Blood Contact Research Articles

Monkeypox: What do we know so far? A short narrative review of literature.

Monkeypox was a zoonotic infection, first detected in parts of northern Africa in the 1970s. Monkeypoxvirus, the causative agent of monkeypox, is a species of genus Orthopoxvirus and is closely related to long-eradicated smallpox caused by variola virus. Outbreaks in the West (in USA, UK, and Ireland) along with periodic re-emergence of the disease in parts of Africa have generated concern among global health bodies due to the existent deficiency of guidelines for management of the disease. Genetic variations and altered mechanisms favoring better survival of the virus have made early identification of the disease during screening difficult, particularly in resource-limited settings like rural areas of Africa. Through evidences gathered from experimental studies conducted after these outbreaks, the virus is known to be transmitted from several animal reservoirs along with human-to-human contact of blood, body fluids, or aerosol. Early diagnosis through immunoassays and polymerase chain reaction (PCR) tests, although not very specific, allows early treatment and subsequently better patient survival and recovery. Presence of lymphadenopathy along with fever, sore throat, and a vesiculopustular rash is diagnostic. The virus affects the gastrointestinal, hematological, ocular, and respiratory systems, in like manner producing afflictions of the specific system. Treatment, through experimental data, has been preferred to be symptomatic, with the aim to prevent superinfections. Antivirals like cidofovir and tecovirimat have been studied upon and used in clinical trials with favorable outcomes. Antiviral immunoglobulins have also been used with success in certain patients for postexposure prophylaxis.

The Effect of Bacterial DNA and Hemodialysis Therapy Conditions on Interleukin 6 Levels Variation in End-stage Renal Disease Patients

Hemodialysis (HD) is the most common therapy to treat end-stage renal disease (ESRD) patients. That is used to clear blood from metabolism end products and maintain water and electrolyte balance in patients’ body when failed kidneys unable to do that. Patient’s blood contact via dialysis filter (dialyzer) about 400 L of dialysis fluid that is mainly form of water and some electrolyte, this quantity of fluid contact can stimulate the production of pre-inflammatory markers due to carrying pathogens such as bacterial DNA fragments even in small quantity that can pass all filters to bloodstream stimulating production of IL-6. A total of 90 blood samples were collected from 45 patients under hemodialysis therapy in Baghdad Teaching Hospital, Gazy Alhariry general hospital, Al-khayal private hospital and Al-Muayad private hospital before and after 3 hours of HD therapy to detect IL-6 by ELISA technique. And from the same centers dialysis fluid and water samples were collected to detect bacterial DNA fragments. PCR technique using 16s universal bacterial primer showed presence of bacterial DNA fragments in dialysis fluid and water used to prepare it.The ELISA readings showed a variety in IL-6 levels higher in patients with low ultrafiltration UF rate than its level in patients with high UF and generally, the level of IL-6 in patients treated in centers with DF preparation direct water distribution system were lower than its level in patients treated in centers with indirect water distribution systems.

The CorInnova Implantable Cardiac Assist System for Direct Cardiac Compression.

The CorInnova cardiac compression device (CorInnova, Inc., Houston, TX, USA) is designed to provide direct biventricular support, increase cardiac output, and improve ventricular unloading in patients with heart failure. Placed within the pericardium and surrounding both ventricles, the device has two concentric sets of thin-film polyurethane chambers: (1) inner (epicardial) saline-filled chambers that conform intimately to the epicardial surface, eradicating any gaps in the interface between the device and the heart; and (2) outer air-filled chambers cycled to provide epicardial compression during systole and negative epicardial pressure during diastole, consistent with physiological cardiac contraction and relaxation. A superelastic, collapsible Nitinol frame gives the device structure, enables minimally invasive self-deployment, and enhances diastolic filling. Preclinical testing has been extremely promising, with improvements in cardiac output and other cardiac parameters in animal heart failure models. This potentially transformative technology is moving rapidly toward first-in-human use. The CorInnova device may provide an effective device-based solution for patients with heart failure who currently have few or limited mechanical cardiac support options, including patients with biventricular cardiac failure, those with right heart failure, those who are older, and those who are of smaller size. It can be removed easily and requires minimal maintenance. An important, unique feature of this technology is that it provides mechanical cardiac assistance without blood contact or need for anticoagulation. The CorInnova device may be particularly important for those patients who have contraindications to anticoagulation due to allergy, neurological bleeds, or preexisting hemorrhage. No other mechanical circulatory support device addresses these underserved heart-failure populations.

TPA or not tPA? Lysis therapy in the setting of COVID‐19 and ECMO

We read with interest the recent article entitled, “Using lysis therapy to treat five critically ill COVID-19 patients who show echocardiographic criteria of right ventricular strain” by Mahdy et al., which described five patients who underwent lysis therapy for COVID-19-associated critical illness with respiratory failure and right heart strain. We find this topic especially relevant in the context of the global COVID-19 pandemic, which has now claimed over 800,000 American lives and over 1.5 million worldwide. Critical illness secondary to COVID-19 is associated with an inflammatory state and coagulopathy; the mechanisms underlying this state are still under investigation [1-4]. There are multiple case reports describing adverse thrombotic events in this population [1-4] and we are particularly interested in the authors’ report of Patient 5, who was receiving extracorporeal membranous oxygenation (ECMO) at the time of lysis therapy. ECMO generally requires systemic anticoagulation due to a hypercoagulable state induced by contact of the patient's blood with the cannulas, but the choice of medication and the intensity of therapy vary in different settings and in patients with different medical conditions. The increased volume of distribution caused by the circuit also calls the standard dosing of alteplase into question. The balance between thrombotic events and bleeding complications is a delicate one without even accounting for the coagulopathy associated with COVID-19. Recently, we provided veno-venous ECMO for a 47-year-old man with severe hypoxemia secondary to acute respiratory distress syndrome (ARDS) associated with COVID-19 pneumonia. His hypoxemia was refractory to mechanical ventilation, neuromuscular blockade, and prone positioning. In addition, the patient had completed a course of dexamethasone and remdesivir as targeted therapy for COVID-19. His medical history was significant for obesity, congenital solitary kidney, hypothyroidism, and hyperlipidemia. While on ECMO, he received therapeutic anticoagulation with unfractionated heparin. On hospital day 17 (ICU day 13 and day 21 since symptom onset), our patient developed a massive pulmonary embolism with acute right ventricle (RV) failure (Figure 1). The patient's coagulation parameters on this day were as follows: PTT 102.3 s, INR 2, d-dimer 85,940 FEU. He was too hemodynamically unstable to transfer for thrombectomy. After a multidisciplinary discussion, we gave intravenous alteplase (10 mg bolus over 1 min followed by 90 mg infusion over 2 h). Within minutes, he stabilized and there were no associated bleeding complications. Anticoagulation decreases mortality in COVID-19-associated critical illness and is recommended while patients are on ECMO [2-4], but studies reporting thrombotic complications despite therapeutic heparin are common [5]. The ideal anticoagulation strategy for these patients is still unclear. Prior to the pandemic, there were scant reports on the use of thrombolytics while on ECMO, leaving little guidance for clinicians at the bedside. We are curious if the authors of this case series are able to report more on Patient 5's coagulation studies, how they chose their alteplase dose, their consideration of bleeding risks, and if they have other recommendations for clinicians considering lytic therapy for patients with COVID-19 disease requiring veno-venous ECMO. We are grateful to the patient described here, and to the patient's family who consented to the publication of this report. The authors declare no conflict of interest. The authors received no specific funding for this work.

Effect of Near-Infrared Blood Photobiomodulation on Red Blood Cell Damage from the Extracorporeal Circuit during Hemodialysis In Vitro

The contact of blood with the bioincompatible membranes of the dialyzer, which is part of the extracorporeal circuit during hemodialysis (HD), causes upregulation of various cellular and non-cellular processes, including massive generation and release of reactive oxygen species (ROS), (which is one of the primary causes of anemia in chronic renal failure). We hypothesize that near-infrared (NIR) radiation possesses antioxidant properties and is considered to protect the red blood cell (RBC) membrane by enhancing its resilience to negative pressures. Our experimental setup consisted of an HD machine equipped with a dialyzer with a polyamide membrane; whole bovine blood was examined in vitro in blood-treated circulation. Blood samples were taken at 0, 5, 15, and 30 min during the HD therapy. We also assessed osmotic fragility, hematocrit, hemolysis, and oxidative stress as a concentration of reactive thiobarbituric acid substances (TBARS). Our results have shown that RBC membrane peroxidation increased significantly after 30 min of circulation, whereas the TBARS level in NIR-treated blood remained relatively steady throughout the experiment. The osmotic fragility of NIR-irradiated samples during dialysis was decreased compared to control samples. Our studies confirm that in vitro, blood photobiomodulation using NIR light diminishes oxidative damage during HD and can be considered a simultaneous pretreatment strategy for HD.

In vitro hemocompatibility screening of a slippery liquid impregnated surface coating for extracorporeal organ support applications.

Clot formation, infection, and biofouling are unfortunate but frequent complications associated with the use of blood-contacting medical devices. The challenge of blood-foreign surface interactions is exacerbated during medical device applications involving substantial blood contact area and extended duration of use, such as extracorporeal life support (ECLS). We investigated a novel surface modification, a liquid-impregnated surface (LIS), designed to minimize protein adsorption and thrombus development on medical plastics. The hemocompatibility and efficacy of LIS was investigated first in a low-shear model with LIS applied to the lumen of blood incubation vials and exposed to human whole blood. Additionally, LIS was evaluated in a 6 h ex vivo circulation model with swine blood using full-scale ECLS circuit tubing and centrifugal pumps with clinically relevant flow rate (1.5 L/min) and shear conditions for extracorporeal carbon dioxide removal. Under low-shear, LIS preserved fibrinogen concentration in blood relative to control polymers (+40 ± 6 mg/dL vs polyvinyl chloride, p < .0001), suggesting protein adsorption was minimized. A fibrinogen adhesion assay demonstrated a dramatic reduction in protein adsorption under low shear (87% decrease vs polyvinyl chloride, p = .01). Thrombus deposition and platelet adhesion visualized by scanning electron microscopy were drastically reduced. During the 6 h ex vivo circulation, platelets in blood exposed to LIS tubing did not become significantly activated or procoagulant, as occurred with control tubing; and again, thrombus deposition was visually reduced. A LIS coating demonstrated potential to reduce thrombus formation on medical devices. Further testing is needed specialized to clinical setting and duration of use for specific medical target applications.

MO662: Effects of Blood Contact with Haemodialysis Membrane on the Kidney in a Rat Extracorporeal Perfusion Model

Abstract BACKGROUND AND AIMS A microcirculatory disturbance was found to occur during hemodialysis in an organ such as the brain or heart, which was recently considered to lead to functional impairment of these organs. Decrease in blood volume due to water removal during hemodialysis and the reaction of blood vessels with activated leukocytes and platelets that have come in contact with the dialysis membrane may cause the microcirculatory disturbance of the organs. Residual renal function decline after initiation of hemodialysis is well-known, but the mechanism has not yet been fully understood. In the present study, we focused on the effects of leucocytes and platelets activated by contact with the dialysis membrane and aimed to clarify the effects of blood contact with the dialysis membrane on the kidney. METHOD Male Sprague–Dawley rats weighing 397.4 ± 38.6 g were used for the experiment. We compared three experimental groups; the sham group, in which only puncture and infusion of Ringer's lactate solution were performed; the extracorporeal perfusion alone group, in which extracorporeal perfusion was performed only through a blood circuit; and the dialyzer group, in which extracorporeal perfusion was performed through a blood circuit and dialyzer. Blood was withdrawn from the femoral artery and returned to the femoral vein. The blood flow rate was 0.5–1.0 mL/min, the perfusion time was 4-h and no water removal was performed. During the perfusion experiment, arterial pressure and percutaneous arterial oxygen saturation (SpO2) were measured and at the end of perfusion, serum interleukin-6 (IL-6), a marker of inflammation and urinary kidney injury molecule-1 (KIM-1), a marker of kidney injury, were measured. After completing the perfusion experiment, kidneys were removed and morphology was evaluated by a hematoxylin and eosin (HE) staining. RESULTS AND DISCUSSION Arterial pressure during perfusion showed a significant upward trend during the first 2-h in the extracorporeal alone and dialyzer groups, while SpO2 showed a significant downward trend in these groups. Serum IL-6 levels were significantly higher in the extracorporeal perfusion alone group (P &amp;lt; .05, n = 8) and the dialyzer group (P &amp;lt; .01, n = 6) than in the sham group (n = 7). Urinary KIM-1 level in the dialyzer group was significantly higher than that in normal rats (P &amp;lt; .01, n = 7). Glomerular congestion was observed in the kidney only in the dialyzer group from the HE staining. There was a significant correlation between the increase in arterial pressure and the decrease in SpO2, suggesting that peripheral circulatory disturbance due to peripheral vasoconstriction occurred in the extracorporeal perfusion alone and the dialyzer groups. In addition, extracorporeal perfusion through the dialyzer caused high levels of IL-6 in serum and KIM-1 in urine, suggesting that systemic inflammatory and kidney injury have occurred. These reactions may contribute to the progression of residual renal dysfunction due to dialysis treatment, especially for the patients after the initiation of hemodialysis. CONCLUSION Extracorporeal perfusion and blood contact with a dialyzer caused systemic inflammation and the microcirculatory disturbance of kidneys, resulting in glomerular congestion and kidney injury in a rat extracorporeal perfusion model.

MO752: Doping Polysulfone Dialysis Membranes with Human Neutrophil Elastase Inhibitors—A Proof-of-Concept Study

Abstract BACKGROUND AND AIMS The recurrent contact of blood with the haemodialysis (HD) membrane during the treatment procedure, triggers neutrophil activation, leading to an increase of blood levels of neutrophil elastase that contributes to the chronic inflammatory response experienced by end-stage renal disease patients with a consequent increase of morbidity and mortality. Based on our group's experience in developing flat-sheet polysulfone (PSF) membranes by using the spin-coating and phase-inversion methods [1], and in the synthesis of human neutrophil elastase inhibitors (HNEIs), namely 4-oxo-β-lactam-based compounds [2], the successful doping of PSF membranes with HNEIs has been achieved [3]. These PSF-HNEI biomaterials have proven to be bioactive and biocompatible, and they included in house synthetized HNEIs alongside Sivelestat (SIV, a second generation HNEI) PSF membranes [3]. In this study, we took a step forward aiming to test the efficacy of such modified membranes when exposed to biological conditions (human plasma). METHOD SIV (Abcam) and an in house synthesized 4-oxo-β-lactam-based compound (D4L-2) [2], from our library, were used. The IC50 of both HNEIs in HEPES buffer was evaluated by performing an HNE activity assay [2]. PSF membranes were prepared as described elsewhere [1] and doped with each HNEI by adsorption [3]. In 3 independent assays, triplicates of PSF membrane circles (Ø = 0.6 cm) were incubated with HNEIs vehicle (2.5% DMSO) or with 10–2000 nM SIV or D4L-2 during 3 h at 25°C, for HNEIs adsorption. Afterwards, all PSF-HNEI membranes were incubated in diluted plasma (50% PBS, pH 7.4) or HEPES buffer for 3 h at 37°C. The bioactivity of PSF-HNEI membranes was assessed before and after incubation using the HNE activity assay [2]. The value obtained for PSF membranes incubated with HNEIs vehicle was used to normalize the results (0% HNE inhibition). RESULTS The IC50 of SIV and D4L-2 in solution were 32.7 and 18.1 nM, respectively. Before incubation with either plasma or HEPES buffer, the HNE inhibition capacity of both PSF-HNEI membranes increased in a concentration-dependent manner, reflecting the HNEIs solutions used during the adsorption process. The highest HNE inhibition ability was presented by PSF-D4L-2 membranes (91.7% ± 0.9% versus 35.3% ± 5.0%). After incubation, PSF-HNEIs membranes immersed in HEPES buffer showed a similar HNE inhibition (84.5% ± 2.2% and 34.0% ± 6.2% for D4L-2 and SIV, respectively). However, the modified membranes incubated in plasma showed a significant decrease in HNE inhibition (D4L-2: 23.7% ± 1.6% and SIV: 7.0% ± 2.1%). CONCLUSION D4L-2 showed the best performance (lower IC50 value and higher HNE inhibitory capacity of doped membranes), which is in accordance with following the assumption that the 4-oxo-β-lactam-based inhibitors are more stable molecules and present higher specificity for HNE. However, both PSF-HNEI biomaterials seem to have fulfiled the objective for which they were developed, since, after being incubated in plasma, they presented a significant decrease in the capacity to inhibit HNE, showing that the HNEIs immobilized in the membranes had captured/bound to the HNE present in the plasma sample.

ZIKA VIRUS AN EPIDEMIOLOGICAL PROFILE

Known scientifically ZIKV, constituted in viruses when so enveloped in the unsegmented single RNA chain of the flaviviridae family and flavivirus genus then discovered and isolated in 1947 the Zika virus emerged in the Zika forest in Uganda in monkey-reso and discovered in humans in 1968. Its main means of transmission is by the Aedes Aegypti mosquito and also by sexual intercourse, blood contact, breast milk and amniotic fluid. In Brazil the zika virus was featured during the World Cup in 2014 because many foreigners are from different nations. Treatment is symptomatic means that there is no specific treatment just to relieve symptoms and protect yourself from mosquito bites so it does not carry the disease to other people. In order to carry out this bibliographic review, the Scienc Direct, SciELO, Medline, Capes Periodicals, Google Scholar and Brazilian Ministry of Health databases were used, being considered articles in the Portuguese language according to the quality and relevance of the proposed theme of this review. This work did not pretend to bring something new but to highlight the great health problem that this pathology can cause to the human being and in all its biogenesis.

Pointing fingers at blood contact: mechanisms of subventricular zone neural stem cell differentiation.

Pointing fingers at blood contact: mechanisms of subventricular zone neural stem cell differentiation.

Developing Integrated Approaches for Testing and Assessment (IATAs) in order to support nanomaterial safety

Due to the unique characteristics of nanomaterials (NM) there has been an increase in their use in nanomedicines and innovative medical devices (MD). Although large numbers of NMs have now been developed, comprehensive safety investigations are still lacking. Current gaps in understanding the potential mechanisms of NM-induced toxicity can make it challenging to determine the safety testing necessary to support inclusion of NMs in MD applications. This article provides guidance for implementation of pre-clinical tailored safety assessment strategies with the aim to increase the translation of NMs from bench development to clinical use. Integrated Approaches to Testing and Assessment (IATAs) are a key tool in developing these strategies. IATAs follow an iterative approach to answer a defined question in a specific regulatory context to guide the gathering of relevant information for safety assessment, including existing experimental data, integrated with in silico model predictions where available and appropriate, and/or experimental procedures and protocols for generating new data to fill gaps. This allows NM developers to work toward current guidelines and regulations, while taking NM specific considerations into account. Here, an example IATA for NMs with potential for direct blood contact was developed for the assessment of haemocompatibility. This example IATA brings together the current guidelines for NM safety assessment within a framework that can be used to guide information and data gathering for the safety assessment of intravenously injected NMs. Additionally, the decision framework underpinning this IATA has the potential to be adapted to other testing needs and regulatory contexts.

Advancements in left ventricular assist devices to prevent pump thrombosis and blood coagulopathy.

Mechanical circulatory support (MCS) devices, such as left ventricular assist devices (LVADs) are very useful in improving outcomes in patients with advanced-stage heart failure. Despite recent advances in LVAD development, pump thrombosis is one of the most severe adverse events caused by LVADs. The contact of blood with artificial materials of LVAD pumps and cannulas triggers the coagulation cascade. Heat spots, for example, produced by mechanical bearings are often subjected to thrombus build-up when low-flow situations impair washout and thus the necessary cooling does not happen. The formation of thrombus in an LVAD may compromise its function, causing a drop in flow and pumping power leading to failure of the LVAD, if left unattended. If a clot becomes dislodged and circulates in the bloodstream, it may disturb the flow or occlude the blood vessels in vital organs and cause internal damage that could be fatal, for example, ischemic stroke. That is why patients with LVADs are on anti-coagulant medication. However, the anti-coagulants can cause a set of issues for the patient-an example of gastrointestinal (GI) bleeding is given in illustration. On account of this, these devices are only used as a last resort in clinical practice. It is, therefore, necessary to develop devices with better mechanics of blood flow, performance and hemocompatibility. This paper discusses the development of LVADs through landmark clinical trials in detail and describes the evolution of device design to reduce the risk of pump thrombosis and achieve better hemocompatibility. Whilst driveline infection, right heart failure and arrhythmias have been recognised as LVAD-related complications, this paper focuses on complications related to pump thrombosis, especially blood coagulopathy in detail and potential strategies to mitigate this complication. Furthermore, it also discusses the LVAD implantation techniques and their anatomical challenges.

Direct Cardiac Compression Devices to Augment Heart Biomechanics and Function.

The treatment of end-stage heart failure has evolved substantially with advances in medical treatment, cardiac transplantation, and mechanical circulatory support (MCS) devices such as left ventricular assist devices and total artificial hearts. However, current MCS devices are inherently blood contacting and can lead to potential complications including pump thrombosis, hemorrhage, stroke, and hemolysis. Attempts to address these issues and avoid blood contact led to the concept of compressing the failing heart from the epicardial surface and the design of direct cardiac compression (DCC) devices. We review the fundamental concepts related to DCC, present the foundational devices and recent devices in the research and commercialization stages, and discuss the milestones required for clinical translation and adoption of this technology.

Superamphiphobic blood-repellent surface modification of porous fluoropolymer membranes for blood oxygenation applications

Biomedical gas exchange membranes used for blood oxygenation, including extracorporeal membrane oxygenators (ECMO) and artificial lung technology, have suffered from the insufficient hemocompatibility of membrane materials. Despite over 50 years of membrane oxygenation (MO) technology development, a few hydrophobic membrane materials are now available on the market. Since the hydrophobic nature of the membrane promotes protein fouling which causes thrombus formation, various anti -thrombogenic and anti-fouling coating techniques have been applied to improve the hemocompatibility and lifetime of membranes for long-term MO and implanted artificial lung applications. Here, for the first time, we have developed a superamphiphobic blood-repellent structure on a porous fluoropolymer (PVDF-HFP) based membrane for blood MO application. The PVDF-HFP nanoparticles were electrosprayed on the porous membrane surface and thermally fused to secure physical stability followed by perfluoro-silane coating with a biocompatible adhesive. A soot-like re-entrance structure was successfully generated on the membrane surface, resulting in high water, blood, and hexadecane contact angles over 150°. The modified membranes have excellent anti-fouling properties with competitive blood oxygen performance, implying promising surface properties for long-term MO and artificial lung applications. • The porous PVDF-HFP membrane surface was modified to have amphiphobicity. • A soot-like re-entrance nanostructure coated with perfluorocarbon silane showed liquid repellent properties. • The modified amphiphobic membrane showed resistance to fouling and wetting in contact with blood. • Competitive gas exchange performance were confirmed by a blood oxygenation test.

Soft Robotic Dynamic Cardiomyoplasty with Electrically Contractile Artificial Muscle (AHM)

<h3>Purpose</h3> Ventricular assist devices (VADs) have clinically evolved as a promising alternative for the treatment of end-stage heart failure. The greatest challenges of these devices still remain infections, bleedings and thromboembolic events. Moreover, non-pulsatile blood flow has led to new complications such as formation of arteriovenous malformations with subsequent bleeding in the gastro-intestinal tract and aortic valve regurgitation. Aim of our experimental study was the development of soft electrically contractile artificial muscles wrapped around the heart. This enables a physiological pulsatile flow of the heart and does not require anticoagulation, the main cause of major adverse cardiac and cerebrovascular events in VAD therapy as there is no direct blood contact between the artificial muscle and blood. <h3>Methods</h3> Silver coated nylon (SCN) conductive actuator filaments were fabricated, aligned in a braided fashion and linked together with silicone akin to human striated muscle. Wrapped in layers around lamb hearts with closed mitral valve as a heart sleeve in-vitro, the aortic pressure and contraction rate during upon electrical stimulation of the AHM with 32.5 V electricity was monitored. <h3>Results</h3> After a series of modifications and improvements, in analogy to the human heart stable pressures of 120 mmHg in systole, 80 mmHg in diastole and a mean stimulation rate was 84 /minute could be achieved. <h3>Conclusion</h3> This represents the first successful study demonstrating that an electrically contractile artificial muscle/soft robot can generate pressures and contraction rates necessary to support the left ventricle of the heart.

Aluminum Leaching from Fluid Warmers: Regulatory Deferral to Clinicians' Decision.

Fluid-warming systems are crucial in surgical and trauma settings because of their key role in preventing or treating hypothermia and enabling proper resuscitation of blood products that are stored cold. Recently, several manufacturers have issued warnings of the possibility of aluminum leaching from their fluid warmers and cautioned about the potential for aluminum toxicity in patients who underwent fluid resuscitation with these devices. Studies suggest that one of the main factors affecting aluminum leaching in this setting is the coating of the aluminum plate itself. Coating, often with a biocompatible material, appears to reduce aluminum leaching by 100- to 200-fold compared with an uncoated plate. Nonetheless, leaching with the coating is still at a level exceeding U.S. regulations. A few aluminum-free warming systems are available on the market, but these are not carried by all providers and some clinicians may be less familiar with their use. Medical device manufacturers will likely design future warming systems with less potential for aluminum blood contact. In the meantime, the risk of inadequate resuscitation, consequent to the proper fluid warmer no longer being available, is contrasted with the risk of potential toxicity. In the situation described here, the regulators deferred the ultimate decision of which fluid warmer to use in a given situation to the risk-benefit decision of the clinician.

Construction of Mussel-Inspired Dopamine-Zn2+ Coating on Titanium Oxide Nanotubes to Improve Hemocompatibility, Cytocompatibility, and Antibacterial Activity.

Zinc ions (Zn2+) are a highly potent bioactive factor with a broad spectrum of physiological functions. In situ continuous and controllable release of Zn2+ from the biomaterials can effectively improve the biocompatibility and antibacterial activity. In the present study, inspired by the adhesion and protein cross-linking in the mussel byssus, with the aim of improving the biocompatibility of titanium, a cost-effective one-step metal–catecholamine assembly strategy was developed to prepare a biomimetic dopamine–Zn2+ (DA-Zn2+) coating by immersing the titanium oxide nanotube (TNT) arrays on the titanium surface prepared by anodic oxidation into an aqueous solution containing dopamine (DA) and zinc ions (Zn2+). The DA-Zn2+ coatings with the different zinc contents exhibited excellent hydrophilicity. Due to the continuous release of zinc ions from the DA-Zn2+ coating, the coated titanium oxide nanotubes displayed excellent hemocompatibility characterized by platelet adhesion and activation and hemolysis assay. Moreover, the DA-Zn2+-coated samples exhibited an excellent ability to enhance endothelial cell (EC) adhesion and proliferation. In addition, the DA-Zn2+ coating can also enhance the antibacterial activity of the nanotubes. Therefore, long-term in situ Zn2+-releasing coating of the present study could serve as the bio-surfaces for long-term prevention of thrombosis, improvement of cytocompatibility to endothelial cells, and antibacterial activity. Due to the easy operation and strong binding ability of the polydopamine on various complicated shapes, the method of the present study can be further applied to other blood contact biomaterials or implantable medical devices to improve the biocompatibility.

Accelerated Endothelialization of Nanofibrous Scaffolds for Biomimetic Cardiovascular Implants.

Nanofiber nonwovens are highly promising to serve as biomimetic scaffolds for pioneering cardiac implants such as drug-eluting stent systems or heart valve prosthetics. For successful implant integration, rapid and homogeneous endothelialization is of utmost importance as it forms a hemocompatible surface. This study aims at physicochemical and biological evaluation of various electrospun polymer scaffolds, made of FDA approved medical-grade plastics. Human endothelial cells (EA.hy926) were examined for cell attachment, morphology, viability, as well as actin and PECAM 1 expression. The appraisal of the untreated poly-L-lactide (PLLA L210), poly-ε-caprolactone (PCL) and polyamide-6 (PA-6) nonwovens shows that the hydrophilicity (water contact angle > 80°) and surface free energy (<60 mN/m) is mostly insufficient for rapid cell colonization. Therefore, modification of the surface tension of nonpolar polymer scaffolds by plasma energy was initiated, leading to more than 60% increased wettability and improved colonization. Additionally, NH3-plasma surface functionalization resulted in a more physiological localization of cell–cell contact markers, promoting endothelialization on all polymeric surfaces, while fiber diameter remained unaltered. Our data indicates that hydrophobic nonwovens are often insufficient to mimic the native extracellular matrix but also that they can be easily adapted by targeted post-processing steps such as plasma treatment. The results achieved increase the understanding of cell–implant interactions of nanostructured polymer-based biomaterial surfaces in blood contact while also advocating for plasma technology to increase the surface energy of nonpolar biostable, as well as biodegradable polymer scaffolds. Thus, we highlight the potential of plasma-activated electrospun polymer scaffolds for the development of advanced cardiac implants.

A novel intrapericardial pulsatile device for individualized, biventricular circulatory support without direct blood contact

ObjectiveDue to severely limited donor heart availability, durable mechanical circulatory support remains the only treatment option for many patients with end-stage heart failure. However, treatment complexity persists due to its univentricular support modality and continuous contact with blood. We investigated the function and safety of reBEAT (AdjuCor GmbH), a novel, minimal invasive mechanical circulatory support device that completely avoids blood contact and provides pulsatile, biventricular support. MethodsFor each animal tested, an accurately sized cardiac implant was manufactured from computed tomography scan analyses. The implant consists of a cardiac sleeve with three inflatable cushions, 6 epicardial electrodes and driveline connecting to an electro-pneumatic, extracorporeal portable driver. Continuous epicardial electrocardiogram signal analysis allows for systolic and diastolic synchronization of biventricular mechanical support. In 7 pigs (weight, 50-80 kg), data were analyzed acutely (under beta-blockade, n = 5) and in a 30-day long-term survival model (n = 2). Acquisition of intracardiac pressures and aortic and pulmonary flow data were used to determine left ventricle and right ventricle stroke work and stroke volume, respectively. ResultsEach implant was successfully positioned around the ventricles. Automatic algorithm electrocardiogram signal annotations resulted in precise, real-time mechanical support synchronization with each cardiac cycle. Consequently, progressive improvements in cardiac hemodynamic parameters in acute animals were achieved. Long-term survival demonstrated safe device integration, and clear and stable electrocardiogram signal detection over time. ConclusionsThe present study demonstrates biventricular cardiac support with reBEAT. Various demonstrated features are essential for realistic translation into the clinical setting, including safe implantation, anatomical fit, safe device–tissue integration, and real-time electrocardiogram synchronized mechanical support, result in effective device function and long-term safety.

Lived Experience and Risk Reduction Behaviors Among Sero-Negative Discordant Male Partners Living with HIV-Positive Women in Addis Ababa, Ethiopia, 2019: A Qualitative Phenomenological Study.

ObjectiveThis study aimed to explore lived experience and risk reduction behaviors among sero-negative, discordant male partners living with HIV-positive women in Addis Ababa, Ethiopia, 2019.MethodsA phenomenological study was conducted to explore lived experience and risk reduction behaviors. The study participants were purposively selected 13 sero-negative male partners living with HIV-positive women. An in-depth interview was used to explore important information. A semi-structured interview guide was used to execute the in-depth interview. The in-depth interview was analyzed thematically through the support of ATLAS-ti 7 software.ResultsScientific explanation of discordant result is not well understood rather, it is associated with religious, cultural, natural resistance, and passive carrier explanations. Sero-negative partners faced several challenges and lived dilemmatic life related to partner mood or behavioral change, maintaining the marital relationship, the desire of child, psychosocial, sexual life, and lack of support system. Risk reduction behaviors like condom use, safe sex practice, preventing sexually transmitted infection, avoiding substance use, continuous checkup and follow-up were not well reflected in their lived experience and were poorly understood. Personalized use of sharp materials to avoid blood contact and support of a partner in the proper use of ART drugs were positively reported risk reduction behaviors.ConclusionSero-negative partners need special attention just as HIV-positive partners in couples with the discordant result. Life suffering is not limited to HIV-positive partners, rather sero-negative partners also faced several challenges and dilemmatic life. HIV transmission risk reduction behavior is not well established and understood.