Immunohistochemical detection of XIAP and p63 in adenomatous hyperplasia, atypical adenomatous hyperplasia, bronchioloalveolar carcinoma and well-differentiated adenocarcinoma.

The critical distinction of bronchioloalveolar carcinoma (BAC), well-differentiated adenocarcinoma (WDAC) of lung, adenomatous hyperplasia (AH) and atypical adenomatous hyperplasia (AAH), is based on morphological criteria alone, and is therefore potentially subjective. We examined expression of two markers, X-linked inhibitor of apoptosis protein (XIAP), the most potent of the inhibitor of apoptosis protein (IAP) family, and p63, a marker of bronchial reserve cells (BRC) and squamous cells, in these entities. H&E slides of 37 tissue blocks from 27 patients were reviewed and classified as AH (n=7), AAH (n=8), BAC (n=9) and WDAC (n=13). Immunostaining was performed on 4 mum sections with monoclonal anti-XIAP and monoclonal anti-p63. Granular or heterogeneous cytoplasmic staining for XIAP and nuclear staining for p63 were considered positive. Neither XIAP nor p63 were detected in normal lung alveolar cells. All seven AHs were negative for XIAP and negative or focally positive for p63. All eight AAHs were positive for XIAP and displayed p63 positivity in scattered cells. All BACs displayed XIAP positivity, which ranged from focal/weak to diffuse/strong. p63 was negative in seven and focally positive in two of nine BACs. Twelve of 13 WDACs showed XIAP positivity in a similar pattern to BAC; all were negative for p63. One aberrant case diagnosed on H & E as WDAC was negative for XIAP but strongly positive for p63. Significant XIAP expression appears to be useful for distinguishing AAH from AH. Commonality of XIAP staining in AAH, BAC and WDAC supports the possibility that AAH may be a pre-malignant lesion. The rarity of p63 expression confirms previous reports and supports a nonbronchial histogenesis of these entities. In contrast, diffuse p63 staining may facilitate the identification of rare cases that may have been misclassified as alveolar in origin based on morphology but may be of BRC origin.     

Matrix Metalloproteinase‐2 and ‐9 Levels in Patients with Dilated Ascending Aorta and Bicuspid Aortic Valve

Background: Predictors of aortic dilatation are not well‐described in patients with bicuspid aortic valve (BAV). Changes in extracellular matrix composition in the aortic wall may play an important role. Our study aimed to examine the relationship between ascending aortic dilatation and biochemical markers for collagen metabolism, such as matrix metalloproteinase‐2 (MMP‐2) and matrix metalloproteinase‐9 (MMP‐9) levels in patients with BAV. Methods: All patients underwent cardiac echocardiography using a standard protocol, and aortic measurements were made in end‐diastole. One hundred twelve BAV patients with no or mild valvular impairment were recruited and grouped according to the aortic dimensions corrected for body surface area (BSA) and age. There were 54 patients with dilated ascending aorta (Group 1) and 58 patients with nondilated ascending aorta (group 2). The plasma levels of MMP‐2 and MMP‐9 were determined by ELISA. Results: The mean ascending aorta diameter was 4.49 ± 0.49 mm in group 1 and 3.51 ± 0.46 mm in group 2 (P < 0.001). There were no significant difference in gender, BSA, presence of hypertension, diabetes mellitus, hyperlipidemia, and smoking between the 2 groups. Nevertheless, no significant difference was observed in the levels of MMP‐2 and MMP‐9 between the 2 groups. The ascending aorta diameter correlated significantly with age (r = 0.438 P < 0.001). No significant correlation was observed between plasma MMP‐2 and MMP‐9 concentration and ascending aorta diameter, respectively (r = ?0.005 P = 0.58, r = ?0.106 P = 0.07). Multivariate analysis showed that age was independent predictor of aortic dilatation (P ≤ 0.001). Conclusion: Age was an independent predictor of aortic dilatation in patients with BAV, whereas MMP‐2 and 9 levels were not relevant by aortic dilatation.     

Immediate and Follow‐Up Results of Repeat Percutaneous Mitral Balloon Commissurotomy for Restenosis After a Succesful First Procedure

Background: The widespread use of percutaneous mitral commissurotomy (PMC) has led to an increase in restenosis cases. The data regarding follow‐up results of repeat PMC are quite limited. The aim of this retrospective analysis is to evaluate the immediate and midterm results of the second PMC, in patients with symptomatic mitral restenosis after a succesful first procedure. Methods: Twenty patients (95% female, mean age 37 ± 4 years) who have undergone a second PMC, 6.3 ± 2.5 years after a first successful intervention built the study group. All were in sinus rhythm, with a mean Wilkins score of 8.5 ± 1.2. Results: The valve area increased from 1.2 ± 0.2 to 1.9 ± 0.2 cm² and mean gradient decreased from 10.5 ± 3.4 to 6.1 ± 1.1 mmHg. There were no complications except for a transient embolic event without sequela (5%) and two cases (10%) of severe mitral regurgitation. The immediate success rate was 90%. The mean follow‐up was 70 ± 29 months (36–156 months). The 5‐year restenosis and intervention (repeat PMC or valve replacement) rates were 9.1 ± 5.2% and 3.6 ± 3.3%, respectively. The intervention free 5‐year survival in good functional capacity (New York Heart Association [NYHA] I–II) was 95.1 ± 5.5% and restenosis and intervention free 5‐year survival with good functional capacity was 89.7 ± 6.8%. Conclusions: Although from a limited number of selected patients, these findings indicate that repeat PMC is a safe and effective method, with follow‐up results similar to a first intervention and should be considered as the first therapeutic option in suitable patients. (Echocardiography 2010;27:765‐769)     

Wide QRS Complex and Lateral ST-T Segment Abnormality Are Associated With Worse Clinical Outcomes in COVID-19 Patients

BackgroundThe information on electrocardiographic features of patients with coronavirus disease 2019 (COVID-19) is limited. Our aim was to determine if baseline electrocardiographic features of hospitalized COVID-19 patients are associated with markers of myocardial injury and clinical outcomes.MethodsIn this retrospective, single center cohort study, we included 223 hospitalized patients with laboratory-confirmed COVID-19. Clinical, electrocardiographic and laboratory data were collected and analyzed. Primary composite endpoint of mortality, need for invasive mechanical ventilation, or admission to the intensive care unit was assessed.ResultsForty patients (17.9%) reached the primary composite endpoint. Patients with the primary composite endpoint were more likely to have wide QRS complex (>120 ms) and lateral ST-T segment abnormality. The multivariable Cox regression showed increasing odds of the primary composite endpoint associated with acute respiratory distress syndrome (odds ratio 7.76, 95% CI 2.67–22.59; p < 0.001), acute cardiac injury (odds ratio 3.14, 95% CI 1.26–7.99; p = 0.016), high flow oxygen therapy (odds ratio 2.43, 95% CI 1.05–5.62; p = 0.037) and QRS duration longer than >120 ms (odds ratio 3.62, 95% CI 1.39–9.380; p = 0.008) Patients with a wide QRS complex (>120 ms) had significantly higher median level of troponin T and pro-BNP than those without it. Patients with abnormality of lateral ST-T segment had significantly higher median level of troponin T and pro-BNP than patients without.ConclusionsThe presence of QRS duration longer than 120 ms and lateral ST-T segment abnormality were associated with worse clinical outcomes and higher levels of myocardial injury biomarkers.     

Analysis of cytotoxic effects of silver nanoclusters on human peripheral blood mononuclear cells ‘in vitro’

The antimicrobial properties of silver nanoparticles (AgNPs) have made these particles one of the most used nanomaterials in consumer products. Therefore, an understanding of the interactions (unwanted toxicity) between nanoparticles and human cells is of significant interest. The aim of this study was to assess the in vitro cytotoxicity effects of silver nanoclusters (AgNC, < 2 nm diameter) on peripheral blood mononuclear cells (PBMC). Using flow cytometry and comet assay methods, we demonstrate that exposure of PBMC to AgNC induced intracellular reactive oxygen species (ROS) generation, DNA damage and apoptosis at 3, 6 and 12 h, with a dose‐dependent response (0.1, 1, 3, 5 and 30 µg ml^–1). Advanced electron microscopy imaging of complete and ultrathin‐sections of PBMC confirmed the cytotoxic effects and cell damage caused by AgNC. The present study showed that AgNC produced without coating agents induced significant cytotoxic effects on PBMC owing to their high aspect ratio and active surface area, even at much lower concentrations (<1 µg ml^–1) than those applied in previous studies, resembling what would occur under real exposure conditions to nanosilver‐functionalized consumer products. Copyright © 2015 John Wiley & Sons, Ltd.     

Dilatation of the ascending aorta and serum alpha 1-antitrypsin level in patients with bicuspid aortic valve

Predictors of aortic dilatation are not well described in patients with bicuspid aortic valves (BAV). This study sought to examine the relationship between proximal aortic dilatation and matrix metalloproteinase-9 (MMP-9) and alpha 1-antitrypsin (α1AT) levels in patients with BAV. All patients underwent echocardiography using a standard protocol, and aortic measurements were taken in end-diastole. We studied 82 patients with BAV and categorized them into two groups according to aortic dimensions corrected for body surface area and age. The plasma level of α1AT was routinely determined using a BN ProSpec analyzer (Siemens Healthcare Diagnostics, Marburg, Germany), and that of MMP-9 were determined by ELISA (RayBiotech Inc. Norcross, GA, USA). Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS; SPSS Inc., Chicago, IL, USA) software for Windows version 12. This study included patients with BAV with no or mild valvular impairment. There were no significant differences between groups in terms of gender, body surface area, associated hypertension, diabetes mellitus, hyperlipidemia, or smoking. The mean ascending aortic diameter was 4.38?±?0.5?mm in group 1 and 3.34?±?0.35?mm in group 2 (p?相似文献   

The relationship between chronic kidney disease and SYNTAX score

Chronic kidney disease (CKD) is associated with increased risk of cardiovascular disease and death. We evaluated the association between CKD and severity of coronary artery stenosis by calculating SYNTAX Score in patients with left main coronary artery and/or 3-vessel coronary artery disease. Coronary angiograms of 217 patients were assessed. Chronic kidney disease was staged using the estimated glomerular filtration rate (eGFR, mL/min per 1.73 m(2)) prior to coronary angiography. Patients were divided into 5 groups according to the National Kidney Foundation Kidney Disease Outcome Quality Initiative (NKF KDOQI) Clinical Practice Guidelines (14). Patients with eGFR >90 mL/min per 1.73 m(2) (group 1), patients with eGFR 60 to 89 mL/min per 1.73 m(2) (group 2), patients with eGFR 30 to 59 mL/min per 1.73 m(2) (group 3), patients with eGFR >15 to < 30 per 1.73 m(2) and dialysis patients with eGFR < 15 per 1.73 m(2) were combined as group 4. The risk of significant lesion complexity increased progressively with decreasing kidney function (P = .001). Estimated glomerular filtration rate was a strong predictor of higher SYNTAX Score.