Higher BSA Research Articles

INTERMACS Profile Does Not Predict Required Flow Rate of CF-LVAD at Discharge

Purpose Recent studies involving partial-support ventricular assist device (VADs) have suggested INTERMACS Profiles may be used as a means of identifying patients with less severe heart failure who require lower flow rates. We explore which preoperative factors are predictive of continuous-flow left VAD (CF-LVAD) flow requirements at discharge. Methods Retrospective review of 206 patients who underwent primary implantation of CF-LVAD from May 2013 through August 2017 at our center and survived to discharge. We performed step-wise multiple linear regression analysis on preoperative factors to identify factors that predicted CF-LVAD flow rates at the time of discharge. Results Of the 206 patients in our study, 27 (13.1%) were INTERMACS Profile 1, 53 (25.7%) were Profile 2, 95 (46.1%) were Profile 3, 14 were Profile 4, and 17 (6.8%) were Profile 5-7. Mean flow rates at discharge were 5.3±1.3, 5.3±1.6, 4.9±1.3, 5.3±1.2, and 5.8±1.0 L/min, respectively. Linear regression analysis showed INTERMACS Profile was not correlated with LVAD flow (p=0.73). Age (Regression Coefficient [RC] = -0.03, p=0.009), body surface area (BSA; RC = 0.23, p=0.03), creatinine (RC = 0.40, p=0.02) and mean right atrial pressure (RC = 0.05, p=0.02) were significantly correlated with higher flow rates (Table). Conclusion INTERMACS Profile was not a predictor of required flow rates for patients on CF-LVAD support at the time of discharge. Younger age, higher BSA, and preoperative creatinine and mean right atrial pressure predicted greater flow requirements. Further studies are warranted to devise predictive models of CF-LVAD flow requirements.

Structure and Performance of Poly(vinylidene chloride‐co‐vinyl chloride) Porous Membranes with Different Additives

AbstractPoly(vinylidene chloride‐co‐vinyl chloride) (P(VDC‐co‐VC) membranes were prepared by non‐solvent‐induced phase separation and adjusted by adding water‐soluble polyethylene glycol (PEG) and water‐insoluble silicon dioxide (SiO2) hydrophilic nanoparticles. The structure of pores and antifouling performance were investigated to illustrate the effect of these nanoparticles. The cross section of the P(VDC‐co‐VC) membrane exhibited more macropores and the typical finger‐like pores turned into more vertically interconnected ones with increasing PEG content, while the number and size of finger‐like pores became less with increasing SiO2 content. Considering the filtration and antifouling experiments, the presence of hydrophilic PEG and SiO2 nanoparticles in the P(VDC‐co‐VC) polymer matrix improved the membrane performance in terms of high flux, high BSA rejection ratio, and fouling resistance.

Highly permeable and antifouling TFC FO membrane prepared with CD-EDA monomer for protein enrichment

The development of thin film composite (TFC) membrane with a high flux, a good fouling resistance and superior rejections remains a challenging task for membrane researchers, due to the inherent permeability-selectivity trade-off of the polymeric selective layer. In this work, highly permeable TFC membranes with excellent fouling resistance are developed by employing hydrophilic pore-containing monomers – ethylenediamine (EDA)-substituted cyclodextrins (α, β, γ-CD-EDA) in interfacial polymerization. Effects of CD-EDA type on the surface properties, pore size, separation performance and antifouling properties of TFC_CD-EDA membranes are investigated by considering the differences in CD cavity size and EDA substitution degree. Superior FO flux up to 26–28 LMH (0.5 M Na2SO4 draw solution) and exceptional antifouling properties with relatively low flux reduction (< 20%) and high flux recovery rate (> 91%) can be achieved by TFC_CD-EDA membranes, owing to the unique structure of CD-EDA with the intramolecular cavity and abundant hydrophilic hydroxyl groups. Furthermore, TFC_β-CD-EDA membrane is applied for the enrichment of high-concentration BSA solution by taking advantage of its high flux, low reverse draw solute leakage and excellent fouling resistance. The obtained high BSA enrichment efficiency and high-quality BSA suggest a great potential of TFC_CD-EDA membrane in this aspect.

Preparation of a novel sulfonated polyphenlene sulfone with flexible side chain for ultrafiltration membrane application

• A series of side-chain sulfonated polyphenylene sulfone were prepared and applied in ultrafiltration field. • A high sulfonation degree was achieved without the destroy of membrane structure. • The selectivity-permeability trade-off was mitigated obviously. In order to mitigate the selectivity-permeability trade-off for ultrafiltration membranes, a series of polyphenylene sulfone (PPSU) with flexible negative charged sulfonated side chains (SPPSU-SC) were synthesized applied in ultrafiltration (UF) field. And tests results showed that the ultrafiltration performance was enhanced greatly. In short, the water flux increased to 380 L · m −2 · h −1 at the sulfonation degree of 20%, which was as two and a half times high as PPSU membranes. However, the membrane SPPSU-SC20 still held a relatively high BSA rejection of 91.6%, which should be attributed to the enrichment of negative charged sulfonic groups on the membrane surface. More importantly, the antifouling properties were also promoted. The total fouling ratio (R t ), reversible fouling ratio (R r ), irreversible fouling ratio (R ir ) and flux recovery ratio (FRR) were all improved to some degree. Besides, compared to the main-chain sulfonated PPSU with the sulfonation degree of 20% (SPPSU-MC20) membranes, SPPSU-SC20 had a better separation structure caused by better phase separation during the membrane preparation period at the sane high sulfonation degree. In a word, the results showed that side-chain sulfonated PPSU possessed a potential bright horizon in ultrafiltration field.

Enhanced separation performance of PES ultrafiltration membranes by imidazole-based deep eutectic solvents as novel functional additives

Herein, high performance polyethersulfone (PES) membranes were fabricated by introducing a series of imidazole-based deep eutectic solvents (DESs) as functional additives, which could tailor membrane structure due to the synergetic effect between DES components in phase inversion process. The addition of those DESs to the casting solutions all improved membrane porous structure, which contributed to a remarkably enhanced permeability and a high selectivity of the resultant membranes. Especially, the PES membrane with tetrabutylammonium chloride/imidazole as additive had a maximum water flux of 781 L/(m2 h), which was about 6.45 times that of the additive-free membrane, and a high BSA rejection of 97.7% at 2 bar. Moreover, the antifouling performance as well as thermal and mechanical properties of the prepared membranes was investigated. Overall, this work indicates the promise of imidazole-based DESs as alternative pore-forming additives for the fabrication of ultrafiltration membranes with superior performance.

Stachytarpheta jamaicensis leaf extract: Chemical composition, antioxidant, anti-arthritic, anti-inflammatory and bactericidal potentials

Stachytarpheta jamaicensis is an important plant with multi therapeutic properties. Hence, this study seeks to screen the leaf extract of S. jamaicensis for its chemical composition and pharmacological activities in order to find possible sources for novel phytochemicals in food and pharmaceutical formulations. The chemical composition, pH, TPC, TFC, TTC, TAA, carotenoid, antioxidant, anti-arthritic, anti-inflammatory and bactericidal potential were measured using GC-MS, pH meter, Folin-Ciocalteu’s, AlCl3, FeCl3/gelatine, 2,4- DNPH, acetone-hexane, DPPH, PTAC, BSA and agar-well diffusion methods respectively. The pH of the aqueous solution was 6.02. The GC and GC-MS analyses revealed the presence of 30 organic compounds. The most abundant components were 3,5-dihydroxy-6-methyl-2,3-dihydro-4H-pyran-4-one (13.7%), D-arabinitol (13.5%), 2-benzylidenemalonic acid (11.9%), 1,3-cyclopentadione (8.9%), α-5-ethyl-2-furylglycine (6.8%), 4,5-dihydro-5-methoxy-4-(2,3-dimethyl-2-buten-4-yl)-2(3H)-furanone (6.4%) and 3-methyl-2H-indazol-2-ol (5.8%). The TPC, TFC, TTC, TAA, β-carotene and lycopene values were 31,882.80 ±0.00 µgmg-1 GAE, 29.29±0.00 µgmg-1 QE, 126.47 µgmg-1 TAE, 53.75±0.01 µgmg-1 AAE, 0.17 mgg-1 and 0.14 mgg-1 , respectively. The antioxidant IC50 and AAI values of the leaf extract were 5.0 µgml-1 and 8.0. The extract was capable of scavenging free radicals in a range between 51.30-78.99%. The PTAC value was 396.15±0.00 µgmg-1 AAE. The extract also gave high egg albumin and BSA anti-arthritic/anti-inflammatory values between 22-80% with IC50 values of 0.04 and 0.15 mgml-1 , respectively. The extract was active against all the tested bacteria with high zones of inhibition (14.0-25.0 mm). These results showed that the leaf extract of S. jamaicensis could be used for the formulation of active compounds with broad activities for food and pharmaceutical industries.

Effects of Excipient Interactions on the State of the Freeze-Concentrate and Protein Stability.

The physical state of excipients in freeze-dried formulations directly affects the stability of the active pharmaceutical ingredient (API). Crystallization of trehalose and mannitol in frozen solutions has been shown to be a function of composition. However, to date a detailed study of the effect of concentrations of the API and other excipients on the crystallinity of mannitol and trehalose in frozen solutions has not been reported. The crystallinity of mannitol and trehalose in frozen solutions was characterized by Differential Scanning Calorimetry, X-ray diffractometry, and FTIR spectroscopy. The secondary structure of BSA was probed by FTIR, and Circular Dichroism spectroscopy in frozen and thawed solutions, respectively. Trehalose crystallization was accompanied by unfolding of BSA. BSA delayed and reduced the extent of mannitol and trehalose crystallization. Similar effects were observed upon adding D2O (≥5% w/w) and low concentrations of polysorbate 20 (≤0.2% w/w) with retention of BSA in its native conformation. At high BSA to trehalose mass ratio, the protein could stabilize itself in the frozen state, but unfolded upon thawing. The API and other excipients, in a concentration-dependent manner, influenced the physical state of the freeze concentrate as well as the stability of the API.

Preparation and characterization of polysulfone membrane incorporating cellulose nanocrystals extracted from corn husks

Cellulose nanocrystals (CNCs) extracted from corn husks were used as additive to modify the hydrophilicity and anti-fouling properties of polysulfone (PSf) membrane. The PSf/CNCs blend membranes were prepared via an immersion phase inversion method. The influence of CNCs content on the morphology, structure, and performances of PSf membrane were carefully investigated by SEM, TG, DTG, DSC, break strength, elongation-at-break, Young modulus, contact angle and filtration experiment. The results showed that the isolated CNCs from corn husks were a promising additive for modifying the properties of PSf membrane. CNCs can improve mechanical property, thermal stability, hydrophilicity and anti-fouling performance of the pure PSf membrane. The PSf/CNCs blend membrane reached optimal properties at 2 wt% CNCs content, which was 2.76 and 1.57 times in pure water flux and FRR values respectively as compared to pure PSf membrane. Meanwhile, PSf-2 also can maintain a relatively high BSA rejection.

Defining the common femoral artery: Insights from the femoral arterial access with ultrasound trial.

We sought to establish the typical location of the common femoral artery (CFA) bifurcation, the origin and most inferior reflection of the inferior epigastric artery (IEA) relative to the femoral head (FH) and whether patient demographics predicted anatomical variations. In the absence of ultrasound guidance or prior imaging, the precise location of the CFA bifurcation and IEA can only be determined following access site angiography. Fluoroscopic landmarks are commonly used to estimate the location of the CFA bifurcation, but the position of the IEA is less well characterized. Prospectively collected data on 989 patients with femoral angiography in the FAUST trial were analyzed. The level of CFA bifurcation and the origin and most inferior reflection of the IEA were classified by angiography. Logistic regression was used to explore whether baseline demographics were associated with anatomic variations. The CFA bifurcation occurs below the middle 1/3rd of the femoral head in 95% of patients, and no patient factors are predictive of a high bifurcation. The IEA origin has a more variable anatomically pattern, with high BSA, male gender, and white race associated with a low IEA origin. Operators should attempt to access the CFA at the level of the middle 1/3rd of the FH to maximize the chance of CFA cannulation. However, this location carries an 11% risk of being at or above the IEA origin. Baseline demographics were of limited utility for predicting anatomic variants of the CFA bifurcation and the course of the IEA. © 2016 Wiley Periodicals, Inc.

Normal myocardial strain values using 2D speckle tracking echocardiography in healthy adults aged 20 to 72years.

Evaluation of left ventricular (LV) myocardial deformation by speckle tracking echocardiography (STE) is useful for clinical and research purposes. However, strain measurements depend on the used software. Normative data for QLAB 10 (Philips) are scarce. Additionally, little is known about the influence of anthropometric factors. We aimed to establish normal adult STE-derived strain and strain rate values and to evaluate associations with anthropometrics. One hundred fifty-five healthy subjects aged 20 to 72years (≥28 subjects per decile) were prospectively gathered and examined with electrocardiography and two-dimensional echocardiography. With STE, we assessed peak systolic LV global longitudinal strain (GLS), segmental longitudinal strain, and strain rate from the three standard apical views. We included 147 healthy subjects (age 44.6±13.7years, 50% female, GLS -20.8±2.0%). Men had significantly lower GLS than women (-20.1±1.8% vs -21.5±2.0%, P<.001). GLS was significantly lower in subjects with age above 55years (P=.029), higher blood pressure (P<.001), higher body surface area (BSA, P<.001), larger LV end-systolic and end-diastolic volumes (both P<.001), lower LV ejection fraction (P<.001), and some indices of diastolic function. After multivariable regression analysis, the correlation with systolic blood pressure, E-wave, and LV end-systolic volume remained significant. The systolic strain rates of most segments correlated with BSA. Our study resulted in normative LV GLS values assessed with QLAB 10. Male sex, higher BSA, and higher blood pressure negatively influence GLS. Therefore, these factors should be taken into account for strain interpretation in clinical practice.

Serum 25-hydroxy vitamin D level in patients with pemphigus and its association with disease severity.

There is a growing number of studies suggesting a key role for vitamin D in the pathogenesis and progression of autoimmune disorders. To determine the serum levels of 25-hydroxy vitamin D [25(OH)D] in patients with pemphigus and association of 25(OH)D with clinical features. We enrolled 52 patients with pemphigus and 56 age- and sex-matched healthy controls (HCs). Only patients newly diagnosed with pemphigus or patients who had relapsed after discontinuing their treatment for > 6 months were included. Serum 25(OH)D and parathyroid hormone (PTH) levels were measured. Data on demographics, body mass index (BMI), disease severity (based on Pemphigus Area and Activity Score; PAAS) and involved surface body area (BSA) were obtained. Suboptimal levels of vitamin D (< 30 ng/mL) were observed in 78.8% and 91.0% of patients and HCs, respectively (P = 0.13). Univariate and multivariate ordinal logistic regression models showed that low vitamin D status was more likely to occur in patients with higher BSA (OR = 1.07, 95% CI 1.01-1.13) and those with higher cutaneous (OR = 1.36, 95% CI 1.11-1.66) and total (OR = 1.24, 95% CI 1.08-1.41) PAAS. However, there was no significant association between vitamin D levels and presence of pemphigus, season of sampling, age, BMI or smoking habit. Vitamin D deficiency is common both in patients with pemphigus and in HCs. Patients with more severe disease (higher PAAS) are likely to have lower vitamin D levels.

Ionic cross‐linking of water‐soluble polyurethane improves protein encapsulation and release

Polymer nanoparticles (NPs) are promising systems for the delivery of protein drugs, as they enhance circulation half‐life, reduce degradation, and increase selectivity of the encapsulated agent. Among the different methods for the preparation of protein‐loaded NPs, ionotropic gelation—which exploits cross‐linking between charged groups in the polymer and counterions in the protein solution—has been extensively investigated for chitosan NPs. The present study aims at exploring the possibility to apply the method to prepare BSA‐loaded polyurethane NPs. A poly(ε‐caprolactone)/poly(ethyleneglicol)‐based polyurethane bearing tert‐butyloxycarbonyl‐protected amino groups was synthesized by a two‐step synthesis procedure. Amino functionalities were exposed under acidic conditions, as confirmed by ninhydrin assay, and then exploited to obtain ionic cross‐linking with sodium tripolyphosphate counterions. The effect of polymer and sodium tripolyphosphate concentration on particles size and BSA encapsulation has been investigated, showing that the PUR concentration plays a major role. Small particles, at 300 nm, with high BSA loading (90%) have been obtained. Sustained BSA release and low burst effect (20%) have been observed, indicating good interaction between the protein and the polymer matrix. The study highlights the possibility of introducing alternative polymers to improve loading and release of proteins from NPs obtained through the ionotropic gelation method.

Preparation of a novel thermo responsive PSF membrane, with cross linked PVCL-co-PSF copolymer for protein separation and easy cleaning

An amphiphilic thermo responsive PVCL-co-PSF copolymer was synthesized with enhanced pore density and hydrophilicity. It was found to have high hydration capacity and low BSA adsorption, with 92.5% and 95% flux recovery ratios achieved for BSA and HA, respectively.

High Body Mass Index (BMI) in North American Elderly Diffuse Large B-Cell Lymphoma (DLBCL) Patients Treated with Rituximab (R)-CHOP Compensates for Negative Impact of Male Gender

Background: Recent reports from prospective clinical trials of R-containing chemotherapy in DLBCL patients suggest that gender, weight and/or BMI influence clinical outcomes. Pharmacokinetic studies by the German High Grade Lymphoma Study Group have shown that R clearance is relatively slow in elderly women compared to men, leading to higher levels and prolonged exposure and hence better clinical outcomes in elderly females. Specifically, it has been suggested that elderly men are underdosed, based on faster R clearance (Muller et al., 2012; Pfreundschuh et al., 2014). Regarding BMI as a predictor of clinical outcome, analysis of the US Veterans Administrative database showed an association between increased BMI and improved survival in DLBCL patients (Carson et al., 2012), while the ECOG clinical trial (E4494) for elderly DLBCL patients failed to reveal a significant association of BMI with clinical outcomes, or a gender difference related to BMI in failure-free survival (Hong et al., 2014). To further investigate these associations, we studied the effect of gender, BMI as well as body surface area (BSA, the actual dosing parameter), and potential interactions among these factors on long-term clinical outcomes for elderly DLBCL patients in the National Comprehensive Cancer Network (NCCN) non-Hodgkin lymphoma database.Methods:De novo DLBCL patients with age > 60 yrs. were identified from the NCCN adult DLBCL cohort. Patients were diagnosed between June 2000 and December 2010. All received R as part of first-line therapy. Outcomes evaluated included progression free survival (PFS) and overall survival (OS) at 3 years based on patient gender, age and BMI/ BSA at presentation. Gender was stratified based on BMI (<=18.5, >18.5-25, >25) or BSA (<=2, >2), and Kaplan-Meier estimates were calculated. Associations with disease progression and survival were additionally adjusted for the International Prognostic Index (IPI) in the multivariable Cox regression analyses.Results: Of the 1,386 DLBCL patients who received R, 627 were elderly with age >60 yrs. The majority of elderly men were either overweight or large: only 13% had BMI <=25 and only 26% had BSA <=2. Elderly men (n=325, 52%) experienced worse PFS (3 yr-Hazard Ratio, HR 1.5, 95% CI: 1.1-2.1, p=0.02) and OS (3 yr-HR 1.6, 1.1-2.4, p=0.01) compared to elderly women. Of note, the poor risk associated with male gender was associated with patients over 60, but not the younger cohort (3 yr-PFS, HR 1.3, 0.9-1.9, p=0.12). The benefit associated with female gender in the elderly cohort decreased with increases in BMI and BSA (Figure). There was a benefit associated with female gender when compared to male gender in the BMI (<=25) (log rank, p<0.01) and BSA <=2 (p=0.04) strata, but not among patients with high BMI (>25) or BSA (>2). In multivariable analysis, low or normal BMI as compared to high BMI was independently associated with poor outcomes (3-yr PFS, HR: 1.6, 1.1-2.2, p<0.01) after adjusting for gender. There was a trend suggesting that BSA <=2 correlated with worse 3-yr PFS in the elderly group adjusting for gender (3 yr-HR 1.4, 0.9-2.0, p=0.12). The HR estimates remained largely unchanged after adjusting for IPI. Notably, higher BMI was not associated with more favorable prognostic clinical factors.Conclusions: Our results, derived from analysis of unselected patients with DLBCL treated with R-containing chemotherapy at major NCCN centers, confirmed an age-dependent disadvantage to male gender in treatment outcomes. The magnitude of this negative effect diminished with higher levels of BMI and BSA, with the greatest negative impact occurring in elderly men with BMI <=25 or BSA <=2. Our findings support efforts to optimize R dosing, especially in the elderly male subset with BMI <=25 or BSA <=2. Future prospective trials should factor size and gender into the study design and analysis. Our results support the ongoing German randomized trial to evaluate enhanced rituximab dosing for older male patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

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Introduction: Orthotopic liver transplantation (OLT) patients requiring renal replacement therapy (RRT) generally experience worse outcomes. The purpose of this study is to identify outcomes and survival predictors among pediatric OLT patients receiving perioperative RRT in the pediatric intensive care unit (PICU) and to identify predictors of successful RRT termination. Methods: An IRB-approved retrospective review of our hospital's pediatric patients (0-21 years of age) between January 1, 2000 and December 31, 2011 was conducted. Categorical associations with survival status were tested for statistical significance using Fisher's exact test. Continuous variables were compared between survival status using the Wilcoxon rank sum test or unpaired t-test as appropriate. A Kaplan-Meier curve was constructed to estimate survival rates over time. A mixed model was used to test for differences in urine output. A P-value <0.05 was considered statistically significant. Results: Seventeen patients received RRT within a perioperative OLT period (mean age, 9.23 years; range, 2 months-19 years). Mean BSA was 0.95 m2 (range, 0.14-1.95 m2). Survivors were older at the time of RRT (mean, 11.8 years v. 3 years, P=0.004) and had a higher BSA than non-survivors (mean, 1.18 years v. 0.40 years, P<0.01). Dialysis included intermittent and continuous modalities. Higher urine output during the last 24 hours of RRT was associated with successful RRT termination (mean, 1.36 mL/kg/h v. 0.47 mL/kg/h, P=0.002). Neither calculated glomerular filtration rate at PICU admission nor prior to starting RRT was associated with survival. Twelve patients (70%) survived to hospital discharge with one receiving a renal transplantation. One required dialysis after discharge. Survival from RRT initiation was 82% at 3 months, 76% at 6 months, 71% at one year and 65% at three years. Conclusions: Among pediatric OLT patients receiving perioperative RRT in the PICU, older age is associated with survival, and urine output during the last 24 hours of RRT predicts successful RRT termination. This study supports the use of RRT in pediatric perioperative OLT patients and may help guide patient selection and timing of RRT termination.

Incidence and Importance of New Postoperative Right Bundle Branch Block after Pediatric Orthotopic Heart Transplantation

Purpose Studies have shown right bundle branch block (RBBB) to be the most common ECG abnormality after orthotopic heart transplantation (OHT) in adults, correlating it to higher mean pulmonary artery pressures (PAP) and poorer clinical outcomes. This has not yet been evaluated in pediatric heart transplantation. Methods and Materials We hypothesized that development of RBBB following pediatric OHT would be associated with higher postoperative mean PAP. A retrospective review was conducted of paired donor and recipient ECGs (24-72 hours post-OHT) and clinical data of all patients who had undergone OHT at our center from 2/5/2000 to 6/13/2011. Students T-test, Mann-Whitney U, Chi-Square and Kaplan-Meier analyses were used as appropriate. Results Of 97 pediatric OHT patients, 24 (25%) developed new RBBB and were more likely to be older (11.62 yrs [0.11-17.7yrs] vs. 4.87 yrs [0.5-18.6yrs], p=0.002) and have a higher BSA (1.17m² [0.35-2.07m²] vs. 0.65m² [0.21-1.83m²], p=0.001). There was no association with new RBBB and presence of donor downtime (p=0.35), graft ischemic time (p=0.11), cardiopulmonary bypass time (p=0.35), or elevated donor cardiac enzymes (p=0.62). Development of RBBB was not associated with pre-transplant recipient hemodynamics, including cardiac index (p=0.72), RVEDP (p=0.37), mean PAP (p=0.84), mean RAP (p=0.44), PVRI (p=0.89), or PCWP (p=0.68). Those with RBBB had lower mean PAP on post-OHT cath (6-15 days), both within the normal range (16.4±4.5mmHg vs. 20.2±6.7mmHg, p=0.012). No association was found with any other post-transplant hemodynamic data, evidence of rejection (8% vs. 4%, p=0.68) or ischemia on the first post-op biopsy (25% vs. 22%, p=0.78). New RBBB was not associated with in-hospital mortality (p=0.57), graft survival (p=0.25), or overall mortality (p=0.08). Conclusions While the development of RBBB is a common finding in ECGs following pediatric heart transplantation (25%), it is not associated with any known risk factors or clinical outcomes.

INCIDENCE AND IMPORTANCE OF NEW POSTOPERATIVE RIGHT BUNDLE BRANCH BLOCK AFTER PEDIATRIC ORTHOTOPIC HEART TRANSPLANTATION

Purpose Studies have shown right bundle branch block (RBBB) to be the most common ECG abnormality after orthotopic heart transplantation (OHT) in adults, correlating it to higher mean pulmonary artery pressures (PAP) and poorer clinical outcomes. This has not yet been evaluated in pediatric heart transplantation. Methods and Materials We hypothesized that development of RBBB following pediatric OHT would be associated with higher postoperative mean PAP. A retrospective review was conducted of paired donor and recipient ECGs (24-72 hours post-OHT) and clinical data of all patients who had undergone OHT at our center from 2/5/2000 to 6/13/2011. Students T-test, Mann-Whitney U, Chi-Square and Kaplan-Meier analyses were used as appropriate. Results Of 97 pediatric OHT patients, 24 (25%) developed new RBBB and were more likely to be older (11.62 yrs [0.11-17.7yrs] vs. 4.87 yrs [0.5-18.6yrs], p=0.002) and have a higher BSA (1.17m² [0.35-2.07m²] vs. 0.65m² [0.21-1.83m²], p=0.001). There was no association with new RBBB and presence of donor downtime (p=0.35), graft ischemic time (p=0.11), cardiopulmonary bypass time (p=0.35), or elevated donor cardiac enzymes (p=0.62). Development of RBBB was not associated with pre-transplant recipient hemodynamics, including cardiac index (p=0.72), RVEDP (p=0.37), mean PAP (p=0.84), mean RAP (p=0.44), PVRI (p=0.89), or PCWP (p=0.68). Those with RBBB had lower mean PAP on post-OHT cath (6-15 days), both within the normal range (16.4±4.5mmHg vs. 20.2±6.7mmHg, p=0.012). No association was found with any other post-transplant hemodynamic data, evidence of rejection (8% vs. 4%, p=0.68) or ischemia on the first post-op biopsy (25% vs. 22%, p=0.78). New RBBB was not associated with in-hospital mortality (p=0.57), graft survival (p=0.25), or overall mortality (p=0.08). Conclusions While the development of RBBB is a common finding in ECGs following pediatric heart transplantation (25%), it is not associated with any known risk factors or clinical outcomes.

Characterization of right atrial function and dimension in top-level athletes: a speckle tracking study

Although many echocardiographic studies are available about the adaptation of left ventricle to intensive training, right heart function has been poorly investigated and no data are available about the right atrial (RA) function in top-level athletes. The aim of the study was to investigate RA function and dimension by standard echocardiography and 2D speckle tracking echocardiography (STE). One hundred top-levels athletes were recruited from professional sports team and were compared with 78 normal subjects. Athletes during an off-training period or during prolonged forced rest resulting from injuries were excluded. Top-level athletes had higher BSA as compared with controls and, as expected, a lower resting heart rate (p ≤ 0.001). RA area, volume, and volume index were significantly greater in athletes than in controls (p ≤ 0.001). This increase was associated with greater right ventricular and inferior vena cava diameters (p ≤ 0.001). Peak atrial longitudinal strain and peak atrial contraction strain values were significantly lower in athletes in comparison with controls (40.92 ± 9.86% vs. 48.00 ± 12.68%, p ≤ 0.001; 13.05 ± 4.84% vs. 15.99 ± 5.74%, p ≤ 0.001, respectively). Interestingly, while athletes presented a higher E/A ratio (p ≤ 0.001) and a lower peak A velocity (p ≤ 0.001), the E/e' ratio did not differ between the two groups. In top-level athletes the RA presents a physiological adaptation to intensive exercise conditioning which determines not only a morphological but also a functional remodeling. We reported for the first time reference values of RA strain in elite athletes, demonstrating that 2D STE is a useful tool to investigate RA longitudinal myocardial deformation dynamics in athlete's heart.

Targeted TFO delivery to hepatic stellate cells

Triplex-forming oligonucleotides (TFOs) represent an antigene approach for gene regulation through direct interaction with genomic DNA. While this strategy holds great promise owing to the fact that only two alleles need silencing to impact gene regulation, delivering TFOs to target cells in vivo is still a challenge. Our recent efforts have focused on conjugating TFOs to carrier molecules like cholesterol to enhance their cellular uptake and mannose-6-phosphate-bovine serum albumin (M6P–BSA) to target TFO delivery to hepatic stellate cells (HSCs) for treating liver fibrosis. These approaches however are rendered less effective owing to a lack of targeted delivery, as seen with lipid-conjugates, and the potential immune reactions due to repeated dosing with high molecular weight BSA conjugated TFO. In this review, we discuss our latest efforts to enhance the effectiveness of TFO for treating liver fibrosis. We have shown that conjugation of TFOs to M6P–HPMA can enhance TFO delivery to HSCs and has the potential to treat liver fibrosis by inhibiting collagen synthesis. This TFO conjugate shows negligible immunogenicity owing to the use of HPMA, one of the least immunogenic copolymers, thereby making it a suitable and more effective candidate for antifibrotic therapy.

Poly(dimethylsiloxane) microchip-based immunoassay with multiple reaction zones: Toward on-chip multiplex detection platform

In this work, a poly(dimethylsiloxane) (PDMS) microchip-based immuno-sensing platform with integrated pneumatic micro valves is described. The microchip was fabricated with multiple layer soft lithography technology. By controlling the activation status of corresponding valves, reagent flows in the microchannel network can be well manipulated so that immuno-reactions only take place at designated reaction zones (DRZs). Four DRZs are included in the prototype microchip. Since these DRZs are all isolated from each other by micro valves, cross contamination is prevented. Using the inner surface of the all-PDMS microchannel as immunoassay substrate, on-chip sandwich format solid phase immunoassay was performed to demonstrate the feasibility of this immuno-sensing platform. Mouse IgG and fluorescein isothiocyanate (FITC) were used as the model analyte and the signal reporter respectively. Only 10 μl sample is needed for the assay and low detection limit of 5 ng/ml (≈33 pM) was achieved though low-cost polyclonal antibodies were used in our experiment for feasibility study only. Much lower detection limit may easily be achieved by using high quality monoclonal antibodies. Through a simple yet effective comparison experiment, it was also found that high concentration BSA blocking solution (5% BSA in PBS buffer) can effectively suppress the non-specific binding in the surface of the microfluidic channels. The encouraging results from mouse IgG immunoassay proved the feasibility of our microchip design. With slight modification of the assay protocol, the same chip design can be used for multi-target detection and can provide a simple, cost-effective and integrated microchip solution for multiplex immunoassay applications.