Search

The authors found that HSCT recipients of grafts carrying the -1082GG interleukin-10 (IL-10) gene promoter region variant had a three-fold lower incidence of grade II-IV acute GVHD compared to IL-10 -1082AA graft recipients. Immunologic complications following organ, cell, or tissue transplantation still raise significant challenges related to their diagnosis and treatment. The pre-transplant crossmatch test between donor cells and recipient sera developed by Terasaki in the mid-1960s has allowed for better organ allocation and reduced immunologic risks after transplantation at a time when immunosuppressive medication was in its infancy. In spite of an increased understanding of transplant immunobiology and the availability of effective immunosuppression, acute rejection or graft-versus-host disease (GVHD) still occur in up to 50% of transplant recipients, depending on the graft type [[1]]. [Extracted from the article]

Intestinal transplantation (ITx) remains a lifesaving option for patients suffering from irreversible intestinal failure and complications from total parenteral nutrition. Since its inception, it became obvious that intestinal grafts are highly immunogenic, due to their high lymphoid load, the abundance in epithelial cells and constant exposure to external antigens and microbiota. This combination of factors and several redundant effector pathways makes ITx immunobiology unique. To this complex immunologic situation, which leads to the highest rate of rejection among solid organs (>40%), there is added the lack of reliable non-invasive biomarkers, which would allow for frequent, convenient and reliable rejection surveillance. Numerous assays, of which several were previously used in inflammatory bowel disease, have been tested after ITx, but none have shown sufficient sensibility and/or specificity to be used alone for diagnosing acute rejection. Herein, we review and integrate the mechanistic aspects of graft rejection with the current knowledge of ITx immunobiology and summarize the quest for a noninvasive biomarker of rejection. [ABSTRACT FROM AUTHOR]

Determining the author of a text is a difficult task. Here, we compare multiple Artificial Intelligence techniques for classifying literary texts written by multiple authors by taking into account a limited number of speech parts (prepositions, adverbs, and conjunctions). We also introduce a new dataset composed of texts written in the Romanian language on which we have run the algorithms. The compared methods are artificial neural networks, multi-expression programming, k-nearest neighbour, support vector machines, and decision trees with C5.0. Numerical experiments show, first of all, that the problem is difficult, but some algorithms are able to generate acceptable error rates on the test set. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is frequent after liver transplantation (LT) and correlates with later development of chronic kidney disease. Its etiology is multifactorial and combines pre-, intra-, and postoperative factors. Additionally, the liver graft itself seems an important element in the development of AKI, yet the detailed mechanisms remain unclear. We hypothesized that grafts of LT recipients developing significant early AKI may show distinct proteomic alterations, and we set out to identify proteome differences between LT recipients developing moderate or severe AKI (n = 7) and LT recipients without early renal injury (n = 7). Liver biopsies obtained one hour after reperfusion were assessed histologically and using quantitative proteomics. Several cytokines and serum amyloid A2 (SAA2) were analyzed in serum samples obtained preoperatively, 2–4 h, and 20–24 h after graft reperfusion, respectively. LT induced mild histological alterations without significant differences between groups but uniformly altered liver function tests peaking on postoperative day 1, with a trend towards more severe alterations in patients developing AKI. Global quantitative proteomic analysis revealed 136 proteins differing significantly in their expression levels (p < 0.05, FC 20%): 80 proteins had higher and 56 had lower levels in the AKI group. Most of these proteins were related to immune and inflammatory responses, host defense, and neutrophil degranulation. No differences between the studied pro- and anti-inflammatory cytokines or SAA2 between groups were found at any moment. Our results suggest that grafts of LT patients who develop early AKI reveal a distinct proteome dominated by an early yet prominent activation of the innate immunity. These findings support the hypothesis that AKI after LT may be favored by certain graft characteristics. [ABSTRACT FROM AUTHOR]

• During COVID-19, organ transplant recipients have developed all forms of the disease. • This Romanian centre has a higher prevalence but similar outcomes as other European centres. • Excellent patient and graft short-term outcomes were found in those with mild and moderate COVID-19. • Targeted antiviral therapies do not seem to impair kidney graft function. The lack of effective treatments for coronavirus disease 2019 (COVID-19) has mandated the repurposing of several drugs, including antiretrovirals and remdesivir (RDV). These compounds may induce acute kidney injury and are not recommended in patients with poor renal function, such as kidney transplant (KTx) recipients. The records of 42 KTx recipients with COVID-19 were reviewed. Some of them were receiving antiretrovirals (n = 10) or RDV (n = 8) as part of COVID-19 management. Most patients were male (71%) and their median age was 52 years. The median glomerular filtration rate in these patients was 56 ml/min. Regarding disease severity, 36% had mild disease, 19% had moderate disease, 31% had severe disease, and 12% had critical disease. Subgroups, i.e., patients receiving antiretrovirals, RDV, or no antivirals, were comparable in terms of patient age, comorbidities, and immunosuppression. Seven patients (16.6%) died during hospitalization. Acute kidney injury was found in 24% of KTx recipients at admission. Upon discharge, estimated glomerular filtration rate (eGFR) increased in 32% and decreased in 39% of the KTx recipients compared with the admission rate. The decrease was more prevalent in the RDV group (80%) compared with KTx recipients without any antiviral treatment (29%) (p < 0.05). Most patients (62%) returned to baseline eGFR values within 1 month of discharge. The proportion was similar between the patients receiving antiviral treatment and those not receiving this treatment. KTx recipients run a high risk of COVID-19-related renal impairment. Antivirals appear to be safe for use without major risks for kidney injury. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) ranges from a mild illness to acute respiratory distress syndrome (ARDS), multiorgan dysfunction, and death. Transplant recipients are vulnerable due to comorbidities and immunosuppressants that render them susceptible to infections. The information on COVID-19 in kidney transplant recipients remains limited to small case series. A systematic literature search was conducted, and 12 case series totalling 204 kidney transplant recipients with COVID-19 were identified. Data were extracted, pooled and analysed. Most patients (74%) were men. The most frequent symptoms were fever (76%), cough (64%) and dyspnoea (43%). At admission, over 70% of the patients had abnormal radiological findings. Leukocyte counts were in the lower normal range. C-reactive protein, ferritin, and D-dimer were consistently increased. Treatments included lowering immunosuppression, hydroxychloroquine, antivirals, tocilizumab and intravenous immunoglobulins. Thirty-one percent of the patients were admitted to intensive care units (ICUs), and 16% required intubation. The overall mortality was 21.2%. Patients who died were significantly older than those who survived (61 ± 12 vs. 51 ± 15, p <.01). Logistic regression revealed that the odds for death increased by 4.3% for each additional year of age (odds ratio [OR] 1.043, 95% confidence interval [CI] 1.005–1.083, p value =.0265). No substantial conclusions could be drawn on the efficacy of any particular treatment. More rigorous patient stratification is needed when analysing and reporting data to facilitate future meta-analyses. [ABSTRACT FROM AUTHOR]

COVID-19, lung function, lung transplantation Impact of COVID-19 on lung transplant recipients: Only time will tell Keywords: COVID-19; lung function; lung transplantation EN COVID-19 lung function lung transplantation 1 2 2 12/23/22 20221201 NES 221201 The coronavirus disease 2019 (COVID-19) pandemic has been challenging for the lung transplant (LTx) community. [Extracted from the article]

Intestinal transplantation (ITx) is a lifesaving procedure for complicated intestinal failure. Specifically for the intestine, IGL-1 demonstrated improved graft viability and epithelial repair compared to UW in animal experimental models [6]. Seven multivisceral and six isolated intestinal grafts were transplanted. [Extracted from the article]

• A precise and accurate estimated glomerular filtration rate (eGFR) is essential following kidney transplantation. • β-trace protein and β2-microglobulin do not improve eGFR in kidney transplant recipients. • eGFR–β-trace protein–β2-microglobulin and eGFR-creatinine-cystatin c perform similarly in detecting the direction of changes in glomerular filtration rate from 3 to 12 months after transplant. Reliable estimates of glomerular filtration rate (eGFR) are important for detecting changes in graft function in kidney transplant recipients. Current eGFR equations are based on plasma creatinine and/or cystatin C; however, these are associated with significant bias. This study investigated if equations based on β-trace protein (BTP) and β2-microglobulin (B2M) performed better than the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations based on creatinine and cystatin C among kidney transplant recipients. We included samples and data from the clinical trial CONTEXT. Glomerular filtration rate (GFR) was measured by plasma clearance of an exogenous marker. The eGFR was calculated using the CKD-EPI equations for estimating GFR from BTP and/or B2M and the 2021 CKD-EPI creatinine and creatinine-cystatin C equations. The GFR estimates were evaluated 3 (n = 82) and 12 (n = 64) months after transplant using mean bias, precision, and accuracy. Furthermore, we analyzed the ability of the equations to correctly classify the direction of changes in measured GFR from 3 to 12 months. Among the BTP- and B2M-based equations, the combined eGFR-BTP-B2M performed best with respect to precision (SD = 7.64 mL/min/1.73 m2) and accuracy (±10% from measured GFR = 36%). The eGFR-BTP-B2M and the eGFR-creatinine-cystatin C (2021) performed similarly when comparing precision, accuracy, and residuals (P =.481). The BTP- and/or B2M-based equations did not perform better than the eGFR-creatinine-cystatin C (2021) in correctly classifying the direction of changes in measured GFR from 3 to 12 months. β-trace protein and/or B2M do not improve the estimation of GFR when compared with creatinine- and cystatin C-based 2021 CKD-EPI equations. [ABSTRACT FROM AUTHOR]

Chronic rejection affects the long-term survival of all solid organ transplants and, among intestinal allografts, occurs in up to 10% of the recipients. The insidious clinical evolution of the chronic allograft enteropathy, the absence of noninvasive biomarkers, and the late endoscopic findings delay its diagnosis. No pharmacological approach has been proven effective, and allograft removal nowadays still represents the only available therapy. The inclusion of the liver in the visceral allograft appears to be the only intervention affecting the development of chronic rejection, as revealed by large-center studies and registry reports. A significant body of evidence emerged from the experimental setting and provided essential knowledge on the complex mechanisms behind the development of chronic allograft enteropathy. More recently, donor-specific antibodies have been suggested as an early, key element in the natural history of chronic allograft enteropathy and several novel approaches, tackling the antibody-mediated graft injury, have gained acceptance in clinical settings and are believed to impact on chronic rejection. The inclusion of a liver allograft is advocated when re-transplanting a sensitized recipient, due to its protective effect against humoral immunity. Multicenter trials are required to understand and tackle chronic rejection, and find the therapeutic answer to this clinical dilemma. [ABSTRACT FROM AUTHOR]

Background Clinical and experimental evidence strongly suggest that ischemia–reperfusion injury after intestinal transplantation has deleterious short- and long-term effects and finding means to reduce ischemia–reperfusion injury is a major research area. The anatomical and physiological similarities between the human and porcine digestive tract favor its use as a preclinical model for translational research. Intriguingly, no systematic appraisal of the development of the intestinal preservation injury in pigs is available. Materials and methods Intestinal procurement was performed in nine pigs using histidine-tryptophan-ketoglutarate solution as preservation fluid. Ileal biopsies were obtained after 8, 14, and 24 h of static cold storage (SCS), and the preservation injury was assessed morphologically (Chiu score) as well as on the molecular level. Tight junction (zonula occludens, claudin-3 and 4, tricellulin, and occludin) and adherens junctions (E-cadherin) proteins were studied using immunofluorescence and Western blot. Results Eight hours of SCS induced minimal mucosal changes (Chiu grade 1) that advanced to significant subepithelial edema (Chiu grade 3) after 24 h; progressive Goblet cell depletion was also noted. Apoptosis (studied by cleaved caspase-3 staining significantly increased after 24 h of SCS. Significant molecular changes with decreasing expression of zonula occludens, tricellulin, and occludin were evident already after 8 h of SCS and continuously worsened. Claudin-3 and Claudin-4 and E-cadherin expression remained relatively unaltered during SCS. Conclusions Important molecular alterations precede histologic changes during SCS of the porcine intestine and may be used as more sensitive injury markers than histologic changes in intestinal ischemia and transplantation. [ABSTRACT FROM AUTHOR]

An evaluation of ischaemic preconditioning as a method of reducing ischaemia reperfusion injury in liver surgery and transplantation. Advanced ischemia-reperfusion injury (IRI) is a serious complication following liver transplantation or after liver resections requiring the intraoperative clamping of the liver pedicle, as it can lead to liver failure or primary graft dysfunction or non-function. This cheap, straightforward and apparently safe approach where short episodes of non-lethal ischemia provided protection against the effects of a subsequent longer, more damaging ischemia spurred extensive animal and clinical investigations with encouraging yet often conflicting results [[4]]. [Extracted from the article]

Objective:Microsurgical techniques are increasingly used in routine surgical practice as well as in biomedical research. The training opportunities at standardised training courses are limited, and no microsurgical training facility orprogrammeexisted in Scandinavia before 2013. Methods:A microsurgery laboratory was set up and two different courses were started, aiming separately at biomedical researchers and surgeons. The course for biomedical researchers teaches basic microsurgical skills such as vessel isolation, cannulation, and arterial microvascular suture under magnification. The more advanced course for surgeons focuses on various techniques of microvascular and nerve anastomosis. Both courses use a combination of theory and practice, with emphasis on the practical part, the course for surgeons also includes clinically relevant information. Results:Twelve 5-day courses using both non-living models and exercises on laboratory animals have been conducted and attended by 49 researchers and 44 surgeons. The organisation and the programme of the training courses as well as ‘The 4E concept’ behind the course (educational curriculum, equipment, ergonomy, and evaluation) are further detailed. Conclusions:We have successfully established the first training laboratory and series of microsurgical training courses in Scandinavia at two different levels. The experience from the first 12 courses shows the need for this type of structured training, and confirms that the microsurgical education curriculums needs to be adapted to participants’ prerequisites and expectations, and various difficulty levels should be considered. [ABSTRACT FROM AUTHOR]

Background. Exogenous bilirubin may reduce experimental ischemia-reperfusion injury (IRI) due to its antioxidant properties. We studied if early graft exposure to high bilirubin levels in the recipient affects the early IRI and outcomes after liver transplantation (LTx). Methods. In 427 LTx patients, the AUROC curve based on bilirubin and AST at day 1 identified a cutoff of 2.04 mg/dL for the recipient pretransplant bilirubin. Recipients were grouped as having low (group L, n=152) or high (group H, n=275) bilirubin. Both groups had similar donor-related variables (age, preservation time, donor BMI > 28, and donor risk index (DRI)). Results. Alanine (ALT) and aspartate (AST) aminotransferase levels were higher in group L at day 1; ALT levels remained higher at day 2 in group L. LTx from high risk donors (DRI > 2) revealed a trend towards lower transaminases during the first two days after transplantation in group H. One month and 1-year patient survival were similar in groups L and H. High preoperative bilirubin did not affect the risk for early graft dysfunction (EGD), death, or graft loss during the first year after transplantation nor the incidence of acute rejection. LTx using donors with DRI > 2 resulted in similar rates of EGD in both groups. Conclusion. Increased bilirubin appears to reduce the early IRI after LTx yet this improvement was insufficient to improve the clinical outcome. [ABSTRACT FROM AUTHOR]

As a final remark, we caution that lowering intracellular Ca SP 2+ sp concentrations may prove a double-edged sword, as many enzymes, repair processes and important antioxidant mechanisms including superoxide dismutase and catalase are also Ca SP 2+ sp dependent. The site of action of dantrolene is the sarcoplasmic reticulum ryanodine receptor Ca SP 2+ sp channel, where it inhibits the depolarization-induced release of Ca SP 2+ sp from the sarcoplasmic reticulum into the cytoplasm, interfering with excitation-contraction coupling. Calcium (Ca SP 2+ sp ) has an essential role in numerous cellular processes such as cell growth and differentiation, membrane excitability, exocytosis, and apoptosis. [Extracted from the article]

Background Mucosal barrier injury during intestinal preservation (IP) and transplantation favors life-threatening infections. Luminal delivery of solutions containing amino acids or polyethylene glycols (PEGs) may improve preservation results and reduce this injury. We tested if solutions containing glutamine and PEG influence the mucosal injury. Materials and methods Rat intestines were perfused and stored in Viaspan-University of Wisconsin solution. Before IP, a PEG 3350 solution was introduced intraluminally alone (group 1) or supplemented with 40 mmol/L L-glutamine (group 2). Controls underwent vascular flush alone (group 3). Preservation injury was evaluated after 8, 14, and 24 h by histology and goblet cell count. Tight-junction proteins zonula occludens-1, claudin-3, claudin-4, and caveolin-1 were studied by immunofluorescence. Maltase and caspase-3 activity were also analyzed. Results Group 1 showed mild edema at 8 h and mucosal disruption by 24 h; these features were greatly improved in group 2 where continuous mucosa was found after 24 h of IP. Intestines in group 3 did worse at all time points with subepithelial edema (Park/Chiu grade 3) and marked goblet cell depletion; caspase-3 activity was lowest in group 2. Tight-junction proteins varied continuously during IP; zonula occludens-1 expression and colocalization with claudins decreased significantly in group 3 but not in other groups. Claudin-3 was distinctly localized in the membrane, but stained diffuse, cytoplasmic at later time-points. Claudin-4 changed to a cytoplasmic granular pattern. No caveolin-1 colocalization was observed. Conclusions Luminal PEG and glutamine delay epithelial breakdown and preserve several important mucosal features during extended IP. [ABSTRACT FROM AUTHOR]

Among the intraabdominal organs, the intestine is the most susceptible to storage injury and as a consequence its safe cold ischemic time in the clinic is restricted to below 10 hours. The current practice for the intestinal preservation (IP) consists of an in-situ vascular flush with iced University of Wisconsin or Histidine-Tryptophan-Ketoglutarate solution followed by cold storage at 4°C. Mucosal injury is initiated within 1 hour and rapidly progresses to mucosal breakdown; tissue injury worsens upon reperfusion and further impairs the mucosal barrier, favoring bacterial translocation and sepsis. In addition of releasing danger signals, an advanced ischemia-reperfusion injury (IRI) may increase graft immunogenicity and promote rejection. Several alternative approaches have been tested as alternatives to the static storage. The aim of this review is to summarize and discuss the various intraluminal interventions as additional strategies aiming to reduce the IP/reperfusion injury and highlight the underlying pathophysiological mechanisms. [ABSTRACT FROM AUTHOR]

Since computer processing mainly depends on sorting and searching methods, a key problem is how to design efficient algorithms in order to solve such problems. This paper describes a new nature-inspired mechanism (called Friction-based Sorting) capable of sorting a given set of numbers. The main idea behind this mechanism is to associate a ball (whose weight is proportional to the considered number) to each number. All the balls being allowed to fall in the presence of friction, the heaviest ball (which corresponds to the greatest input number) will reach the ground first and the lightest ball (associated with the smallest number) will reach the ground last. The proposed mechanism is analyzed, together with its strengths and weaknesses. [ABSTRACT FROM AUTHOR]

Background: The postischemic intestine liberates pro-inflammatory mediators (cytokines, lipopolysaccharide [LPS], free radicals) proportional with the local injury that may trigger a systemic inflammatory response and multi-system organ failure. Previously, intestines from donors receiving Tacrolimus revealed improved morphology and abrogated nuclear factor kappa B (NF-κB) activation. Because of its pivotal role in inflammation, we investigated if NF-κB intragraft inhibition influences the posttransplant inflammatory response and remote organ injury. Materials and methods: Donor Sprague Dawley rats received tacrolimus (0.3 mg/kg) or saline i.v. 6 h before graft harvest. The intestines were preserved for 3 h and then transplanted heterotopically. Hepatic microcirculation was assessed at 20 min, 6 h, 12 h, or 24 h post-reperfusion (postR) using laser-Doppler flowmetry (n = 10/group). Blood pressure measurements and liver sampling were performed at 6, 12, or 24 h postR. Blood samples were obtained at 1, 3, 6, 12, and 24 h postR. Hepatic intercellular adhesion molecule 1 (ICAM-1) expression, caspase-3 and -9 activity, and circulating tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), IL-6, and LPS were studied. Results: Pretreated graft (PG) recipients had superior cardiovascular parameters at 6 and 12 h postR, while liver perfusion was similar between groups at all time points. Recipients of PG had lower transaminase levels and ICAM-1 liver expression. Liver caspase 3 and 9 activity were similar at 6 and 12 h but increased at 24 h in both groups. At every time point, circulating tumor necrosis factor alph, IL-1β, and IL-6 were lower in animals receiving PG. LPS was found increased only at the last time point. Conclusions: Transplantation of tacrolimus-pretreated intestines triggered a milder inflammatory response and decreased liver injury early posttransplantation compared with untreated grafts. Cytokines, but not neutrophils, hypoperfusion, or LPS may underlie the dysfunction. [Copyright &y& Elsevier]

Genetic Programming (GP) is an automated method for creating computer programs starting from a high-level description of the problem to be solved. Many variants of GP have been proposed in the recent years. In this paper we are reviewing the main GP variants with linear representation. Namely, Linear Genetic Programming, Gene Expression Programming, Multi Expression Programming, Grammatical Evolution, Cartesian Genetic Programming and Stack-Based Genetic Programming. A complete description is provided for each method. The set of applications where the methods have been applied and several Internet sites with more information about them are also given. [ABSTRACT FROM AUTHOR]

We suggest a new optical solution for solving the YES/NO version of the Exact Cover problem by using the massive parallelism of light. The idea is to build an optical device which can generate all possible solutions of the problem and then to pick the correct one. In our case the device has a graph-like representation and the light is traversing it by following the routes given by the connections between nodes. The nodes are connected by arcs in a special way which lets us to generate all possible covers (exact or not) of the given set. For selecting the correct solution we assign to each item, from the set to be covered, a special integer number. These numbers will actually represent delays induced to light when it passes through arcs. The solution is represented as a subray arriving at a certain moment in the destination node. This will tell us if an exact cover does exist or not. [ABSTRACT FROM AUTHOR]

An intelligent system should be able to solve a wide range of problems from different domains. In this paper we propose a complex and adaptive system capable of solving various data analysis problems without needing human help for parameter settings. The system, called A-Brain, consists of several interconnected components (a decision-maker, a trainer, and several problem solvers) which provide a base for building complex problem solvers. The parameters of the trainer's algorithm are problem independent. This fact is a requirement for intelligent systems which cannot rely on human intervention while operating. The A-Brain system is used to solve some well-known problems in the field of symbolic regression and classification. Numerical experiments show that the A-Brain system is able to perform very well on the considered test problems. [ABSTRACT FROM AUTHOR]

Traceless genetic programming (TGP) is a genetic programming (GP) variant that is used in cases where the focus is on the output of the program rather than the program itself. The main difference between TGP and other GP techniques is that TGP does not explicitly store the evolved computer programs. Two genetic operators are used in conjunction with TGP: crossover and insertion. In this paper, we will focus on applying TGP to solving multi-objective optimization problems, which are quite unusual in GP. Each TGP individual stores the output of a computer program (tree), representing a point in the search space. Numerical experiments show that TGP is able to solve the considered test problems both rapidly and accurately. [ABSTRACT FROM AUTHOR]

A complex model for evolving the update strategy of a Particle Swarm Optimisation (PSO) algorithm is described in this paper. The model is a hybrid technique that combines a Genetic Algorithm (GA) and a PSO algorithm. Each GA chromosome is an array encoding a meaning for updating the particles of the PSO algorithm. The Evolved PSO algorithm is compared to several human-designed PSO algorithms by using ten artificially constructed functions and one real-world problem. Numerical experiments show that the Evolved PSO algorithm performs similarly and sometimes even better than the Standard approaches for the considered problems. The Evolved PSO is highly scalable (regarding the size of the problem's input), being able to solve problems having different dimensions. [ABSTRACT FROM AUTHOR]

Keywords: B-cells; immunoglobulins; immunosuppression; septic shock; survival EN B-cells immunoglobulins immunosuppression septic shock survival 923 924 2 05/23/20 20200601 NES 200601 Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection ([1]). This approach allowed a detailed account of five different subsets of peripheral blood B cells (immature/transitional B cells, naive B cells, tissue-like memory B cells, resting memory B cells, and activated memory B cells). [Extracted from the article]

A new model for evolving Evolutionary Algorithms is proposed in this paper. The model is based on the Linear Genetic Programming (LGP) technique. Every LGP chromosome encodes an EA which is used for solving a particular problem. Several Evolutionary Algorithms for function optimization, the Traveling Salesman Problem and the Quadratic Assignment Problem are evolved by using the considered model. Numerical experiments show that the evolved Evolutionary Algorithms perform similarly and sometimes even better than standard approaches for several well-known benchmarking problems. [ABSTRACT FROM AUTHOR]

The accurate assessment of glomerular filtration rate (GFR) is important in the follow-up of kidney transplant recipients in order to identify graft dysfunction. A number of formulas have been proposed to calculate GFR from endogenous plasma markers such as creatinine or cystatin C since measuring GFR using exogenous markers is troublesome. This study compares and evaluates the ability of four different GFR formulas to estimate kidney graft function and to detect changes in GFR in kidney transplant recipients. The study included patients from the prospective, multicenter CONTEXT trial in kidney transplant recipients. GFR was measured using plasma clearance of 51Cr-EDTA and estimated using the MDRD, CKD-EPI Creatinine, CKD-EPI Cystatin C and CKD-EPI Cystatin C + Creatinine equations at three (n = 83) and twelve (n = 65) months post-transplantation. For each formula mean bias, precision, and accuracy were evaluated. The MDRD equation had the lowest mean bias (0.2 ml/min/1.73 m2), whereas the CKD-EPI Cystatin C + Creatinine equation had the highest precision (8 ml/min/1.73 m2). Accuracy at three months were similar for all equations (P30 > 80%) except for the CKD-EPI Cystatin C equation, which performed poorer (P30 = 55%). None of the formulas evaluated avoided misclassification of changes in GFR. The most optimal combination of precision and accuracy suggests the use of CKD-EPI Creatinine + Cystatin C equation in kidney transplant recipients. [ABSTRACT FROM AUTHOR]

Transplantation faces an unprecedented shortage of organs available for transplantation, resulting in longer waiting times and transplant candidates on the waiting list dying before getting a transplant. This dramatic situation triggered the search for new approaches and innovations to increase the donor pool, such as extending the acceptance criteria concerning donor age or organ transplantation across blood group barriers. Herein, leading experts detailed the immunological and molecular concepts behind the successful clinical translation of these strategies. Organ rejection remains a constant challenge and transplantation tolerance is still elusive as the current paradigm aims for immunosuppression rather than immune modulation. Two contributions in this issue review two different molecular paradigms in harnessing the immunologic response after transplantation. The interplay between the intestinal innate and adaptive immunity is particularly intricate and the intestine remains the organ with the highest rate of acute rejection after transplantation. Experts in the field summarized both time-honored and recent knowledge in intestinal preservation and tolerance in intestinal transplantation with potential for further basic and translational research. [ABSTRACT FROM AUTHOR]

The article explores the Scientific and technical advancements in the donor-specific antibodies and organ transplantation. Topics discussed include information on the host immunity and its clinical significance in various aspects of human health; discussions on the development of HLA antibodies; and the discusses the challenges linked with the donor-specific HLA antibodies.

Ischemia reperfusion injury (IRI) is a life threatening condition that may develop after elective liver surgery or liver transplantation. Numerous surgical and pharmacological approaches have shown varying degrees of protection against liver IRI. A group of protective compounds are the flavonoids but their intestinal absorbtion and bioavailability are low and impredictible. In this issue Tsaroucha et al. reports significantly decreased hepatocellular injury, Fas/FasL expression and inhibited HMGB1 release in rats receiving a hydrosoluble, lyophilized complex of SLB and hydroxypropyl-β-cyclodextrin (SLB-HP-β-CD) intravenously. [ABSTRACT FROM AUTHOR]

Humoral immunity emerges as a risk factor for graft failure after visceral transplantation (VTx) and development of donor-specific anti-HLA antibodies (DSAs) has been linked with poor outcomes. In most cases, a simultaneous liver transplant can be safely performed in sensitized patients with DSA and appears protective against lymphocytotoxic antibodies. We investigated the incidence of acute (AR) and chronic rejection (CR) in 32 VTx without any B cell-depleting pre-treatment (6 isolated intestinal transplants (IT) and 26 liver-containing, multivisceral transplants (MVT) and assessed the presence of donor-specific antibodies (DSA) pre- and post-transplantation. Twenty-one patients (65 %) developed AR, 15 (57 %) of the MVT and 6 (100 %) of the IT (p = 0.05). CR occurred in 4 IT (60 %, p < 0.001). At one month, de novo DSA were present in 71 % of VTx (66 % MVT vs 100 % IT, p = 0.09). At the last available follow-up, 69 % of the MVT and 50 % of the IT patients were DSA-free. D e novo DSA seemed more persistent (7/19, 37 %) than pre-Tx DSA (1/6, 17 %; p = n.s.), de novo DSA were more frequently specific for HLA class II than class I, 16/19 (84 %) vs. 7/19 (37 %; p = 0.003), and HLA-DQ was their most frequent target HLA. DQ mismatches appeared to be a risk factor for developing de novo DSA. In conclusion, liver-containing visceral allografts have superior short- and long-term outcomes compared with liver-free allografts. De novo DSA develop early and frequently after VTx performed without B cell-depleting induction therapy, but the exact role of DSA in the pathogenesis of rejection remains unclear. [ABSTRACT FROM AUTHOR]

Background: Organ transplantation using grafts from elderly donors entails a higher risk for severe ischemia‐reperfusion injury (IRI). Advanced IRI after liver transplantation (LT) seems to be associated with the development of acute kidney injury (AKI). We studied if end‐ischemic hypothermic oxygenated machine perfusion (HOPE) of liver grafts, aimed at mitigating liver IRI, impacts on the frequency and severity of AKI after LT. Methods: LTs performed at our center between January 2017 and December 2022 using organs from deceased brain‐dead donors aged 70 or older were reviewed. From November 2020 on, HOPE was performed routinely in this donor category. The frequency and severity of AKI (KDIGO criteria) within 48 hours of graft reperfusion and the model of early allograft function (MEAF) were compared between HOPE‐LTs (n = 30) and control LTs (n = 71). Results: AKI developed in 23/30 (77%) HOPE‐LTs and in 40/71 (56%) control LTs (p = n.s.), with no difference in severity and timing between groups. Renal replacement therapy was required in 3/30 (10%) HOPE‐LTs and 6/71 (8%) control LTs. In addition, transaminase leak during the first week (marker of IRI) and MEAF were similar between groups. These findings persisted after propensity matching. Histology showed more hepatocyte vacuolization and higher Suzuki score in HOPE‐LTs. Although this analysis could have been underpowered, no trends supporting the benefit of HOPE on liver and renal injury after LT were ever identified. Conclusions: In conclusion, HOPE in this group of older donors does not seem to improve either graft IRI, or the incidence of early AKI after LT. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the authors discuss various reports within the issue on topics including optical computing, optics translation, and computing system.

The gastrointestinal tract is the second most involved organ for graft-versus-host disease where involvement of the small intestine is present in 50% of the cases. Therefore, the use of a non-invasive investigation i.e., video capsule endoscopy (VCE) seems ideal in the diagnostic work-up, but this has never been systematically evaluated before. The aim of this systematic review was to determine the efficacy and safety of VCE, in comparison with conventional endoscopy in patients who received hematopoietic stem cell transplantation. Databases searched were PubMed, Scopus, EMBASE, and Cochrane CENTRAL. All databases were searched from their inception date until June 17, 2022. The search identified 792 publications, of which 8 studies were included in our analysis comprising of 232 unique patients. Efficacy was calculated in comparison with the golden standard i.e., histology. Risk of bias assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The pooled sensitivity was higher for VCE at 0.77 (95% CI: 0.60–0.89) compared to conventional endoscopy 0.62 (95% CI: 0.47–0.75) but the difference was not statistically significant (p = 0.155, Q = 2.02). Similarly, the pooled specificity was higher for VCE at 0.68 (95% CI: 0.46–0.84) than for conventional endoscopy at 0.58 (95% CI: 0.40–0.74) but not statistically significant (p = 0.457, Q = 0.55). Moreover, concern for adverse events such as intestinal obstruction or perforation was not justified since none of the capsules were retained in the small bowel and no perforations occurred in relation to VCE. A limitation to the study is the retrospective approach seen in 50% of the studies The role of video capsule endoscopy in diagnosing or dismissing graft-versus-host disease is not yet established and requires further studies. However, the modality appears safe in this cohort. [ABSTRACT FROM AUTHOR]

The author expresses his views on renal protection during liver transplantation in relation to a study conducted by researcher A. Mukhtar and colleagues, published in a 2011 issue of the journal "Critical Care Medicine." He offers information on acute renal dysfunction as a complication following orthotopic liver transplantation (OLT). He also talks about the routine use of decompression systems and the popularity of OLT.

This document is a correction notice for an article titled "P-NGAL Day 1 predicts early but not one year graft function following deceased donor kidney transplantation–The CONTEXT study." The correction states that there is an error in Table 4 of the article, where the estimated glomerular filtration (eGFR) values were calculated using an incorrect version of the MDRD-formula. The correct reference for the study is also provided. The document includes a graph and a table showing correlations between biomarkers or urine output measured on Day 1 and kidney graft function at three and twelve months. The authors of the article are Marie B. Nielsen, Nicoline V. Krogstrup, Gertrude J. Nieuwenhuijs-Moeke, Mihai Oltean, Frank J. M. F. Dor, Bente Jespersen, and Henrik Birn. [Extracted from the article]

Introduction: Intestinal cold ischemia and subsequent reperfusion during transplantation result in various degrees of mucosal injury ranging from mild edema to extensive mucosal loss. Mucosal barrier impairment favors bacterial translocation and fluid loss and raises nutritional challenges. The injured intestine also releases proinflammatory mediators and upregulates various epitopes toward an inflammatory phenotype. We studied the process of mucosal injury and repair during the early period after intestinal transplantation from a histological and molecular standpoint. Materials and Methods: Adult Sprague-Dawley rats were used as donors and recipients. Donor intestines were perfused and stored in saline for 3 h, then transplanted heterotopically using microvascular anastomoses. Intestinal graft segments were obtained after 20 min, 6 h, 12 h, and 24 h after reperfusion. Histology studies (goblet cell count, morphometry), immunofluorescence, and western blot for several tight junction proteins, apoptosis, and inflammation-related proteins were performed. Results: Cold storage led to extensive epithelial detachment, whereas reperfusion resulted in extensive villus loss (about 60% of the initial length), and goblet cell numbers were drastically reduced. Over the first 24 h, gradual morphologic and molecular recovery was noted, although several molecular alterations persisted (increased apoptosis and inflammation, altered expression of several tight junctions). Conclusions: The current data suggest that a near-complete morphologic recovery from a moderate mucosal injury occurs within the first 24 h after intestinal transplantation. However, several molecular alterations persist and need to be considered when designing intestinal transplant experiments and choosing sampling and endpoints. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Immediate postconditioning during reperfusion attenuates intestinal injury" by K. X. Liu and colleagues in the previous issue.

Decellularized tissue is generally considered immune privileged after transplantation and is an attractive scaffold type for tissue regeneration, including applications for infertility treatment. However, the immune response following transplantation of decellularized tissue is insufficiently studied, in particular after they have been recellularized with mesenchymal stem cells (MSCs). Therefore, we replaced a large uterus segment with a bioengineered graft developed from decellularized uterus tissue and analyzed the immune response during the first 4 months in acellular or MSCs-recellularized scaffolds in the rat. Immunohistochemistry-stained infiltrating immune cells and plasma levels for 16 cytokines and chemokines were quantified. Results revealed that MSCs created an advantageous microenvironment by increasing anti-inflammatory interleukin 10 levels, and increasing the population of FOXP3+ TRegs and CD163+ M2 macrophages, and by reducing the CD8+ cytotoxic T cell population. Hence, MSCs should be considered an immunotherapeutic cell source with the ability to dictate regeneration success after decellularized tissue transplantation. [ABSTRACT FROM AUTHOR]

• Studies on remdesivir as COVID-19 therapy excluded patients with poor renal function • Kidney transplant recipients frequently have impaired renal function • No negative effect on the renal function was seen after 5 days of remdesivir • Remdesivir significantly improved intensive care survival • Remdesivir did not seem to reduce overall mortality The aim of the study was to evaluate the impact of remdesivir on overall mortality, ICU mortality, and renal functional outcome in hospitalized patients with COVID-19 who received kidney transplant. We reviewed 165 patients with KTx hospitalized owing to COVID-19 between March 1, 2020, and May 31, 2021. A total of 38 patients with KTx received a 5-day RDV treatment, whereas 127 received standard of care (SOC). Overall and ICU mortality along with functional outcome were assessed. The 2 groups had similar baseline characteristics. RDV treatment was completed in all patients without any adverse effects attributable to RDV. In terms of overall mortality, there was no difference between the RDV and SOC groups (18% vs 23%, p >0.05), but the ICU mortality was significantly reduced in the RDV group (39% vs 83%, p <0.05). RDV seems to have no nephrotoxic effect on patients with KTx because there was no difference in the incidence of AKI between RDV and SOC groups (50% vs 43%, p >0.05), and the discharge eGFR values significantly improved in the RDV group compared with the admission values (57 ± 23 vs 44 ± 22, p <0.05). Five-day RDV treatment appears safe in KTx recipients, and without obvious nephrotoxic effects. Also, RDV may decrease ICU mortality attributed to COVID-19. [ABSTRACT FROM AUTHOR]

Background and aims. Gastroesophageal reflux disease (GERD) is associated with impaired epithelial barrier function. However, the influence of acid and/or bile acids on human esophageal epithelial barrier function and the tight junction (TJ) proteins has not been fully elucidated. The aim of the study is to investigate the esophageal barrier function and TJ expression in healthy subjects and patients with GERD. The functionality of esophageal mucosa exposed to bile salt deoxycholic acid (DCA) and trypsin has been studied in vitro. Material and methods. Endoscopic biopsies from healthy controls and patients with GERD-related symptom with endoscopic erosive signs, as well as esophageal mucosa taken from patients undergoing esophagectomy were evaluated in Ussing chambers and by western blot and immunohistochemistry. Results. The esophageal epithelium from GERD patients had lower electrical resistance and higher epithelial currents than controls. Claudin-1 and -4 were significantly decreased in GERD patients. The bile salt DCA in the low concentration of 1.5 mM and trypsin increased the resistance and claudin-1 expression, while the higher concentration of 2.5 mM DCA and trypsin decreased the resistance and the claudin-3, -4 and E-cadherin expressions. Conclusion. In addition to acidic reflux, duodenal reflux components, such as bile salts and trypsin, have the potential to disrupt the esophageal barrier function, partly by modulating the TJ proteins. However, the expression of TJ is dependent on both the refluxed material as well as the concentration of the bile salt. [ABSTRACT FROM AUTHOR]

Background: The present study examined whether patient characteristics, management, and outcome of kidney transplant recipients (KTx) with COVID-19 changed in the second versus the first pandemic wave. Methods: We reviewed all available data (demographics, medical history, comorbidities, therapeutic interventions, and outcome) on our KTx with COVID-19 during the first wave (March–September 2020, n = 33) and the second wave (October 2020–February 2021, n = 149) of the COVID-19 pandemic. Results: One hundred eighty-two out of our 1,503 KTx in active follow-up got COVID-19 during 12-month period, corresponding to a prevalence of 12.1%. No difference was found in age, gender distribution, comorbidities, body mass index, or baseline immunosuppression between the 2 COVID-19 waves. Bilateral COVID pneumonia was more frequent during the first wave. More KTx were managed as outpatients during the second wave (15 vs. 39%, p < 0.01). Calcineurin inhibitors were more sparingly reduced during the second wave, whereas antimetabolites were similarly reduced (91 vs. 86, p = ns). Admission to intensive care units was comparable between the first (27%) and second waves (23%). During the first wave, 8 out of 9 patients (89%) requiring intensive care died, whereas the mortality of the ICU patients in the second wave was 68% (23 deaths) (p = 0.2). The overall mortality was 24% during the first wave and 16% during the second wave (p = 0.21), while in-hospital mortality was identical between the CO-VID-19 waves (27%). Increasing age and poor allograft function were significant predictors of mortality. Conclusions: Most patient characteristics and outcome were comparable between the first 2 COVID-19 waves. More KTx were managed as outpatients without an overall negative impact on outcome. [ABSTRACT FROM AUTHOR]

Decellularized tissue is generally considered immune privileged after transplantation and is an attractive scaffold type for tissue regeneration, including applications for infertility treatment. However, the immune response following transplantation of decellularized tissue is insufficiently studied, in particular after they have been recellularized with mesenchymal stem cells (MSCs). Therefore, we replaced a large uterus segment with a bioengineered graft developed from decellularized uterus tissue and analyzed the immune response during the first 4 months in acellular or MSCs-recellularized scaffolds in the rat. Immunohistochemistry-stained infiltrating immune cells and plasma levels for 16 cytokines and chemokines were quantified. Results revealed that MSCs created an advantageous microenvironment by increasing anti-inflammatory interleukin 10 levels, and increasing the population of FOXP3+ TRegs and CD163+ M2 macrophages, and by reducing the CD8+ cytotoxic T cell population. Hence, MSCs should be considered an immunotherapeutic cell source with the ability to dictate regeneration success after decellularized tissue transplantation. [ABSTRACT FROM AUTHOR]

Summary: Although it is known that solid organ transplant recipients fare worse after COVID‐19 infection, data on the impact of COVID‐19 on clinical outcomes and allograft function in lung transplant (LTx) recipients are limited and based mainly on reports with short follow‐up. In this nationwide study, all LTx recipients with COVID‐19 diagnosed from 1 February 2020 to 30 April 2021 were included. The patients were followed until 1 August 2021 or death. We analysed demographics, clinical features, therapeutic management and outcomes, including lung function. Forty‐seven patients were identified: median age was 59 (10–78) years, 53.1% were male, and median follow‐up was 194 (23–509) days. COVID‐19 was asymptomatic or mild at presentation in 48.9%. Nine patients (19.1%) were vaccinated pre‐COVID infection. Two patients (4.3%) died within 28 days of testing positive, and the overall survival rate was 85.1%. The patients with asymptomatic or mild symptoms had a higher median % expected forced expiratory volume during the first second than the patients with worse symptoms (P = 0.004). LTx recipients develop the entire spectrum of COVID‐19, and in addition to previously acknowledged risk factors, lower pre‐COVID lung function was associated with more severe disease presentation. [ABSTRACT FROM AUTHOR]

Inflammation resulting from ischaemia/reperfusion injury can cause kidney graft dysfunction, increase the risk of delayed graft function and possibly reduce long‐term graft survival. Remote ischaemic conditioning may protect against ischaemia/reperfusion injury and mitigate the immunological response to the graft. We investigated the immunological effects of remote ischaemic conditioning on kidney transplantation from deceased donors in the randomized CONTEXT study. Three circulating dendritic cell (DC) subtypes identified in peripheral blood from kidney transplant recipients [myeloid DCs, plasmacytoid DCs and immunoglobulin‐like transcript (ILT)3+ DCs] were measured at baseline, days 1, 3 and 5 and 1 and 3 months after transplantation. We also quantified 21 cytokines at baseline, days 1 and 5 and 3 months after transplantation. Neither DC counts nor cytokine levels differed between patients receiving remote ischaemic conditioning and controls; however, several parameters exhibited dynamic and parallel alterations in the two groups over time, reflecting the immunological response to the kidney transplantation and immunosuppression. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the authors discuss various reports within the issue on topics including optical multiplexing techniques for photonic Clos networks in high performance computing architecture, optical spatial image processing and on how lossless logic systems could be built.

Background: Ischaemia-reperfusion injury in kidney transplantation leads to delayed graft function (DGF), which is associated with reduced long term graft function. Remote ischaemic conditioning (RIC) improved early kidney graft function in a porcine model of donation after brain death and was associated with improved long-term cardiac outcome after myocardial ischaemia. This randomised, double-blinded trial evaluated the effect of RIC on kidney graft outcome in the first year, and examined the predictive value of a new measure of initial kidney graft function, i.e. the estimated time to a 50% reduction in plasma creatinine post-transplantation (tCr50). Methods: A total of 225 patients undergoing deceased donor kidney transplantation were randomised to RIC or a sham procedure performed prior to kidney reperfusion. Up to four repetitive cycles of five minutes of leg ischaemia and five minutes of reperfusion were given. GFR, plasma creatinine, cystatin C and neutrophil gelatinase associated lipocalin (NGAL) were measured at three and twelve months and estimated GFR was calculated using four different equations. Other secondary outcomes were identified from patient files. Results: RIC did not affect GFR or other outcomes when compared to the sham procedure at three or twelve months. tCr50 correlated with one year graft function (p<0.0001 for both mGFR and eGFR estimates). In contrast, DGF i.e. "need of dialysis the first week" did not correlate significantly with one year GFR. Conclusion: RIC during deceased donor kidney transplantation did not improve one year outcome. However, tCr50 may be a relevant marker for studies aiming to improve graft onset. Trial registration: www.ClinicalTrials.gov Identifier: NCT01395719. [ABSTRACT FROM AUTHOR]

Introduction: Uterus transplantation has recently proved that infertility in women with uterine factor infertility can be cured. It is still an experimental procedure with numerous critical details remaining to be established, including tolerance to warm and cold ischemic insults. In preparation for human uterus transplantation trials, most teams use the sheep as a model system for research and team training, since the vasculature and the uterus is of similar size as in the human. We, therefore, aimed to develop an ex vivo sheep uterus reperfusion platform that mimics the reperfusion situation so that initial assessments and comparisons can be performed without the need for costly and labor‐intensive in vivo transplantation experiments. Material and methods: Isolated sheep uteri were perfused with the preservation solution IGL‐1 and were then exposed to cold ischemia for either 4 (n = 6) or 48 hours (n = 7). Uteri were then reperfused for 48 hours under normothermic conditions with an oxygenated recirculating perfusate containing growth factors and synthetic oxygen carriers. Histological and biochemical analysis of the perfusate was conducted to assess reperfusion injury. Results: Quantification of cell density indicated no significant edema in the myometrium or in the endometrium of uteri exposed to 4 hours cold ischemia and then a normothermic ex vivo reperfusion for 48 hours. Only the outer serosa layer and the inner columnar luminal epithelial cells were affected by the reperfusion. However, a much faster and severe reperfusion damage of all uterine layers were evident during the reperfusion experiment following 48 hours of cold ischemia. This was indicated by major accumulation of extracellular fluid, presence of apoptotic‐labeled glandular epithelial layer and vascular endothelium. A significant accumulation of lactate was measured in the perfusate with a subsequent decrease in pH. Conclusions: We developed a novel ex vivo sheep uterus model for prolonged perfusion. This model proved to be able to distinguish reperfusion injury‐related differences associated to organ preservation. The experimental setup is a platform that can be used to conduct further studies on uterine ischemia‐ and reperfusion injury that may lead to improved human uterus transplantation protocols. [ABSTRACT FROM AUTHOR]

Background: Early markers to predict delayed kidney graft function (DGF) may support clinical management. We studied the ability of four biomarkers (neutrophil gelatinase associated lipocalin (NGAL), liver-type fatty acid-binding protein (L-FABP), cystatin C, and YKL-40) to predict DGF after deceased donor transplantation, and their association with early graft function and GFR at three and twelve months. Methods: 225 deceased donor kidney transplant recipients were included. Biomarkers were measured using automated assays or ELISA. We calculated their ability to predict the need for dialysis post-transplant and correlated with the estimated time to a 50% reduction in plasma creatinine (tCr50), measured glomerular filtration rate (mGFR) and estimated GFR (eGFR). Results: All biomarkers measured at Day 1, except urinary L-FABP, significantly correlated with tCr50 and mGFR at Day 5. Plasma NGAL at Day 1 and a timed urine output predicted DGF (AUC = 0.91 and AUC 0.98). Nil or only weak correlations were identified between early biomarker levels and mGFR or eGFR at three or twelve months. Conclusion: High plasma NGAL at Day 1 predicts DGF and is associated with initial graft function, but may not prove better than P-creatinine or a timed urine output. Early biomarker levels do not correlate with one-year graft function. Trial registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

BACKGROUND: Remote ischemic preconditioning (RIPC) can be protective against the damage. However, there is no consensus on the optimal amount of tissue, the number and duration of the ischemic cycles, and the timing of the preconditioning. The hemorheological background of the process is also unknown. OBJECTIVE: To investigate the effects of remote organ ischemic preconditioning on micro-rheological parameters during liver ischemia-reperfusion in rats. METHODS: In anesthetized rats 60-minute partial liver ischemia was induced with 120-minute reperfusion (Control, n = 7). In the preconditioned groups a tourniquet was applied on the left thigh for 3×10 minutes 1 hour (RIPC-1, n = 7) or 24 hours (RIPC-24, n = 7) prior to the liver ischemia. Blood samples were taken before the operation and during the reperfusion. Acid-base, hematological parameters, erythrocyte aggregation and deformability were tested. RESULTS: Lactate concentration significantly increased by the end of the reperfusion. Erythrocyte deformability was improved in the RIPC-1 group, erythrocyte aggregation increased during the reperfusion, particularly in the RIPC-24 group. CONCLUSIONS: RIPC alleviated several hemorheological changes caused by the liver I/R. However, the optimal timing of the RIPC cannot be defined based on these results. [ABSTRACT FROM AUTHOR]