Liver transplantation as an alternative for the treatment of intrahepatic cholangiocarcinoma: Past, present, and future directions

Intrahepatic cholangiocarcinoma(iCCA)is a rare biliary tract cancer with high mortality rate.Complete resection of the iCCA lesion is the first choice of treatment,with good prognosis after margin-negative resection.Unfortunately,only 12%-40% of patients are eligible for resection at presentation due to cirrhosis,portal hypertension,or large tumor size.Liver transplantation(LT)offers margin-negative iCCA extirpation for patients with unresectable tumors.Initially,iCCA was a contraindication for LT until size-based selection criteria were introduced to identify patients with satisfied post-LT outcomes.Recent studies have shown that tumor biology-based selection can yield high post-LT survival in patients with locally advanced iCCA.Another selection criterion is the tumor response to neoadjuvant therapy.Patients with response to neoadjuvant therapy have better outcomes after LT compared with those without tumor response to neoadjuvant therapy.Another index that helps predict the treatment outcome is the biomarker.Improved survival outcomes have also opened the door for living donor LT for iCCA.Patients undergoing LT for iCCA now have statistically similar survival rates as patients undergoing resection.The combination of surgery and locoregional and systemic therapies improves the prognosis of iCCA patients.

Mitochondrial transplantation confers protection against the effects of ischemic stroke by repressing microglial pyroptosis and promoting neurogenesis

Transferring healthy and functional mitochondria to the lateral ventricles confers neuroprotection in a rat model of ischemia-reperfusion injury.Autologous mitochondrial transplantation is also beneficial in pediatric patients with cardiac ischemia-reperfusion injury.Thus,transplantation of functional exogenous mitochondria may be a promising therapeutic approach for ischemic disease.To explore the neuroprotective effect of mitochondria transplantation and determine the underlying mechanism in ischemic stroke,in this study we established a photo-thrombosis-induced mouse model of focal ischemia and administered freshly isolated mitochondria via the tail vein or to the injury site(in situ).Animal behavior tests,immunofluorescence staining,2,3,5-triphenyltetrazolium chloride(TTC)staining,mRNA-seq,and western blotting were used to assess mouse anxiety and memory,cortical infarct area,pyroptosis,and neurogenesis,respectively.Using bioinformatics analysis,western blotting,co-immunoprecipitation,and mass spectroscopy,we identified S100 calcium binding protein A9(S100A9)as a potential regulator of mitochondrial function and determined its possible interacting proteins.Interactions between exogenous and endogenous mitochondria,as well as the effect of exogenous mitochondria on recipient microglia,were assessed in vitro.Our data showed that:(1)mitochondrial transplantation markedly reduced mortality and improved emotional and cognitive function,as well as reducing infarct area,inhibiting pyroptosis,and promoting cortical neurogenesis;(2)microglial expression of S100A9 was markedly increased by ischemic injury and regulated mitochondrial function;(3)in vitro,exogenous mitochondria enhanced mitochondrial function,reduced redox stress,and regulated microglial polarization and pyroptosis by fusing with endogenous mitochondria;and(4)S100A9 promoted internalization of exogenous mitochondria by the microglia,thereby amplifying their pro-proliferation and anti-inflammatory effects.Taken together,our findings show that mitochondrial transplantation protects against the deleterious effects of ischemic stroke by suppressing pyroptosis and promoting neurogenesis,and that S100A9 plays a vital role in promoting internalization of exogenous mitochondria.

Liver transplantation as an alternative for the treatment of perihilar cholangiocarcinoma: A critical review

Background:Perihilar cholangiocarcinoma(phCCC)is a dismal malignancy.There is no consensus regard-ing the best treatment for patients with unresectable phCCC.The present review aimed to gather the current pieces of evidence for liver transplantation and liver resection as a treatment for phCCC and to build better guidance for clinical practice.Data sources:The search was conducted in PubMed,Embase,Cochrane,and LILACS.The related references were searched manually.Inclusion criteria were:reports in English or Portuguese literature that a)patients with confirmed diagnosis of phCCC;b)patients treated with a curative intent;c)patients with the outcomes of liver resection and liver transplantation.Case reports,reviews,letters,editorials,conference abstracts and papers with full-text unavailability were excluded from the analysis.Results:Most of the current literature is based on observational retrospective studies with low grades of evidence.Liver resection has better long-term outcomes than systemic chemotherapy or palliation ther-apy and liver transplantation is a good alternative for selected patients with unresectable phCCC.All candidates for resection or transplantation should be medically fit and free of intrahepatic or extrahep-atic diseases.As a general rule,patients presenting with a tumor having a longitudinal size>3 cm or extending below the cystic duct,lymph node disease,confirmed extrahepatic dissemination;intraoper-atively diagnosed metastatic disease;a history of other malignancies within the last five years,and did not complete chemoradiation regimen and were medically unfit should not be considered for transplan-tation.Some of these criteria should be individually assessed.Liver transplantation or resection should only be considered in highly experienced hepatobiliary centers,and any decision-making must be based on a multidisciplinary evaluation.Conclusions:phCCC is a complex condition with high morbidity.Surgical therapies,including hepatec-tomy and liver transplantation,are the best option for better long-term disease-free survival.

Liver transplantation as an alternative for the treatment of non-resectable liver colorectal cancer: Advancing the therapeutic algorithm

Colorectal cancer is a leading cause of cancerrelated mortality,with nearly half of the affected patients developing liver metastases.For three decades,liver resection(LR)has been the primary curative strategy,yet its applicability is limited to about 20%of cases.Liver transplantation(LT)for unresectable metastases was attempted unsuccessfully in the 1990s,with high rates of perioperative death and recurrence.There is now more interest in this strategy due to improvements in systemic therapies and surgical techniques.A significant study conducted by the Oslo group showed that patients receiving liver transplants had a 60%chance of survival after five years.Significantly better results have been achieved by using advanced imaging for risk stratification and further refining selection criteria,especially in the Norvegian SECA trials.This review carefully charts the development and history of LT as a treatment option for colorectal cancer liver metastases.The revolutionary path from the early days of exploratory surgery to the current situation of cautious optimism is traced,highlighting the critical clinical developments and improved patient selection standards that have made LT a potentially curative treatment for such challenging very well selected cases.

Role of gut microbiota in Crohn’s disease pathogenesis:Insights from fecal microbiota transplantation in mouse model

BACKGROUND Inflammatory bowel disease,particularly Crohn’s disease(CD),has been associated with alterations in mesenteric adipose tissue(MAT)and the phenomenon termed“creeping fat”.Histopathological evaluations showed that MAT and intestinal tissues were significantly altered in patients with CD,with these tissues characterized by inflammation and fibrosis.AIM To evaluate the complex interplay among MAT,creeping fat,inflammation,and gut microbiota in CD.METHODS Intestinal tissue and MAT were collected from 12 patients with CD.Histological manifestations and protein expression levels were analyzed to determine lesion characteristics.Fecal samples were collected from five recently treated CD patients and five control subjects and transplanted into mice.The intestinal and mesenteric lesions in these mice,as well as their systemic inflammatory status,were assessed and compared in mice transplanted with fecal samples from CD patients and control subjects.RESULTS Pathological examination of MAT showed significant differences between CDaffected and unaffected colons,including significant differences in gut microbiota structure.Fetal microbiota transplantation(FMT)from clinically healthy donors into mice with 2,4,6-trinitrobenzene sulfonic acid(TNBS)-induced CD ameliorated CD symptoms,whereas FMT from CD patients into these mice exacerbated CD symptoms.Notably,FMT influenced intestinal permeability,barrier function,and levels of proinflammatory factors and adipokines.Furthermore,FMT from CD patients intensified fibrotic changes in the colon tissues of mice with TNBS-induced CD.CONCLUSION Gut microbiota play a critical role in the histopathology of CD.Targeting MAT and creeping fat may therefore have potential in the treatment of patients with CD.

Liver transplantation and resection in patients with hepatocellular cancer and portal vein tumor thrombosis: Feasible and effective?

Patients with locally advanced hepatocellular cancer(HCC)and portal vein tumor thrombosis(PVTT)have a dismal prognosis since limited treatment options are available for them.In recent years,effective systemic therapy,and advances in the understanding of technicalities and effectiveness of ablative therapies especially radiotherapy,have given some hope to prolong survival in them.This review summarized recent evidence in literature regarding the possible role of liver resection(LR)and liver transplantation(LT)in patients with locally advanced HCC and PVTT with no extrahepatic disease.Downstaging therapies have helped make curative resection or LT a reality in selected patients.This review emphasizes on the key points to focus on when considering surgery in these patients,who are usually relegated to palliative systemic therapy alone.Meticulous patient selection based on tumor biology,documented downstaging based on imaging and decrease in tumor marker levels,and an adequate waiting period to demonstrate stable disease,may help obtain satisfactory long-term outcomes post LR or LT in an intention to treat strategy in patients with HCC and PVTT.

Transplantation of fibrin-thrombin encapsulated human induced neural stem cells promotes functional recovery of spinal cord injury rats through modulation of the microenvironment

Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury microenvironment.Here,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord injury.Induced neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury model.Basso,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion core.Examination of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the microenvironment.Altogether,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion site.Graft-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats.

Clinical application of COVID-19 vaccine in liver transplant recipients

Background:Solid organ transplant(SOT)activities,such as liver transplant,have been greatly influenced by the pandemic of coronavirus disease 2019(COVID-19),a disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Immunosuppressed individuals of liver transplant recipients(LTRs)tend to have a high risk of COVID-19 infection and related complications.Therefore,COVID-19 vaccination has been recommended to be administered as early as possible in LTRs.Data sources:The keywords“liver transplant”,“SARS-CoV-2”,and“vaccine”were used to retrieve articles published in PubMed.Results:The antibody response following the 1st and 2nd doses of vaccination was disappointingly low,and the immune responses among LTRs remarkably improved after the 3rd or 4th dose of vaccination.Although the 3rd or 4th dose of COVID-19 vaccine increased the antibody titer,a proportion of patients remained unresponsive.Furthermore,recent studies showed that SARS-CoV-2 vaccine could trigger adverse events in LTRs,including allograft rejection and liver injury.Conclusions:This review provides the recently reported data on the antibody response of LTRs following various doses of vaccine,risk factors for poor serological response and adverse events after vaccination.

Fecal microbiota transplantation:whole grain highland barley improves glucose metabolism by changing gut microbiota

Highland barley(HB)is a high-altitude cereal with rich nutritional components and potential health benefits.To clarify its hypoglycemic effect and mechanism,we investigated the effect of whole grain HB and fecal microbiota transplantation(FMT)on glucose metabolism and gut microbiota in high-fat diet and streptozotocin(HFD/STZ)-induced diabetic mice.The results showed that HB(40%)significantly decreased fasting blood glucose and the area under the glucose tolerance curve,significantly increased insulin secretion and improved insulin resistance in HFD/STZ-induced diabetic mice(P<0.05).Inflammatory factors and blood lipid indices were also significantly alleviated after 12 weeks of 40%HB intervention(P<0.05).Additionally,beneficial bacteria,such as Bifidobacterium and Akkermansia,were significantly enriched in the gut of diabetic mice after whole grain HB intervention.Meanwhile,the results of further FMT experiments verified that the fecal microbiota after the 40%HB intervention not only significantly increased the relative abundance of Bifidobacterium and Akkermansia but also effectively improved glucose metabolism and alleviated the inflammatory state in HFD/STZ-induced diabetic mice.Collectively,our study confirmed the bridge role of gut microbiota in improving glucose metabolism of whole grain HB,which could promote the development of precision nutrition.

Validation and performance of three scoring systems for predicting primary non-function and early allograft failure after liver transplantation

Background: Primary non-function(PNF) and early allograft failure(EAF) after liver transplantation(LT) seriously affect patient outcomes. In clinical practice, effective prognostic tools for early identifying recipients at high risk of PNF and EAF were urgently needed. Recently, the Model for Early Allograft Function(MEAF), PNF score by King's College(King-PNF) and Balance-and-Risk-Lactate(BAR-Lac) score were developed to assess the risks of PNF and EAF. This study aimed to externally validate and compare the prognostic performance of these three scores for predicting PNF and EAF. Methods: A retrospective study included 720 patients with primary LT between January 2015 and December 2020. MEAF, King-PNF and BAR-Lac scores were compared using receiver operating characteristic(ROC) and the net reclassification improvement(NRI) and integrated discrimination improvement(IDI) analyses. Results: Of all 720 patients, 28(3.9%) developed PNF and 67(9.3%) developed EAF in 3 months. The overall early allograft dysfunction(EAD) rate was 39.0%. The 3-month patient mortality was 8.6% while 1-year graft-failure-free survival was 89.2%. The median MEAF, King-PNF and BAR-Lac scores were 5.0(3.5–6.3),-2.1(-2.6 to-1.2), and 5.0(2.0–11.0), respectively. For predicting PNF, MEAF and King-PNF scores had excellent area under curves(AUCs) of 0.872 and 0.891, superior to BAR-Lac(AUC = 0.830). The NRI and IDI analyses confirmed that King-PNF score had the best performance in predicting PNF while MEAF served as a better predictor of EAD. The EAF risk curve and 1-year graft-failure-free survival curve showed that King-PNF was superior to MEAF and BAR-Lac scores for stratifying the risk of EAF. Conclusions: MEAF, King-PNF and BAR-Lac were validated as practical and effective risk assessment tools of PNF. King-PNF score outperformed MEAF and BAR-Lac in predicting PNF and EAF within 6 months. BAR-Lac score had a huge advantage in the prediction for PNF without post-transplant variables. Proper use of these scores will help early identify PNF, standardize grading of EAF and reasonably select clinical endpoints in relative studies.

Liver transplantation as an alternative for the treatment of neuroendocrine liver metastasis: Appraisal of the current evidence

Background:Liver transplantation(LT)for neuroendocrine liver metastases(NELM)is still in debate.Studies comparing LT with liver resection(LR)for NELM are scarce,as patient selection is heterogeneous and experience is limited.The goal of this review was to provide a critical analysis of the evidence on LT versus LR in the treatment of NELM.Data sources:A scoping literature search on LT and LR for NELM was performed with PubMed,including English articles up to March 2023.Results:International guidelines recommend LR for NELM in resectable,well-differentiated tumors in the absence of extrahepatic metastatic disease with superior results of LR compared to systemic or liver-directed therapies.Advanced liver surgery has extended resectability criteria whilst entailing increased perioperative risk and short disease-free survival.In highly selected patients(based on the Milan criteria)with unresectable NELM,oncologic results of LT are promising.Prognostic factors include tumor biology(G1/G2)and burden,waiting time for LT,patient age and extrahepatic spread.Based on low-level evi-dence,LT for low-grade NELM within the Milan criteria resulted in improved disease-free survival and overall survival compared to LR.The benefits of LT were lost in patients beyond the Milan NELM-criteria.Conclusions:With adherence to strict selection criteria especially tumor biology,LT for NELM is becoming a valuable option providing oncologic benefits compared to LR.Recent evidence suggests even stricter selection criteria with regard to tumor biology.

Prognostic value of ultrasound in early arterial complications post liver transplant

Liver transplantation is the primary therapeutic intervention for end-stage liver disease.However,vascular complications,particularly those involving the hepatic artery,pose significant risks to patients.The clinical manifestations associated with early arterial complications following liver transplantation are often non-specific.Without timely intervention,these complications can result in graft fai-lure or patient mortality.Therefore,early diagnosis and the formulation of an op-timal treatment plan are imperative.Ultrasound examination remains the pre-dominant imaging modality for detecting complications post liver transplan-tation.This article comprehensively reviews common causes and clinical present-ations of early hepatic artery complications in the post-transplantation period and delineates abnormal sonographic findings for accurate diagnosis of these con-ditions.Overall,ultrasound offers the advantages of convenience,safety,effect-iveness,and non-invasiveness.It enables real-time,dynamic,and precise evalua-tion,making it the preferred diagnostic method for post-liver transplantation assessments.INTRODUCTION Liver transplantation stands as the primary therapeutic approach for end-stage liver disease.Continuous advancements in surgical techniques and the application of novel immunosuppressive agents contribute to ongoing improvements in the success rate and overall survival in patients undergoing liver transplantation procedures.Despite these advan-cements,vascular complications,particularly those involving the hepatic artery,pose significant risks to patients.During the early stages following liver transplantation(within the first 30 d),proper hepatic artery function is crucial for hepatic arterial blood flow.During later stages,collateral circulation,including arteries such as the phrenic artery,right gastric artery,and gastroduodenal artery,becomes important for maintaining hepatic blood supply.It is now understood that the establishment of effective collateral circulation is pivotal for determining the prognosis of hepatic artery complic-ations.The clinical manifestations of these complications are closely linked to factors such as timing,severity,and the specific type of onset.Insufficient hepatic arterial blood flow can lead to abnormal liver function,hepatic infarction,and the formation of hepatic abscesses.Additionally,since the hepatic artery is the sole blood supply to the biliary tract,hepatic artery-related ischemia may result in biliary stricture,obstruction,and the formation of bile ducts.Ultrasound examination remains the primary imaging modality for diagnosing complications post liver transplantation.This article comprehensively reviews common causes and clinical presentations of early hepatic artery complications in the post-transplantation period and outlines abnormal sonographic findings for accurately diagnosing these conditions.NORMAL HEPATIC ARTERY During the intraoperative phase,an ultrasound examination is typically conducted to evaluate the hepatic artery anas-tomosis.The normal internal diameter of the hepatic artery typically ranges from 2 to 5 mm.Two strong echo points are typically identified near the anastomosis.To assess blood flow dynamics,peak systolic velocity,end-diastolic velocity,and resistance index are measured at the donor and recipient sides of the anastomosis following angle correction.Anastomotic stenosis presence and severity can be evaluated by comparing the velocity at the anastomotic site with that at the recipient side.Postoperatively,direct visualization of the anastomosis site through gray ultrasound scans is often challenging.The surgical approach has a significant impact on the proper hepatic artery’s position,resulting in a lower overall success rate of continuous visualization.Color Doppler ultrasound is primarily employed to trace the artery’s path,and spectral measurements are taken at the brightest position of the Color Doppler blood flow signal,primarily used to identify the presence of high-speed turbulence.Hepatic artery spectrum examination plays a crucial role,as a favorable arterial spectral waveform and appropriate hepatic artery flow velocity typically indicate a successful anastomosis,even in cases where the hepatic artery anastomosis cannot be directly visualized by ultrasound.The hepatic artery runs alongside the portal vein,often selected as a reference due to its larger inner diameter.A normal hepatic artery spectrum displays a regular pulsation pattern with a rapid rise in systole and a slow decline in diastole.Parameters for assessing hepatic artery resistance include a resistance index between 0.5 to 0.8 and an artery systolic acceleration of less than 80 ms.Instantaneous increases in the resistance index(RI>0.8)often occur within 2 d after surgery,followed by a subsequent return to normal hepatic arterial parameters.It has been established that the maximum blood flow velocity during systole in the hepatic artery should not exceed 200 cm/s[1].

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.

HSP110 aggravates ischemia-reperfusion injury after liver transplantation by promoting NF-κB pathway

Background:Ischemia-reperfusion injury(IRI)poses a significant challenge to liver transplantation(LT).The underlying mechanism primarily involves overactivation of the immune system.Heat shock protein 110(HSP110)functions as a molecular chaperone that helps stabilize protein structures.Methods:An IRI model was established by performing LT on Sprague-Dawley rats,and HSP110 was silenced using siRNA.Hematoxylin-eosin staining,TUNEL,immunohistochemistry,ELISA and liver enzyme analysis were performed to assess IRI following LT.Western blotting and quantitative reverse transcription-polymerase chain reaction were conducted to investigate the pertinent molecular changes.Results:Our findings revealed a significant increase in the expression of HSP110 at both the mRNA and protein levels in the rat liver following LT(P<0.05).However,when rats were injected with siRNAHSP110,IRI subsequent to LT was notably reduced(P<0.05).Additionally,the levels of liver enzymes and inflammatory chemokines in rat serum were significantly reduced(P<0.05).Silencing HSP110 with siRNA resulted in a marked decrease in M1-type polarization of Kupffer cells in the liver and downregulated the NF-κB pathway in the liver(P<0.05).Conclusions:HSP110 in the liver promotes IRI after LT in rats by activating the NF-κB pathway and inducing M1-type polarization of Kupffer cells.Targeting HSP110 to prevent IRI after LT may represent a promising new approach for the treatment of LT-associated IRI.

Fecal microbiota transplantation for treatment of non-alcoholic fatty liver disease:Mechanism,clinical evidence,and prospect

The population of non-alcoholic fatty liver disease(NAFLD)patients along with relevant advanced liver disease is projected to continue growing,because currently no medications are approved for treatment.Fecal microbiota transplantation(FMT)is believed a novel and promising therapeutic approach based on the concept of the gut-liver axis in liver disease.There has been an increase in the number of pre-clinical and clinical studies evaluating FMT in NAFLD treatment,however,existing findings diverge on its effects.Herein,we briefly summarized the mechanism of FMT for NAFLD treatment,reviewed randomized controlled trials for evaluating its efficacy in NAFLD,and proposed the prospect of future trials on FMT.

Comparison of different preoperative objective nutritional indices for evaluating 30-d mortality and complications after liver transplantation

BACKGROUND The nutritional status is closely related to the prognosis of liver transplant re-cipients,but few studies have reported the role of preoperative objective nutri-tional indices in predicting liver transplant outcomes.AIM To compare the predictive value of various preoperative objective nutritional indicators for determining 30-d mortality and complications following liver transplantation(LT).METHODS A retrospective analysis was conducted on 162 recipients who underwent LT at our institution from December 2019 to June 2022.RESULTS This study identified several independent risk factors associated with 30-d mor-tality,including blood loss,the prognostic nutritional index(PNI),the nutritional risk index(NRI),and the control nutritional status.The 30-d mortality rate was 8.6%.Blood loss,the NRI,and the PNI were found to be independent risk factors for the occurrence of severe postoperative complications.The NRI achieved the highest prediction values for 30-d mortality[area under the curve(AUC)=0.861,P<0.001]and severe complications(AUC=0.643,P=0.011).Compared to those in the high NRI group,the low patients in the NRI group had lower preoperative body mass index and prealbumin and albumin levels,as well as higher alanine aminotransferase and total bilirubin levels,Model for End-stage Liver Disease scores and prothrombin time(P<0.05).Furthermore,the group with a low NRI exhibited significantly greater incidences of intraabdominal bleeding,primary graft nonfunction,and mortality.CONCLUSION The NRI has good predictive value for 30-d mortality and severe complications following LT.The NRI could be an effective tool for transplant surgeons to evaluate perioperative nutritional risk and develop relevant nutritional therapy.

Interplay between mesenchymal stromal cells and the immune system after transplantation: implications for advanced cell therapy in the retina

Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical models.Mesenchymal stromal cells are well positioned as therapeutics because they address the underlying mechanisms of neurodegeneration,namely trophic factor deprivation and neuroinflammation.Most studies have focused on the beneficial effects of mesenchymal stromal cell transplantation on neuronal survival or functional improvement.However,little attention has been paid to the interaction between mesenchymal stromal cells and the host immune system due to the immunomodulatory properties of mesenchymal stromal cells and the long-held belief of the immunoprivileged status of the central nervous system.Here,we review the crosstalk between mesenchymal stromal cells and the immune system in general and in the context of the central nervous system,focusing on recent work in the retina and the importance of the type of transplantation.

Klebsiella pneumoniae infections after liver transplantation:Drug resistance and distribution of pathogens,risk factors,and influence on outcomes

BACKGROUND Liver transplantation(LT)is the only curative treatment for end-stage liver disease.However,LT recipients are susceptible to infection,which is the leading cause of early mortality after LT.Klebsiella pneumoniae infections(KPIs)in the bloodstream are common in LT recipients.We hypothesized that KPIs and carbapenemresistant Klebsiella pneumoniae(CRKP)infections may affect the outcomes of LT recipients.AIM To assess KPI incidence,timing,distribution,drug resistance,and risk factors following LT and its association with outcomes.METHODS This retrospective study included 406 patients undergoing LT at The Third Xiangya Hospital of Central South University,a tertiary hospital,from January 2015 to January 2023.We investigated the risk factors for KPIs and assessed the impact of KPIs and CRKP infections on the prognosis of LT recipients using logistic regression analysis.RESULTS KPI incidence was 7.9%(n=32),with lung/thoracic cavity the most frequent site of infection;the median time from LT to KPI onset was 7.5 d.Of 44 Klebsiella pneumoniae isolates,43(97.7%)and 34(77.3%)were susceptible to polymyxin B or ceftazidime/avibactam and tigecycline,respectively;>70%were resistant to piperacillin/tazobactam,ceftazidime,cefepime,aztreonam,meropenem,and levofloxacin.Female sex[odds ratio(OR)=2.827,95%confidence interval(CI):1.256-6.364;P=0.012],pre-LT diabetes(OR=2.794,95%CI:1.070-7.294;P=0.036),day 1 post-LT alanine aminotransferase(ALT)levels≥1500 U/L(OR=3.645,95%CI:1.671-7.950;P=0.001),and post-LT urethral catheter duration over 4 d(OR=2.266,95%CI:1.016-5.054;P=0.046)were risk factors for KPI.CRKP infections,but not KPIs,were risk factors for 6-month all-cause mortality post-LT.CONCLUSION KPIs occur frequently and rapidly after LT.Risk factors include female sex,pre-LT diabetes,increased post-LT ALT levels,and urethral catheter duration.CRKP infections,and not KPIs,affect mortality.

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.

Role of fecal microbiota transplant in management of hepatic encephalopathy: Current trends and future directions

Fecal microbiota transplantation(FMT)offers a potential treatment avenue for hepatic encephalopathy(HE)by leveraging beneficial bacterial displacement to restore a balanced gut microbiome.The prevalence of HE varies with liver disease severity and comorbidities.HE pathogenesis involves ammonia toxicity,gut-brain communication disruption,and inflammation.FMT aims to restore gut microbiota balance,addressing these factors.FMT's efficacy has been explored in various conditions,including HE.Studies suggest that FMT can modulate gut microbiota,reduce ammonia levels,and alleviate inflammation.FMT has shown promise in alcohol-associated,hepatitis B and C-associated,and non-alcoholic fatty liver disease.Benefits include improved liver function,cognitive function,and the slowing of disease progression.However,larger,controlled studies are needed to validate its effectiveness in these contexts.Studies have shown cognitive improvements through FMT,with potential benefits in cirrhotic patients.Notably,trials have demonstrated reduced serious adverse events and cognitive enhancements in FMT arms compared to the standard of care.Although evidence is promising,challenges remain:Limited patient numbers,varied dosages,administration routes,and donor profiles.Further large-scale,controlled trials are essential to establish standardized guidelines and ensure FMT's clinical applications and efficacy.While FMT holds potential for HE management,ongoing research is needed to address these challenges,optimize protocols,and expand its availability as a therapeutic option for diverse hepatic conditions.