tbuckley/cabot-search huggingface dataset:
Prognostic Value of a New Clinically-Based Classification System in Patients with CMML Undergoing Allogeneic Hematopoietic Stem Cell Transplantation: A Retrospective Analysis of the EBMT Chronic Malignancies Working Party
Authors: Francesco Onida, Giulia Sbianchi, Linda Koster, Simona Iacobelli, Peter Dreger, Martin Bornhäuser, Nicolaus Kröger, Jorge Sierra, Gérard Socié, Jan J Cornelissen, Xavier Poire, Edgar Faber, Jean-Henri Bourhis, Jürgen Finke, Jakob R. Passweg, Urpu Salmenniemi, Harry C. Schouten, Yves Beguin, Sonja Martin, Eric Deconinck, Arnold Ganser, Samo Zver, Bruno Lioure, Nigel H. Russell, Marie Robin, Ibrahim Yakoub-Agha
Journal: Blood (2018)
FRI0059 Interstitial lung disease in patients with rheumatoid arthritis of a cohort treated with methotrexate monotherapy
Authors: E. Chamizo-Carmona, C. Carrasco Cubero, S.M. Rojas Herrera, J. Malave Calzada, R. Veroz Gonzalez, L.M. Chaves Chaparro
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Diffuse interstitial lung disease (ILD) is a common extra-articular manifestation of rheumatoid arthritis (RA) and an important cause of morbidity and mortality in this patient population. The predisposing and prognostic factors of this complication are a matter of debate. <h3>Objectives</h3> To determine the characteristics associated with the development of ILD in a cohort of patients with RA who received Methotrexate (MTX) monotherapy. <h3>Methods</h3> Case-control study in a cohort of patients with RA who had received MTX monotherapy, being cases those who developed ILD and controls, those who did not develop it. <h3>Results</h3> The cohort consisted of 301 patients (67% women), with a mean age of 49.6 (±13.2) years and a follow-up of 135.8 (±93.5) months. There were 15 (5%) cases of ILD, classified by high resolution chest CT as usual interstitial pneumonitis 7, nonspecific interstitial pneumonitis 7 and interstitial bronchiolitis 1. The distribution by sex was 8 ILD among 202 women (3.9%) and 7 ILD among the 99 men (7.1%). They all had RF and/or ACPA positive. ILD was associated with longer duration of the disease (p&lt;0.05), exposure to DMARDs prior to MTX (OR=3.3, p&lt;0.05), history of chronic lung disease (OR=6.5;&lt;0.01) and coexistence with secondary Sjögren syndrome (OR=3.2, p&lt;0.05). We did not find significant differences in mean values of age, RF, ACPA, baseline CRP and DAS28, dose, route and time of exposure to MTX, smoking, functional capacity, presence of erosions, MTX response and toxicity. The predictive factors in the logistic regression were the history of chronic pneumopathy, extra-articular involvement, time of evolution and basal biological activity (CRP) of the disease. Of the 15 patients with ILD, 5 (33.3%) had good response (DAS28-CRP&lt;3.2) with MTX and remained on monotherapy, another 3 continued with MTX combined with another DMARD and 7 (46.7%) discontinued MTX. In addition, 8 of these 10 patients received a biological therapy. Eleven patients died during follow-up, 3 (20%) cases (ILD) and 8 (2.8%) controls (p&lt;0.01). <h3>Conclusions</h3> ILD is a frequent and serious complication in RA. It appears more frequently in patients with previous pneumopathy and long-term disease and with extra-articular involvement of RA. <h3>Disclosure of Interest</h3> None declared
OP0048 A double-blind, placebo-controlled dose ranging study to evaluate the efficacy of valdecoxib, a novel cox-2 specific inhibitor, in treating the signs and symptoms of osteoarthritis of the knee
Authors: JJ Fiechtner, D Sikes, D Recker
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Valdecoxib is a novel oral COX-2 specific inhibitor being developed for the treatment of pain and inflammation, which does not cause the side effects commonly associated with the COX-1 inhibition of conventional NSAIDs. <h3>Objectives</h3> The objective of this study was to evaluate the efficacy of multiple doses of valdecoxib in treating the signs and symptoms of osteoarthritis (OA) of the knee. <h3>Methods</h3> In this multicenter, double-blind, placebo-controlled, parallel-group, dose-ranging study, 642 OA patients were randomised to receive valdecoxib 0.5, 1.25, 2.5, 5 or 10 mg BID, valdecoxib 10 mg QD, naproxen 500 mg BID, or placebo BID for 6 weeks. Patient's Assessment of Arthritis Pain (visual analogue scale, VAS), Patient's Global Assessment of Arthritis (VAS) and Western Ontario and McMasters Universities (WOMAC) OA Index were assessed at Baseline and after 1, 2, and 6 weeks of treatment. Vital signs and adverse events were monitored throughout the study. <h3>Results</h3> Valdecoxib demonstrated efficacy that was significantly greater than placebo (p &lt; = 0.05) in all primary efficacy measures listed above, at every dose except 0.5 mg BID. Improvements in OA signs and symptoms in response to valdecoxib were dose-dependent, with the greatest improvements in primary efficacy measures observed at 5 mg BID, 10 mg QD, and 10 mg BID, compared with placebo (p &lt; = 0.004). Valdecoxib doses of 5 mg BID, 10 mg QD, and 10 mg BID were also as effective as naproxen 500 mg in the treating signs and symptoms of OA. There were no statistically significant differences between any of the treatment groups in the number of adverse events or in vital signs or clinical laboratory measurements. <h3>Conclusion</h3> Valdecoxib is an effective therapy among patients with symptomatic OA of the knee. Valdecoxib doses of 5 mg BID, 10 mg QD, and 10 mg BID are maximally efficacious, as they are superior to placebo and comparable to naproxen 500 mg BID in all primary efficacy measures. Valdecoxib is well tolerated at all doses. Sponsored by Pharmacia Corporation and Pfizer, Inc.
Surgery or radiotherapy for stage I lung cancer? An intention-to-treat analysis
Authors: Katie L. Spencer, Martyn P.T. Kennedy, Katie L. Lummis, Deborah A.B. Ellames, Michael Snee, Alessandro Brunelli, Kevin Franks, Matthew E.J. Callister
Journal: European Respiratory Journal (2019)

Introduction Surgery is the standard of care for early-stage lung cancer, with stereotactic ablative body radiotherapy (SABR) a lower morbidity alternative for patients with limited physiological reserve. Comparisons of outcomes between these treatment options are limited by competing comorbidities and differences in pre-treatment pathological information. This study aims to address these issues by assessing both overall and cancer-specific survival for presumed stage I lung cancer on an intention-to-treat basis. Methods This retrospective intention-to-treat analysis identified all patients treated for presumed stage I lung cancer within a single large UK centre. Overall survival, cancer-specific survival, and combined cancer and treatment-related survival were assessed with adjustment for confounding variables using Cox proportional hazards and Fine–Gray competing risks analyses. Results 468 patients (including 316 surgery and 99 SABR) were included in the study population. Compared with surgery, SABR was associated with inferior overall survival on multivariable Cox modelling (SABR HR 1.84 (95% CI 1.32–2.57)), but there was no difference in cancer-specific survival (SABR HR 1.47 (95% CI 0.80–2.69)) or combined cancer and treatment-related survival (SABR HR 1.27 (95% CI 0.74–2.17)). Combined cancer and treatment-related death was no different between SABR and surgery on Fine–Gray competing risks multivariable modelling (subdistribution hazard 1.03 (95% CI 0.59–1.81)). Non-cancer-related death was significantly higher in SABR than surgery (subdistribution hazard 2.16 (95% CI 1.41–3.32)). Conclusion In this analysis, no difference in cancer-specific survival was observed between SABR and surgery. Further work is needed to define predictors of outcome and help inform treatment decisions.
Modelling the Progression of a Preleukemic Stage to Overt Leukemia in Children with Down Syndrome
Authors: Maurice Labuhn, Kelly Perkins, Elli Papaemmanuil, Catherine Garnett, Soeren Matzk, Vyacheslav Amstislavskiy, Marlen Metzner, Alison Kennedy, Carina Scheer, Kenichi Yoshida, Adrian Schwarzer, John D. Crispino, Jeffrey W. Taub, Mitchell J. Weiss, Etsuro Ito, Seishi Ogawa, Dirk Reinhardt, Marie-Laure Yaspo, Peter J. Campbell, Dirk Heckl, Jan-Henning Klusmann, Paresh Vyas
Journal: Blood (2018)
Abstract 16005: Antihypertensive Efficacy of Long-Acting Nitrates
Authors: Karan Wats, Lawrence H Kwon, Steven A Atlas
Journal: Circulation (2017)

Introduction: The organic nitrates are a class of vasoactive drugs that act as nitric oxide (NO) donors and thus stimulate cGMP production, leading to vascular smooth muscle relaxation and vasodilation. Nitrates are commonly used for treatment of patients with angina and heart failure, with benefits mainly attributable to their venodilator action, but they also lower arterial blood pressure. This meta-analysis was performed to better define the efficacy of long-acting nitrates as antihypertensive agents. Hypothesis: Long-acting nitrates effectively lower blood pressure in patients with hypertension when used either alone or as add on therapy. Methods: We conducted a meta-analysis of prospective trials that provided both baseline and follow-up peripheral or central blood pressure after at least two weeks of long-acting nitrate therapy (either isosorbide mononitrate or dinitrate) given as mono- or add-on therapy in patients with hypertension. We used Ovid MEDLINE, EMBASE and PubMed, all without date restric...
Abstract 12886: In-hospital and Early Post-discharge Troponin Elevations Among Patients Hospitalized for Heart Failure: Insights From the ASTRONAUT Trial
Authors: Stephen J Greene, Faiez Zannad, Gregg C Fonarow, Haris Subacius, Marco Triggiani, Andrew P Ambrosy, Michael Böhm, Javed Butler, Ovidiu Chioncel, Aldo P Maggioni, Scott D Solomon, Muthiah Vaduganathan, Mihai Gheorghiade, Michele Senni
Journal: Circulation (2016)

Introduction: Troponin level is commonly elevated among patients hospitalized for heart failure (HF) and may correlate with worse clinical outcomes. The prognostic significance of early post-discharge troponin level and persistent troponin elevation is unclear. Methods: The ASTRONAUT trial randomized 1,615 hospitalized HF patients with ejection fraction ≤40% to daily aliskiren or placebo, in addition to standard care. Troponin I was measured per protocol at baseline and 1-month in a core lab with elevated level defined as &gt;0.04 ng/mL. Outcomes were compared by presence/ absence of troponin I elevation at baseline and 1-month. Landmark analysis was performed to account only for events subsequent to troponin measurement. Results: Overall, 1,469 (91.0%) patients had troponin data at baseline, of which 609 (41.5%) had elevated levels (median 0.10 ng/mL). At 1 month, 1,301 (80.6%) patients had troponin data, of which 389 (29.9%) had elevated levels (median 0.10 ng/mL). Among patients with baseline elevated troponin with troponin data at 1 month, 313/518 (60.4%) had persistently elevated troponin level. After adjustment, elevated baseline troponin was not significantly associated with 1-year all-cause death or cardiovascular mortality/ HF hospitalization (Table). However, 1-month troponin elevation was independently predictive of 1-year clinical outcomes. The association between 1-month troponin elevation and outcomes was not influenced by presence/ absence of baseline troponin elevation (P for interaction ≥ 0.69). Conclusion: Troponin I was elevated in &gt;40% of hospitalized HF patients, and remained persistently elevated in &gt;60% of these patients early post-discharge. Elevated troponin I levels at 1-month follow-up, but not during hospitalization, were independently predictive of increased clinical events. Measurement of troponin I during the early post-discharge vulnerable phase should be considered as a practical means of risk stratification.
Abstract 18692: High Flavanol Dark Chocolate Reduces NT-proBNP in Patients with Chronic Heart Failure
Authors: Rodney de Palma, Imelda Sotto, Noorafza Q Khan, Elizabeth G Wood, Jane Butler, Atholl Johnston, Martin T Rothman, Roger Corder
Journal: Circulation (2012)

Background: Endothelial dysfunction in patients with heart failure (HF) has been linked to a worse prognosis. High flavanol cocoa products improve endothelial function, but it has yet to be established whether such changes are sufficient to confer medical benefit. We investigated whether high flavanol dark chocolate (HFDC) reduces the severity of HF by measuring changes in amino-terminal pro-B type natriuretic peptide (NT-proBNP). Methods: Patients with HF and a history of ischemic heart disease (n = 32), stable on optimal medication according to standard guidelines, were randomized to consume 50 g per day of either HFDC or low flavanol dark chocolate (LFDC) for 4 weeks, and then crossed over to consume the alternative dark chocolate for a further 4 week. The flavanol contents of the HFDC and LFDC were 1094 and 95 mg/50 g. NT-proBNP, blood pressure, and aortic pulse waveform derived from radial artery applanation tonometry were assessed at baseline, after each 4-week treatment phase, and at follow-up 4 weeks after completion of chocolate consumption. Results: 24 subjects completed the study. After 4 weeks consumption of HFDC, NT-proBNP was significantly lower compared to baseline (P = 0.016), LFDC (P = 0.019) and at follow-up (P = 0.004). After HFDC, diastolic blood pressure (DBP) was decreased compared to LFDC (mean decrease ± SD; -7 ± 10 mmHg, P = 0.003 and compared to baseline measurements (-4 ± 9 mmHg, P = 0.047). Figure 1 shows a comparison of mean changes in DBP and NT-proBNP after HFDC compared to baseline, LFDC and follow-up values. Mean decrease in NT-proBNP was &gt;30% in 12 patients. Conclusions: Reductions in NT-proBNP and blood pressure after HFDC are consistent with a decrease in vascular resistance resulting in reduced left ventricular afterload. Post treatment reductions of NT-proBNP &gt;30% have previously been associated with improved outcome in patients with HF. Hence, long-term benefits of high flavanol interventions in HF merit further investigation. <!--<inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="g18692_1"/>-->
Novel Form of Alternative Splicing of NFKB1. Its Role in Polycythemia and Adaptation to High Altitude in Andean Aymara
Authors: Jihyun Song, Seonggyun Han, Ricardo Amaru, Teddy Quispe, Dongwook Kim, Jacob E. Crawford, Josef Stehlik, Rasmus Nielsen, Younghee Lee, Josef T. Prchal
Journal: Blood (2018)
Dietary Fats in Relation to Total and Cause-Specific Mortality in a Prospective Cohort of 521 120 Individuals With 16 Years of Follow-Up
Authors: Pan Zhuang, Yu Zhang, Wei He, Xiaoqian Chen, Jingnan Chen, Lilin He, Lei Mao, Fei Wu, Jingjing Jiao
Journal: Circulation Research (2019)

Rationale: Evidence linking saturated fat intake with cardiovascular health is controversial. The associations of unsaturated fats with total and cardiovascular disease (CVD) mortality remain inconsistent, and data about non-CVD mortality are limited. Objective: To assess dietary fat intake in relation to total and cause-specific mortality. Methods and Results: We analyzed data of 521 120 participants aged 50 to 71 years from the National Institutes of Health-American Association of Retired Persons Diet and Health Study with 16 years of follow-up. Intakes of saturated fatty acids (SFAs), trans-fatty acids, monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) were assessed via food frequency questionnaires. Hazard ratios and 95%CIs were estimated using the Cox proportional hazards model. Overall, 129 328 deaths were documented during 7.3 million person-years of follow-up. In the replacement of carbohydrates, multivariable-adjusted hazard ratios of total mortality comparing extreme quintiles were 1.29 (95% CI, 1.25–1.33) for SFAs, 1.03 (1.00–1.05) for trans-fatty acids, 0.98 (0.94–1.02) for MUFAs, 1.09 (1.06–1.13) for animal MUFAs, 0.94 (0.91–0.97) for plant MUFAs, 0.93 (0.91–0.95) for PUFAs, 0.92 (0.90–0.94) for marine omega-3 PUFAs, 1.06 (1.03–1.09) for α-linolenic acid, 0.88 (0.86–0.91) for linoleic acid, and 1.10 (1.08–1.13) for arachidonic acid. CVD mortality was inversely associated with marine omega-3 PUFA intake ( P trend &lt;0.0001), whereas it was positively associated with SFA, trans-fatty acid, and arachidonic acid intake. Isocalorically replacing 5% of the energy from SFAs with plant MUFAs was associated with 15%, 10%, 11%, and 30% lower total mortality, CVD, cancer, and respiratory disease mortality, respectively. Isocaloric replacement of SFA with linoleic acid (2%) was associated with lower total (8%), CVD (6%), cancer (8%), respiratory disease (11%), and diabetes mellitus (9%) mortality. Conclusions: Intakes of SFAs, trans-fatty acids, animal MUFAs, α-linolenic acid, and arachidonic acid were associated with higher mortality. Dietary intake of marine omega-3 PUFAs and replacing SFAs with plant MUFAs or linoleic acid were associated with lower total, CVD, and certain cause-specific mortality. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00340015.
Dead space ventilation promotes alveolar hypocapnia reducing surfactant secretion by altering mitochondrial function
Authors: Martina Kiefmann, Sascha Tank, Marc-Oliver Tritt, Paula Keller, Kai Heckel, Leonie Schulte-Uentrop, Cynthia Olotu, Sonja Schrepfer, Alwin E Goetz, Rainer Kiefmann
Journal: Thorax (2019)

Background In acute respiratory distress syndrome (ARDS), pulmonary perfusion failure increases physiologic dead space ventilation (V D /V T ), leading to a decline of the alveolar CO 2 concentration [CO 2 ] iA . Although it has been shown that alveolar hypocapnia contributes to formation of atelectasis and surfactant depletion, a typical complication in ARDS, the underlying mechanism has not been elucidated so far. Methods In isolated perfused rat lungs, cytosolic or mitochondrial Ca 2+ concentrations ([Ca 2+ ] cyt or [Ca 2+ ] mito , respectively) of alveolar epithelial cells (AECs), surfactant secretion and the projected area of alveoli were quantified by real-time fluorescence or bright-field imaging (n=3–7 per group). In ventilated White New Zealand rabbits, the left pulmonary artery was ligated and the size of subpleural alveoli was measured by intravital microscopy (n=4 per group). Surfactant secretion was determined in the bronchoalveolar lavage (BAL) by western blot. Results Low [CO 2 ] iA decreased [Ca 2+ ] cyt and increased [Ca 2+ ] mito in AECs, leading to reduction of Ca 2+ -dependent surfactant secretion, and alveolar ventilation in situ. Mitochondrial inhibition by ruthenium red or rotenone blocked these responses indicating that mitochondria are key players in CO 2 sensing. Furthermore, ligature of the pulmonary artery of rabbits decreased alveolar ventilation, surfactant secretion and lung compliance in vivo. Addition of 5% CO 2 to the inspiratory gas inhibited these responses. Conclusions Accordingly, we provide evidence that alveolar hypocapnia leads to a Ca 2+ shift from the cytosol into mitochondria. The subsequent decline of [Ca 2+ ] cyt reduces surfactant secretion and thus regional ventilation in lung regions with high V D /V T . Additionally, the regional hypoventilation provoked by perfusion failure can be inhibited by inspiratory CO 2 application.
SAT0314 To describe and characterise the patient group defined as complex in a joint rheumatology/dermatology clinic (PAIDER)
Authors: A. Garcia-Guillen, A. Laiz, A. Lopez-Ferrer, P. Moya, I. Castellví, B. Magallares, C. Diaz-Torné, H. Corominas, H. Park
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> To describe and characterise the patient group defined as complex in a joint Rheumatology/Dermatology clinic (PAIDER). <h3>Methods</h3> We performed a retrospective chart review of patients evaluated between May 2012 and November 2017 at a weekly joint Rheumatology/Dermatology clinic at Hospital de Sant Pau (Autonomous University of Barcelona), Spain. We reviewed the medical records for demographic information, source of referral, complexity, cardiovascular risk factors and the number of visits. Complexity or complex patient was defined by at least one of the following characteristics: liver disease, neoplastic disease, psychiatric disorders, communication difficulties, adverse drug reactions to previous treatment, or paradoxical effects of biological therapy. The degree of complexity was a number (from 1 to 6) resulting from the sum of the previous characteristics. A descriptive analysis was carried out and the correlation between variables was studied through the application of nonparametric tests. The statistical package SPSS v. 21 was used to analyse the data. <h3>Results</h3> 494 patients were evaluated (52% women) with a total of 1110 visits. The mean age was 53 years. Patients were referred from Rheumatology, Dermatology, primary care physicians and other specialties in 47%, 40%, 6.5% and 5.5% of cases, respectively. The average number of visits per patient was 2.25. 164 patients (33%) were defined as complex with a total of 546 visits. 48.8% were women. The mean age was 55 years. They were referred from Rheumatology, Dermatology, primary care physicians and other specialties in 50.6%, 35.4%, 7.3% and 6.7% of cases, respectively. The mean number of following-up visits for the complex patients was 3.33. The features that defined complexity and the number of visits required are shown in table 1. The number of visits according to the degree of complexity is shown in table 2. <h3>Conclusions</h3> A third of the patients visited in our joint clinic were defined as complex, although the great majority showed a low level of complexity. Of all the features used to define complexity, only a few were associated with a greater number of visits. However, the degree of complexity of the patients was associated with an increased number of visits. <h3>Disclosure of Interest</h3> None declared