Hemolysis Index Research Articles

Comparison of a Novel Thin-Walled 25-gauge Needle Push Button Blood Collection Set to a Standard 23-gauge Needle in a Cancer Patient Population.

Phlebotomy can be an uncomfortable and even painful experience that increases in likelihood in patients who require frequent blood draws, such as those with cancer. The 25-gauge BD Vacutainer® UltraTouch™ Push Button Blood Collection Set has a smaller outer bore needle size and unique bevel configuration, which in theory should reduce pain associated with phlebotomy. Smaller needles typically cause less pain, however, they have a higher incidence of compromising the specimen integrity. Innovative engineering allows this particular needle to maintain a larger inner bore size similar to a standard 23-gauge needle. This study compares pain and specimen integrity between this novel device and a standard 23-gauge needle. Two cohorts of 190 patients each had phlebotomy performed with either needle. Pain experienced was assessed by patient surveys, rating pain from 0 (low) to 10 (high). Sample integrity was assessed by determining the hemolysis index (Abbott Architect c8000). No statistically significant difference in median pain scores was observed between the 2 cohorts, P-value: 0.068. The 23-gauge cohort more frequently reported 3+ pain than the 25-gauge cohort, 14/190 vs 5/190. Pain scoring 1 and 2 was more frequent in the 25-gauge cohort, 84/190 vs 54/190. Pain scores of 0 were more frequent in the 23-gauge cohort, 122/190 vs 101/190. This stratification is statistically significant, P-value: 0.003. The 25-gauge needle showed no increase in hemolysis rates, P-value: 0.5. Sample integrity was identical between both needles. The 25-gauge needle resulted in less 3+ pain, while pain scoring 1 and 2 was more frequent in the 25-gauge cohort.

Lipid Profile, Nutritional Status and Severity Biomarkers in Adults With Sickle Cell Anemia

BACKGROUND Lipid alterations have been described in sickle cell anemia (SCA), but their association with the disease severity is not fully understood and their correlation with the nutritional status of this population has not been widely studied. OBJECTIVES This study aimed to assess the lipid profile and its relation with the nutritional status, including anthropometric characteristics and daily macronutrient intake, and with the severity biomarkers in adults with SCA in a steady state. DESIGN Cross-sectional study METHODS This was an analytical cross-sectional study with 55 adults with SCA and 60 members of the control group. Sociodemographic, anthropometric, nutritional, and laboratory data were collected between March 2019 and June 2020. Mann–Whitney test was used to compare groups and Spearman's correlation coefficient was used to test the relation between variables. RESULTS The SCA group presented higher calorie, protein, and carbohydrate intake, lower levels of high-density lipoprotein-cholesterol (HDL-c), and a higher triglyceride (TG)/HDL-c ratio than the control. HDL-c showed a positive correlation with hemoglobin and hematocrit (HcT) and a negative correlation with indirect bilirubin and lactate dehydrogenase (LDH). The TG/HDL-c ratio was positively linked with reticulocyte count, LDH, and leukocyte count and negatively linked with Hb. CONCLUSIONS The study findings showed hypocholesterolemia in SCA and its independent correlation with macronutrient intake. The links of HDL-c and TG/HDL-c ratio with hemolysis indices indicate that they are easily accessible, low-cost markers capable of predicting SCA severity.

Protein-Bound Uremic Toxins and Inflammation Process in Hemodialysis Patients: Is There a Role for Adsorption Hemodiafiltration?

Introduction: Despite major advances in the field of dialysis, there are still some unmet needs such as reducing inflammation through adequate depuration. It is well known that the wide spectrum of pro-inflammatory and pro-atherosclerotic uremic toxins are inefficiently removed by current dialysis techniques. Adsorption seems to be an extra tool to remove toxins, but its effect and optimization have not been widely studied. The aim of this report was to present preliminary results regarding the possibility of performing hemodiafiltration with a highly adsorptive polymethylmethacrylate membrane. Methods: The study was first conducted in 10 patients in which the safety and feasibility of hemodiafiltration with PMMA BG-U 2.1 membrane were tested through measurement of hemolysis indices, transmembrane pressures, and dialysis adequacy. Twenty patients were prospectively observed for 18-month period in which they consecutively underwent standard hemodialysis, standard post-dilution hemodiafiltration, and polymethylmethacrylate-based post-dilution hemodiafiltration. Protein-bound uremic toxins concentrations and inflammatory markers were measured throughout the observed period. Results: HDF-PMMA was inferior to HDF in convective volume, but KT/V was similar, and no differences were noted in operating pressures during the two treatments. During HDF-PMMA period of treatment, we observed a significant reduction of CPR levels, and HDF-PMMA was superior to all other treatments in hepcidin removal even if this did not significantly affect hemoglobin levels. HDF-PMMA could significantly reduce indoxyl sulfate (indoxyl) concentration over a period of 6 months but not for p-cresyl sulfate (p-cresyl). Conclusion: PMMA BG-U 2.1 membrane can be safely and efficiently used in hemodiafiltration. Moreover, as these preliminary results show, adding adsorption properties to convection and diffusion enabled an increased removal of indoxyl uremic toxin associated to a reduction in inflammation markers as CRP and hepcidin without any negative impact on albumin levels.

P634: Development of a hemolysis index for Vanadis® cfDNA NIPT sample acceptance

P634: Development of a hemolysis index for Vanadis® cfDNA NIPT sample acceptance

Design of ciprofloxacin impregnated dietary fiber psyllium-moringa gum-alginate network hydrogels via green approach for use in gastro-retentive drug delivery system

In order to improve the pharmacokinetic deficiencies and bioavailability of therapeutic agent used in the upper gastro intestinal tract (GIT), herein this article gastro-retentive drug delivery system (DDS) were developed via green approach from medicinally important polysaccharides psyllium, moringa gum and alginate. The antibiotic drug ciprofloxacin was impregnated into DDS. These polymeric DDS were characterized by cryo-SEMs, FTIR, 13C NMR and XRD analysis. The simulated gastric fluid uptake was reduced with rise in crosslinking during ionotropic gelation. The diffusion of ciprofloxacin was non-Fickian and it was fitted in Korsmeyer-Peppas model. The porous nature of the crosslinked network hydrogel beads was observed in cryo SEM images. XRD indicated the amorphous nature of the hydrogel beads. The haemolytic index value of beads was observed less than 5%. The results of the polymer interactions with blood indicated the non-hemolytic nature of the polymers with their suitability for controlled drug delivery applications. The antioxidant property indicated 64.03 ± 0.29% DPPH radicals scavenging assay of the beads. Overall, anti-ulcer activity of the DDS for gastric ulceration could be enhanced due to slow release of ciprofloxacin drug from drug delivery carrier which itself has antiulcer therapeutic potential due to composed dietary fibers psyllium-moringa gum-alginate.

The impact of rotor configurations on hemodynamic features, hemocompatibility and dynamic balance of the centrifugal blood pump: A numerical study.

To investigate the effect of rotor design configuration on hemodynamic features, hemocompatibility and dynamic balance of blood pumps. Computational fluid dynamics was employed to investigate the effects of rotor type (closed impeller, semi-open impeller), clearance height and back vanes on blood pump performance. In particular, the Eulerian hemolysis model based on a power-law function and the Lagrangian thrombus model with integrated stress accumulation and residence time were applied to evaluate the hemocompatibility of the blood pump. This study shows that compared to the closed impeller, the semi-open impeller can improve hemolysis at a slight sacrifice in head pressure, but increase the risk of thrombogenic potential and disrupt rotor dynamic balance. For the semi-open impeller, the pressure head, hemolysis, and axial thrust of the blood pump decrease with increasing front clearance, and the risk of thrombosis increases first and then decreases with increasing front clearance. Variations in back clearance have little effect on pressure head, but larger on back clearance, worsens hemolysis, thrombogenic potential and rotor dynamic balance. The employment of back vanes has little effect on the pressure head. All back vanes configurations have an increased risk of hemolysis in the blood pump but are beneficial for the improvement of the rotor dynamic balance of the blood pump. Reasonable back vanes configuration (higher height, wider width, longer length and more number) decreases the flow separation, increases the velocity of blood in the back clearance, and reduces the risk of blood pooling and thrombosis. It was also found that hemolysis index (HI) was highly negatively correlated with pressure difference between the top and back clearances (r=-.87), and thrombogenic potential was positively correlated with pressure difference between the top and back clearances (r=.71). This study found that rotor type, clearance height, and back vanes significantly affect the hydraulic performance, hemocompatibility and rotor dynamic balance of centrifugal blood pumps through secondary flow. These parameters should be carefully selected when designing and optimizing centrifugal blood pumps for improving the blood pump clinical outcomes.

Design and evaluation of a pulsatile flow rotary vane blood pump

Artificial cardiovascular organs, termed as mechanical circulatory support (MCS) devices, provide patients with hemodynamics circulatory restoration effectively and vitally but yet are hampered by device-induced adverse events such as thrombotic, embolic and bleeding, which are consequences of blood being chronically exposed to non-pulsatile flow motion and high shear stress. A step forward to better assist heart failure patients, a novel MCS device was proposed aiming at generating a pulsatile blood flow under different systemic vascular resistance and imposing low shear stress on blood elements. Detailed design methods and geometry governing equations were derived first. For this human heart blood circulation application with a flowrate of [Formula: see text] and pressure range around [Formula: see text], a first-generation prototype with a positive displacement of [Formula: see text] directly driven by a [Formula: see text] brushless direct current (DC) motor was designed, manufactured and assembled. Computational fluid dynamics (CFD) simulations and bench top experiments were conducted next to characterize the MCS pump and to verify with mathematical models. Finally, the proposed MCS device-mediated hemolysis index was evaluated via CFD simulations and compared with an FDA-benchmark centrifugal MCS pump. This demonstrates potentially higher device hemocompatibility and paves the way for in vitro test in the future.

Exploration of the high energy radiation for the designing of psyllium-poly(MEDSAH) zwitterionic superabsorbent hydrogels for biomedical uses

The main objective of the present work is to develop the hydrogels as drug delivery carrier for the antibiotic drug ciprofloxacin by using graft copolymerization reaction of poly 2-(Methacryloyloxy)ethyl dimethyl-(3-sulfopropyl)ammonium hydroxide [poly(MEDSAH)] onto a bioactive dietary fiber psyllium. High energy gamma radiations were applied for the formation and sterilization of network hydrogels simultaneously. The release profile of the antibiotic drug ciprofloxacin was determined to evaluate the diffusion mechanism. Biomedical assay of polymers was also evaluated by determining the blood compatibility, antioxidant, mucoadhesive and degradation properties of the psyllium-poly(MEDSAH) network hydrogels prepared for drug delivery (DD) applications. The polymers were characterized by 13C NMR, FTIR, TGA/DTG, DSC, SEM, AFM and XRD. TGA confirmed thermal stability while SEM and AFM indicated porous and rough surface of the polymers. Both, zwitterionic monomer and radiation dose changed mesh size (from 87.94 to 529.33 nm) and crosslinking density (from 0.33 × 10−6 to 12.13 × 10−6 mol/cm3). The grafted polymers showed antioxidant nature of the material which exhibited 48.99 ± 1% free radical scavenging in DPPH assay. Polymer indicated biocompatible nature which showed 81.02 ± 5.91% thromboses percentage and less than 2% hemolytic index during blood-polymer interactions. Furthermore, detachment force required to detach the polymer from mucous membrane was Fmax=0.169 ± 0.035 N which required work of adhesion Wad=0.125 ± 0.014 N.sec showing the mucoadhesive nature of the polymeric hydrogels. The antibiotic drug ciprofloxacin diffusion occurred slowly with non-Fickian mechanism and Korsmeyer-Peppas model. Overall, results reflected their suitability of these DD carriers for colon in slow and sustained manner.

Use of a Vanadate Oxidation Conjugated Bilirubin Assay to Reduce Test Cancellations Resulting from Hemolyzed Specimens in Pediatric Patients.

We sought to replace the highly hemolysis-susceptible diazo conjugated bilirubin (Bc) assay with the more robust vanadate oxidation method and determine its impact on test cancellation in the pediatric population. Analytical validation of the Randox vanadate assay and comparison with the Roche diazo method were performed. The frequency of pediatric sample cancellation because of hemolysis was compared between the diazo and vanadate methods by retrospective analysis of clinical test data. The vanadate assay demonstrated no clinically significant interference from hemolysis up to a hemolysis index of 1,300 (approximately 13 g/L hemoglobin). There was a strong correlation with the diazo method (r2 = 0.97) but with a positive slope bias of 1.27. Implementing the vanadate method resulted in a significantly lower proportion of pediatric samples cancelled because of hemolysis compared with the diazo method (0.6% of 688 patients vs 30.6% of 10,464 patients, respectively; P < .001), with a 0.6% (n = 513) vs 43.2% (n = 6,464) reduction in test cancellations (P < .001) for children younger than 6 months of age. The vanadate method showed robust performance against hemolysis. Its implementation resulted in a significant decrease in pediatric tests cancelled because of hemolysis.

Numerical assessment of hemodynamic perspectives of a left ventricular assist device and subsequent proposal for improvisation

Due to the unavailability of donors, the use of left ventricular assist devices has emerged to be a reliable line of alternative treatment for heart failure. However, ventricular assist devices (VAD) have been associated with several postoperative complications such as thrombosis, hemolysis, etc. Despite considerable improvements in technology, blood trauma due to high shear stress generation has been a major concern that is largely related to the geometrical feature of the VAD. This study aims to establish the design process of a centrifugal pump by considering several variations in the geometrical feature of a base design using the commercial solver ANSYS-CFX. To capture the uncertain behavior of blood as fluid, Newtonian, as well as non-Newtonian (Bird-Carreau model), models are used for flow field prediction. To assess the possibility of blood damage maximum wall shear stress and hemolysis index have been estimated for each operating point. The results of the simulations yield an optimized design of the pump based on parameters like pressure head generation, maximum shear stress, hydraulic efficiency, and hemolysis index. Further, the design methodology and the steps of development discussed in the paper can serve as a guideline for developing small centrifugal pumps handling blood.

Blood Transfusion Ameliorates Free Haem-Induced Loss of Thrombomodulin and Endothelial Cell Activation in Paediatric Sickle Cell Anaemia

Background Sickle cell anaemia (SCA) is responsible for major paediatric morbidity including risk of stroke in up to 10% of children. Mainstays of therapy include hydroxyurea (HU) and chronic blood transfusion (BT), with BT considered gold standard for stroke prevention. However, the biological mechanisms through which BT is significantly superior to HU in reducing stroke risk have not been clearly defined. SCA complications are due in part to free haem-mediated damage, leading to endothelial cell (EC) activation, tissue factor (TF) expression and release of von Willebrand Factor (VWF), which binds platelets and sickle RBCs. Recently loss of EC Thrombomodulin (TM) has been shown to promote EC activation and VWF release and soluble TM (sTM) plays a role in disseminated intravascular coagulation and COVID-19. Hypothesis We hypothesize free haem alters EC TM expression, promoting EC activation and VWF release. Intravascular hemolysis and free haem may be reduced in children on chronic BT, maintaining EC quiescence and enhancing protection against stroke compared with HU. Methods Following ethical approval and informed consent 180 SCA children (median age 12 years, 49% male) were recruited. Steady-state plasma samples were collected prior to BT (n=84) or at outpatient clinic for HU (n=96). Paired crisis samples were obtained in a subset of HU (n=30). EC activation markers and Weibel Palade Body (WPB) proteins were evaluated by ELISA, VWF multimers were assessed by 1.8% agarose gels and ADAMTS13 activity assessed by FRET. Free haem levels were quantified and thrombin generation (TG) assays performed. Factor VIII:C was measured in the National Coagulation Centre at St James's Hospital. Human umbilical vein endothelial cells (HUVEC) were exposed to cell-free haem (Hemin), hydroxyurea, cytokines (IL-1β and TNFα) or patient plasma; VWF was measured in the supernatant and HUVEC TM expression assessed by flow cytometry. Results VWF:Ag and VWF propeptide (VWFpp) levels were significantly increased in HU compared to BT children, suggesting acute EC activation (median plasma VWF:Ag levels 1.29 v 1.03 IU/ml; p=0.0005, median VWFpp levels 1.63 v 1.17 IU/ml p=0.006). Furthermore, plasma levels of other WPB stored proteins were also significantly elevated in the HU cohort, including Angiopoietin-2 (Ang-2) (4214 v 2337 pg/ml, p<0.0001 and Osteoprotegerin (OPG) (1825 v 1507 pg/ml p=0.006). Abnormalities of high-, intermediate- and low molecular weight VWF multimers were noted in HU but not BT. While putative inhibitors of ADAMTS13 were increased in HU, including Platelet Factor 4 and Interleukin-6, ADAMTS13 activity did not differ between groups. FVIII:C levels were significantly elevated in 65% of the total cohort and were higher in HU than BT (1.62 IU/ml v 1.30 IU/ml p<0.0001). Free haem levels were increased in HU versus BT (12.5 v 9.5μM p=0.0003), as well as levels of LDH and reticulocyte %, pointing to increased intravascular hemolysis. EC markers and FVIII:C correlated strongly with hemolytic indices. In addition to increased EC activation, increased endogenous thrombin potential (ETP), peak thrombin and velocity index were observed in HU versus BT, pointing to enhanced TG, possibly driven by elevated circulating TF. TG parameters correlated with plasma FVIII:C levels. Exposure of HUVEC to free haem in vitro resulted in a significant decrease in surface TM expression and increased VWF secretion (p<0.05). Conversely exposure to hydroxyurea or cytokines did not alter TM expression. Exposure of HUVEC to plasma from crisis but not paired steady-state plasma induced EC activation and VWF release compared with control plasma. Importantly, free haem levels ≥20 μM were observed in 25% HU children in steady state and 40% in crisis, compared with 0% of BT. Furthermore, significantly elevated sTM levels in SCA children with a history of cerebrovascular disease compared to those without (5.7 v 4.6 ng/ml p=0.02), suggesting that sTM may predict end-organ dysfunction. Conclusions We have shown in a large cohort of SCA children that EC activation, TG and intravascular haemolysis are increased in HU-treated children compared with BT. Free haem induces loss of EC TM and VWF release in vitro, leading to EC activation. Elevated sTM levels were a biomarker of end-organ damage. These data suggest that reduction of free haem in children undergoing regular BT is a key mechanism through which EC quiescence is maintained in paediatric SCA.

Preparation and properties of chitin/silk fibroin biocompatible composite fibers

In the present world chitin is used enormously in various fields, such as biopharmaceuticals, medical and clinical bioproducts, food packaging, etc. However, its development has been curbed by the impaired performance and cumbersome dissolution process when chitin materials are dissolved and regenerated by physical or chemical methods. To further obtain the regenerated chitin fiber material with improved performance, silk fibroin was introduced into the chitin matrix material, and chitin/silk fibroin biocompatible composite fibers were obtained by formic acid/calcium chloride/ethanol ternary system and top-down wet spinning technology. The produced composite fibers outperformed previously reported chitin-silk composites in terms of the tensile strength (160 MPa) and failure strain (25%). The fibers also performed good cell compatibility and strong cellular affinity for non-toxicity. The cell viabilities of the fibers were about 20% greater than those of silk fiber after three days of co-culture with NIH-3T3. Furthermore, no hemolysis occurs in the presence of chitin/silk fibers, demonstrating their superior hemocompatibility. The fibers had a hemolysis index as low as 1%, which is far lower than the acceptable level of 5%. The material offers prospective opportunities for biomaterial applications in anticoagulation, absorbable surgical sutures, etc.

Design of moxifloxacin encapsulated network hydrogel wound dressings: Evaluation of polymer‐drug, polymer‐blood, and polymer‐bio membrane interactions

AbstractIt is an exploration of the inherent wound‐healing tendency of Azadirachta indica gum (AIG) or neem gum polysaccharides to develop the hydrogel wound dressings with enhanced potential during wound management. Herein this research work, antibiotic moxifloxacin encapsulated AIG network copolymeric hydrogels were developed by functionalizing with carbapol and poly(acrylamide) [poly(AAm)] for better wound healing. The polymer‐drug, polymer‐blood, and polymer‐bio membrane interactions were evaluated in biomedical properties. The copolymeric network structure was confirmed by scanning electron micrographs (SEMs), atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), and 13C solid‐state nuclear magnetic resonance (NMR) spectroscopy. The results confirmed sustained release of the moxifloxacin with diffusion by non‐Fickian process and Korsmeyer–Peppas kinetic model in the phosphate buffer saline (PBS). These interactions inferred the blood‐compatible (hemolytic index 3.41 ± 0.70%) and mucoadhesive nature (polymer‐biomembrane detachment force 0.09 ± 0.01 mN) of hydrogel dressing. The per gram of hydrogel dressings absorbed 10.22 ± 0.23 g of simulated wound fluid which is very useful to maintain moist wound environment for better wound healing. All these interactions and properties indicated the suitability of the hydrogel material for wound dressing applications for better wound care.

The erythrocyte destruction mechanism in non-physiological shear mechanical hemolysis

Increasingly heart failure patients need to use Ventricular Assist Devices (VADs) to keep themselves alive. During treatment, hemolysis is an inevitable complication of interventional devices. The most common method for evaluating mechanical hemolysis is to calculate Hemolysis Index (HI) by the power-law formula. However, the HI formula still has obvious flaws. With an intention of further understanding the phenomenon of mechanical hemolysis in non-physiological flow, our study developed a coarse-grained erythrocyte destruction model at the cellular scale and explored the mechanism of the single erythrocyte shear destruction utilizing the Dissipative Particle Dynamics, including the erythrocyte stretching destruction process and the erythrocyte non-physiological shearing destruction process. In the process of stretching and shearing, the high-strain distribution areas of erythrocytes are entirely different. The high-strain areas during stretching are concentrated on the central axis. After the stretch failure, the erythrocyte changes from fusiform to shriveled biconcave. In the shear breaking process, the high strain areas are focused on the erythrocyte edge, causing the red blood cells to evolve from an ellipsoid shape to a plate shape. In addition to the flow shear stress, the shear rate acceleration is also an important factor in the erythrocyte shear damage. The erythrocyte placed in low shear stress flow is still unstably destroyed under high shear rate acceleration. Consequently, the inclusion of flow-buffering structures in the design of VADs may improve non-physiological hemolysis.

Blood Cell Responses Following Heavy Alcohol Consumption Coincide with Changes in Acute Phase Reactants of Inflammation, Indices of Hemolysis and Immune Responses to Ethanol Metabolites.

Aberrations in blood cells are common among heavy alcohol drinkers. In order to shed further light on such responses, we compared blood cell status with markers of hemolysis, mediators of inflammation and immune responses to ethanol metabolites in alcohol-dependent patients at the time of admission for detoxification and after abstinence. Blood cell counts, indices of hemolysis (LDH, haptoglobin, bilirubin), calprotectin (a marker of neutrophil activation), suPAR, CD163, pro- and anti-inflammatory cytokines and autoantibodies against protein adducts with acetaldehyde, the first metabolite of ethanol, were measured from alcohol-dependent patients (73 men, 26 women, mean age 43.8 ± 10.4 years) at baseline and after 8 ± 1 days of abstinence. The assessments also included information on the quantities of alcohol drinking and assays for biomarkers of alcohol consumption (CDT), liver function (AST, ALT, ALP, GGT) and acute phase reactants of inflammation. At baseline, the patients showed elevated values of CDT and biomarkers of liver status, which decreased significantly during abstinence. A significant decrease also occurred in LDH, bilirubin, CD163 and IgA and IgM antibodies against acetaldehyde adducts, whereas a significant increase was noted in blood leukocytes, platelets, MCV and suPAR levels. The changes in blood leukocytes correlated with those in serum calprotectin (p &lt; 0.001), haptoglobin (p &lt; 0.001), IL-6 (p &lt; 0.02) and suPAR (p &lt; 0.02). The changes in MCV correlated with those in LDH (p &lt; 0.02), MCH (p &lt; 0.01), bilirubin (p &lt; 0.001) and anti-adduct IgG (p &lt; 0.01). The data indicates that ethanol-induced changes in blood leukocytes are related with acute phase reactants of inflammation and release of neutrophil calprotectin. The studies also highlight the role of hemolysis and immune responses to ethanol metabolites underlying erythrocyte abnormalities in alcohol abusers.

The influence of hemolysis upon admission on the performance of neuron-specific enolase in predicting death after resuscitated out-of-hospital cardiac arrest – a substudy of the IMICA trial

Abstract Background The predominant cause of mortality among out-of-hospital cardiac arrest (OHCA) patients admitted to the intensive care unit in a comatose state is hypoxic-ischemic brain injury and consequent withdrawal of life sustaining therapies. Current guideline for post-resuscitation care suggests a multimodal approach for neuroprognostication including measuring a blood-born biomarker of neuronal injury termed neuron-specific enolase (NSE). However, NSE is also present in erythrocytes and therefore hemolysis – which frequently occurs immediately after resuscitation – must be assessed by measuring free-hemoglobin (free-hgb), and samples discarded if the threshold index is surpassed to minimize false positive results. In addition, the plasma half-life of NSE is much longer than free-hgb, and hemolysis occurring prior to the sampling point of NSE measurement, may cause elevated NSE levels due to destruction of erythrocytes rather than neurons, although free-hgb is no longer detectable in plasma. Purpose To investigate the relationship between hemolysis at hospital admission and NSE measured at 48 hours, and to determine the influence of hemolysis on the clinical performance of NSE in predicting all-cause mortality in comatose OHCA patients. Methods Free-hgb was measured at admission (0h) to quantify hemolysis. NSE was measured at 48 hours after admission. In each NSE sample hemolysis index was measured and mathematically corrected according to standard laboratory procedure. The relationship between free-hgb at 0h and NSE at 48h was investigated by Pearson's correlation analysis. The area under the receiver operating characteristic curves (AUROC) for prediction of all-cause mortality at 30 days were determined for both NSE and free-hgb, and the difference in AUROC between the two was calculated. Further, the positive and negative predictive values (PPV and NPV respectively) of NSE with a cut-off value at &amp;gt;60 μg/l (as recommended by guidelines) in predicting all-cause mortality were calculated. Results Admission free-hgb and NSE at 48 hours were available for 64 consecutive patients surviving beyond 48 hours. The 30-day mortality in this population was 33%. There was no correlation between free-hgb at 0h and NSE at 48h (r=0.13, p=0.30; Figure 1). The AUROC for NSE was 0.92 (Figure 2), and 0.59 for free-hgb at 0h. The PPV for NSE&amp;gt;60 μg/l was 1.0 (1.0–1.0) and NPV 0.84 (0.74–0.94). Conclusions The performance of NSE at 48 hours for predicting all-cause mortality among out-of-hospital cardiac arrest patients was not influenced by the degree of hemolysis at the time of admission, and NSE at 48 hours had both high positive and negative predictive values irrespectively of early hemolysis. Funding Acknowledgement Type of funding sources: None.

Facile fabrication of Bi-layered perfusable hydrogel tubes as biomimetic 3D arterial construct

Small-diameter arterial conduits with native physiological and biological equivalence continues to be a constant global demand posing critical challenges in fabrication. Advent of various strategies towards mimicking the structural hierarchy of a native blood vessel, often involve complex instrumentation and template-assistance with post-processing complications eventually compromising structural fidelity. In the present research, we report a template-free, facile strategy- ‘3D wet writing’ by peripheral-core differential ionic gelation to fabricate perfusable customizable constructs of any dimension, thickness and length in <5 mins. Dual-crosslinking using di-diol complexation of borax with Alginate- poly (vinyl alcohol) was performed to enhance the stability of fabricated bi-layered tubular constructs (BLT). These fabricated BLTs demonstrated non-linear mechanical characteristics of native blood vessels in withstanding physiological (120/80 mmHg) hemodynamic loading conditions with cyclic strain (5.82 ± 0.88%). The BLTs also ensured adequate longitudinal (0.176 ± 0.03 MPa) & circumferential (0.29 ± 0.012 MPa) tensile strength and burst pressure strength of 353.875 ± 22.69 mmHg. Hemocompatible characteristics of BLT were clearly evident with lower hemolytic index (0.21 ± 0.03%) and maintenance of erythrocyte structural integrity under dynamic conditions. Further, non-thrombogenic and non-inflammatory characteristics of BLTs were confirmed by in-activated platelets and monocytes under dynamic conditions. The developed wet-writing technique exhibited facile integration of layer-specific cells concurrently with the BLT fabrication. The spatial cell-specific expressions of smooth muscle (α-SMA) and endothelial (CD-31) cells in BLT were comparable to native hierarchical cellular organization with the multi-layered medial and mono-layered intimal layers. Further, ex-vivo dynamic studies on anastomotic interface between BLT and rat abdominal aorta clearly evidenced the functional efficacy of fabricated BLTs as physiologically relevant small-diameter vascular construct.

Nitrogen Doped Carbon-Dot Embedded Poly(lactic acid-co-glycolic acid) Composite Films for Potential Use in Food Packing Industry and Wound Dressing

Here, nitrogen-doped carbon dots (N-doped CDs) were synthesized by the hydrothermal method embedded within poly(lactic acid-co-glycolic acid) ((PLGA)) films at different amounts. The N-doped CDs (or CD) that possess fluorescence properties also have antimicrobial properties against S. aureus and E. coli microorganisms, determined by the disc diffusion method with 19 ± 2 and 18 ± 1 mm zone diameters, respectively. The CD embedded PLGA films (CD@PLGA) with different CD contents revealed an increased fluorescence intensity with the increased amount of CD. Moreover, the antibacterial potency of 50% CD containing PLGA (50-CD@PLGA) films (by weight) against S. aureus and E. coli microorganisms was examined and the zone diameters were found to be 14 ± 1 and 13 ± 1 mm, respectively. In addition, CD release studies from different amounts of CD (2.5–50 by weight) containing composite films showed that 50-CD@PLGA film released 127 ± 16 mg/g CD dots, which is 38 ± 5% of the embedded CDs in about 12 days, suggesting their potential application in food packing and wound dressing. Moreover, all CD@PLGA films were found to be blood compatible via hemolysis and blood clotting index tests with &lt;5% hemolysis and &gt;90% blood clotting indices regardless of their CD content.

Numerical study on the performance of centrifugal blood pump with superhydrophobic surface.

In order to reduce the blood damage of an artificial heart pump and optimize its hydraulic performance, a centrifugal blood pump with superhydrophobic characteristics is proposed in this study. To study the influence of superhydrophobic surface characteristics on the performance of centrifugal blood pumps, the Navier slip model is used to simulate the slip characteristics of superhydrophobic surfaces, which is realized by the user defined function of ANSYS fluent. The user defined functions with different values of slip length are verified by two benchmark solutions of laminar flow and turbulence in the pipeline. The blood pump model adopts the designed centrifugal blood pump, and its head, hydraulic efficiency and hemolysis index are calculated. The Navier slip boundary condition (a constant slip-length of 50 μm) is applied to the walls of the blood pump impeller and a volute at different positions, and the influence of the superhydrophobic surface on the performance of the blood pump at the design point Q = 6 L/min was compared and analyzed. The results show that the centrifugal blood pump model used in this paper has good blood compatibility and meets the design requirements; the superhydrophobic surface can significantly reduce the scalar shear stress in the blood pump. At the design point, when the slip length is 50 μm, the mass-average scalar shear stress in the impeller area and the volute area reduction rate is about 5.9%, the hydraulic efficiency growth rate is about 3.8%, the hemolysis index reduction rate is about 18.4%, and the pressure head changes little with a growth rate of 0.3%. Centrifugal blood pumps with superhydrophobic surfaces can improve the efficiency of blood pumps and reduce hemolysis. Based on these encouraging results, vitro investigations for actual blood damage would be practicable.

Impact of volute design features on hemodynamic performance and hemocompatibility of centrifugal blood pumps used in ECMO.

The centrifugal blood pump volute has a significant impact on its hemodynamic performance hemocompatibility. Previous studies about the effect of volute design features on the performance of blood pumps are relatively few. In the present study, the computational fluid dynamics (CFD) method was utilized to evaluate the impact of volute design factors, including spiral start position, volute tongue radius, inlet height, size, shape and diffuser pipe angle on the hemolysis index and thrombogenic potential of the centrifugal blood pump. Correlation analysis shows that flow losses affect the hemocompatibility of the blood pump by influencing shear stress and residence time. The closer the spiral start position of the volute, the better the hydraulic performance and hemocompatibility of the blood pump. Too large or too small volute inlet heights can worsen hydraulic performance and hemolysis, and higher volute inlet height can increase the thrombogenic potential. Small volute sizes exacerbate hemolysis and large volute sizes increase the thrombogenic risk, but volute size does not affect hydraulic performance. When the diffuser pipe is tangent to the base circle of the volute, the best hydraulic performance and hemolysis performance of the blood pump is achieved, but the thrombogenic potential is increased. The trapezoid volute has poor hydraulic performance and hemocompatibility. The round volute has the best hydraulic and hemolysis performance, but the thrombogenic potential is higher than that of the rectangle volute. This study found that the hemolysis index shows a significant correlation with spiral start position, volute size, and diffuser pipe angle. Thrombogenic potential exhibits a good correlation with all the studied volute design features. The flow losses affect the hemocompatibility of the blood pump by influencing shear stress and residence time. The finding of this study can be used to guide the optimization of blood pump for improving the hemodynamic performance and hemocompatibility.