Use of machine learning models for the prognostication of liver transplantation: A systematic review

BACKGROUND Liver transplantation(LT)is a life-saving intervention for patients with end-stage liver disease.However,the equitable allocation of scarce donor organs remains a formidable challenge.Prognostic tools are pivotal in identifying the most suitable transplant candidates.Traditionally,scoring systems like the model for end-stage liver disease have been instrumental in this process.Nevertheless,the landscape of prognostication is undergoing a transformation with the integration of machine learning(ML)and artificial intelligence models.AIM To assess the utility of ML models in prognostication for LT,comparing their performance and reliability to established traditional scoring systems.METHODS Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines,we conducted a thorough and standardized literature search using the PubMed/MEDLINE database.Our search imposed no restrictions on publication year,age,or gender.Exclusion criteria encompassed non-English studies,review articles,case reports,conference papers,studies with missing data,or those exhibiting evident methodological flaws.RESULTS Our search yielded a total of 64 articles,with 23 meeting the inclusion criteria.Among the selected studies,60.8%originated from the United States and China combined.Only one pediatric study met the criteria.Notably,91%of the studies were published within the past five years.ML models consistently demonstrated satisfactory to excellent area under the receiver operating characteristic curve values(ranging from 0.6 to 1)across all studies,surpassing the performance of traditional scoring systems.Random forest exhibited superior predictive capabilities for 90-d mortality following LT,sepsis,and acute kidney injury(AKI).In contrast,gradient boosting excelled in predicting the risk of graft-versus-host disease,pneumonia,and AKI.CONCLUSION This study underscores the potential of ML models in guiding decisions related to allograft allocation and LT,marking a significant evolution in the field of prognostication.

Management strategies for common viral infections in pediatric renal transplant recipients

Viral infections have been considered as a major cause of morbidity and mortality after kidney transplantation in pediatric cohort.Children are at high risk of acquiring virus-related complications due to immunological immaturity and the enhanced alloreactivity risk that led to maintenance of high immunosuppressive regimes.Hence,prevention,early detection,and prompt treatment of such infections are of paramount importance.Among all viral infections,herpes viruses(herpes simplex virus,varicella zoster virus,Epstein-Barr virus,cytomegalovirus),hepatitis B and C viruses,BK polyomavirus,and respiratory viruses(respiratory syncytial virus,parainfluenza virus,influenza virus and adenovirus)are common in kidney transplant recipients.These viruses can cause systemic disease or allograft dysfunction affecting the clinical outcome.Recent advances in technology and antiviral therapy have improved management strategies in screening,monitoring,adoption of prophylactic or preemptive therapy and precise treatment in the immunocompromised host,with significant impact on the outcome.This review discusses the etiology,screening and monitoring,diagnosis,prevention,and treatment of common viral infections in pediatric renal transplant recipients.

Liver transplantation for hepatocellular carcinoma in India: Are we ready for 2040?

BACKGROUND Liver transplantation(LT)for hepatocellular carcinoma(HCC)has been widely researched and is well established worldwide.The cornerstone of this treatment lies in the various criteria formulated by expert consensus and experience.The variations among the criteria are staggering,and the short-and long-term outcomes are controversial.AIM To study the differences in the current practices of LT for HCC at different centers in India and discuss their clinical implications in the future.METHODS We conducted a survey of major centers in India that performed LT in December 2022.A total of 23 responses were received.The centers were classified as high-and low-volume,and the current trend of care for patients undergoing LT for HCC was noted.RESULTS Of the 23 centers,35%were high volume center(>500 Liver transplants)while 52%were high-volume centers that performed more than 50 transplants/year.Approximately 39%of centers had performed>50 LT for HCC while the percent distribution for HCC in LT patients was 5%–15%in approximately 73%of the patients.Barring a few,most centers were divided equally between University of California,San Francisco(UCSF)and center-specific criteria when choosing patients with HCC for LT,and most(65%)did not have separate transplant criteria for deceased donor LT and living donor LT(LDLT).Most centers(56%)preferred surgical resection over LT for a Child A cirrhosis patient with a resectable 4 cm HCC lesion.Positron-emission tomography-computed tomography(CT)was the modality of choice for metastatic workup in the majority of centers(74%).Downstaging was the preferred option for over 90%of the centers and included transarterial chemoembolization,transarterial radioembolization,stereotactic body radiotherapy and atezolizumab/bevacizumab with varied indications.The alphafetoprotein(AFP)cut-off was used by 74%of centers to decide on transplantation as well as to downstage tumors,even if they met the criteria.The criteria for successful downstaging varied,but most centers conformed to the UCSF or their center-specific criteria for LT,along with the AFP cutoff values.The wait time for LT from downstaging was at least 4–6 wk in all centers.Contrast-enhanced CT was the preferred imaging modality for post-LT surveillance in 52%of the centers.Approximately 65%of the centers preferred to start everolimus between 1 and 3 months post-LT.CONCLUSION The current predicted 5-year survival rate of HCC patients in India is less than 15%.The aim of transplantation is to achieve at least a 60%5-year disease free survival rate,which will provide relief to the prediction of an HCC surge over the next 20 years.The current worldwide criteria(Milan/UCSF)may have a higher 5-year survival(>70%);however,the majority of patients still do not fit these criteria and are dependent on other suboptimal modes of treatment,with much lower survival rates.To make predictions for 2040,we must prepare to arm ourselves with less stringent selection criteria to widen the pool of patients who may undergo transplantation and have a chance of a better outcome.With more advanced technology and better donor outcomes,LDLT will provide a cutting edge in the fight against liver cancer over the next two decades.

Update on the reciprocal interference between immunosuppressive therapy and gut microbiota after kidney transplantation

Gut microbiota is often modified after kidney transplantation.This principally happens in the first period after transplantation.Antibiotics and,most of all,immunosuppressive drugs are the main responsible.The relationship between immunosuppressive drugs and the gut microbiota is bilateral.From one side immunosuppressive drugs modify the gut microbiota,often generating dysbiosis;from the other side microbiota may interfere with the immunosuppressant pharmacokinetics,producing products more or less active with respect to the original drug.These phenomena have influence over the graft outcomes and clinical consequences as rejections,infections,diarrhea may be caused by the dysbiotic condition.Corticosteroids,calcineurin inhibitors such as tacrolimus and cyclosporine,mycophenolate mofetil and mTOR inhibitors are the immunosuppressive drugs whose effect on the gut microbiota is better known.In contrast is well known how the gut microbiota may interfere with glucocorticoids,which may be transformed into androgens.Tacrolimus may be transformed by microbiota into a product called M1 that is 15-fold less active with respect to tacrolimus.The pro-drug mycophenolate mofetil is normally transformed in mycophenolic acid that according the presence or not of microbes producing the enzyme glucuronidase,may be transformed into the inactive product.

Improving the radiological diagnosis of hepatic artery thrombosis after liver transplantation: Current approaches and future challenges

Hepatic artery thrombosis(HAT)is a devastating vascular complication following liver transplantation,requiring prompt diagnosis and rapid revascularization treatment to prevent graft loss.At present,imaging modalities such as ultrasound,computed tomography,and magnetic resonance play crucial roles in diagnosing HAT.Although imaging techniques have improved sensitivity and specificity for HAT diagnosis,they have limitations that hinder the timely diagnosis of this complication.In this sense,the emergence of artificial intelligence(AI)presents a transformative opportunity to address these diagnostic limitations.The development of machine learning algorithms and deep neural networks has demonstrated the potential to enhance the precision diagnosis of liver transplant complications,enabling quicker and more accurate detection of HAT.This article examines the current landscape of imaging diagnostic techniques for HAT and explores the emerging role of AI in addressing future challenges in the diagnosis of HAT after liver transplant.

Pediatric and adult liver transplantation in Bahrain: The experiences in a country with no available liver transplant facilities

BACKGROUND Liver transplantation(LT)is a life-saving procedure for patients with end-stage liver disease and has become the standard and most effective treatment method for these patients.There are many indications for LT that vary between countries and settings.The outcome of LT depends on the available facilities and surgical expertise,as well as the types of liver graft donors available.AIM To assess the clinical characteristics of patients from Bahrain who underwent LT overseas,and analyze factors affecting their survival.METHODS In this retrospective cohort study,we reviewed the medical records and overseas committee registry information of all pediatric and adult patients who were sent overseas to undergo LT by the Pediatric and Medical Departments of Salmaniya Medical Complex and Bahrain Defence Force Hospital via the Overseas Treatment Office,Ministry of Health,Kingdom of Bahrain,between 1997 and 2023.Demographic data,LT indication,donor-recipient relationship,overseas LT center,graft type,post-LT medications,and LT complications,were collected.Outcomes measured included the overall and 5-year LT survival rate.Fisher’s exact,Pearsonχ2,and Mann-Whitney U tests were used to compare the pediatric and the adults’group in terms of clinical characteristics,donor-recipient relationship,medication,complications,and outcome.Survival analysis was estimated via the Kaplan-Meier’s method.Univariate and multivariate analyses were used to detect predictors of survival.RESULTS Of the 208 eligible patients,170(81.7%)were sent overseas to undergo LT while 38(18.3%)remained on the waiting list.Of the 170 patients,167(80.3%)underwent LT and were included in the study.The majority of the patients were Bahraini(91.0%),and most were males(57.5%).One-hundred-and-twenty(71.8%)were adults and 47(28.3%)were children.The median age at transplant was 50.0[interquartile range(IQR):14.9–58.4]years.The main indication for pediatric LT was biliary atresia(31.9%),while that of adult LT was hepatitis C-related cirrhosis(35.0%).Six(3.6%)patients required re-transplantation.Most patients received a living-related liver graft(82%).Pediatric patients received more living and related grafts than adults(P=0.038 and P=0.041,respectively),while adult patients received more cadaveric and unrelated grafts.Most patients required long-term immunosuppressive therapy after LT(94.7%),of which tacrolimus was the most prescribed(84.0%),followed by prednisolone(50.7%),which was prescribed more frequently for pediatric patients(P=0.001).Most patients developed complications(62.4%)with infectious episodes being the most common(38.9%),followed by biliary stricture(19.5%).Tonsilitis and sepsis(n=12,8.1%for each)were the most frequent infections.Pediatric patients experienced higher rates of infection,rejection,and early poor graft function than adult patients(P<0.001,P=0.003,and P=0.025,respectively).The median follow-up time was 6.5(IQR:2.6–10.6)years.The overall survival rate was 84.4%,the 5-year survival rate,86.2%,and the mortality rate,15.6%.Younger patients had significantly better odds of survival(P=0.019)and patients who survived had significantly longer follow-up periods(P<0.001).CONCLUSION Patients with end-stage liver disease in Bahrain shared characteristics with those from other countries.Since LT facilities are not available,an overseas LT has offered them great hope.

New therapeutic strategy with extracorporeal membrane oxygenation for refractory hepatopulmonary syndrome after liver transplant: A case report

BACKGROUND Due to the lack of published literature about treatment of refractory hepatopulmonary syndrome(HPS)after liver transplant(LT),this case adds information and experience on this issue along with a treatment with positive outcomes.HPS is a complication of end-stage liver disease,with a 10%-30%incidence in cirrhotic patients.LT can reverse the physiopathology of this process and restore normal oxygenation.However,in some cases,refractory hypoxemia persists,and extracorporeal membrane oxygenation(ECMO)can be used as a rescue therapy with good results.CASE SUMMARY A 59-year-old patient with alcohol-related liver cirrhosis and portal hypertension was included in the LT waiting list for HPS.He had good liver function(Model for End-Stage Liver Disease score 12,Child-Pugh class B7).He had pulmonary fibrosis and a mild restrictive respiratory pattern with a basal oxygen saturation of 82%.The macroaggregated albumin test result was>30.Spirometry demonstrated a forced expiratory volume in one second(FEV1)of 78%,forced vital capacity(FVC)of 74%,FEV1/FVC ratio of 81%,diffusion capacity for carbon monoxide of 42%,and carbon monoxide transfer coefficient of 57%.He required domiciliary oxygen at 2 L/min(16 h/d).The patient was admitted to the intensive care unit(ICU)and extubated in the first 24 h,needing high-flow therapy and non-invasive ventilation and inhaled nitric oxide afterwards.Reintubation was needed after 72 h.Due to the non-response to supportive therapies,installation of ECMO was decided with progressive recovery after 9 d.Extubation was possible on the tenth day,maintaining a high-flow nasal cannula and de-escalating to conventional oxygen therapy after 48 h.He was discharged from ICU on postoperative day(POD)20 with a 90%-92%oxygen saturation.Steroid recycling was needed twice for acute rejection.The patient was discharged from hospital on POD 27 with no symptoms,with an 89%-90%oxygen saturation.CONCLUSION Due to the favorable results observed,ECMO could become the central axis of treatment of HPS and refractory hypoxemia after LT.

Comparison of resistive index and shear-wave elastography in the evaluation of chronic kidney allograft dysfunction

BACKGROUND Detection of early chronic changes in the kidney allograft is important for timely intervention and long-term survival.Conventional and novel ultrasound-based investigations are being increasingly used for this purpose with variable results.AIM To compare the diagnostic performance of resistive index(RI)and shear wave elastography(SWE)in the diagnosis of chronic fibrosing changes of kidney allograft with histopathological results.METHODS This is a cross-sectional and comparative study.A total of 154 kidney transplant recipients were included in this study,which was conducted at the Departments of Transplantation and Radiology,Sindh Institute of Urology and Transplantation,Karachi,Pakistan,from August 2022 to February 2023.All consecutive patients with increased serum creatinine levels and reduced glomerular filtration rate(GFR)after three months of transplantation were enrolled in this study.SWE and RI were performed and the findings of these were evaluated against the kidney allograft biopsy results to determine their diagnostic utility.RESULTS The mean age of all patients was 35.32±11.08 years.Among these,126(81.8%)were males and 28(18.2%)were females.The mean serum creatinine in all patients was 2.86±1.68 mg/dL and the mean estimated GFR was 35.38±17.27 mL/min/1.73 m2.Kidney allograft biopsy results showed chronic changes in 55(37.66%)biopsies.The sensitivity,specificity,positive predictive value(PPV),and negative predictive value(NPV)of SWE for the detection of chronic allograft damage were 93.10%,96.87%%,94.73%,and 95.87%,respectively,and the diagnostic accuracy was 95.45%.For RI,the sensitivity,specificity,PPV,and NPV were 76.92%,83.33%,70.17%,and 87.62%,respectively,and the diagnostic accuracy was 81.16%.CONCLUSION The results from this study show that SWE is more sensitive and specific as compared to RI in the evaluation of chronic allograft damage.It can be of great help during the routine follow-up of kidney transplant recipients for screening and early detection of chronic changes and selecting patients for allograft biopsy.

Primary liver transplantation vs transplant after Kasai portoenterostomy in children with biliary atresia: A retrospective Brazilian single-center cohort

BACKGROUND Biliary atresia(BA)is the most common indication for pediatric liver transplantation,although portoenterostomy is usually performed first.However,due to the high failure rate of portoenterostomy,liver transplantation has been advocated as the primary procedure for patients with BA.It is still unclear if a previous portoenterostomy has a negative impact on liver transplantation outcomes.AIM To investigate the effect of prior portoenterostomy in infants un-dergoing liver transplantation for BA.METHODS This was a retrospective cohort study of 42 pediatric patients with BA who underwent primary liver transplantation from 2013 to 2023 at a single tertiary center in Brazil.Patients with BA were divided into two groups:Those undergoing primary liver transplantation without portoenterostomy and those undergoing liver transplantation with prior portoenterostomy.Continuous variables were compared using the Student’s t-test or the Kruskal-Wallis test,and categorical variables were compared using theχ2 or Fisher’s exact test,as appropriate.Multivariable Cox regression analysis was performed to determine risk factors for portal vein thrombosis.Patient and graft survival analyses were conducted with the Kaplan–Meier product-limit estimator,and patient subgroups were compared using the two-sided log-rank test.RESULTS Forty-two patients were included in the study(25[60%]girls),23 undergoing liver transplantation without prior portoenterostomy,and 19 undergoing liver transplantation with prior portoenterostomy.Patients with prior portoenterostomy were older(12 vs 8 months;P=0.02)at the time of liver transplantation and had lower Pediatric End-Stage Liver Disease scores(13.2 vs 21.4;P=0.01).The majority of the patients(35/42,83%)underwent livingdonor liver transplantation.The group of patients without prior portoenterostomy appeared to have a higher incidence of portal vein thrombosis(39 vs 11%),but this result did not reach statistical significance.Prior portoenterostomy was not a protective factor against portal vein thrombosis in the multivariable analysis after adjusting for age at liver transplantation,graft-to-recipient weight ratio,and use of vascular grafts.Finally,the groups did not significantly differ in terms of post-transplant survival.CONCLUSION In our study,prior portoenterostomy did not significantly affect the outcomes of liver transplantation.

Autologous hematopoietic stem cell transplantation conditioning regimens and chimeric antigen receptor T cell therapy in various diseases

Conditioning regimens employed in autologous stem cell transplantation have been proven useful in various hematological disorders and underlying malignancies;however,despite being efficacious in various instances,negative consequences have also been recorded.Multiple conditioning regimens were extracted from various literature searches from databases like PubMed,Google scholar,EMBASE,and Cochrane.Conditioning regimens for each disease were compared by using various end points such as overall survival(OS),progression free survival(PFS),and leukemia free survival(LFS).Variables were presented on graphs and analyzed to conclude a more efficacious conditioning regimen.In multiple myeloma,the most effective regimen was high dose melphalan(MEL)given at a dose of 200/mg/m2.The comparative results of acute myeloid leukemia were presented and the regimens that proved to be at an admirable position were busulfan(BU)+MEL regarding OS and BU+VP16 regarding LFS.In case of acute lymphoblastic leukemia(ALL),BU,fludarabine,and etoposide(BuFluVP)conferred good disease control not only with a paramount improvement in survival rate but also low risk of recurrence.However,for ALL,chimeric antigen receptor(CAR)T cell therapy was preferred in the context of better OS and LFS.With respect to Hodgkin’s lymphoma,mitoxantrone(MITO)/MEL overtook carmustine,VP16,cytarabine,and MEL in view of PFS and vice versa regarding OS.Non-Hodgkin’s lymphoma patients were administered MITO(60 mg/m2)and MEL(180 mg/m2)which showed promising results.Lastly,amyloidosis was considered,and the regimen that proved to be competent was MEL 200(200 mg/m2).This review article demonstrates a comparison between various conditioning regimens employed in different diseases.

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?

Thrombotic microangiopathy after kidney transplantation: Expanding etiologic and pathogenetic spectra

Thrombotic microangiopathy(TMA)is an uncommon but serious complication that not only affects native kidneys but also transplanted kidneys.This review is specifically focused on post-transplant TMA(PT-TMA)involving kidney transplant recipients.Its reported prevalence in the latter population varies from 0.8%to 14%with adverse impacts on both graft and patient survival.It has many causes and associations,and the list of etiologic agents and associations is growing constantly.The pathogenesis is equally varied and a variety of pathogenetic pathways lead to the development of microvascular injury as the final common pathway.PT-TMA is categorized in many ways in order to facilitate its management.Ironically,more than one causes are contributory in PT-TMA and it is often difficult to pinpoint one particular cause in an individual case.Pathologically,the hallmark lesions are endothelial cell injury and intravascular thrombi affecting the microvasculature.Early diagnosis and classification of PT-TMA are imperative for optimal outcomes but are challenging for both clinicians and pathologists.The Banff classification has addressed this issue and has developed minimum diagnostic criteria for pathologic diagnosis of PT-TMA in the first phase.Management of the condition is also challenging and still largely empirical.It varies from simple maneuvers,such as plasmapheresis,drug withdrawal or modification,or dose reduction,to lifelong complement blockade,which is very expensive.A thorough understanding of the condition is imperative for an early diagnosis and quick treatment when the treatment is potentially effective.This review aims to increase the awareness of relevant stakeholders regarding this important,potentially treatable but under-recognized cause of kidney allograft dysfunction.

Current status and future perspectives on stem cell transplantation for spinal cord injury

BACKGROUND Previous assessments of stem cell therapy for spinal cord injuries(SCI)have encountered challenges and constraints.Current research primarily emphasizes safety in early-phase clinical trials,while systematic reviews prioritize effectiveness,often overlooking safety and translational feasibility.This situation prompts inquiries regarding the readiness for clinical adoption.AIM To offer an up-to-date systematic literature review of clinical trial results concerning stem cell therapy for SCI.METHODS A systematic search was conducted across major medical databases[PubMed,Embase,Reference Citation Analysis(RCA),and Cochrane Library]up to October 14,2023.The search strategy utilized relevant Medical Subject Heading(MeSH)terms and keywords related to"spinal cord","injury","clinical trials","stem cells","functional outcomes",and"adverse events".Studies included in this review consisted of randomized controlled trials and non-randomized controlled trials reporting on the use of stem cell therapies for the treatment of SCI.RESULTS In a comprehensive review of 66 studies on stem cell therapies for SCI,496 papers were initially identified,with 237 chosen for full-text analysis.Among them,236 were deemed eligible after excluding 170 for various reasons.These studies encompassed 1086 patients with varying SCI levels,with cervical injuries being the most common(42.2%).Bone marrow stem cells were the predominant stem cell type used(71.1%),with various administration methods.Follow-up durations averaged around 84.4 months.The 32.7%of patients showed functional improvement from American spinal injury association Impairment Scale(AIS)A to B,40.8%from AIS A to C,5.3%from AIS A to D,and 2.1%from AIS B to C.Sensory improvements were observed in 30.9%of patients.A relatively small number of adverse events were recorded,including fever(15.1%),headaches(4.3%),muscle tension(3.1%),and dizziness(2.6%),highlighting the potential for SCI recovery with stem cell therapy.CONCLUSION In the realm of SCI treatment,stem cell-based therapies show promise,but clinical trials reveal potential adverse events and limitations,underscoring the need for meticulous optimization of transplantation conditions and parameters,caution against swift clinical implementation,a deeper understanding of SCI pathophysiology,and addressing ethical,tumorigenicity,immunogenicity,and immunotoxicity concerns before gradual and careful adoption in clinical practice.

Predicting outcomes after kidney transplantation: Can Pareto’s rules help us to do so?

Kidney transplantation is the best option for kidney replacement therapy,even considering that most of the times the grafts do not survive as long as their recipients.In the Khalil et al's experience,published in this issue of the Journal,they analyze their second kidney graft survival and describe those significant predictors of early loss.This editorial comments on the results and put in perspective that most of the times,long-term graft survival could be inadvertently jeopardized if the immunosuppressive therapy is reduced or withdrawn for any reason,and that it could happen frequently if the transplant physician intends to innovate with the clinical care without proper evidence-based data.

Pros and cons of live kidney donation in prediabetics: A critical review and way forward

There is shortage of organs,including kidneys,worldwide.Along with deceased kidney transplantation,there is a significant rise in live kidney donation.The prevalence of prediabetes(PD),including impaired fasting glucose and impaired glucose tolerance,is on the rise across the globe.Transplant teams frequently come across prediabetic kidney donors for evaluation.Prediabetics are at risk of diabetes,chronic kidney disease,cardiovascular events,stroke,neuropathy,retinopathy,dementia,depression and nonalcoholic liver disease along with increased risk of all-cause mortality.Unfortunately,most of the studies done in prediabetic kidney donors are retrospective in nature and have a short follow up period.There is lack of prospective long-term studies to know about the real risk of complications after donation.Furthermore,there are variations in recommendations from various guidelines across the globe for donations in prediabetics,leading to more confusion among clinicians.This increases the responsibility of transplant teams to take appropriate decisions in the best interest of both donors and recipients.This review focuses on pathophysiological changes of PD in kidneys,potential complications of PD,other risk factors for development of type 2 diabetes,a review of guidelines for kidney donation,the potential role of diabetes risk score and calculator in kidney donors and the way forward for the evaluation and selection of prediabetic kidney donors.

Association of donor hepatectomy time with liver transplantation outcomes: A multicenter retrospective study

BACKGROUND Prolonged donor hepatectomy time may be implicated in early and late complications of liver transplantation.AIM To evaluate the impact of donor hepatectomy time on outcomes of liver transplant recipients,mainly early allograft dysfunction.METHODS This multicenter retrospective study included brain-dead donors and adult liver graft recipients.Donor-recipient matching was obtained through a crossover list.Clinical and laboratory data were recorded for both donors and recipients.Donor hepatectomy,cold ischemia,and warm ischemia times were recorded.Primary outcome was early allograft dysfunction.Secondary outcomes included need for retransplantation,length of intensive care unit and hospital stay,and patient and graft survival at 12 months.RESULTS From January 2019 to December 2021,a total of 243 patients underwent a liver transplant from a brain-dead donor.Of these,57(25%)developed early allograft dysfunction.The median donor hepatectomy time was 29(23–40)min.Patients with early allograft dysfunction had a median hepatectomy time of 25(22–38)min,whereas those without it had a median time of 30(24–40)min(P=0.126).CONCLUSION Donor hepatectomy time was not associated with early allograft dysfunction,graft survival,or patient survival following liver transplantation.

Immunology demystified: A guide for transplant hepatologists

Liver transplantation has become standard practice for treating end-stage liver disease.The success of the procedure relies on effective immunosuppressive medications to control the host's immune response.Despite the liver's inherent capacity to foster tolerance,the early post-transplant period is marked by significant immune reactivity.To ensure favorable outcomes,it is imperative to identify and manage various rejection types,encompassing T-cell-mediated,antibody-mediated,and chronic rejection.However,the approach to prescribing immunosuppressants relies heavily on clinical judgment rather than evidencebased criteria.Given that the majority of patients will require lifelong immunosuppression as the mechanisms underlying operational tolerance are still being investigated,healthcare providers must possess an understanding of immune responses,rejection mechanisms,and the pathways targeted by immunosuppressive drugs.This knowledge enables customization of treatments and improved patient care,even though a consensus on an optimal immunosuppressive regimen remains elusive.

Impact of sex on the outcomes of deceased donor liver transplantation

BACKGROUND Data examining the impact of sex on liver transplant(LT)outcomes are limited.It is clear that further research into sex-related differences in transplant patients is necessary to identify areas for improvement.Elucidation of these differences may help to identify specific areas of focus to improve on the organ matching process,as well as the peri-and post-operative care of these patients.AIM To utilize data from a high-volume Eurotransplant center to compare characteristics of male and female patients undergoing liver transplant and assess association between sex-specific variables with short-and long-term post-transplant outcomes.METHODS A retrospective review of the University of Essen’s transplant database was performed with collection of baseline patient characteristics,transplant-related data,and short-term outcomes.Comparisons of these data were made with Shapiro-Wilk,Mann-Whitney U,χ2 and Bonferroni tests applied where appropriate.A P value of<0.05 was accepted as statistically significant.RESULTS Of the total 779 LT recipients,261(33.5%)were female.Female patients suffered higher incidences of acute liver failure and lower incidences of alcohol-related or viremic liver disease(P=0.001).Female patients were more likely to have received an organ from a female donor with a higher donor risk index score,and as a high urgency offer(all P<0.05).Baseline characteristics of male and female recipients were also significantly different.In multivariate hazard regression analysis,recipient lab-Model for End-Stage Liver Disease score and donor cause of death were associated with long-term outcomes in females.Pre-operative diagnosis of hepatocellular carcinoma,age at time of listing,duration of surgery,and units transfused during surgery,were associated with long-term outcomes in males.Severity of complications was associated with long-term outcomes in both groups.Overall survival was similar in both males and females;however,when stratified by age,females<50 years of age had the best survival.CONCLUSION Female and male LT recipients have different baseline and transplant-related characteristics,with sex-specific variables which are associated with long-term outcomes.Female recipients<50 years of age demonstrated the best long-term outcomes.Pre-and post-transplant practices should be individualized based on sex-specific variables to optimize long-term outcomes.

Islet transplantation-immunological challenges and current perspectives

Pancreatic islet transplantation is a minimally invasive procedure aiming to reverse the effects of insulin deficiency in patients with type 1 diabetes(T1D)by transplanting pancreatic beta cells.Overall,pancreatic islet transplantation has improved to a great extent,and cellular replacement will likely become the mainstay treatment.We review pancreatic islet transplantation as a treatment for T1D and the immunological challenges faced.Published data demonstrated that the time for islet cell transfusion varied between 2 and 10 h.Approximately 54%of the patients gained insulin independence at the end of the first year,while only 20%remained insulin-free at the end of the second year.Eventually,most transplanted patients return to using some form of exogenous insulin within a few years after the transplantation,which imposed the need to improve immunological factors before transplantation.We also discuss the immunosuppressive regimens,apoptotic donor lymphocytes,anti-TIM-1 antibodies,mixed chimerism-based tolerance induction,induction of antigen-specific tolerance utilizing ethylene carbodiimide-fixed splenocytes,pretransplant infusions of donor apoptotic cells,B cell depletion,preconditioning of isolated islets,inducing local immunotolerance,cell encapsulation and immunoisolation,using of biomaterials,immunomodulatory cells,etc.

Primary graft dysfunction following lung transplantation:From pathogenesis to future frontiers

Lung transplantation is the treatment of choice for patients with end-stage lung disease.Currently,just under 5000 lung transplants are performed worldwide annually.However,a major scourge leading to 90-d and 1-year mortality remains primary graft dysfunction.It is a spectrum of lung injury ranging from mild to severe depending on the level of hypoxaemia and lung injury post-transplant.This review aims to provide an in-depth analysis of the epidemiology,pathophysiology,risk factors,outcomes,and future frontiers involved in mitigating primary graft dysfunction.The current diagnostic criteria are examined alongside changes from the previous definition.We also highlight the issues surrounding chronic lung allograft dysfunction and identify the novel therapies available for ex-vivo lung perfusion.Although primary graft dysfunction remains a significant contributor to 90-d and 1-year mortality,ongoing research and development abreast with current technological advancements have shed some light on the issue in pursuit of future diagnostic and therapeutic tools.