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Background: Ischemic-reperfusion injury resulting from kidney transplantation declines the post-transplant graft function. Remote ischemic conditioning (RIC) is known to be able to reduce the criticality of ischemic reperfusion injury. This study aimed to meta-analyze whether the application of remote ischemic conditioning to kidney transplantation patients improves clinical outcomes. Methods: Researchers included randomized controlled studies of the application of RIC to either kidney donors or recipients. Articles were retrieved from PubMed, Embase, Web of Science, and Cochrane Library. The risk of bias was evaluated using RoB 2.0. The primary outcome was mortality after transplantation. Secondary outcomes were the incidence of delayed graft function, graft rejection, and post-transplant laboratory results. All outcomes were integrated by RevMan 5.4.1. Results: Out of 90 papers, 10 articles (8 studies, 1977 patients) were suitable for inclusion criteria. Mortality collected at all time points did not show a significant difference between the groups. Three-month mortality (RR, 3.11; 95% CI, 0.13–75.51, P = 0.49) tended to increase in the RIC group, but 12-month (RR, 0.70; 95% CI, 0.14–3.45, P = 0.67) or final-reported mortality (RR, 0.49; 95% CI, 0.23–1.06, P = 0.07) was higher in the sham group than the RIC group. There was no significant difference between the RIC and sham group in delayed graft function (RR, 0.64; 95% CI, 0.30–1.35, P = 0.24), graft rejection (RR, 1.13; 95% CI, 0.73–1.73, P = 0.59), and the rate of time required for a 50% reduction in baseline serum creatinine concentration of less than 24 h (RR, 0.98; 95% CI, 0.61–1.56, P = 0.93). Conclusions: It could not be concluded that the application of RIC is beneficial to kidney transplantation patients. However, it is noteworthy that long-term mortality tended to decrease in the RIC group. Since there were many limitations due to the small number of included articles, researchers hope that large-scale randomized controlled trials will be included in the future. Systematic review registration: PROSPERO CRD42022336565. [ABSTRACT FROM AUTHOR]

Background: Large and complex defects requiring reconstruction are challenging for orthopaedic surgeons. The use of human acellular dermal (HAD) matrices to augment large soft tissue defects such as those seen in massive rotator cuff tears, knee extensor mechanism failures and neglected Tendo-Achilles tears has proven to be a valuable tool in surgeons reconstructive armamentarium. Different methods for allograft decellularization and preservation alter the native properties of the scaffold. Traditional processing and preservation methods have shown to have drawbacks that preclude its widespread use. Some of the common issues include inferior biomechanical properties, the risk of rejection, limited customization, difficulty in storing and transporting, the requirement of pre-operative preparation, and last but not the least increased cost. Methods: We describe a novel processing and preservation method utilizing a two-step non-denaturing decellularization method coupled with preservation using a water-sequestering agent (glycerol) to remove immunogenic components while retaining biomechanical properties. The efficiency of this novel process was compared with the traditional freeze-drying method and verified by histological evaluation and biomechanical strength analysis. Results: The absence of cellular components and matrix integrity in hematoxylin and eosin-stained glycerol-preserved HAD (gly-HAD) samples compared to freeze-dried HAD (FD-HAD) demonstrated effective yet gentle decellularization. Biomechanical strength analysis revealed that gly-HADs are stronger with an ultimate tensile load to the failure strength of 210 N compared to FD-HAD (124N). The gly-HADs were found to have an optimal suture–retention strength of 126 N. Finally, sterility testing of the resultant grafts was checked to ensure a sterility assurance level of 10−6 to establish implantability. Conclusion: The novel processing and preservation technique is described in this paper to create a Human Acellular Dermis with higher biomechanical strength and superior histological characteristics. The processing and preservation technique ensured high sterility assurance levels to establish implantability. [ABSTRACT FROM AUTHOR]

I read with interest the paper entitled I The impact of tacrolimus exposure on extra-renal adverse effects in adult renal transplant recipients i that was published in the I Journal i (2019, Vol 85, pp. 516-529). Patients receiving tacrolimus have their doses individualized (based upon tacrolimus trough concentration) and this (at least partially) I normalizes i exposure to account for differences in patient factors. [Extracted from the article]

As heart failure with preserved ejection fraction (HFpEF) rises to epidemic proportions, major steps in patient management and therapeutic development are badly needed. With the current position paper we seek to update our view on HFpEF as a highly complex systemic syndrome, from risk factors and mechanisms to long-term clinical manifestations. We will revise recent advances in animal model development, experimental set-ups and basic and translational science approaches to HFpEF research, highlighting their drawbacks and advantages. Directions are provided for proper model selection as well as for integrative functional evaluation from the in vivo setting to in vitro cell function testing. Additionally, we address new research challenges that require integration of higher-order inter-organ and inter-cell communication to achieve a full systems biology perspective of HFpEF. [ABSTRACT FROM AUTHOR]

Background White adipose tissue secretes a number of peptide hormones. The aim of this paper was to determine the role of leptin, adiponectin and interleukin-10 and interleukin-6 on the development of graft rejection in protocol biopsy after kidney transplantation. Methods In a prospective analysis (n = 104), we monitored the values of leptin, adiponectin, IL-6, and IL-10 prior to the transplantation and in the 3rd month after the transplantation. The protocol biopsy of the graft was performed in the 3rd month after the transplantation. The group was divided into the following according to the biopsy result: negative result, IFTA 1, borderline, and DSA positive. Results After adjusting for the differences in the baseline recipient and donor characteristics, we identified the hyperleptinaemia baseline (HR = 2.0444, P = 0.0341) and month 3 (HR = 49.8043, P < 0.0001) as independent risk factors for borderline changes in the protocol biopsy. The hyperleptinaemia baseline (HR = 7.4979, P = 0.0071) and month 3 (HR = 9.7432, P = 0.0057) are independent risk factors for de novo DSA positivity. A low value of IL-10 month 3 is a risk factor for de novo DSA positivity (HR = 3.0746, P = 0.0388). Conclusions Higher leptin levels and low values of IL-10 might play a role in rejection and de novo DSA production. [ABSTRACT FROM AUTHOR]

Lung transplantation. like other transplants, carries a risk of graft rejection due to genetic differences between the donor and the recipient. In this paper, we focus on antibody-mediated rejection, which can cause acute and more importantly chronic graft dysfunction and subsequently shortened allograft survival. We present the case of a 46-year-old patient who, two months after lung transplantation (LTx), developed AMR manifested by the deterioration of graft function and de novo production of donor-specific antibodies (DSA): DQ3 (DQ7, DQ8. DQ9). As the patient was after left single LTx and heavily oxygen dependent a transbronchial biopsy was deemed to be high risk and it was decided to determine the clinical significance of the detected antibodies by their ability to bind complement. The test confirmed that the detected DSAs have the ability cause cytotoxicity of the transplanted organ. After treatment with methotrexate, intravenous immunoglobulin G (IVIg) and alemtuzumab, the patient's condition improved and a complete decrease in DSA was obtained. However, after a year, the production of antibodies increased sharply. Treatment with IVIg, cyclophosphamide and plasmapheresis slightly improved the patient's condition, reducing the MFI DSA values by half, but leaving them at high levels. Based on this clinical case, we discuss problems with making a diagnosis, choosing the right AMR treatment and monitoring the patient's condition during treatment. We also indicate a poor prognosis in the case of the production of DSA antibodies at tlie DQ locus. [ABSTRACT FROM AUTHOR]

Introduction: Monitoring for graft rejection is a fundamental tenet of post‐transplant follow‐up. In heart transplantation (HT) in particular, rejection has been traditionally assessed with endomyocardial biopsy (EMB). EMB has potential complications and noted limitations, including interobserver variability in interpretation. Additional tests, such as basic cardiac biomarkers, cardiac imaging, gene expression profiling (GEP) scores, donor‐derived cell‐free DNA (dd‐cfDNA) and the novel molecular microscope diagnostic system (MMDx) have become critical tools in rejection surveillance beyond standard EMB. Methods: This paper describes an illustrative case followed by a review of MMDx within the context of other noninvasive screening modalities for rejection. Conclusions: We suggest MMDx be used to assist with early detection of rejection in cases of discordance between EMB and other noninvasive studies. [ABSTRACT FROM AUTHOR]

The widespread use of immunosuppressive drugs makes it possible to reduce inflammation in autoimmune diseases, as well as prevent transplant rejection in organ recipients. Despite their key action in blocking the body's immune response, these drugs have many side effects. These actions primarily affect the cardiovascular system, and the incidence of complications in patients using immunosuppressive drugs is significant, being associated with a higher incidence of cardiovascular incidents such as myocardial infarction and stroke. This paper analyzes the mechanisms of action of commonly used immunosuppressive drugs and their impact on the cardiovascular system. The adverse effect of immunosuppressive drugs is associated with toxicity within the cardiovascular system, which may be a problem in the clinical management of patients after transplantation. Immunosuppressants act on the cardiovascular system in a variety of ways, including fibrosis and myocardial remodeling, endothelium disfunction, hypertension, atherosclerosis, dyslipidemia or hyperglycaemia, metabolic syndrome, and hyperuricemia. The use of multidrug protocols makes it possible to develop regimens that can reduce the incidence of cardiovascular events. A better understanding of their mechanism of action and the range of complications could enable physicians to select the appropriate therapy for a given patient, as well as to reduce complications and prolong life. [ABSTRACT FROM AUTHOR]

• Ischemic conditioning, which can be simply performed during surgery, has been known to have the possibility to reduce mortality after liver transplantation. • Implementation of ischemic conditioning has no positive effect on short-term mortality in recipients after liver transplantation but may reduce graft loss within 1 year and long-term mortality after 1 year. • Subgroup analyses were performed according to the location of ischemic conditioning, but no significant results were obtained. Although liver transplantation (LT) is one of the definitive treatments for patients with end-stage liver failure, it inevitably results in ischemic reperfusion injury. It is known that prognosis is improved when temporary ischemic conditioning (IC) is applied to patients with ischemic reperfusion injury. The objective of this meta-analysis was to determine the short-term and long-term effects of IC on the clinical outcomes of LT recipients. Randomized controlled studies on IC in patients with LTs were included. Patients were compared between an IC group and a sham group. Studies were retrieved from PubMed, Embase, and Cochrane Library. The risk of bias was evaluated using RoB 2.0. Mortality, graft function, and major complications were synthesized using RevMan 5.4.1. Among 316 papers, 17 articles (1196 patients) were included. There was an insignificant increase in short-term mortality (risk ratio [RR]: 3.00, 95% CI: 0.32-28.14, P =.34). However, long-term mortality was lower in the IC group than in the sham group, but not significantly (RR: 0.75; 95% CI: 0.47-1.20, P =.23). Short-term graft function (acute graft rejection and primary graft non-function) was not improved by IC. One-year graft loss tended to show better results in the IC group (RR: 0.53, 95% CI: 0.26-1.07, P =.08). Ischemic conditioning did not have a beneficial effect on LT. Although long-term outcomes appear to be better in the IC group than in the sham group, further randomized controlled trials are needed. [Display omitted] [ABSTRACT FROM AUTHOR]

Renal transplantation (RT) is the preferred treatment for end-stage renal disease. However, clinical challenges persist, i.e., early detection of graft dysfunction, timely identification of rejection episodes, personalization of immunosuppressive therapy, and prediction of long-term graft survival. Biomarkers have emerged as valuable tools to address these challenges and revolutionize RT patient care. Our review synthesizes the existing scientific literature to highlight promising biomarkers, their biological characteristics, and their potential roles in enhancing clinical decision-making and patient outcomes. Emerging non-invasive biomarkers seemingly provide valuable insights into the immunopathology of nephron injury and allograft rejection. Moreover, we analyzed biomarkers with intra-nephron specificities, i.e., glomerular vs. tubular (proximal vs. distal), which can localize an injury in different nephron areas. Additionally, this paper provides a comprehensive analysis of the potential clinical applications of biomarkers in the prediction, detection, differential diagnosis and assessment of post-RT non-surgical allograft complications. Lastly, we focus on the pursuit of immune tolerance biomarkers, which aims to reclassify transplant recipients based on immune risk thresholds, guide personalized immunosuppression strategies, and ultimately identify patients for whom immunosuppression may safely be reduced. Further research, validation, standardization, and prospective studies are necessary to fully harness the clinical utility of RT biomarkers and guide the development of targeted therapies. [ABSTRACT FROM AUTHOR]

Background: The Portland intensive insulin therapy effectively controls acute hyperglycemic change after graft reperfusion during liver transplantation. However, the time-consuming sophistication acts as a barrier leading to misinterpretation and decreasing compliance to the protocol; thus, we newly introduced an application software “Insulin protocol calculator” which automatically calculates therapeutic bolus/continuous insulin doses based on the Portland protocol. Methods: Of 144 patients who underwent liver transplantation, 74 patients were treated before the introduction of “Insulin protocol calculator” by using a paper manual, and 70 patients were treated by using the application. Compliance was defined as the proportion of patients treated with exact bolus/continuous insulin dose according to the Portland protocol. Results: Compliance was significantly greater in app group than in paper group regarding bolus dose (94.5% and 86.9%, P < 0.001), continuous dose (88.9% and 77.3%, P = 0.001), and both doses (86.6% and 73.8%, P < 0.001). Blood glucose concentration was significantly lower in app group at 3 h (125 ± 17 mg/dl vs. 136 ± 19 mg/dl, P = 0.014) and 4 h (135 ± 22 mg/dl vs. 115 ± 15 mg/dl, P = 0.029) after graft reperfusion. Acute hyperglycemic change during 30 min was more prominent in app group while hyperglycemia incidence was 71.4% vs. 54.1% (P = 0.031). However, hyperglycemia risk was comparable at 2 h (31.4% vs. 31.1%, P = 0.964), and even insignificantly lower in app group at 3 h (7.1% vs. 19.5%, P = 0.184). Conclusions: Compliance to the Portland protocol was significantly improved after introducing the application software; post-reperfusion hyperglycemia was better controlled. “Insulin protocol calculator” is cost-effective and time-saving with potential clinical benefits. [ABSTRACT FROM AUTHOR]

Although the WHO has declared the end of the pandemic emergency, COVID-19 still poses a threat to immunocompromised patients. The COVID-19 pandemic has spread throughout the world over the last two years, causing a significant number of deaths. After three years, SARS-CoV-2 has lost its initial lethality but has shown a significantly worse prognosis for immunocompromised patients, especially those who have undergone lung transplantation, compared with the general population. This paper presents two compelling case studies that highlight the complex challenges of COVID-19 infection in lung transplant recipients. The first case involves a patient who received a bilateral lung transplant for pulmonary artery hypertension in 2009, followed by a kidney transplant in 2022. Surprisingly, despite an initially favorable clinical course after contracting COVID-19, the patient deteriorated rapidly and died within a few days due to extensive lung involvement. This case highlights the unpredictable nature of COVID-19 and its potentially devastating impact on lung transplant recipients. The second case involves a patient who underwent bilateral lung transplantation five years earlier for chronic obstructive pulmonary disease (COPD). This individual also contracted COVID-19 and had pre-existing complications, including chronic lung allograft rejection (CLAD) and diffuse bronchial stenosis. Following viral infection, the patient's clinical condition deteriorated rapidly, with worsening bronchial stenosis. This case highlights the ability of COVID-19 to exacerbate pre-existing pulmonary complications in transplant recipients. These cases highlight the urgent need for increased vigilance and tailored management strategies when dealing with COVID-19 in lung transplant recipients. The unpredictable and detrimental course of the disease observed in these patients highlights the importance of implementing stringent preventive measures, such as vaccination and strict adherence to infection control protocols, in this vulnerable population. Further research is essential to gain a full understanding of the unique dynamics of COVID-19 in lung transplant recipients and to develop targeted interventions to improve their outcomes. [ABSTRACT FROM AUTHOR]

• Preanalytical variables influence the quality and quantity of isolated cfDNA. • This paper compares preanalytical aspects published for cfDNA analysis. • Blood drawing, collection tube, centrifugation, storage and isolation are crucial. The analysis of circulating cell free DNA is an important tool for the analysis of tumor resistance, tumor heterogeneity, detection of minimal residual disease and detection of allograft rejection in kidney or heart transplant patients. The proper use of this technique is important, and starts with considering pre-analytic aspects. The current paper addresses some important technical considerations to ensure the proper and harmonized use of cfDNA techniques. [ABSTRACT FROM AUTHOR]

Ectopic lymphoid structures (ELS) or tertiary lymphoid organs are structures with the organization similar to the one of secondary lymphoid organs, formed in non-lymphoid tissues. They are considered to be an important site for the lymphocytic physiological and pathological role in conditions such are chronic infections, autoimmune diseases, cancer, and allograft rejection. Although similar to the secondary lymphoid tissues, the initiation of ELS formation is not preprogramed and requires chronic inflammation, expression of homeostatic chemokines, and lymphotoxin beta receptor activation. Importantly, while ELS formation may be considered beneficiary in antimicrobial and antitumor immunity, the persistence of these active lymphoid structures within the tissue increase the chance for development of autoimmunity and lymphoma. This paper is providing an overview of biological mechanisms involved in ELS formation, as well as the overview of the pathophysiological role of these structures. In addition, the paper discusses the possibility to therapeutically target ELS formation, bearing in mind their bivalent nature and role in different pathophysiological conditions. [ABSTRACT FROM AUTHOR]

Mycophenolic acid is commonly prescribed in adult kidney transplant recipients for preventing graft rejection. A therapeutic target for total mycophenolic acid area under the concentration-time curve (30-60 mg h/L) has been established in adult kidney transplant recipients and widely referenced today. However, this specific target range does not adequately characterize mycophenolic acid-associated adverse effects. The primary objective of this qualitative and critical review was to characterize the exposure-toxicity relationships of mycophenolic acid in an attempt to determine whether exposure thresholds can be identified. The secondary objective was to determine the associations of clinical variables with specific adverse effects. The inclusion criteria consisted of all peer-reviewed papers in adult kidney transplant subjects (average study age > 18 years) with both exposure (area under the concentration-time curve) and toxicity data. The exclusion criteria were papers involving the pediatric population, studies lacking either area under the concentration-time curve or toxicity data, or studies with no apparent reported variations in area under the concentration-time curves. Of the 28 papers identified, inconsistent findings have been reported for the most frequently characterized adverse events of mycophenolic acid (gastrointestinal, infectious, and hematological), while promising exposure thresholds (i.e., > 40-60 mg h/L for total mycophenolic acid) have been suggested by a few studies. The roles of free mycophenolic acid exposure, mycophenolic acid metabolites, or clinical factors influencing the manifestation of the toxicities also remain to be clarified. Although it is not yet possible to define toxicity threshold(s) for the purpose of mycophenolic acid therapeutic drug monitoring, the information obtained and the limitations identified in this comprehensive literature body have provided a good foundation for future investigations. [ABSTRACT FROM AUTHOR]

This paper describes two cases of allograft corneal transplant rejection after the application of two types of COVID-19 vaccines - Coronavac (Sinopharm/Butantan) and MRNA BNT162&2 (Pfizer-BioNTech) vaccines - with an interval of 1 to 10 days, respectively. The rejection manifested in the form of corneal edema, hyperemia and blurred vision, which responded rapidly to the use of topical and subconjunctival corticosteroid. As far as we know, this is the first published report of immunological rejection of penetrating corneal transplant after COVID-19 vaccination. As a preventative measure, we now recommend the use of 1% prednisolone eye drop 4 days before and during 2 weeks after having received any type of COVID-19 vaccine. [ABSTRACT FROM AUTHOR]

In modeling many longitudinal count clinical studies, the excess of zeros is a common problem. To take into account the extra zeros, the zero-inflated power series (ZIPS) models have been applied. These models assume a latent mixture model consisting of a count component and a degenerated zero component that has a unit point mass at zero. Usually, the current response measurement in a longitudinal sequence is a function of previous outcomes. For example, in a study about acute renal allograft rejection, the number of acute rejection episodes for a patient in current time is a function of this outcome at previous follow-up times. In this paper, we consider a transition model for accounting the dependence of current outcome on the previous outcomes in the presence of excess zeros. New variable selection methods for the ZIPS transition model using least absolute shrinkage and selection operator (LASSO), minimax concave penalty (MCP) and smoothly clipped absolute deviation (SCAD) penalties are proposed. An expectation-maximization (EM) algorithm using the penalized likelihood is applied for both parameters estimations and conducting variable selection. Some simulation studies are performed to investigate the performance of the proposed approach and the approach is applied to analyze a real dataset. [ABSTRACT FROM AUTHOR]

Intestinal transplantation has since its inception evolved as a lifesaving treatment option for patients with irreversible intestinal failure who can no longer be sustained on parenteral nutrition. Improvement in short-term survival after transplantation has also justified the expansion of treatment indications. Unfortunately, success is somewhat limited by a plateau observed in long-term survival. The reason for this sub-optimal long-term result experienced in this cohort may in part be attributed to the intestinal graft with the lymphoid content it carries inflicting the host with multiple complications where acute cellular rejection is one of the most common causes for graft loss. Graft monitoring is for this reason of paramount importance and detection of rejection at an early stage essential to enable early instigation of treatment and successful reversal of the pathology. Due to the challenges in diagnosing acute rejection with a noninvasive marker we are still limited to a surveillance protocol using endoscopy and biopsies for the diagnosis of rejection. The purpose of our paper is to review the adequacy of different methods in monitoring the graft for acute rejection using biomarkers, endoscopy and imaging. In conclusion, the evidence base continues to support the use of histology for the diagnosis of acute rejection. The role of biomarkers are still debatable, although markers such as calprotectin might be beneficial in excluding an ongoing process. [ABSTRACT FROM AUTHOR]

Angiostatins comprise a group of kringle-containing proteolytically-derived fragments of plasminogen/plasmin, which act as potent inhibitory mediators of endothelial cells proliferation and migration. Angiostatins are involved in modulation of vessel growth in healthy tissues and various pathological conditions associated with aberrant neovascularization. The aim of the present paper was to summarize available information, including our own experimental data, on prospects of angiostatin application for treatment of ocular neovascular diseases (OND), focusing on retinal pathologies and corneal injury. In particular, literature data on prospective and retrospective studies, clinical trials and animal models relating to the pathophysiology, investigation and management of OND are described. Special emphasis was made on the laboratory approaches of production of different angiostatin isoforms, as well as comparison of antiangiogenic capacities of native and recombinant angiostatin polypeptides. Several studies reported that angiostatins may completely abolish pathologic angiogenesis in diabetic proliferative retinopathy without affecting normal retinal vessel development and without exhibiting adverse side effects. Angiostatins have been tested as a tool for corneal antiangiogenesis target therapy in order to manage diverse ocular surface pathological conditions induced by traumas, chemical burns, previous surgery, chronic contact lens wear, autoimmune diseases, keratitis and viral infections (herpes, COVID-19), corneal graft rejection, etc. Among all known angiostatin species, isolated K5 plasminogen fragment was shown to display the most potent inhibitory activity against proliferation of endothelial cells via triggering multiple signaling pathways, which lead to cell death and resulting angiogenesis suppression. Application of adenoviral genetic construct encoding angiostatin K5 as a promising tool for OND treatment illustrates a vivid example of upcoming revolution in local gene therapy. Further comprehensive studies are necessary to elucidate the clinical potential and optimal regimes of angiostatinbased intervention modalities for treating ocular neovascularization. [ABSTRACT FROM AUTHOR]

Aims. We aimed to summarize available evidence about intraoperative and postoperative donors' and recipients' outcomes following stone surgery in renal grafts from living donors performed either before donation or as ex vivo bench surgery at the time of living-donor nephrectomy. Methods. A systematic review of PubMed, ISI Web of Knowledge, and Scopus databases was performed in September 2020. We included full papers that met the following criteria: original research, English language, human studies, and describing the results of stone surgery in renal grafts from living donors performed either before transplantation or as ex vivo bench surgery. Results. We identified 11 studies involving 106 patients aged between 22 and 72 years. Predonation and bench stone surgery was performed in 9 (8.5%) and 96 (90.6%) patients, respectively. Predonation stone surgery involved extracorporeal shock wave lithotripsy, retrograde intrarenal surgery, and percutaneous nephrolithotomy in 8, 1, and 1 patient, respectively. The overall success rate of predonation stone surgery was 78%, and the complication rate was 0%. Bench stone surgery involved ureteroscopy, pyelolithotomy, or a combination of both in 79 (82.3%), 10 (10.4%), and 7 (7.3%) cases, respectively, with an overall success rate of 95.8% and an overall complication rate of 9.37%. Conclusions. Predonation and bench stone surgery in grafts from living donors represents efficacious and safe procedures. Further studies on wider series with a longer follow-up are required. [ABSTRACT FROM AUTHOR]

Purpose: Urinary tract infection (UTI) is the most common bacterial infection among infectious complications in kidney transplant recipients (KTR). After transplantation, infections can result from surgical complications, donor-derived infections, pre-existing recipient infections, and nosocomial infections. Post-transplant infection is still a major cause of morbidity, mortality, graft dysfunction and rejection. In this paper, we aimed to review a few compelling questions in kidney transplantation (KTX). Methods: To identify relevant clinical questions regarding KTX and UTI a meeting was conducted among physicians involved in the KT program in our hospital. After discussion, several clinically relevant questions related to UTI after KTX. The 5 first rated in importance were judged generalizable to other clinical settings and selected for the purposes of this review. Results: Nearly half of the patients present in the first three months of transplant with UTI. The most common uropathogens in post-transplant UTIs are Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecalis. Risk factors for UTI include female sex, advanced age, recurrent UTI before transplant, prolonged urethral catheterization, delayed graft function, and cadaveric kidney transplant. Conclusion: The incidence of post-transplant UTI is similar in both developed and developing countries. E.coli is the most common pathogen in most of studies. Cadaveric donor and post-dialysis transplantation are defined as independent risk factors for post-transplant UTI. Further studies are still required to identify risk factors after kidney transplantation and UTI's importance for graft function and patient outcome. [ABSTRACT FROM AUTHOR]

Objective: It has been recommended that professionals who are planning to perform uterine transplantation should first carry out animal experiments. This paper describes the procedure for uterine transplant in sheep, as well as short and medium- term results. Materials and methods: Experimental surgery study in sheep subjected to uterine explantation and transplant. Four 40-50 kg sheep received uteri transplantation (orthotopic) from four live donors. End-to-side vascular anastomosis was used, the vagina was sutured on one plane and the uterus was fixed to the pelvic wall. Complications and 180-day evolution are described. Results: Transplant surgery was accomplished in the 4 sheep. Surgical time in the first procedure was 240 minutes, while the last procedure lasted 185 minutes. Warm ischemia time was reduced from 42 to 22 minutes. One sheep died on the seventh postoperative day due to an intraoperative complication unrelated to the vascular anastomosis. A second sheep developed local vaginal infection treated with metronidazole and evolved satisfactorily. No transplant rejection had occurred in the remaining 3 sheep after 6 months. Conclusions: The ovine model allowed surgical training in experimental uterine transplant surgery. For the authors, it offered an opportunity to gain knowledge and make progress towards future uterus transplantation in women with absolute uterine factor infertility in Colombia. [ABSTRACT FROM AUTHOR]

Monitoring of donor‐specific HLA antibodies (DSA) has become part of the clinical routine in kidney transplantation. This paper gives a brief overview on data from the Collaborative Transplant Study (CTS) and the Heidelberg Transplant Center on the clinical relevance of post‐transplant DSA monitoring in patients undergoing renal transplantation. The obtained findings underline the importance of DSA monitoring in the post‐operative course in immunologically high‐risk patients and patients with deterioration of graft function. Especially in patients with a pre‐activated immune system, a gap in the immunosuppressive therapy appear to lead to persistence, reappearance or de novo occurrence of strong, complement‐activating DSA, resulting in severe antibody‐mediated rejection (AMR) and, without timely intervention, in AMR‐related graft loss. [ABSTRACT FROM AUTHOR]

It has become anticipated that regenerative medicine will extend into the field of veterinary medicine as new treatments for various disorders. Although the use of allogeneic stem cells for tissue regeneration is more attractive than that of autologous cells in emergencies, the therapeutic potential of allogeneic transplantation is often limited by allo-immune responses inducing graft rejection. Therefore, a methodology for quantifying and monitoring alloreactive T cells is necessary for evaluating allo-immune responses. The mixed lymphocyte reaction (MLR) is widely used to evaluate T cell alloreactivity. In human, flow cytometric MLR with carboxyfluorescein diacetate succinimidyl ester has been established and used as a more useful assay than conventional MLR with radioisotope labeling. However, the available information about alloreactivity based on the differences of dog major histocompatibility complex (MHC) (dog leukocyte antigen, DLA) is quite limited in dog. In this paper, we describe our established flow cytometric MLR method that can quantify the T cell alloreactivity while distinguishing cell phenotypes in dog, and T cell alloreactivity among DLA-type matched pairs was significantly lower than DLA-mismatched pairs, suggesting that our developed flow cytometric MLR method is useful for quantifying T cell alloreactivity. In addition, we demonstrated the advantage of DLA homozygous cells as a donor (stimulator) for allogeneic transplantation. We also elucidated that the frequency of alloreactive T cell precursors was almost the same as that of mouse and human (1–10%). To our knowledge, this is the first report to focus on the degree of allo-immune responses in dog based on the differences of DLA polymorphisms. [ABSTRACT FROM AUTHOR]

Finding a non-invasive biomarker to monitor allograft status after transplantation could contribute to better control of the post-transplant status of transplant recipients and, if possible, could be used instead of invasive biopsy for proving rejection. On the other hand, reducing the dosage of immunosuppression or stopping lifelong use of them because of their severe side effects is an important goal in order to dispose of their severe side effects. The ability of exosomes as a biomarker of rejection and as a therapeutic strategy was investigated in the human kidney, heart, and lung transplantation or in transplantation models with interesting results. Moreover, the ability of exosome was assessed as antigen-presenting vesicles (APVs), in which exosomes can either participate in immune stimulation (semi-direct recognition) or immune suppression thereby, influence on the transplantation outcome. In this paper, authors try to provide comprehensive information about triple role of exosomes in the transplantation medicine. • Exosomal content are different between transplant recipients with rejection and those without rejection. • Exosomal content remarkably discriminate patients with rejection and those without rejection. • Exosomes could be novel biomarkers of rejection in transplantation. • Exosomes can both directly and indirectly activate T cells and therefore can participate in graft rejection/tolerance. • Exosomes as a therapeutic strategy promote the allograft survival time in the transplantation. [ABSTRACT FROM AUTHOR]

Objectives: Poor adherence to immunosuppressive treatment is common in patients with systemic lupus erythematosus and may identify those with lupus nephritis (LN) who have a poorer prognosis. Non-adherence has also been reported to be a potential adverse outcome predictor in renal transplantation (rTp). We investigated whether non-adherence is associated with increased rTp graft rejection and/or failure in patients with LN. Methods: Patients with LN undergoing rTp in two major London hospitals were retrospectively included. Medical and electronic records were reviewed for documented concerns of non-adherence as well as laboratory biochemical drug levels. The role of non-adherence and other potential predictors of graft rejection/failure including demographics, comorbidities, age at systemic lupus erythematosus and LN diagnosis, type of LN, time on dialysis prior to rTp and medication use were investigated using logistic regression. Results: Out of 361 patients with LN, 40 had rTp. During a median follow-up of 8.7 years, 17/40 (42.5%) of these patients had evidence of non-adherence. A total of 12 (30.0%) patients experienced graft rejection or failure or both. In the adherent group 2/23 (8.7%) had graft rejection, whilst in the non-adherent this rose to 5/17 (29.4%, p = 0.11). Graft failure was seen in 5/23 (21.7%) patients from the adherent group and 4/17 (23.5%) in the non-adherent group (p = 0.89). Non-adherent patients had a trend towards increased graft rejection, hazard ratio 4.38, 95% confidence interval = 0.73–26.12, p = 0.11. Patients who spent more time on dialysis prior to rTp were more likely to be adherent to medication, p = 0.01. Conclusion: Poor adherence to immunosuppressive therapy is common and has been shown to associate with a trend towards increased graft failure in patients with LN requiring rTp. This is the first paper to report that shorter periods on dialysis prior to transplantation might lead to increased non-adherence in lupus patients. [ABSTRACT FROM AUTHOR]

Objective: Early diagnosis of acute renal transplant rejection (ARTR) is critical for accurate treatment. Although the current gold standard, diagnostic technique is renal biopsy, it is not preferred due to its invasiveness, long recovery time (1–2 weeks), and potential for complications, e.g., bleeding and/or infection. Methods: This paper presents a computer-aided diagnostic (CAD) system for early ARTR detection using (3D + $b$ -value) diffusion-weighted (DW) magnetic resonance imaging (MRI) data. The CAD process starts from kidney tissue segmentation with an evolving geometric (level-set-based) deformable model. The evolution is guided by a voxel-wise stochastic speed function, which follows from a joint kidney-background Markov–Gibbs random field model accounting for an adaptive kidney shape prior and on-going kidney-background visual appearances. A B-spline-based three-dimensional data alignment is employed to handle local deviations due to breathing and heart beating. Then, empirical cumulative distribution functions of apparent diffusion coefficients of the segmented DW-MRI at different $b$ -values are collected as discriminatory transplant status features. Finally, a deep-learning-based classifier with stacked nonnegative constrained autoencoders is employed to distinguish between rejected and nonrejected renal transplants. Results: In our initial “leave-one-subject-out” experiment on 100 subjects, $\text{97.0}\%$ of the subjects were correctly classified. The subsequent four-fold and ten-fold cross-validations gave the average accuracy of $\text{96.0}\%$ and $\text{94.0}\%$ , respectively. Conclusion: These results demonstrate the promise of this new CAD system to reliably diagnose renal transplant rejection. Significance: The technology presented here can significantly impact the quality of care of renal transplant patients since it has the potential to replace the gold standard in kidney diagnosis, biopsy. [ABSTRACT FROM AUTHOR]

Decision process about the acceptance of the deceased donor kidney for transplantation might be challenging. Although histological evaluation of pretransplant donor kidney biopsy provides reliable information regarding cortical necrosis, vascular thrombosis, extensive global glomerulosclerosis, and interstitial fibrosis/tubular atrophy, only electron microscopy enables thorough and reliable insights into microvasculature changes of kidney graft. The aim of the present paper is to briefly present two cases of early kidney graft loss. In one case, the donor was exposed to long-term extracorporeal membrane oxygenation (ECMO); in the other case, the donor experienced Takotsubo cardiomyopathy. In both cases, light microscopy of pretransplant biopsy found no pathology or significant discrepancy in morphology of kidney graft, while electron microscopy revealed severe endothelial dysfunction of renal microvasculature. Our results suggest that severe injury of renal microvasculature with relatively preserved tubular epithelium may be associated with some conditions of deceased kidney donors leading to early kidney graft nonfunction and loss. Further studies are needed to determine prognostic significance of severe ultrastructural microvasculature lesions and to evaluate disease states and conditions that could be associated with severe endothelial dysfunction of kidney graft. [ABSTRACT FROM AUTHOR]

Abstract: The complement system is a cascade of multiple proteins that have been known to mediate inflammatory response. This tightly regulated system has been recognized to play a role in adaptive immunity via humoral and cell‐mediated processes. There is evidence from animal and human studies that the complement system is involved in various outcomes of solid organ transplantation. Most of the studies have been done in the field of kidney transplantation. In this paper, we review the studies looking at lung transplantation. The complement cascade appears to have a prominent role in mediating lung allograft damage in the setting of ischemia‐reperfusion injury, humoral rejection, as well as chronic allograft dysfunction. In this review, we look at the available data regarding the role of complement in these outcomes and propose some ideas about future direction of research in this field. [ABSTRACT FROM AUTHOR]

Coronary artery bypass grafting (CABG) remains a vital treatment for patients with multivessel coronary artery disease (CAD), especially diabetics. The long-term benefit of the internal thoracic artery graft is well established and remains the gold standard for revascularization of severe CAD. It is not always possible to achieve complete revascularization through arterial grafts, necessitating the use of saphenous vein grafts (SVG). Unfortunately, SVGs do not have the same longevity, and their failure is associated with significant adverse cardiac outcomes and mortality. This paper reviews the pathogenesis of SVG failure, highlighting the difference between early, intermediate, and late failure. It also addresses the different surgical techniques that affect the incidence of SVG failure, as well as the medical and percutaneous prevention and treatment options in contemporary practice. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been considered as a valuable approach in treatment of numerous malignant and none malignant hematologic disorders. However, relapse and poor graft function (PGF) after allo-SCT remain to be controversial issues which may affect the transplantation outcome. Relevant articles were searched in MEDLINE database (2000-2016) using keywords and phrases: donor lymphocyte infusions, allogeneic stem cells transplantation, relapsed hematologic malignancies, booster schedules, cell dose, laboratory monitoring protocols and technical aspects of apheresis. Relapse of disease and PGF could be reduced via noting some main points such as choosing the suitable time and patient for donor lymphocyte infusion (DLI) and also determination of patients who ought to candidate for second allogeneic HSCT or for the use of stem cell boost. DLI and stem cell booster are promising treatment strategies noted in this review. Finally, this paper discusses indications and technical aspects of DLI and stem cell booster in hematological malignancies and emphasizes their therapeutic or pre-emptive potentials. [ABSTRACT FROM AUTHOR]

Sensitization to human leukocyte antigens (HLA) in organ transplant patients causes graft rejection, according to the humoral theory of transplantation. Sensitization is almost ubiquitous as anti-HLA antibodies are found in almost all sera of transplant recipients. Advances in testing assays and amino acid sequencing of HLA along with computer software contributed further to the understanding of antibody-antigen reactivity. It is commonly understood that antibodies bind to HLA antigens. With current knowledge of epitopes, it is more accurate to describe that antibodies bind to their target epitopes on the surface of HLA molecular chains. Epitopes are present on a single HLA (private epitope) or shared by multiple antigens (public epitope). The phenomenon of cross-reactivity in HLA testing, often explained as cross-reactive groups (CREGs) of antigens with antibody, can be clearly explained now by public epitopes. Since 2006, we defined and reported 194 HLA class I unique epitopes, including 56 cryptic epitopes on dissociated HLA class I heavy chains, 83 HLA class II epitopes, 60 epitopes on HLA-DRB1, 15 epitopes on HLA-DQB1, 3 epitopes on HLA-DQA1, 5 epitopes on HLA-DPB1, and 7 MICA epitopes. In this paper, we provide a summary of our findings. [ABSTRACT FROM AUTHOR]

Understanding the role of toll-like receptors (TLRs) in the immunomodulation potential, differentiation, migration, and survival of mesenchymal stem cells (MSCs) is absolutely vital to fully exploiting their MSC-based therapeutic potential. Furthermore, through recognition of exogenous or endogenous ligands produced upon injury, TLRs have been linked to allograft rejection and maintenance of chronic inflammatory diseases, including Crohn’s disease, rheumatoid arthritis. Characterizing the effect of TLRs in biological control of MSCs fate and function could improve our knowledge about the MSC-based cell therapy and immunotherapy. In this paper, we outline the impacts of TLR activation and mechanisms on MSCs immunomodulatory functions, differentiation, migration, and survivability. Moreover, we indicate that the expression patterns of TLRs in MSCs from different sources. [ABSTRACT FROM AUTHOR]

Orthotopic heart transplantation (OHT) is a necessity for patients with end-stage heart disease. Despite advancements made in cardiac allograft preservation, there remains ambiguity as to which heart preservation solution provides improved outcomes - especially during a national healthcare flux. Many papers compare University of Wisconsin (UW) and Celsior (CS), the two most commonly used solutions in the USA, in abdominal organ transplants but few describe relative outcomes related to the adult heart. Here, we compare the two commonly used preservation solutions and hypothesize that UW shows superior postoperative patient outcomes. The United Network for Organ Sharing (UNOS) database was retrospectively reviewed from 5/31/2020 to 5/31/2021 for adult OHT recipients. Primary stratification was by solution type with evaluation of only UW and CS preservation solutions. Primary endpoints were survival and length of stay. Secondary endpoints were acute graft rejection, intubation status, and use of ECMO, IABP, and inotropes. After exclusion criteria, a total of 2,388 adult OHT recipients were identified. 1,941 (81.3%) transplants utilized UW. Analysis of Cox regression models for survival revealed no significant difference between both solutions. Fisher's exact test showed decreased rates of inotrope use (p = 0.008) and acute rejection episodes (p = 0.002) for UW solution (Fig. 1). There was no statistical significance between UW and CS with length of stay, intubation status, and use of ECMO, IABP at 72-hrs post-transplant (Fig. 1). Evaluation of the two most commonly used heart preservation solutions nationwide reveals that CS is non-inferior to UW with regards to patient survival, length of stay, and use of ECMO and IABP. However, UW shows significantly reduced acute graft rejection and use of inotropes. [ABSTRACT FROM AUTHOR]

Purpose: Long-term outcomes of anterior cruciate ligament (ACL) reconstruction are good or excellent; however, 0.7%-20% of patients suffer from recurrent instability due to graft failure. The purpose of this paper was to analyse failure aetiology and the possibilities of revision surgical strategies, with a description of our experience. We obtained optimal and good results in most of our patients. Materials and Methods: We retrospectively reviewed 42 patients who underwent revision surgery (43 revisions) due to relapsing instability after ACL reconstruction between 2006 and 2015. We used allografts in 39 cases and autografts in 4 cases. Results: The 85.7% of the patients obtained optimal results (normal knee; group A) and the 7.2% obtained good results (nearly normal knee; group B) according to the International Knee Documentation Committee score. The most frequent failure causes were traumatic events, non-anatomic tunnel placement, and lack of graft incorporation. Conclusions: A correct revision surgery requires accurate patient evaluation and knee imaging. Preoperative planning starts with the identification of the cause of failure of the primary reconstruction. Then, the most suitable procedure should be determined for each case. It is also important to accurately inform the patient of all the complexity of an ACL revision surgery even if it is a procedure with high rates of excellent and good outcomes. [ABSTRACT FROM AUTHOR]

Effect of serum parathyroid hormone on tacrolimus therapy in kidney transplant patients: a possible biomarker for a tacrolimus dosage schedule. In our paper, time points of measurements for tacrolimus (TAC) and intact parathyroid hormone (iPTH) were not standardized, and logistic regression analysis did not partition TAC concentration/dose (per body weight) ratio (C/D) into a binary dependent variable. [Extracted from the article]

• A three-phase RDA-based clustering undersampling method to handle class imbalance. • An RDA-based clustering feature extraction technique to reduce data dimensionality. • The proposed method could efficiently address the class imbalance problem. • The performance of SVM, ANN, KNN, DT, and an ensemble method is compared. • Decision tree outperformed other classifiers with the value of 0.95 for AUC. The prevalence of chronic kidney diseases has raised the demand for kidney replacement therapy over recent years. Although kidney transplantation provides better life quality than other alternatives, the replacement might face rejection and endanger individuals' lives. Therefore, predicting this rejection is of great importance, and due to the complexity of the human body's immune system, it is a complicated task. Machine learning has been widely used in disease diagnoses such as graft rejection. One of the common issues in disease diagnosis is the class imbalance problem. The predictive model is likely to misclassify all of the minority class samples in such cases. This paper proposes a method that can accurately predict kidney rejection in an imbalanced dataset. We have adopted kidney transplantation data from 378 patients collected from 1994 to 2011. Our main contribution is to develop a novel clustering method using Red Deer Algorithm (RDA), which is later utilized in proposing a three-stage clustering-based undersampling approach to handle the class imbalance problem so that the final predictive models can classify the given data more accurately. The undersampling method includes denoising, RDA clustering, and sample selection. Moreover, the proposed clustering method is also used to reduce the data dimensionality. Subsequently, five different classification algorithms such as Support Vector Machine (SVM), Artificial Neural Network (ANN), K-Nearest Neighbor (KNN), Decision Tree (DT), and an ensemble method are used to predict kidney graft rejection. Then, these classifiers are compared in terms of five performance evaluation metrics: accuracy, sensitivity, specificity, F1 score, and area under the Receiver Operating Characteristic (ROC) curve (AUC). The obtained results indicate that the decision tree model outperformed other algorithms and achieved 0.96, 0.94, 0.97, 0.95, and 0.95 for accuracy, sensitivity, specificity, F1 score, and AUC, respectively. Hence, it is highly recommended to use the proposed method as a decision support system for clinical experts to predict kidney transplantation failure. [ABSTRACT FROM AUTHOR]

Aim To describe the design, development and evaluation of a consumer-centred video, which was underpinned by the Theory of Planned Behaviour and it was created to educate newly transplanted kidney recipients about the importance of medication adherence. Background Kidney transplantation is a treatment whereby medication adherence is critical to ensure long-term kidney graft success. To date, many interventions aimed to improve medication adherence in kidney transplantation have been conducted but consumers remain largely uninvolved in the interventional design. Design Qualitative sequential design. Methods Twenty-two participants who had maintained their kidney transplant for at least 8 months and three participants who had experienced a kidney graft loss due to non-adherence were interviewed from March-May 2014 in Victoria, Australia. These interviews were independently reviewed by two researchers and were used to guide the design of the story plot and to identify storytellers for the video. The first draft of the video was evaluated by a panel of seven experts in the field, one independent educational expert and two consumers using Lynn's content validity questionnaire. The content of the video was regarded as highly relevant and comprehensive, which achieved a score of >3·7 out of a possible 4. Results/findings The final 18-minute video comprised 15 sections. Topics included medication management, the factors affecting medication adherence and the absolute necessity of adherence to immunosuppressive medications for graft survival. Conclusion This paper has demonstrated the feasibility of creating a consumer-driven video that supports medication adherence in an engaging way. [ABSTRACT FROM AUTHOR]

Despite recent progress in vascularized composite allotransplantation (VCA), limitations including complex, high dose immunosuppression regimens, lifelong risk of toxicity from immunosuppressants, acute and most critically chronic graft rejection, and suboptimal nerve regeneration remain particularly challenging obstacles restricting clinical progress. When properly configured, customized, and implemented, biomaterials derived from the extracellular matrix (ECM) retain bioactive molecules and immunomodulatory properties that can promote stem cell migration, proliferation and differentiation, and constructive functional tissue remodeling. The present paper reviews the emerging implications of ECM-based technologies in VCA, including local immunomodulation, tissue repair, nerve regeneration, minimally invasive graft targeted drug delivery, stem cell transplantation, and other donor graft manipulation. [ABSTRACT FROM AUTHOR]

The presence of preformed donor-specific HLA antibodies leads to early antibody mediated kidney allograft rejection. Therefore, detection and avoidance of donor reactive HLA antibodies prior to transplantation is of outmost importance in order to minimize the risk of rejection. Detection of pre-formed HLA antibodies is currently performed using complement-dependent cytotoxicity (CDC) assay alone or together with a flow cytometry based crossmatch (FCXM). This study was initiated to further evaluate our recently developed flow cytometry based procedure for determination of both cytotoxicity of and IgG binding to donor-derived lymphocytes by HLA antibodies. Highly enriched immuno-magnetic bead purified T and B lymphocytes were used as target cells for patient sera using 96-well plates. Importantly, the assay shows high sensitivity and specificity as determined by HLA typed donor cells and serum with defined HLA antibody IgG and C1q. Based on this and additional data generated in this paper, such as evaluation of appropriate serum and complements incubation times and assay reproducibility and stability, will enable us to more rapidly implement this assay in our clinical laboratory routines. In addition, we demonstrate that FCtox crossmatching of deceased donor cells has superior specificity compared to conventional CDC assay especially regarding high frequencies of false-positive reactions. [ABSTRACT FROM AUTHOR]

Patients returning to dialysis after kidney transplant failure represent approximately 5%–15% of the population starting hemodialysis. These patients exhibit a high risk of morbidity and mortality attributed mainly to the exposure to immunosuppressive medications and to a uremic environment. The purpose of this paper was to review data regarding survival after renal allograft failure and the optimal management of patients before returning to dialysis. Moreover, issues surrounding nephrectomy after renal allograft failure, the tapering of immunosuppression and the possibility of retransplantation are examined, because they seem to be crucial for patient survival and the quality of life. [ABSTRACT FROM AUTHOR]

Our previous studies in rats showed that incubation of monocytic dendritic cells (DCs) with the chemotherapeutic drug mitomycin C (MMC) renders the cells immunosuppressive. Donor-derived MMC-DCs injected into the recipient prior to transplantation prolonged heart allograft survival. Although the generation of DCs is labour-intensive and time-consuming, peripheral blood mononuclear cells (PBMCs) can be easily harvested. In the present study, we analyse under which conditions DCs can be replaced by PBMCs and examine their mode of action. When injected into rats, MMC-incubated donor PBMCs (MICs) strongly prolonged heart allograft survival. Removal of monocytes from PBMCs completely abrogated their suppressive effect, indicating that monocytes are the active cell population. Suppression of rejection was donor-specific. The injected MICs migrated into peripheral lymphoid organs and led to an increased number of regulatory T-cells (Tregs) expressing cluster of differentiation (CD) markers CD4 and CD25 and forkhead box protein 3 (FoxP3). Tolerance could be transferred to syngeneic recipients with blood or spleen cells. Depletion of Tregs from tolerogenic cells abrogated their suppressive effect, arguing for mediation of immunosuppression by CD4+CD25+FoxP3+ Tregs. Donor-derived MICs also prolonged kidney allograft survival in pigs. MICs generated from donor monocytes were applied for the first time in humans in a patient suffering from therapy-resistant rejection of a haploidentical stem cell transplant. We describe, in the present paper, a simple method for in vitro generation of suppressor blood cells for potential use in clinical organ transplantation. Although the case report does not allow us to draw any conclusion about their therapeutic effectiveness, it shows that MICs can be easily generated and applied in humans. [ABSTRACT FROM AUTHOR]

The number of patients requiring lung transplantation is increasing, with a significant unmet demand for grafts. Ex vivo lung perfusion has been developed to increase graft recruitment. The major complications of lung transplantation include chronic allograft dysfunction (CLAD) whose cumulative incidence ranges from 43–80% within the first 5 years of transplantation. Many risk factors are listed for development of CLAD and almost all of those risk factors would involve activation of Toll-like receptors. This paper represents the author's overview regarding the development of CLAD as a complication of lung transplantation and the possible protective potential of ex vivo lung perfusion in this regard. [ABSTRACT FROM AUTHOR]

Cardiac allograft rejection following heart transplantation is challenging to diagnose. Tissue biopsies are the gold standard in monitoring the different types of rejection. The last decade has seen an increased emphasis on identifying non-invasive methods to improve rejection diagnosis and overcome tissue biopsy invasiveness. Liquid biopsy, as an efficient non-invasive diagnostic and prognostic oncological monitoring tool, seems to be applicable in heart transplant follow-ups. Moreover, molecular techniques applied on blood can be translated to tissue samples to provide novel perspectives on tissue and reveal new diagnostic and prognostic biomarkers. This review aims to provide a comprehensive overview of the state-of-the-art of the new methodologies in cardiac allograft rejection monitoring and investigate the future perspectives on invasive and non-invasive rejection biomarkers identification. We reviewed literature from the most used scientific databases, such as PubMed, Google Scholar, and Scopus. We extracted 192 papers and, after a selection and exclusion process, we included in the review 81 papers. The described limitations notwithstanding, this review show how molecular biology techniques and omics science could be deployed complementarily to the histopathological rejection diagnosis on tissue biopsies, thus representing an integrated approach for heart transplant patients monitoring. [ABSTRACT FROM AUTHOR]

Knowledge of renal blood circulation is considered as an important physiological value, particularly for fast detection of acute allograft rejection as well as the management of critically ill patients with acute renal failure. The electrical impedance signal obtained from kidney with an appropriate electrode system and optimal electrode system position regarding to the kidney projection on skin surface reflects the nature of renal blood circulation and tone of renal blood vessels. This paper proposes a specific numerical modelling based on prior information from MRI-data. The numerical modelling was conducted for electrical impedance change estimation due to renal blood distribution. The proposed model takes into the account the geometrical and electrophysiological parameters of tissues around the kidney as well as the actual blood distribution within the kidney. The numerical modelling had shown that it is possible to register the electrical impedance signal caused by renal blood circulation with an electrode system commensurate with the size of kidney, which makes it possible to reduce the influence of surrounding tissues and organs. Experimental studies were obtained to prove the numerical modelling and the effectiveness of developed electrode systems based on the obtained simulation results. The obtained electrical impedance signal with the appropriate electrode system shows very good agreement with the renal blood change estimated using Doppler ultrasound. For the measured electrical impedance signal, it is possible to obtain the amplitude-time parameters, which reflect the hemodynamic characteristics of the kidneys and used in diagnostics, which is the subject of further research. [ABSTRACT FROM AUTHOR]

[Display omitted] • The difference in adsorption amounts of SWNTs using APTES. • Surface deposition amounts of en-APTAS as a function of dipping time. • The resistance curve for 100 ppb NO gas after 10-times rinsing at room temperature. • The highly sensitive and selective NO gas sensors using defect-functionalized SWNTs. One of the most important trends in modern medicine is the development of non-invasive methods that diagnose diseases by analyzing specific gases from human exhalation. Examination of such gases helps monitor various diseases. The ability of nanosensors to potentially detect conditions such as Rhinitis digestive diseases, liver transplant rejection, inflammation in the stomach, cystic fibrosis, encephalopathy, helicobacter pylon digestive cancer, respiratory diseases, and COVID-19, by examining nitric oxide (NO), has been discussed as well as studied increasingly in recent years. In this paper, we have proposed a low-cost detector that can measure NO gas from the exhaled air, which is applied to the ppb level at room temperature. A sensor that detects NO gas with high sensitivity by using single-walled carbon nanotubes (SWNTs) as nanomaterials, has been fabricated. The semiconductor-type gas sensors using SWNTs showed characteristics such as rapid detection, long-term reliability, reproducibility, and miniaturization at room temperature. To improve the selectivity for NO gas, SWNT network channels were formed between the Au electrodes, and SWNTs were functionalized with en-APTAS. A new rinse process was introduced to solve the problem of low sensitivity in SWNT-based NO sensors. With the introduction of the improved rinsing process, the recovery of the fabricated sensor increased from less than 20% to 90.34% when the device was rinsed ten times under optimized conditions. The improved rinsing process effectively straightened the rearrangement of the large amount of amine-functionalized SWNTs attached during the electrostatic self-assembled deposition. In addition, a 28.64% response for a 100 ppb concentration of NO gas was measured at room temperature. We also confirmed that the fabricated sensor does not react with carbon monoxide (CO) and volatile organic compounds (VOCs) gases owing to its high selectivity to NO gas. [ABSTRACT FROM AUTHOR]

Aim The first heart transplant in Panama, made in March 2016, involved two hospitals, the Metropolitan Panama Complex and Punta Pacifica Hospital. The National Transplant Laboratory algorithm included all aspects of immunological compatibility in order to minimize one of the most common complications of transplantation: rejection such as acute heart donor. This paper presents the algorithm developed in the Laboratory in this first heart transplant. Methods The patient is female, 52 years old, blood type “A”. Molecular HLA typing use amplified DNA with specific HLA primer and hybridized with a panel of sequence specific oligonucleotide probes (SSOP) (LIFECODES HLA-SSO-Typing kits) The results of HLA recipient are: A ∗ 02, A ∗ 24, B ∗ 51, B ∗ 58, DRB1 ∗ 04, DRB1 ∗ 13, C ∗ 05, Cw ∗ 15, DQB1 ∗ 03(08), DQB1 ∗ 03(07), DPB1 ∗ 04, DPB1 ∗ 05. The studies to establish the presence of anti-HLA preformed antibodies included LIFECODES Antibody Screen, identification of anti-HLA Class I, II using LIFECODES Class I, II ID, and LIFECODES LSA Class I, II. The patient has in his serum anti-A ∗ 36,anti-B ∗ 14(B64) and anti DQB1 ∗ 02 with PRA Class I and Class II, 4%, 30%. The deceased donor was male, 24 years old, blood “A”, and HLA: A ∗ 02, A ∗ 24, B ∗ 58, B ∗ 63, DRB1 ∗ 13, DRB1 ∗ 13, Cw ∗ 07, C w ∗ 07, DQB1 ∗ 06, DQB ∗ 01. DPB1 01, DPB1 ∗ 02. The virtual Crossmatch was negative and actual crossmatching Test (DSA) was negative (LIFE CODES Donor Specific antibodies). In the Bank Laboratory we keep historical sera of the recipient and the pre-transplant serum and preserve HLA glycoproteins of the deceased donor for future humoral antibody-mediated rejection. Conclusion The time used by the laboratory to complete the algorithm was 4 h and the patient was successfully transplanted. Subsequent studies at 15, 30, 45 days have shown the absence of donor specific antibodies. The Laboratory has developed an algorithm that includes all high-tech procedures that avoid the risk of acute antibody-mediated rejection and guarantee further studies to monitor AMR presence. Final del formulario. [ABSTRACT FROM AUTHOR]