Search

Objectives: Limited data exist on the optimal treatment duration for chronic pulmonary aspergillosis (CPA). We investigated the treatment outcome and recurrence rate according to treatment duration in CPA patients.Methods: A total of 196 patients who completed at least 6 months of antifungal therapy (99% oral itraconazole) and achieved favorable treatment responses were analyzed. A Cox's proportional hazards regression model was used to adjust for potential confounding factors in the association between the duration of antifungal therapy (6-12 months vs. ≥ 12 months) and recurrence.Results: All patients were treated with antifungal agents for at least 6 months (median: 12.5, interquartile range: 8.5-18.4 months) and categorized into 6-12 months group (79/196, 40%) and ≥ 12 months group (117/196, 60%). The 6-12 months group had significantly higher recurrence rates owing to CPA aggravation after the completion of treatment compared with the ≥ 12 months group (51% vs. 25%, P  =  0.003). In a Cox's proportional hazards regression model, treatment duration ≥ 12 months was independently associated with a lower risk of recurrence (adjusted hazard ratio: 0.48, 95% confidence interval: 0.28-0.80).Conclusions: Our data suggest that prolonging antifungal therapy beyond 12 months could reduce the recurrence rate in CPA patients. [ABSTRACT FROM AUTHOR]

Study Objective: Coronary artery calcium score (CACS) is a well-established test for risk stratifying asymptomatic patients. Recent studies also indicate that CACS may accurately risk stratify stable patients presenting to the emergency department (ED) with acute chest pain; however, many were underpowered. The purpose of this systematic review and meta-analysis is to evaluate the prognostic value and accuracy of a zero (normal) CACS for identifying patients at acceptable low risk for future cardiovascular events who might be safely discharged home from the ED.Methods: We searched multiple databases for longitudinal studies of CACS in symptomatic patients without known coronary artery disease that reported major adverse cardiovascular events (MACEs), including death and myocardial infarction. Pooled risk ratios, sensitivity, specificity, and likelihood ratios were analyzed.Results: Eight studies evaluated 3,556 patients, with a median follow-up of 10.5 months. Pooled prevalence of zero CACS was 60%. Patients with CACS=0 had a significantly lower risk of cardiovascular events compared with those with CACS greater than 0 (MACEs: relative risk 0.06, 95% confidence interval 0.04 to 0.11, I2=0%; death/myocardial infarction: relative risk 0.19; 95% confidence interval 0.08 to 0.47, I2=0%). The pooled event rates for CACS=0 (MACEs 0.8%/year; death/myocardial infarction 0.5%/year) were significantly lower than for CACS greater than 0 (MACEs 14.6%/year; death/myocardial infarction 3.5%/year). Analysis of summary testing parameters showed a sensitivity of 96%, specificity of 60%, positive likelihood ratio of 2.36, and negative likelihood ratio of 0.07.Conclusion: Acute chest pain patients without history of coronary artery disease, ischemic ECG changes, or increased cardiac enzyme levels commonly have a CACS of zero, with a very low subsequent risk of MACEs or death or myocardial infarction. This meta-analysis proffers the potential role of initial CACS testing for avoiding unnecessary hospitalization and further cardiac testing in acute chest pain patients with a CACS of zero. [ABSTRACT FROM AUTHOR]

Purpose To evaluate protective effect of pterostilbene against testicular ischemia/reperfusion (I/R) injury, which results in increased formation of oxidative stress, leading to testicular apoptosis and impaired spermatogenesis. Methods Thirty two pubertal male Sprague–Dawley rats weighing 180–220 g were selected and randomly divided into the following four groups: group A (normal control group), group B (sham-operated group), group C (induced I/R injury group), group D (induced I/R injury group receiving pterostilbene treatment). Johnsen's scores and mean seminiferous tubule diameters were evaluated for histopathologic assessment; germinal cell apoptosis was evaluated by the transferase dUTP nick end labeling (TUNEL) assay and immunohistochemistry for caspases. Malondialdehyde (MDA) levels were assessed as an indicator of oxidative stress and total antioxidant capacity (TAC) was measured. Results Germ cell apoptosis and MDA level significantly increased whereas TAC significantly decreased in group C; moreover, abnormal morphology and impaired spermatogenesis were observed in group C. In contrast, treatment with pterostilbene inhibited lipid peroxidation and apoptosis induced by ROS and restored the antioxidant capacity in group D. Conclusions These results show that treatment with pterostilbene may be a promising therapy for testicular I/R injury. [ABSTRACT FROM AUTHOR]

Background: The pulmonary autograft remodels when subjected to systemic pressure and subsequent dilation can lead to reoperation. Inherent material property differences between pulmonary and aortic roots may influence remodeling but are currently unknown. The objective of this study was to determine stiffness across a wide range of strain and compare nonlinear material properties of corresponding regions of native aortic and pulmonary roots. Methods: Tissue samples from porcine aortic and pulmonary roots—sinuses and supravalvular artery distal to the sinotubular junction—were subjected to displacement-controlled equibiaxial stretch testing. Stress-strain data recorded were used to derive strain energy functions for each region. Stiffness from low to high strains at 0.15, 0.3, and 0.5 strain were determined for comparisons. Results: Aortic and pulmonary roots exhibited qualitatively similar material properties; both had greater nonlinearity in the sinus than supravalvular artery. The pulmonary artery was significantly more compliant than the ascending aorta both circumferentially and longitudinally throughout the strain range (p < 0.03), except at high strain circumferentially (p = 0.06). However, no differences in stiffness were seen circumferentially or longitudinally between pulmonary and aortic sinuses (p ≥ 0.3) until high strain, when the pulmonary sinuses were significantly stiffer (p < 0.05) in both directions. Conclusions: Differences in stiffness between porcine aortic and pulmonary roots are regionally specific, supravalvular artery versus sinus. These regional differences may impact the mode of remodeling to influence late autograft dilation. [Copyright &y& Elsevier]

Background: Passive constraint is used to prevent left ventricular dilation and subsequent remodeling. However, there has been concern about the effect of passive constraint on diastolic left ventricular chamber stiffness and pump function. This study determined the relationship between constraint, diastolic wall stress, chamber stiffness, and pump function. We tested the hypothesis that passive constraint at 3 mm Hg reduces wall stress with minimal change in pump function. Methods: A three-dimensional finite-element model of the globally dilated left ventricle based on left ventricular dimensions obtained in dogs that had undergone serial intracoronary microsphere injection was created. The model was adjusted to match experimentally observed end-diastolic left ventricular volume and midventricular wall thickness. The experimental results used to create the model were previously reported. A pressure of 3, 5, 7, and 9 mm Hg was applied to the epicardium. Fiber stress, end-diastolic pressure–volume relationship, end-systolic pressure–volume relationship, and the stroke volume–end-diastolic pressure (Starling) relationship were calculated. Results: As epicardial constraint pressure increased, fiber stress decreased, the end-diastolic pressure–volume relationship shifted to the left, and the Starling relationship shifted down and to the right. The end-systolic pressure–volume relationship did not change. A constraining pressure of 2.3 mm Hg was associated with a 10% reduction in stroke volume, and mean end-diastolic fiber stress was reduced by 18.3% (inner wall), 15.3% (mid wall), and 14.2% (outer wall). Conclusions: Both stress and cardiac output decrease in a linear fashion as the amount of passive constraint is increased. If the reduction in cardiac output is to be less than 10%, passive constraint should not exceed 2.3 mm Hg. On the other hand, this amount of constraint may be sufficient to reverse eccentric hypertrophy after myocardial infarction. [Copyright &y& Elsevier]

Background: Surgical glues are used in mechanical, stentless bioprosthetic, and homograft aortic root replacements to seal and reinforce anastomotic suture lines. The aortic root normally undergoes substantial physiologic dilation and may be affected by the stiffness of applied sealants. We determined the material properties of four common commercial glues, comparing them with known properties of aortic root replacements. Methods: Samples of BioGlue (CryoLife, Inc, Kennesaw, GA), CoSeal (Baxter Healthcare International, Palo Alto, CA), Tisseel (Baxter Healthcare Corp, Glendale, CA), and Crosseal (OMRIX Biopharmaceuticals, Inc, New York, NY) sealants underwent biaxial tensile testing. A Hookean strain energy function was fit to the stress-strain response of each sample, and the Young''s modulus was obtained for comparison of material stiffness. Results: Sealants demonstrate a relatively linear response to loading; mean elastic moduli for BioGlue (3,122.04 ± 1,639.68 kPa), CoSeal (100.02 ± 67.60 kPa), Tisseel (102.59 ± 41.13 kPa), and Crosseal (53.56 ± 32.59 kPa) varied greatly. CoSeal and Tisseel have no significant difference in stiffness (p = 0.897) while Crosseal is more compliant than Tisseel (p = 0.004) and CoSeal (p = 0.055). BioGlue is stiffer than CoSeal, Tisseel, and Crosseal (p < 0.001). Furthermore, BioGlue is much stiffer than cited properties of Dacron grafts, glutaraldehyde-fixed porcine roots, and human aortic tissue. However, CoSeal and Tisseel are much more compliant than the aortic root conduits. Conclusions: BioGlue is much less compliant than the other sealants studied and materials available for aortic root replacement. A surgeon''s choice of glue should be determined by stiffness as well as sealant efficacy. Sealants with greater stiffness than aortic root replacement material may restrict normal physiologic dilation and cause anastomotic strictures. [Copyright &y& Elsevier]

Background: Plasminogen activator inhibitor (PAI)–1 is a key regulator of the fibrinolytic system. PAI-1 levels are markedly elevated in the asthmatic airways. The 4G/5G polymorphism of the PAI-1 gene is associated with allergic asthma. Objective: To characterize the mechanisms of the 4G/5G-dependent PAI-1 expression in mast cells (MCs), a major source of PAI-1 and key effector cells in asthma. Methods: Transcription of PAI-1 was assessed by transiently transfecting human MC line (HMC-1) cells with the luciferase-tagged PAI-1 promoters containing the 4G or 5G allele (4G–PAI-1 or 5G–PAI-1 promoter). Upstream stimulatory factor (USF)–1 and the E-box interactions were studied by electrophoretic mobility shift assays and supershift assays. Expression of USF-1 was determined by Western blot analysis. Results: The 4G–PAI-1 promoter has higher promoter activity than the 5G–PAI-1 promoter in stimulated HMC-1 cells, and the E-box adjacent to the 4G/5G site (E-4G/5G) regulates the genotype-specific PAI-1 transcription. USF-1 binds to the E-4G with greater affinity than to the E-5G. USF-1 level is increased in HMC-1 cells after stimulation, and elevated USF-1 enhances PAI-1 transcription. Overexpression of wild-type USF-1 or dominant-negative USF remedies the 4G/5G-dependent PAI-1 transcription. Conclusion: Binding of USF-1 to the E-4G/5G regulates the 4G/5G polymorphism–dependent PAI-1 expression in MCs. [Copyright &y& Elsevier]

Pain in sickle cell disease (SCD) is complex and heterogeneous. In this study, we examine the influence of single nucleotide polymorphisms (SNP) in the S100B gene on acute and chronic pain variation in SCD. 136 subjects with SCD recorded their baseline, non-crisis pain experience on a digital version of the McGill Pain Questionnaire, from which we obtained composite pain index (CPI) scores as a measurement for chronic pain. Utilization of emergency or urgent care owing to painful crisis was recorded as a marker for acute pain. Blood/buccal swab samples were collected and genotyped using MassARRAY iPLEX platform. Multiple linear regression analyses revealed association with higher CPI scores for rs9983698 T allele (additive: B= 4.91, p= 0.014; dominant: B= 6.43, p= 0.009), rs9722 A allele (additive: B= 4.81, p= 0.005; dominant: B= 7.80, p= 0.003), and rs11911834 T allele (additive: B= 4.75, p= 0.016; dominant: B= 6.13, p= 0.011). On the other hand, the G allele of rs1051169 associated with decreased CPI (additive: B= -6.14, p= 0.001; dominant: B= -6.56, p= 0.009; recessive: B= -9.78, p= 0.005). Further, ordinal logistic regression of utilization groups showed that the G allele of rs1051169 also associated with lower utilization (additive: B= -1.02, p= 0.0003; dominant: B= -1.20, p= 0.002; recessive: B= -1.26, p= 0.015). Employing linkage disequilibrium plot, we identified two haploblocks for these 4 SNPs. In block 1 (rs9983698-rs9722), haplotypes T-A and C-G significantly associated with CPI (B= 5.63, -4.81; p= 0.007, 0.005, respectively). In block 2 (rs1051169-rs11911834), C-T and G-G haplotypes showed significant association with CPI (B= 4.52, -6.02; p= 0.024, 0.001, respectively). S100B SNPs and haplotypes were found to associate with acute and chronic pain in SCD indicating the potential role of S100B in sickle cell pain heterogeneity. Supported by grants from the NIH (R01HL124945, R01HL098141, T32DE018381) and IDPH. [ABSTRACT FROM AUTHOR]