Pulmonary autograft versus homograft replacement of the aortic valve: A prospective randomized trial

AbstractBackground: Pulmonary autografts offer many theoretical advantages. However, the operation is complex, may interfere with right ventricular and pulmonary outflow function, and requires a longer operative time than does the homograft operation. The effects of these potential disadvantages are unknown. Methods: To clarify these issues we randomized 70 patients undergoing aortic valve replacement to an aortic homograft group (group A = 37 patients; 53%; 34 male, 3 female) or a pulmonary autograft group (group B = 33 patients; 47%; 28 male, 5 female). Ages varied from 12 to 65 years (mean 39 ± 15 years) for group A and from 3 to 54 years (mean 29 ± 15 years) for group B (p = not significant). Eleven patients in group A (30%) and eight in group B (24%) had previous aortic valve surgery. All patients were operated on by the same surgeon. The mean cardiopulmonary bypass time was 113 ± 29 minutes (range 66 to 175 minutes) for group A and 151 ± 31 minutes (range 115 to 226 minutes) for group B (p < 0.002). Mean aortic crossclamp time was 85 ± 19 minutes (range 45 to 140 minutes) for group A and 109 ± 20 minutes (range 74 to 164 minutes) for group B (p = 0.02). In 32 patients (86.5%) the aortic homograft was implanted as a root with coronary reimplantation. All pulmonary autografts were implanted as a root. Results: No early or late deaths had occurred in this series at a mean follow-up time of 16 months (range 3 to 21 months). Two patients (one in each group) required reexploration for bleeding. No statistically significant differences were observed between the two groups with regard to ventilatory support (group A, mean 10 ± 8.5 hours; group B, mean 29 ± 85 hours), total blood loss (group A, mean 471 ± 347 ml; group B, mean 543 ± 404 ml), intensive care unit stay (group A, mean 1.2 ± 0.6 days; group B, mean 2 ± 3.7 days), and hospital stay (group A, mean 9.5 = 3.2 days; group B, mean 12 ± 6 days). Postoperatively, all patients are in New York Heart Association class I (93%) or II (7%) (p = not significant). Ejection fraction for the two groups did not change significantly over the follow-up period. Left ventricular mass and diastolic diameter showed progressive regression, with no apparent difference between the two treatment groups to date. Echocardiographic evalu- ation of aortic valve function at 6 months showed good valve function in all patients with no evidence of aortic regurgitation in 80% of both groups. In group B the right ventricular outflow gradient was below 15 mm Hg over the follow-up period. Holter monitoring, available only in 44 patients (63%), showed most of the arrhythmias to be grade 0 to 1 of the modified Lown grading system. Conclusion: Although the pulmonary autograft requires a significantly longer operating time, this does not seem to affect early and medium-term outcome when compared with results obtained with aortic homografts. Continued patient evaluation is warranted, particularly with regard to evidence of valve degeneration and right ventricular function and arrhythmias in the long term. (J Thorac Cardiovasc Surg 1997;113:894-900

A simple device for multiplex ELISA made from melt-extruded plastic microcapillary film

We present a simple device for multiplex quantitative enzyme-linked immunosorbant assays (ELISA) made from a novel melt-extruded microcapillary film (MCF) containing a parallel array of 200µm capillaries along its length. To make ELISA devices different protein antigens or antibodies were immobilised inside individual microcapillaries within long reels of MCF extruded from fluorinated ethylene propylene (FEP). Short pieces of coated film were cut and interfaced with a pipette, allowing sequential uptake of samples and detection solutions into all capillaries from a reagent well. As well as being simple to produce, these FEP MCF devices have excellent light transmittance allowing direct optical interrogation of the capillaries for simple signal quantification. Proof of concept experiments demonstrate both quantitative and multiplex assays in FEP MCF devices using a standard direct ELISA procedure and read using a flatbed scanner. This new multiplex immunoassay platform should find applications ranging from lab detection to point-of-care and field diagnostics

Association between smoking and chronic kidney disease: a case control study

<p>Abstract</p> <p>Background</p> <p>The progression of chronic kidney disease (CKD) remains one of the main challenges in clinical nephrology. Therefore, identifying the pathophysiological mechanisms and the independent preventable risk factors helps in decreasing the number of patients suffering end stage renal disease and slowing its progression.</p> <p>Methods</p> <p>Smoking data was analyzed in patients with CKD throughout 2005-2009. One hundred and ninety-eight patients who had recently been diagnosed with stage three CKD or higher according to the National Kidney Foundation (NKF) 2002 Classification were studied. The control group was randomly selected and then matched with the case subjects using a computerized randomization technique. The relative risk was estimated by computing odds ratio (OR) by using multinomial logistic regression in SPSS ® for Windows between the two groups.</p> <p>Results</p> <p>Smoking significantly increases the risk of CKD (OR = 1.6, <it>p </it>= 0.009, 95% CI = 1.12-2.29). When compared to nonsmokers, current smokers have an increased risk of having CKD (OR = 1.63 <it>p </it>= 0.02, 95% CI = 1.08-2.45), while former smokers did not have a statistically significant difference. The risk increased with high cumulative quantity (OR among smokers with > 30 pack-years was 2.6, <it>p </it>= 0.00, 95% CI = 1.53-4.41). Smoking increased the risk of CKD the most for those classified as hypertensive nephropathy (OR = 2.85, <it>p </it>= 0.01, 95% CI = 1.27-6.39) and diabetic nephropathy (2.24, <it>p </it>= 0.005, 95% CI = 1.27-3.96). No statistically significant difference in risk was found for glomerulonephritis patients or any other causes.</p> <p>Conclusion</p> <p>This study suggests that heavy cigarette smoking increases the risk of CKD overall and particularly for CKD classified as hypertensive nephropathy and diabetic nephropathy.</p

Cardiovascular autonomic control in patients undergoing left ventricular assist device (LVAD) support and pharmacologic therapy

Objectives The objective of the study is to determine cardiac autonomic control in patients undergoing assessment for and/or LVAD therapy. Methods Heart rate variability (HRV) was measured in 17 explanted LVAD, 17 implanted LVAD and 23 NYHA III-IV classified chronic heart failure (CHF) patients and ten healthy matched controls under three conditions: supine free breathing, standing and supine controlled breathing. Five measures of HRV were assessed: mean R-R interval (mR-R), high frequency (HF) and low frequency (LF) spectral power, LF in normalised units (LFnu), and LF to HF (LF:HF) ratio. Results Repeat measures ANOVA showed significant (p < 0.05) differences in HRV between all three conditions within groups. Lower values were observed in CHF for LF(in log natural units) compared with explanted patients (- 1.4 [95% CI - 2.6 to - 0.7], p = 0.04) and controls (- 2.1 [- 3.5 to - 0.7], p = 0.001) and for LF:HF compared with implanted patients under paced breathing conditions (z = - 2.7, p = 0.007) and controls in standing (z = - 2.9, p = 0.004) and paced breathing conditions (z = - 2.3, p = 0.02). However, no significant differences were seen between explanted, implanted and control groups under any condition. Conclusions Patients implanted with an LVAD and explanted from a LVAD following myocardial recovery demonstrate a more normal dynamic response to autonomic stimuli and have a lower HRV risk profile compared to CHF patients. © 2013 Elsevier Ireland Ltd

In Vivo Aortic Valve Thermal Heterogeneity in Patients With Nonrheumatic Aortic Valve Stenosis The First In Vivo Experience in Humans

ObjectivesWe investigated in vivo in aortic valve stenosis (AVS) whether there is: 1) thermal heterogeneity within the valve leaflets; 2) temperature difference between the leaflets and the ascending aortic wall; and 3) a possible correlation between heat production, inflammation, and neoangiogenesis.BackgroundHistological studies have demonstrated a potential role of inflammation and neoangiogenesis in AVS.MethodsWe examined 96 leaflets scheduled for aortic valve replacement. Twenty-five patients had AVS, and 7 had aortic valve insufficiency (AVI). Temperature measurements were performed right before hypothermic cardioplegia. Temperature difference (ΔT) was assigned as the mean temperature of each leaflet minus the temperature of the aortic wall. Histological, immunohistological analysis, and vascular endothelial growth factor (VEGF) immunoreactivity was performed.ResultsSignificant thermal heterogeneity was recorded within the leaflets of AVS, compared with AVI (1.52 ± 1.35°C vs. 0.13 ± 0.11°C, p < 0.01). In AVS ΔT was greater in all leaflets compared with the AVI group (p < 0.01). Leaflets of AVS had increased inflammatory cell infiltration, calcium deposit, and anti-VEGF expression compared with AVI (p < 0.01).ConclusionsThermal heterogeneity is increased in AVS and correlates with inflammatory mononuclear cell infiltration, expression of pro-inflammatory cytokines and neoangiogenic factors

Microfluidic Systems for Pathogen Sensing: A Review

Rapid pathogen sensing remains a pressing issue today since conventional identification methodsare tedious, cost intensive and time consuming, typically requiring from 48 to 72 h. In turn, chip based technologies, such as microarrays and microfluidic biochips, offer real alternatives capable of filling this technological gap. In particular microfluidic biochips make the development of fast, sensitive and portable diagnostic tools possible, thus promising rapid and accurate detection of a variety of pathogens. This paper will provide a broad overview of the novel achievements in the field of pathogen sensing by focusing on methods and devices that compliment microfluidics

Heart Valve Tissue Engineering: Concepts, Approaches, Progress, and Challenges

Potential applications of tissue engineering in regenerative medicine range from structural tissues to organs with complex function. This review focuses on the engineering of heart valve tissue, a goal which involves a unique combination of biological, engineering, and technological hurdles. We emphasize basic concepts, approaches and methods, progress made, and remaining challenges. To provide a framework for understanding the enabling scientific principles, we first examine the elements and features of normal heart valve functional structure, biomechanics, development, maturation, remodeling, and response to injury. Following a discussion of the fundamental principles of tissue engineering applicable to heart valves, we examine three approaches to achieving the goal of an engineered tissue heart valve: (1) cell seeding of biodegradable synthetic scaffolds, (2) cell seeding of processed tissue scaffolds, and (3) in-vivo repopulation by circulating endogenous cells of implanted substrates without prior in-vitro cell seeding. Lastly, we analyze challenges to the field and suggest future directions for both preclinical and translational (clinical) studies that will be needed to address key regulatory issues for safety and efficacy of the application of tissue engineering and regenerative approaches to heart valves. Although modest progress has been made toward the goal of a clinically useful tissue engineered heart valve, further success and ultimate human benefit will be dependent upon advances in biodegradable polymers and other scaffolds, cellular manipulation, strategies for rebuilding the extracellular matrix, and techniques to characterize and potentially non-invasively assess the speed and quality of tissue healing and remodeling

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

Functional genomic screen and network analysis reveal novel modifiers of tauopathy dissociated from tau phosphorylation

A functional genetic screen using loss-of-function and gain-of-function alleles was performed to identify modifiers of tau-induced neurotoxicity using the 2N/4R (full-length) isoform of wild-type human tau expressed in the fly retina. We previously reported eye pigment mutations, which create dysfunctional lysosomes, as potent modifiers; here, we report 37 additional genes identified from ∼1900 genes screened, including the kinases shaggy/GSK-3beta, par-1/MARK, CamKI and Mekk1. Tau acts synergistically with Mekk1 and p38 to down-regulate extracellular regulated kinase activity, with a corresponding decrease in AT8 immunoreactivity (pS202/T205), suggesting that tau can participate in signaling pathways to regulate its own kinases. Modifiers showed poor correlation with tau phosphorylation (using the AT8, 12E8 and AT270 epitopes); moreover, tested suppressors of wild-type tau were equally effective in suppressing toxicity of a phosphorylation-resistant S11A tau construct, demonstrating that changes in tau phosphorylation state are not required to suppress or enhance its toxicity. Genes related to autophagy, the cell cycle, RNA-associated proteins and chromatin-binding proteins constitute a large percentage of identified modifiers. Other functional categories identified include mitochondrial proteins, lipid trafficking, Golgi proteins, kinesins and dynein and the Hsp70/Hsp90-organizing protein (Hop). Network analysis uncovered several other genes highly associated with the functional modifiers, including genes related to the PI3K, Notch, BMP/TGF-β and Hedgehog pathways, and nuclear trafficking. Activity of GSK-3β is strongly upregulated due to TDP-43 expression, and reduced GSK-3β dosage is also a common suppressor of Aβ42 and TDP-43 toxicity. These findings suggest therapeutic targets other than mitigation of tau phosphorylation