Objective To assess the risk and predictors of lymphoma development in a large cohort of patients with primary Sjögren's syndrome (pSS). Methods Cox-regression analyses were used to study the ...predictive value of clinical and laboratory findings at pSS diagnosis, and Kaplan-Meier survival curves to compare survival probability between patients who developed lymphoma and the total cohort. Expected risk for lymphoma was calculated by comparison with the background population. Results Eleven (4.5%) from 244 patients developed a non-Hodgkin lymphoma (NHL). Diffuse large B-cell and mucosa-associated lymphoid tissue lymphomas occurred at a similar frequency. Three (27.3%) patients died: 2 due to transformation from mucosa-associated lymphoid tissue to diffuse large B-cell. Purpura (HR 8.04, 95% confidence interval CI 2.33-27.67), parotidomegaly (HR 6.75, 95%CI 1.89-23.99), anemia (HR 3.43, 95%CI 1.04-11.35), leukopenia (HR 8.70, 95%CI 2.38-31.82), lymphocytopenia (HR 16.47, 95%CI 3.45-78.67), hypergammaglobulinemia (HR 4.06, 95%CI 1.06-15.58), low C3 (HR 36.65, 95%CI 10.65-126.18), and low C4 (HR 39.70, 95%CI 8.85-126.18) levels at pSS diagnosis were significant predictors of NHL development, but only hypocomplementemia and lymphocytopenia were independent risk factors. Hypocomplementemia was related to earlier development of NHL and higher mortality. The cumulative risk of developing lymphoma ranged from 3.4% in the first 5 years to 9.8% at 15 years. Standardized incidence ratio (95%CI) for NHL development was 15.6 (95%CI 8.7-28.2). Conclusions Patients with pSS have a 16-fold increased risk of developing lymphoma. This risk increases with time. Hypocomplementemia and lymphocytopenia at pSS diagnosis are the strongest predictors. Survival is clearly reduced in patients with hypocomplementemia. Indolent lymphomas tend to evolve over time toward a more aggressive histologic type.
Summary Background Everolimus-eluting stent (EES) reduces the risk of restenosis in elective percutaneous coronary intervention. However, the use of drug-eluting stent in patients with ST-segment ...elevation myocardial infarction (STEMI) is still controversial. Data regarding the performance of second-generation EES in this setting are scarce. We report the 1-year result of the EXAMINATION (clinical Evaluation of the Xience-V stent in Acute Myocardial INfArcTION) trial, comparing EES with bare-metal stents (BMS) in patients with STEMI. Methods This multicentre, prospective, randomised, all-comer controlled trial was done in 12 medical centres in three countries. Between Dec 31, 2008, and May 15, 2010, we recruited patients with STEMI up to 48 h after the onset of symptoms requiring emergent percutaneous coronary intervention. Patients were randomly assigned (ratio 1:1) to receive EES or BMS. Randomisation was in blocks of four or six patients, stratified by centre and centralised by telephone. Patients were masked to treatment. The primary endpoint was the patient-oriented combined endpoint of all-cause death, any recurrent myocardial infarction, and any revascularisation at 1 year and was analysed by intention to treat. The secondary endpoints of the study included the device-oriented combined endpoint of cardiac death, target vessel myocardial infarction or target lesion revascularisation, and rates of all cause or cardiac death, recurrent myocardial infarction, target lesion or target vessel revascularisation, stent thrombosis, device and procedure success, and major and minor bleeding. This trial is registered with ClinicalTrials.gov , number NCT00828087. Findings Of the 1504 patients randomised, 1498 patients were randomly assigned to receive EES (n=751) or BMS (n=747). The primary endpoint was similar in both groups (89 11·9% of 751 patients in the EES group vs 106 14·2% of 747 patients in the BMS group; difference −2·34 95% CI −5·75 to 1·07; p=0·19). Device-oriented endpoint (44 5·9% in the EES group vs 63 8·4% in the BMS group; difference −2·57 95% CI −5·18 to 0·03; p=0·05) did not differ between groups, although rates of target lesion and vessel revascularisation were significantly lower in the EES group (16 2·1% vs 37 5·0%, p=0·003, and 28 3·7% vs 51 6·8%, p=0·0077, respectively). Rates of all cause (26 3·5% for EES vs 26 3·5% for BMS, p=1·00) or cardiac death (24 3·2% for EES vs 21 2·8% for BMS, p=0·76) or myocardial infarction (10 1·3% vs 15 2·0%, p=0·32) did not differ between groups. Stent thrombosis rates were significantly lower in the EES group (4 0·5% patients with definite stent thrombosis in the EES group vs 14 1·9% in the BMS group and seven 0·9% patients with definite or probable stent thrombosis in the EES group vs 19 2·5% in the BMS group, both p=0·019). Although device success rate was similar between groups, procedure success rate was significantly higher in the EES group (731 97·5% vs 705 94·6%; p=0·0050). Finally, Bleeding rates at 1 year were comparable between groups (29 3·9% patients in the EES group vs 39 5·2% in the BMS group; p=0·19). Interpretation The use of EES compared with BMS in the setting of STEMI did not lower the patient-oriented endpoint. However, at the stent level both rates of target lesion revascularisation and stent thrombosis were reduced in recipients of EES. Funding Spanish Heart Foundation.
Objectives This study sought to study the efficacy and safety of newer-generation drug-eluting stents (DES) compared with bare-metal stents (BMS) in an appropriately powered population of patients ...with ST-segment elevation myocardial infarction (STEMI). Background Among patients with STEMI, early generation DES improved efficacy but not safety compared with BMS. Newer-generation DES, everolimus-eluting stents, and biolimus A9-eluting stents, have been shown to improve clinical outcomes compared with early generation DES. Methods Individual patient data for 2,665 STEMI patients enrolled in 2 large-scale randomized clinical trials comparing newer-generation DES with BMS were pooled: 1,326 patients received a newer-generation DES (everolimus-eluting stent or biolimus A9-eluting stent), whereas the remaining 1,329 patients received a BMS. Random-effects models were used to assess differences between the 2 groups for the device-oriented composite endpoint of cardiac death, target-vessel reinfarction, and target-lesion revascularization and the patient-oriented composite endpoint of all-cause death, any infarction, and any revascularization at 1 year. Results Newer-generation DES substantially reduce the risk of the device-oriented composite endpoint compared with BMS at 1 year (relative risk RR: 0.58; 95% confidence interval CI: 0.43 to 0.79; p = 0.0004). Similarly, the risk of the patient-oriented composite endpoint was lower with newer-generation DES than BMS (RR: 0.78; 95% CI: 0.63 to 0.96; p = 0.02). Differences in favor of newer-generation DES were driven by both a lower risk of repeat revascularization of the target lesion (RR: 0.33; 95% CI: 0.20 to 0.52; p < 0.0001) and a lower risk of target-vessel infarction (RR: 0.36; 95% CI: 0.14 to 0.92; p = 0.03). Newer-generation DES also reduced the risk of definite stent thrombosis (RR: 0.35; 95% CI: 0.16 to 0.75; p = 0.006) compared with BMS. Conclusions Among patients with STEMI, newer-generation DES improve safety and efficacy compared with BMS throughout 1 year. It remains to be determined whether the differences in favor of newer-generation DES are sustained during long-term follow-up.
Vascular complications in transcatheter aortic valve implantation using transfemoral approach are related to higher mortality. Complete percutaneous approach is currently the preferred technique for ...vascular access. However, some centers still perform surgical cutdown. Our purpose was to determine complications related to vascular access technique in the population of the Spanish TAVI National Registry. From January 2010 to July 2015, 3,046 patients were included in this Registry. Of them, 2,465 underwent transfemoral approach and were treated with either surgical cutdown and closure (cutdown group, n = 632) or percutaneous approach (puncture group, n = 1,833). Valve Academic Research Consortium-2 definitions were used to assess vascular and bleeding complications. Propensity matching resulted in 615 matched pairs. Overall, 30-day vascular complications were significantly higher in the puncture group (109 18% vs 42 6.9%; relative risk RR 2.60; 95% confidence interval CI 1.85 to 3.64, p <0.001) due mostly by minor vascular events (89 15% vs 25 4.1%, RR 3.56, 95% CI 2.32 to 5.47, p <0.001). Bleeding rates were lower in the puncture group (18 3% vs 40 6.6%, RR 0.45, 95% CI 0.26 to 0.78, p = 0.003) mainly driven by major bleeding (9 1.5% vs 21 3.4%, RR 0.43, 95% CI 0.20 to 0.93, p = 0.03). At a mean follow-up of 323 days, complication rates remained significantly different between groups (minor vascular complications 90 15% vs 31 5.1%, hazard ratio 2.99, 95% CI 1.99 to 4.50, p <0.001 and major bleeding 10 1.6% vs 21 3.4%, hazard ratio 0.47, 95% CI 0.22 to 1.0, p = 0.04, puncture versus cutdown group, respectively). In conclusion, percutaneous approach yielded higher rates of minor vascular complications but lower rates of major bleeding compared with the surgical cutdown, both at 30-day and at mid-term follow-up in our population.
Background The primary rescue medication to treat acute asthma exacerbation is the short-acting β2 -adrenergic receptor agonist; however, there is variation in how well a patient responds to ...treatment. Although these differences might be due to environmental factors, there is mounting evidence for a genetic contribution to variability in bronchodilator response (BDR). Objective To identify genetic variation associated with bronchodilator drug response in Latino children with asthma. Methods We performed a genome-wide association study (GWAS) for BDR in 1782 Latino children with asthma using standard linear regression, adjusting for genetic ancestry and ethnicity, and performed replication studies in an additional 531 Latinos. We also performed admixture mapping across the genome by testing for an association between local European, African, and Native American ancestry and BDR, adjusting for genomic ancestry and ethnicity. Results We identified 7 genetic variants associated with BDR at a genome-wide significant threshold ( P < 5 × 10−8 ), all of which had frequencies of less than 5%. Furthermore, we observed an excess of small P values driven by rare variants (frequency, <5%) and by variants in the proximity of solute carrier (SLC) genes. Admixture mapping identified 5 significant peaks; fine mapping within these peaks identified 2 rare variants in SLC22A15 as being associated with increased BDR in Mexicans. Quantitative PCR and immunohistochemistry identified SLC22A15 as being expressed in the lung and bronchial epithelial cells. Conclusion Our results suggest that rare variation contributes to individual differences in response to albuterol in Latinos, notably in SLC genes that include membrane transport proteins involved in the transport of endogenous metabolites and xenobiotics. Resequencing in larger, multiethnic population samples and additional functional studies are required to further understand the role of rare variation in BDR.
Summary We investigated the expression of Aurora kinases A and B by immunohistochemistry in 68 ovarian carcinomas to analyze their prognostic value. The amplification of AURKA gene by fluorescence in ...situ hybridization was also assessed. Overall, 58.8% and 85.3% of ovarian carcinomas showed expression of Aurora A and B, respectively. Amplification of AURKA was found in 27.6% of cases examined. Tumors with Aurora A expression showed a lower rate of recurrence than those tumors without Aurora A expression (65% versus 91.7%, P = .019). In the univariate analysis, patients with Aurora A and B expression showed an increased progression-free survival ( P = .023 and .06, respectively, log-rank test) and overall survival ( P = .03 and .02, respectively, log-rank test). The multivariate analysis adjusted to optimal surgery by Cox proportional hazards regression showed Aurora A expression as an independent prognostic factor for progression-free survival ( P = .03) and overall survival ( P = .02). In conclusion, Aurora A expression seems to have a prognostic value in ovarian carcinoma.
Abstract An 81-year-old woman was referred for primary angioplasty due to a myocardial infarction. Upon her arrival, the patient was in cardiogenic shock. Coronarography revealed a large filling ...defect within the left main coronary artery. Thromboaspiration was performed, obtaining thrombotic material and tissue of different consistencies. Balloon angioplasty in the left anterior descending and left main arteries was performed, resulting in incomplete reperfusion, leading to irreversible electromechanical dissociation. Analysis of the aspirated material was consistent with thrombus, atheroma, and calcified tissue. Autopsy revealed a heavily calcified mitral valve, and distal embolization of amorphous material in the microvasculature identical to that found in the mitral valve subapparatus. < Learning objective: Acute myocardial infarction due to left main embolization of tissue from mitral valve subapparatus is a rare condition but lethal. Early recognition of this condition is important for establishing the best option of treatment, between a percutaneous or surgical approach.>
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