of defects included duplication of pelvic organs attributable to hindgut twinning. Perhaps certain anomalies near teratomas are not due to the effects of local tumor growth, but result from the same developmental aberration responsible for the formation of teratomas.
Myelodysplastic Syndromes with I(17)(q10) and Prognostic Implications of Mutations of TP53 and SETBP1
Authors: Vera Adema, Larrayoz Maria Jose, Calasanz Maria Jose, Laura Palomo, Ana Patiño-Garcia, Xabier Aguirre, Jesús María Hernández-Rivas, Eva Lumbreras, Ismael Buno, Carolina Martínez-Laperche, Mar Mallo, Olga Garcia, Paula Gomez-Marzo, Sara Alvarez, Beatriz Blazquez, Jose Cervera, Elisa Luño, Alberto Valiente, Teresa Vallespi, Ana Vicente, Leonor Arenillas, Rosa Collado, Jaime Perez-Oteyza, Francesc Sole
Journal: Blood (2014)