Critical considerations for the management of acute abdomen in transplant patients.

The number of solid organ transplantations performed annually is increasing and are increasing in the following order: Kidney, liver, heart, lung, pancreas, small bowel, and uterine transplants. However, the outcomes of transplants are improving (organ survival > 90% after the 1st year). Therefore, there is a high probability that a general surgeon will be faced with the management of a transplant patient with acute abdomen. Surgical problems in immunocompromised patients may not only include graft-related problems but also nongraft-related problems. The perioperative regulation of immunosuppression, the treatment of accompanying problems of immunosuppression, the administration of cortisol and, above all, the realization of a rapidly deteriorating situation and the accurate evaluation and interpretation of clinical manifestations are particularly important in these patients. The perioperative assessment and preparation includes evaluation of the patient's cardiovascular system and determining if the patient has hypertension or suppression of the hypothalamic-pituitary-adrenal axis, or if the patient has had any coagulation mechanism abnormalities or thromboembolic episodes. Immunosuppression in transplant patients is associated with the use of calcineurin inhibitors, corticosteroids, and antiproliferation agents. Many times, the clinical picture is atypical, resulting in delays in diagnosis and treatment and leading to increased morbidity and mortality. Multidetector computed tomography is of utmost importance for early diagnosis and management. Transplant recipients are prone to infections, especially specific infections caused by cytomegalovirus and Clostridium difficile, and they are predisposed to intraoperative or postoperative complications that require great care and vigilance. It is necessary to follow evidence-based therapeutic protocols. Thus, it is required that the clinician choose the correct therapeutic plan for the patient (conservative, emergency open surgery or minimally invasive surgery, including laparoscopic or even robotic surgery).

Evaluation of Regulatory B Cell Subpopulations CD24++CD38++, CD24++CD27+, Plasmablasts and Their Correlation with T Regs CD3+CD4+CD25+FOXP3+ in Dialysis Patients and Early Post-Transplant Rejection-Free Kidney Recipients.

Background: B and T regulatory cells, also known as Bregs and Tregs, are involved in kidney transplantation. The purpose of this study is to monitor changes in the frequency and absolute numbers of Tregs (CD3+CD4+CD25+FoxP3+), transitional Bregs (tBregs) (CD24++CD38++), memory Bregs (mBregs) (CD24++CD27+), and plasmablasts before (T0) and six months (T6) after transplantation. Additionally, we aim to investigate any correlation between Tregs and tBregs, mBregs, or plasmablasts and their relationship with graft function. Methods: Flow cytometry was used to immunophenotype cells from 50 kidney recipients who did not experience rejection. Renal function was assessed using the estimated glomerular filtration rate (eGFR). Results: At T6, there was a significant decrease in the frequency of Tregs, plasmablasts, and tBregs, as well as in the absolute number of tBregs. The frequency of mBregs, however, remained unchanged. Graft function was found to have a positive correlation with the frequency of tBregs and plasmablasts. A significant correlation was observed between the frequency and absolute number of tBregs only when the eGFR was greater than 60 but not at lower values. At an eGFR greater than 60, there was a positive correlation between the absolute numbers of Tregs and mBregs but not between Tregs and tBregs. No correlation was observed for any cell population in dialysis patients. Conclusions: The data show a correlation between the frequency and absolute number of tBregs and the absolute number of Tregs and mBregs with good renal function in the early post-transplant period.

Clinical Prediction Models for Prognosis of Colorectal Liver Metastases: A Comprehensive Review of Regression-Based and Machine Learning Models.

Colorectal liver metastasis (CRLM) is a disease entity that warrants special attention due to its high frequency and potential curability. Identification of "high-risk" patients is increasingly popular for risk stratification and personalization of the management pathway. Traditional regression-based methods have been used to derive prediction models for these patients, and lately, focus has shifted to artificial intelligence-based models, with employment of variable supervised and unsupervised techniques. Multiple endpoints, like overall survival (OS), disease-free survival (DFS) and development or recurrence of postoperative complications have all been used as outcomes in these studies. This review provides an extensive overview of available clinical prediction models focusing on the prognosis of CRLM and highlights the different predictor types incorporated in each model. An overview of the modelling strategies and the outcomes chosen is provided. Specific patient and treatment characteristics included in the models are discussed in detail. Model development and validation methods are presented and critically appraised, and model performance is assessed within a proposed framework.

Artificial kidney: Challenges and opportunities.

This review aims to present the developments occurring in the field of artificial organs and particularly focuses on the presentation of developments in artificial kidneys. The challenges for biomedical engineering involved in overcoming the potential difficulties are showcased, as well as the importance of interdisciplinary collaboration in this marriage of medicine and technology. In this review, modern artificial kidneys and the research efforts trying to provide and promise artificial kidneys are presented. But what are the problems faced by each technology and to what extent is the effort enough to date?

Humoral and Cellular Immunity Are Significantly Affected in Renal Transplant Recipients, following Vaccination with BNT162b2.

BACKGROUND: Renal transplant recipients (RTRs) tend to mount weaker immune responses to vaccinations, including vaccines against the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: Humoral immunity was assessed using anti-receptor binding domain (RBD) and neutralizing antibodies (NAb) serum levels measured by ELISA, and cellular immunity was assessed using T-, B-, NK, natural killer-like T (NKT)-cell subpopulations, and monocytes measured by flow cytometry, and also specific T-cell immunity, at predefined time points after BNT162b2 vaccination, in 57 adult RTRs. RESULTS: Administration of three booster doses was necessary to achieve anti-RBD and NAb protective levels in almost all patients (92.98%). Ab production, at several time points, was positively correlated with the corresponding renal function and inversely correlated with hemodialysis vintage (HDV) and treatment with mycophenolic acid (MPA). A gradual rise in several cell subpopulations, including total lymphocytes (p = 0.026), memory B cells (p = 0.028), activated CD4 (p = 0.005), and CD8 cells (p = 0.001), was observed even after the third vaccination dose, while a significant reduction in CD3+PD1+ (p = 0.002), NKT (p = 0.011), and activated NKT cells (p = 0.034) was noted during the same time interval. Moreover, SARS-CoV-2-specific T-cells were present in 41% of the patients who were unable to develop Nabs, and their positivity rates four months after the second dose were in inverse correlation with monocytes (p = 0.045) and NKT cells (p = 0.01). CONCLUSIONS: SARS-CoV-2-specific T-cell responses preceded the humoral ones, while two booster doses were needed for this group of immunocompromised patients to mount a protective immune response.

Immune Profile Determines Response to Vaccination against COVID-19 in Kidney Transplant Recipients.

BACKGROUND AND AIM: Immune status profile can predict response to vaccination, while lymphocyte phenotypic alterations represent its effectiveness. We prospectively evaluated these parameters in kidney transplant recipients (KTRs) regarding Tozinameran (BNT162b2) vaccination. METHOD: In this prospective monocenter observational study, 39 adult KTRs, on stable immunosuppression, naïve to COVID-19, with no protective humoral response after two Tozinameran doses, received the third vaccination dose, and, based on their immunity activation, they were classified as responders or non-responders. Humoral and cellular immunities were assessed at predefined time points (T0: 48 h before the first, T1: 48 h prior to the third and T2: three weeks after the third dose). RESULTS: Responders, compared to non-responders, had a higher total and transitional B-lymphocyte count at baseline (96.5 (93) vs. 51 (52)cells/µL, p: 0.045 and 9 (17) vs. 1 (2)cells/µL, p: 0.031, respectively). In the responder group, there was a significant increase, from T0 to T1, in the concentrations of activated CD4+ (from 6.5 (4) to 10.08 (11)cells/µL, p: 0.001) and CD8+ (from 8 (19) to 14.76 (16)cells/µL, p: 0.004) and a drop in CD3+PD1+ T-cells (from 130 (121) to 30.44 (25)cells/µL, p: 0.001), while naïve and transitional B-cells increased from T1 to T2 (from 57.55 (66) to 1149.3 (680)cells/µL, p < 0.001 and from 1.4 (3) to 17.5 (21)cells/µL, p: 0.003). The percentages of memory and marginal zone B-lymphocytes, and activated CD4+, CD8+ and natural killer (NK) T-cells significantly increased, while those of naïve B-cells and CD3+PD1+ T-cells reduced from T0 to T1. CONCLUSIONS: Responders and non-responders to the third BNT162b2 dose demonstrated distinct initial immune cell profiles and changes in cellular subpopulation composition following vaccination.

Hepatic ischemia-reperfusion syndrome and its effect on the cardiovascular system: The role of treprostinil, a synthetic prostacyclin analog.

Hepatic ischemia-reperfusion syndrome has been the subject of intensive study and experimentation in recent decades since it is responsible for the outcome of several clinical entities, such as major hepatic resections and liver transplantation. In addition to the organ's post reperfusion injury, this syndrome appears to play a central role in the dysfunction of distant tissues and systems. Thus, continuous research should be directed toward finding effective therapeutic options to improve the outcome and reduce the postoperative morbidity and mortality rates. Treprostinil is a synthetic analog of prostaglandin I2, and its experimental administration has shown encouraging results. It has already been approved by the Food and Drug Administration in the United States for pulmonary arterial hypertension and has been used in liver transplantation, where preliminary encouraging results showed its safety and feasibility by using continuous intravenous administration at a dose of 5 ng/kg/min. Treprostinil improves renal and hepatic function, diminishes hepatic oxidative stress and lipid peroxidation, reduces hepatictoll-like receptor 9 and inflammation, inhibits hepatic apoptosis and restores hepatic adenosine triphosphate (ATP) levels and ATP synthases, which is necessary for functional maintenance of mitochondria. Treprostinil exhibits vasodilatory properties and antiplatelet activity and regulates proinflammatory cytokines; therefore, it can potentially minimize ischemia-reperfusion injury. Additionally, it may have beneficial effects on cardiovascular parameters, and much current research interest is concentrated on this compound.

DermAI 1.0: A Robust, Generalized, and Novel Attention-Enabled Ensemble-Based Transfer Learning Paradigm for Multiclass Classification of Skin Lesion Images.

Skin lesion classification plays a crucial role in dermatology, aiding in the early detection, diagnosis, and management of life-threatening malignant lesions. However, standalone transfer learning (TL) models failed to deliver optimal performance. In this study, we present an attention-enabled ensemble-based deep learning technique, a powerful, novel, and generalized method for extracting features for the classification of skin lesions. This technique holds significant promise in enhancing diagnostic accuracy by using seven pre-trained TL models for classification. Six ensemble-based DL (EBDL) models were created using stacking, softmax voting, and weighted average techniques. Furthermore, we investigated the attention mechanism as an effective paradigm and created seven attention-enabled transfer learning (aeTL) models before branching out to construct three attention-enabled ensemble-based DL (aeEBDL) models to create a reliable, adaptive, and generalized paradigm. The mean accuracy of the TL models is 95.30%, and the use of an ensemble-based paradigm increased it by 4.22%, to 99.52%. The aeTL models' performance was superior to the TL models in accuracy by 3.01%, and aeEBDL models outperformed aeTL models by 1.29%. Statistical tests show significant p-value and Kappa coefficient along with a 99.6% reliability index for the aeEBDL models. The approach is highly effective and generalized for the classification of skin lesions.

Exploring Perturbations in Peripheral B Cell Memory Subpopulations Early after Kidney Transplantation Using Unsupervised Machine Learning.

BACKGROUND: B cells have a significant role in transplantation. We examined the distribution of memory subpopulations (MBCs) and naïve B cell (NBCs) phenotypes in patients soon after kidney transplantation. Unsupervised machine learning cluster analysis is used to determine the association between the cellular phenotypes and renal function. METHODS: MBC subpopulations and NBCs from 47 stable renal transplant recipients were characterized by flow cytometry just before (T0) and 6 months after (T6) transplantation. T0 and T6 measurements were compared, and clusters of patients with similar cellular phenotypic profiles at T6 were identified. Two clusters, clusters 1 and 2, were formed, and the glomerular filtration rate was estimated (eGFR) for these clusters. RESULTS: A significant increase in NBC frequency was observed between T0 and T6, with no statistically significant differences in the MBC subpopulations. Cluster 1 was characterized by a predominance of the NBC phenotype with a lower frequency of MBCs, whereas cluster 2 was characterized by a high frequency of MBCs and a lower frequency of NBCs. With regard to eGFR, cluster 1 showed a higher value compared to cluster 2. CONCLUSIONS: Transplanted kidney patients can be stratified into clusters based on the combination of heterogeneity of MBC phenotype, NBCs and eGFR using unsupervised machine learning.

Three-Dimensional Printing and Bioprinting in Renal Transplantation and Regenerative Medicine: Current Perspectives.

For patients with end-stage kidney disease (ESKD), renal transplantation is the treatment of choice, constituting the most common solid organ transplantation. This study aims to provide a comprehensive review regarding the application of three-dimensional (3D) printing and bioprinting in renal transplantation and regenerative medicine. Specifically, we present studies where 3D-printed models were used in the training of surgeons through renal transplantation simulations, in patient education where patients acquire a higher understanding of their disease and the proposed operation, in the preoperative planning to facilitate decision-making, and in fabricating customized, tools and devices. Three-dimensional-printed models could transform how surgeons train by providing surgical rehearsal platforms across all surgical specialties, enabling training with tissue realism and anatomic precision. The use of 3D-printed models in renal transplantations has shown a positive impact on surgical outcomes, including the duration of the operation and the intraoperative blood loss. Regarding 3D bioprinting, the technique has shown promising results, especially in the field of microfluidic devices, with the development of tissue demonstrating proximal tubules, glomerulus, and tubuloinerstitium function, and in renal organoid development. Such models can be applied for renal disease modeling, drug development, and renal regenerative medicine.

Global dissemination of minimally invasive living donor hepatectomy: What are the barriers?

Minimally invasive donor hepatectomy (MIDH) is a relatively novel procedure that can potentially increase donor safety and contribute to faster rehabilitation of donors. After an initial period in which donor safety was not effectively validated, MIDH currently seems to provide improved results, provided that it is conducted by experienced surgeons. Appropriate selection criteria are crucial to achieve better outcomes in terms of complications, blood loss, operative time, and hospital stay. Beyond a pure laparoscopic technique, various approaches have been recommended such as hand-assisted, laparoscopic-assisted, and robotic donation. The latter has shown equal outcomes compared to open and laparoscopic approaches. A steep learning curve seems to exist in MIDH, mainly due to the fragility of the liver parenchyma and the experience needed for adequate control of bleeding. This review investigated the challenges and the opportunities of MIDH and the barriers to its global dissemination. Surgeons need expertise in liver transplantation, hepatobiliary surgery, and minimally invasive techniques to perform MIDH. Barriers can be categorized into surgeon-related, institutional-related, and accessibility. More robust data and the creation of international registries are needed for further evaluation of the technique and the acceptance from more centers worldwide.

Translational research and innovation in modern transplant practice: Paradigms from Greece and around the world.

The continuous clinical and technological advances, together with the social, health and economic challenges that the global population faces, have created an environment where the evolution of the field of transplantation is essentially necessary. The goal of this special issue is to provide a picture of the current status of transplantation in Greece as well as in many other countries in Europe and around the world. Authors from Greece and several other countries provide us with valuable insight into their respective areas of transplant expertise, with a main focus on the field of translational research and innovation. The papers that are part of this Special Issue "Translational Research and Innovation and the current status of Transplantation in Greece" have presented innovative and meaningful approaches in modern transplant research and practice. They provide us with a clear overview of the current landscape in transplantation, including liver transplantation in the context of a major pandemic, the evolution of living donor kidney transplantation or the evolution of the effect of hepatitis C virus infection in transplantation, while at the same time explore more recent challen ges, such as the issue of frailty in the transplant candidate and the changes brought by newer treatments, such as immunotherapy, in transplant oncology. Additionally, they offer us a glimpse of the effect that technological innovations, such as virtual reality, can have on transplantation, both in terms of clinical and educational aspects. Just as critical is the fact that this Special Issue emphasizes the multidisciplinary, collaborative efforts currently taking place that link transplant research and innovation with other cutting-edge disciplines such as bioengineering, advanced information technology and artificial intelligence. In this Special Issue, in addition to the clinical and research evolution of the field of transplantation, we are witnessing the importance of interdisciplinary collaboration in medicine.

Analysis of the effects of donor and recipient hepatitis C infection on kidney transplant outcomes in the United States.

BACKGROUND: As Hepatitis C virus infection (HCV+) rates in kidney donors and transplant recipients rise, direct-acting antivirals (DAA) may affect outcomes. AIM: To analyze the effects of HCV+ in donors, recipients, or both, on deceased-donor (DD) kidney transplantation (KT) outcomes, and the impact of DAAs on those effects. METHODS: The Organ Procurement and Transplantation Network data of adult first solitary DD-KT recipients 1994-2019 were allocated into four groups by donor and recipient HCV+ status. We performed patient survival (PS) and death-censored graft survival (DCGS) pairwise comparisons after propensity score matching to assess the effects of HCV+ in donors and/or recipients, stratifying our study by DAA era to evaluate potential effect modification. RESULTS: Pre-DAA, for HCV+ recipients, receiving an HCV+ kidney was associated with 1.28-fold higher mortality (HR 1.151.281.42) and 1.22-fold higher death-censored graft failure (HR 1.081.221.39) compared to receiving an HCV- kidney and the absolute risk difference was 3.3% (95%CI: 1.8%-4.7%) for PS and 3.1% (95%CI: 1.2%-5%) for DCGS at 3 years. The HCV dual-infection (donor plus recipient) group had worse PS (0.56-fold) and DCGS (0.71-fold) than the dual-uninfected. Donor HCV+ derived worse post-transplant outcomes than recipient HCV+ (PS 0.36-fold, DCGS 0.34-fold). In the DAA era, the risk associated with HCV+ in donors and/or recipients was no longer statistically significant, except for impaired PS in the dual-infected vs dual-uninfected (0.43-fold). CONCLUSION: Prior to DAA introduction, donor HCV+ negatively influenced kidney transplant outcomes in all recipients, while recipient infection only relatively impaired outcomes for uninfected donors. These adverse effects disappeared with the introduction of DAA.

Exploring the use of virtual reality in surgical education.

Virtual reality (VR) technologies have rapidly developed in the past few years. The most common application of the technology, apart from gaming, is for educational purposes. In the field of healthcare, VR technologies have been applied in several areas. Among them is surgical education. With the use of VR, surgical pathways along with the training of surgical skills can be explored safely, in a cost-effective manner. The aim of this mini-review was to explore the use of VR in surgical education and in the 3D reconstruction of internal organs and viable surgical pathways. Finally, based on the outcomes of the included studies, an ecosystem for the implementation of surgical training was proposed.

Systematic review and meta-analysis of open versus laparoscopy-assisted versus pure laparoscopic versus robotic living donor hepatectomy.

The value of minimally invasive approaches for living donor hepatectomy remains unclear. Our aim was to compare the donor outcomes after open versus laparoscopy-assisted versus pure laparoscopic versus robotic living donor hepatectomy (OLDH vs. LALDH vs. PLLDH vs. RLDH). A systematic literature review of the MEDLINE, Cochrane Library, Embase, and Scopus databases was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement (up to December 8, 2021). Random-effects meta-analyses were performed separately for minor and major living donor hepatectomy. The risk of bias in nonrandomized studies was assessed using the Newcastle-Ottawa Scale. A total of 31 studies were included. There was no difference in donor outcomes after OLDH versus LALDH for major hepatectomy. However, PLLDH was associated with decreased estimated blood loss, length of stay (LOS), and overall complications versus OLDH for minor and major hepatectomy, but also with increased operative time for major hepatectomy. PLLDH was associated with decreased LOS versus LALDH for major hepatectomy. RLDH was associated with decreased LOS but with increased operative time versus OLDH for major hepatectomy. The scarcity of studies comparing RLDH versus LALDH/PLLDH did not allow us to meta-analyze donor outcomes for that comparison. There seems to be a marginal benefit in estimated blood loss and/or LOS in favor of PLLDH and RLDH. The complexity of these procedures limits them to transplant centers with high volume and experience. Future studies should investigate self-reported donor experience and the associated economic costs of these approaches.

Challenges involved in the application of artificial intelligence in gastroenterology: The race is on!

Gastroenterology is a particularly data-rich field, generating vast repositories of data that are a fruitful ground for artificial intelligence (AI) and machine learning (ML) applications. In this opinion review, we initially elaborate on the current status of the application of AI/ML-based software in gastroenterology. Currently, AI/ML-based models have been developed in the following applications: Models integrated into the clinical setting following real-time patient data flagging patients at high risk for developing a gastrointestinal disease, models employing non-invasive parameters that provide accurate diagnoses aiming to either replace, minimize, or refine the indications of endoscopy, models utilizing genomic data to diagnose various gastrointestinal diseases, computer-aided diagnosis systems facilitating the interpretation of endoscopy images, models to facilitate treatment allocation and predict the response to treatment, and finally, models in prognosis predicting complications, recurrence following treatment, and overall survival. Then, we elaborate on several challenges and how they may negatively impact the widespread application of AI in healthcare and gastroenterology. Specifically, we elaborate on concerns regarding accuracy, cost-effectiveness, cybersecurity, interpretability, oversight, and liability. While AI is unlikely to replace physicians, it will transform the skillset demanded by future physicians to practice. Thus, physicians are expected to engage with AI to avoid becoming obsolete.

Effects of an active lifestyle on the physical frailty of liver transplant candidates.

BACKGROUND: Liver transplantation is the most important therapeutic intervention for end-stage liver disease (ELD). The prioritization of these patients is based on the model for end-stage liver disease (MELD), which can successfully predict short-term mortality. However, despite its great validity and value, it cannot fully incor porate several comorbidities of liver disease, such as sarcopenia and physical frailty, variables that can sufficiently influence the survival of such patients. Subsequently, there is growing interest in the importance of physical frailty in regard to mortality in liver transplant candidates and recipients, as well as its role in improving their survival rates. AIM: To evaluate the effects of an active lifestyle on physical frailty on liver transplant candidates. METHODS: An observational study was performed within the facilities of the Department of Transplant Surgery of Aristotle University of Thessaloniki. Twenty liver tran splant candidate patients from the waiting list of the department were included in the study. Patients that were bedridden, had recent cardiovascular incidents, or had required inpatient treatment for more than 5 d in the last 6 mo were excluded from the study. The following variables were evaluated: Activity level via the International Physical Activity Questionnaire (IPAQ); functional capacity via the 6-min walking test (6MWT) and cardiopulmonary exercise testing; and physical frailty via the Liver Frailty Index (LFI). RESULTS: According to their responses in the IPAQ, patients were divided into the following two groups based on their activity level: Active group (A, 10 patients); and sedentary group (S, 10 patients). Comparing mean values of the recorded variables showed the following results: MELD (A: 12.05 ± 5.63 vs S: 13.99 ± 3.60; P > 0.05); peak oxygen uptake (A: 29.78 ± 6.07 mL/kg/min vs S: 18.11 ± 3.39 mL/kg/min; P < 0.001); anaerobic threshold (A: 16.71 ± 2.17 mL/kg/min vs S: 13.96 ± 1.45 mL/kg/min; P < 0.01); 6MWT (A: 458.2 ± 57.5 m vs S: 324.7 ± 55.8 m; P < 0.001); and LFI (A: 3.75 ± 0.31 vs S: 4.42 ± 0.32; P < 0.001). CONCLUSION: An active lifestyle can be associated with better musculoskeletal and functional capacity, while simultaneously preventing the evolution of physical frailty in liver transplant candidates. This effect appears to be independent of the liver disease severity.