We tested the hypothesis that disseminated intravascular coagulation (DIC) predicts a poor prognosis in patients with out-of-hospital cardiac arrest (OHCA) treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Fifty-seven patients with cardiogenic OHCA who immediately underwent VA-ECMO upon admission to the emergency department were divided into 27 non-DIC and 30 DIC patients. DIC scores were calculated on admission and 24 h later (day 1). The primary outcome measure was the all-cause in-hospital mortality. The basic characteristics did not differ between the two groups; however, patients with DIC showed higher in-hospital mortality rates. Receiver operating characteristic curve analysis showed a moderate predictive ability of DIC scores on day 1 for in-hospital mortality. A lower probability of survival was observed in patients with DIC. The adjusted odds ratio for DIC on day 1 of in-hospital death was 5.67, confirmed by the adjusted hazard ratio of 3.472. The results indicate an association between DIC diagnosis 24 h following VA-ECMO induction for OHCA and poor outcome in these patients.

Using autologous orthotopic liver transplantation (AOLT) model in rats, the effect of lipid reactive oxygen species (L-ROS) inhibitor Ferrostain-1 on ferroptosis signal pathway was observed to determine whether ferroptosis occurred in rat liver injury after cold ischemia-reperfusion (I/R). Thirty-two healthy adult SPF male SD rats, 8 ~ 10 weeks old, weight 240 ~ 260 g, were divided into four groups by the method of random number table (n = 8): sham group, I/R group, I/R + Fer-1 group, I/R + DFO group. In the I/R + Fer-1 group, ferristatin-1(5 mg /kg) was intraperitoneally injected 30 min before surgery; in the I/R + DFO group, DFO 100 mg/kg was injected intraperitoneally 1 h before operation and 12 h after operation. Blood samples were taken from the inferior hepatic vena cava 24 h after reperfusion. After anesthesia, the rats were killed and part of their liver tissue was removed. The pathological changes of liver tissue sections were observed under a high-power microscope, and the liver injury was evaluated. Serum malondialdehyde (MDA) and serum levels of ALT, AST and IL-6 were determined by the ELISA method, Reduced glutathione (GSH), glutathione peroxidase 4 (GPX4), MDA, Fe2 + and superoxide dismutase (SOD) were determined in the liver tissue. Compared with the sham group, the serum levels of the IL-6,MDA, AST and ALT in I/R group were obviously higher (P < 0.05); The levels of MDA and Fe in liver tissue were significantly increased (P < 0.05).The levels of SOD, GSH and GPX4 in liver tissue were decreased. The levels of serum MDA, IL-6, AST, and ALT in the I/R + Fer-1 and I/R + DFO groups were significantly lower than those in the I/R group at 24 h after reperfusion. In the I/R + Fer-1 group, the level of MDA in liver tissue decreased significantly, while the level of SOD, GSH and GPX4 in intestinal tissue increased (P < 0.05). In The I/R + DFO group, the levels of MDA and Fe in liver tissue decreased significantly, while the level of SOD in intestinal tissue increased (P < 0.05). Ferroptosis is involved in pathophysiological process of liver injury after cold ischemia-reperfusion in AOLT rats.

Neutrophil extracellular traps (NETs) were detected in blood samples and in cellular deposits of oxygenator membranes during extracorporeal membrane oxygenation (ECMO) therapy and may be responsible for thrombogenesis. The aim was to evaluate the effect of the base material of gas fiber (GF, polymethylpentene) and heat exchange (HE) membranes and different antithrombogenic coatings on isolated granulocytes from healthy volunteers under static culture conditions. Contact of granulocytes with membranes from different ECMO oxygenators (with different surface coatings) and uncoated-GFs allowed detection of adherent cells and NETotic nuclear structures (normal, swollen, ruptured) using nuclear staining. Flow cytometry was used to identify cell activation (CD11b/CD62L, oxidative burst) of non-adherent cells. Uncoated-GFs were used as a reference. Within 3 h, granulocytes adhered to the same extent on all surfaces. In contrast, the ratio of normal to NETotic cells was significantly higher for uncoated-GFs (56-83%) compared to all coated GFs (34-72%) (p < 0.001) with no difference between the coatings. After material contact, non-adherent cells remained vital with unchanged oxidative burst function and the proportion of activated cells remained low. The expression of activation markers was independent of the origin of the GF material. In conclusion, the polymethylpentene surfaces of the GFs already induce NET formation. Antithrombogenic coatings can already reduce the proportion of NETotic nuclei. However, it cannot be ruled out that NET formation can induce thrombotic events. Therefore, new surfaces or coatings are required for future ECMO systems and long-term implantable artificial lungs.

This review traces the evolution of centrifugal blood pumps in mechanical circulatory support (MCS) systems. Initially met with concerns over blood damage and thrombus formation, centrifugal pumps have become crucial components in ventricular assist devices (VADs) and extracorporeal membrane oxygenation (ECMO) due to their simplified drive mechanisms and adaptability. This paper outlines three generations of centrifugal pump development: first-generation pumps with sealing components, second-generation pumps utilizing pivot bearings, and third-generation pumps employing contactless bearings. Each iteration addressed previous limitations, particularly regarding thrombus formation and durability. Current regulatory challenges surrounding the duration of pump use in MCS are examined, highlighting the discrepancy between approved usage times and clinical needs. This paper notes ongoing efforts to extend approved use periods, citing examples of pumps cleared for extended use in various jurisdictions. This historical perspective provides insights into the technological advancements that have enhanced the safety, efficacy, and durability of centrifugal blood pumps in MCS applications.

Abel JJ, Rowntree LG and Turner BB (Baltimore Trio) proposed the concept of vividiffusion and developed a vividiffusion apparatus in 1912. In a 1914 paper, they laid out the most important rule of device design. We named this rule an ART law taken from the initials of the Baltimore Trio. The ART law means that a blood purification device with a shape that can secure as large a dialysis membrane area as possible for as small a volume of blood filling as possible will achieve high dialysis performance. Rather than using 8 mm inner diameter collodion tubes in the original vividiffusion apparatus, the solution to the device shape that fits this rule is to hold down the tube from both top and bottom to make it as flat as possible, or if it is a flat membrane, to bring two flat membranes as close together as possible, and in the case of tubes and hollow fibers, to make their inner diameter as small as possible of approximately 200 μm. In other words, the dialysis performance is greatly improved by narrowing the blood flow path. This is exactly the ART law, predicting the shape of today's blood purification devices.

The use of veno-venous extracorporeal membrane oxygenation (VV-ECMO) has become increasingly prevalent, particularly in respiratory disease pandemics such as H1N1-influenza and SARS-CoV-2. This surge has emphasized the importance of clear therapy recommendations, improved accessibility to ECMO technology, established ECMO teams, and structured networks to ensure access to specialized care throughout the course of the disease for patients with severe ARDS. Although the initiation criteria for VV-ECMO are well defined, treatment strategies while on ECMO regarding e.g., ventilator management or ECMO weaning strategies remain variable and with lack of consensus. NAVA (Neurally Adjusted Ventilatory Assist), as an assisted mechanical ventilation modality, offers real-time electromyographic feedback, which has been shown to enhance prolonged weaning processes from mechanical ventilation. We present a case of penetrating thoracic trauma complicated by ARDS, successfully managed with VV-ECMO. NAVA was employed to monitor and facilitate ECMO. This approach integrates ECMO weaning with ventilation settings, considering both gas exchange lung function, such as carbon dioxide removal, and respiratory mechanics in the form of neuromuscular coupling. This is a new approach to VV-ECMO weaning. More research is planned to validate the efficacy of this method in conjunction with additional parameters, such as diaphragm activity evaluated sonographically in a randomized design. This case underscores the potential of NAVA in VV-ECMO weaning, offering a promising avenue for optimizing patient care and outcomes.

Left ventricular assist devices (LVADs) are implanted in patients with heart failure to support cardiac circulation. However, no standardized methods have been established for LVAD driveline exit site management for the prevention of infections. Therefore, this study evaluated the efficacy of modified driveline management compared with that of conventional driveline management. We retrospectively assessed the outcomes of 262 patients who underwent continuous-flow LVAD implantation between January 2005 and March 2023 at Osaka University in Japan. In conventional driveline management, an LVAD driveline penetrates the skin along the body surface and is fixed near the penetration site (n = 224). In contrast, in our modified fixation method, the LVAD driveline vertically penetrates the skin to prevent ischemia at the driveline exit site and is fixed at a distant abdominal site to prevent the movement of the driveline exit site due to body movement (n = 38). The rates of freedom from LVAD driveline infection in patients with conventional driveline management were 86, 75, and 63% at 1, 2, and 3 years after LVAD implantation, respectively. The rate of freedom from LVAD driveline infection in patients managed by the modified fixation method was 91% at 1, 2, as well as 3 years after LVAD implantation. The freedom rates from LVAD driveline infection in the patients with modified fixation method was lower than in the patients with the conventional method (p = 0.04). Our study revealed that the modified fixation method may offer the possibility for preventing LVAD driveline infection.

Cardiac surgery patients are potentially exposed to an acute inflammatory host response with a huge release of both pro- and anti-inflammatory cytokines both through intrinsic (e.g., tissue damage, endothelial injury) and extrinsic (e.g., anesthesia, extracorporeal circuits) mechanisms. Current standard of care therapy includes several invasive supportive treatments such as mechanical ventilation, continuous renal replacement therapy, ECMO, and/or cardiopulmonary bypass which may be responsible for an important inflammatory response. The inflammatory cytokine levels and hemodynamic status following these artificial treatments along with the current standard therapy are not always well controlled and may lead to worsened acute clinical conditions with prolonged in-hospital length of stay and increased mortality. In these settings, the administration of hemadsorption therapy with CytoSorb® has been supported by the successful results in several clinical studies as it has shown improvement of both the inflammatory profile and the hemodynamic vascular status of the patients. Therefore, in this narrative review, we summarized and discussed the current scientific literature on the role of CytoSorb treatment in case of cardiac surgery. According to the current evidences, the raised inflammatory levels and both inotropic and vasopressor requests in cardiac surgery patients need more tailored therapies and, in this contest, the hemadsorption with CytoSorb could play a pivotal role, especially on heart transplant patients. Furthermore, CytoSorb is currently the only hemadsorption sorbent authorized and efficiently applied for removing anticoagulant agents such as ticagrelor or rivaroxaban in patients undergoing cardiac surgery, to reduce perioperative bleeding complications and should be considered in high-risk patients.

Three-dimensional bioprinting is getting enormous attention among the scientific community for its application in complex regenerative tissue engineering applications. One of the focus areas of 3-D bioprinting is Skin tissue engineering. Skin is the largest external organ and also the outer protective layer is prone to injuries due to accidents, burns, pathologic diseases like diabetes, and immobilization of patients due to other health conditions, etc. The demand for skin tissue and the need for an off-the-shelf skin construct to treat patients is increasing on an alarming basis. Conventional approaches like skin grafting increase morbidity. Other approaches include acellular grafts, where integration with the host tissue is a major concern. The emerging technology of the future is 3D bioprinting, where different biopolymers or hybrid polymers together provide the properties of extracellular matrix (ECM) and tissue microenvironment needed for cellular growth and proliferation. This raises the hope for the possibility of a shelf skin construct, which can be used on demand or even skin can be printed directly on the wound site (in-situ printing) based on the depth and complex structure of the wound site. In the present review article, we have tried to provide an overview of Skin tissue engineering, Conventional advancement in technology, 3D bioprinting and bioprinters for skin 3D printing, different biomaterials for skin 3D bioprinting applications, desirable properties of biomaterials and future challenges.

Right ventricular (RV) failure following surgical repair of congenital heart disease affects survival. Human induced pluripotent stem cell-derived cardiomyocyte (hiPS-CM) sheet transplantation ameliorated left ventricular dysfunction in preclinical studies, indicating its efficacy in RV failure in congenital heart disease. This study aimed to evaluate whether hiPS-CMs could improve RV function in rats with pressure-overloaded RV failure. F344/NJcl-rnu/rnu rats underwent pulmonary artery banding (PAB) via left thoracotomy. Four weeks after PAB, hiPS-CM patch transplantation to the RV was performed in the hiPS-CM group (n = 33), and a sham operation was performed in the sham group (n = 18). We evaluated cardiac catheterization, positron emission tomography data, and pathological results 8 weeks following PAB. RV end-diastolic pressure, the time constant of isovolumic relaxation, and end-diastolic pressure-volume relation were significantly ameliorated in the hiPS-CM group compared with in the sham group. Picrosirius red staining revealed that anti-fibrotic effects were significantly higher in the hiPS-CM group than in the sham group. Von Willebrand factor staining revealed significantly higher myocardial capillary vascular density in the hiPS-CM group than in the sham group. hiPS-CMs were detected in the epicardium 4 weeks after hiPS-CM sheet transplantation. The angiogenic gene expression in the myocardium was significantly higher in the hiPS-CM group than in the sham group. Overall, in rats with pressure-overloaded RV failure, hiPS-CM patch transplantation could improve diastolic function, suppress ventricular fibrosis, and increase capillary density, suggesting that it is a promising treatment for RV failure.

This case report details a rare instance of total reversal of the pulmonary circulation (RPC) in a 56-year-old male patient on veno-arterial extracorporeal membrane oxygenation (V-A ECMO) during emergency cardiopulmonary resuscitation (eCPR) following a myocardial infarction and cardiac arrest. Previously unrecognized aortic and mitral valve regurgitations, along with V-A ECMO flow, resulted in severe pulmonary edema. We describe how pulmonary artery cannulation and modifying the ECMO circuit to veno-pulmonary arterial-arterial (VPa-A) ECMO successfully alleviated the severe pulmonary edema but may have caused reversal of the pulmonary circulation (RPC). To our knowledge, this is the first reported case of this phenomenon in a human.

Critically acute and ill and Obstetrical patients constitute a unique clinical population with a high mortality rate. Extracorporeal membrane oxygenation (ECMO) is gradually being used in obstetrical acute and critically ill patients and has shown great advantages. PubMed, Embase, Web of Science, Chinese CNKI Database, and Cochrane Library databases were systematically searched from the earliest available date to March 15, 2024, to obtain relevant studies on extracorporeal membrane oxygenation in obstetric patients. After screening the literature, data were independently extracted and summarized using random effects or fixed effects models, depending on the magnitude of heterogeneity. A total of 38 studies (917 patients) were included. The overall survival rate for critically ill obstetric patients supported by ECMO was 65% (56-74%). Among these, the survival rates for antepartum and postpartum patients were 70% (55-84%) and 63% (47-78%) respectively. The survival rates of obstetric patients supported by VV-ECMO and VA-ECMO were 70% (56-83%) and 56% (44-68%), respectively. This article systematically reports the survival rate of critically ill obstetric patients under ECMO support. The survival rate for these patients is significantly higher than the overall survival rate of all patients receiving ECMO support. Survival rates were similar for prenatal and postpartum patients but survival rates for patients supported by VV-ECMO were significantly higher than those supported by VA-ECMO. Further research is needed to explore the benefits of ECMO for obstetric patients with different disease types.

Model systems are critical in biomedical and preclinical research. Animal and in vitro models serve an important role in our current understanding of human physiology, disease pathophysiology, and therapy development. However, if the system is between cell culture and animal models, it may be able to overcome the knowledge gap that exists in the current system. Studies employing ex vivo organs as models have not been thoroughly investigated. Though the integration of other organs and systems has an impact on many biological mechanisms and disorders, it can add a new dimension to modeling and aid in the identification of new possible therapeutic targets. Here, we have discussed why the ex vivo organ model is desirable and the importance of the inclusion of organs from diverse species, described its historical aspects, studied organs as models in scientific research, and its ex vivo stability. We also discussed, how an ex vivo organ model might help researchers better understand organ physiology, as well as organ-specific diseases and therapeutic targets. We emphasized how this ex vivo organ dynamics will be more competent than existing models, as well as what tissues or organs would have potentially viable longevity for ex vivo modeling including human tissues, organs, and/or at least biopsies and its possible advantage in clinical medicine including organ transplantation procedure and precision medicine.

We established a compact machine perfusion system for whole blood perfusion of rat liver by making use of oxygenation filters as an artificial lung. Livers removed from rats were divided into Krebs-Henseleit (control), 50% blood (hemoglobin: 7 g/dL), and whole blood (hemoglobin: 14 g/dL) groups, then perfused (total perfusate volume: 25 ml) with a small oxygenation filter at 37 °C for 120 min. Blood or perfusate was collected over time, and blood gas and blood cell were measured. In addition, bile volume and portal venous pressure measurements were taken. In all groups, the partial pressure of oxygen was controlled to approximately 400 mmHg. Flow rates were maintained at approximately about 20-30 ml/min according to liver size. Portal venous pressure was normal in the 50% blood and whole blood groups, while lower than the reference value in the Krebs-Henseleit group. Twice as much bile was produced in the 50% blood and whole blood groups relative with the Krebs-Henseleit group. We observed no differences in hemoglobin and red blood cell levels. Lactate levels were normal in the 50% blood and whole blood groups, but were elevated in the Krebs-Henseleit group. Our compact perfusion system using oxygenation filters was able to maintain rat liver function by perfusing a small amount of extracorporeal blood. This system is simple and stable, and may contribute to the future development of machine perfusion systems.

A thyroid storm is the most extreme and life-threatening presentation of thyrotoxicosis. Thyroidectomy can be used for definitive treatment. It should be performed after euthyroidism is accomplished. The use of therapeutic plasma exchange (TPE) is a last resort option in cases where standard pharmacological therapy proves to be ineffective. Due to its rare prevalence, there are limited data evaluating the usefulness and efficacy of TPE as a bridging therapy to thyroidectomy. The absence of relevant literature prompted us to conduct a scoping review. The following bibliographic databases were searched for articles dated 30 November 2023: Medline, EMBASE, Web of Science and Google Scholar. The search identified 1047 records, of which 42 articles were accepted with a total of 234 patients. The dominant indications for TPE were side effects due to conventional treatment. The mean fT4 level decreased 51.9% of baseline after TPE, while the mean fT3 level decreased 66.6% of baseline. The main side effects observed with FFP were allergic reactions, while the use of an albumin solution was associated with perioperative bleeding. Based on the limited data available in the literature, we recognize plasmapheresis as an effective treatment option for reducing thyroid hormone levels prior to thyroidectomy in patients with thyrotoxicosis. Available data suggest that it might be reasonable to limit the number of sessions in favor of an earlier surgical intervention. To reduce the risk of bleeding, FFP may be a better option as a replacement fluid, especially in the session prior to thyroidectomy.

Continuous renal replacement therapy (CRRT) is a lifesaving therapy for critically ill patients with acute renal failure. Some patients supported with CRRT suffer from cardiac arrhythmias, which are often treated with amiodarone. While amiodarone is a very effective antiarrhythmic, it has a relatively narrow therapeutic window and a long half-life, making it challenging to dose safely. This is especially true in patients supported with CRRT, where drug pharmacokinetics are likely altered. This ex vivo study measured the extent of amiodarone extraction by the CRRT circuit. Amiodarone was administered to a closed-loop CRRT circuit. Drug was dosed to achieve therapeutic concentrations. Circuits were primed with a human blood-plasma mixture and maintained at physiologic temperature and pH. Serial blood samples were collected over time and drug concentrations were quantified. Amiodarone was heavily extracted by the ex vivo CRRT circuit with only 23% amiodarone remaining in the plasma at 6 h. The relative concentration was significantly greater in the controls than in the CRRT circuits within 2 h (n = 3; p = 0.0059). Amiodarone is heavily adsorbed by CRRT circuit components, suggesting that clinical dosing adjustments are likely required to achieve therapeutic targets.

Soft robots have found extensive applications in the medical field, particularly in rehabilitation exercises, assisted grasping, and artificial organs. Despite significant advancements in simulating various components of the digestive system, the rectum has been largely neglected due to societal stigma. This study seeks to address this gap by developing soft circular muscle actuators (CMAs) and rectum models to replicate the defecation process. Using soft materials, both the rectum and the actuators were fabricated to enable seamless integration and attachment. We designed, fabricated, and tested three types of CMAs and compared them to the simulated results. A pneumatic system was employed to control the actuators, and simulated stool was synthesized using sodium alginate and calcium chloride. Experimental results indicated that the third type of actuator exhibited superior performance in pressure generation, enabling the area contraction to reach a maximum value of 1. The successful simulation of the defecation process highlights the potential of these soft actuators in biomedical applications, providing a foundation for further research and development in the field of soft robotics.

The spleen size may be associated with mortality and morbidity in patients with heart failure, whereas its clinical implication in patients with cardiogenic shock receiving Impella-incorporated temporary mechanical circulatory support (MCS) remains unknown. Patients who received Impella-incorporated temporary MCS in our institute between March 2018 and August 2023 were eligible. The splenic volume index (SVI) was retrospectively calculated in all participants by measuring spleen size on the computed tomography obtained at the time of Impella placement. The impact of baseline SVI/central venous pressure (CVP) ratio on the 30-day mortality after Impella placement was evaluated. A total of 74 patients (70 years old, 62% men) were included. Median baseline SVI was 71.6 (50.3, 92.1) mL/m. A lower SVI was associated with more decreased cardiac output and a higher SVI was associated with more elevated CVP (p < 0.05 for both). A lower SVI/CVP ratio was associated with higher 30-day mortality with an adjusted hazard ratio of 3.734 (95% confidence interval 1.397-9.981, p = 0.009). A baseline lower SVI/CVP ratio was associated with short-term mortality in patients receiving Impella-incorporated temporary MCS.

A portable axial-flow polymer bridge pump with hydrodynamic bearings has been developed for bridge-to-bridge use. The pump is inexpensive to manufacture and disposable. It weighs 185 g and was verified to have a lifetime of 3 months with silent operation. For partial circulatory assist at a flow rate of 2 L/min, the clinical limit of hemolysis was verified for a rotational speed below 9000 rpm, at which a pressure of 100 mmHg was generated. In an anti-thrombogenic test, the pump stably operated for 6 h without thrombus formation.

Improvements in the roll porous scaffold (RPS) 3D bioproduction technology will increase print density of 10-15 µm cells by ~ 20% up to ~ 1.5 × 10 cells/mL and purity of organoid formation by > 17%. The use of 360 and 1200 dpi inkjet printheads immediately enables biomanufacturing with 10-30 µm cells in a single organoid with performance > 1.8 L/h for 15 µm layer thickness. The spongy bioresorbable ribbon for RPS technology is designed to solve the problems of precise placement, leakage and increasing in the number of instantly useable cell types and superior to all currently dominant 3D bioprinting methods in speed, volume, and print density without the use of expensive equipment and components. The potential of RPS for parallel testing of new substances studied was not on animals, but using generated 3D biomodels "organ on a chip". Solid organoids are more suitable for personalized medicine with simultaneous checking of several treatment methods and drugs, targeted therapy for a specific patient in vitro using the 3D composition of his personal cells, and selection of the most effective ones with the least toxicity. Overcoming the shortage of organs for implantation and personal hormone replacement therapy for everyone was achieved using printed endocrine glands based on their DNA.