Patients admitted in the intensive care unit after solid organ or bone marrow transplantation:Retrospective cohort study

BACKGROUND Solid organ transplantation(SOT)and hematopoietic stem cell transplantation(HSCT)revolutionized the survival and quality of life of patients with malignant diseases,various immunologic,and metabolic disorders or those associated with a significant impairment in a patient's quality of life.AIM To investigate admission causes and treatment outcomes of patients after SOT or HSCT treated in a medical intensive care unit(ICU).METHODS We conducted a single-center,retrospective epidemiological study in the medical ICU at the University Hospital Centre Zagreb,Croatia covering the period from January 1,2018 to December 31,2023.RESULTS The study included 91 patients with either SOT[28 patients(30.8%)]or HSCT[63 patients(69.2%)].The median age was 56(43.2-64.7)years,and 60.4%of the patients were male.Patients with SOT had more comorbidities than patients after HSCT[χ^(2)(5,n=141)=18.513,P<0.001].Sepsis and septic shock were the most frequent reasons for admission,followed by acute respiratory insufficiency in patients following HSCT.Survival rate significantly differed between SOT and HSCT[χ^(2)(1,n=91)=21.767,P<0.001].ICU survival was 57%in the SOT and 12.7%in the HSCT group.The need for mechanical ventilation[χ^(2)(1,n=91)=17.081,P<0.001]and vasopressor therapy[χ^(2)(1,n=91)=36.803,P<0.001]was associated with survival.The necessity for acute renal replacement therapy did not influence patients'survival[χ^(2)(1,n=91)=0.376,P=0.54].In the subgroup of patients with infection,90%had septic shock,and the majority had positive microbiological samples,mostly Gram-negative bacteria.The ICU survival of patients with sepsis/septic shock cumulatively was 15%.The survival of SOT patients with sepsis/shock was 45%.CONCLUSION Patients with SOT or HSCT are frequently admitted to the ICU due to sepsis and septic shock.Despite advancements in critical care,the mortality rate of patients with refractory septic shock and multiorgan failure in this patient population is extremely high.Early recognition and timely ICU admittance might improve the outcome of patients,especially after HSCT.

Global transplantation:Lessons from organ transplantation organizations worldwide

Although national transplant organizations share common visions and goals,the creation of a unified global organization remains impractical.Differences in ethnicity,culture,religion,and education shape local practices and infrastructure,making the establishment of a single global entity unfeasible.Even with these social disparities aside,logistical factors such as time and distance between organ procurement and transplantation sites pose significant challenges.While technological advancements have extended organ preservation times,they have yet to support the demands of transcontinental transplantations effectively.This review presents a comparative analysis of the structures,operational frameworks,policies,and legislation governing various transplant organizations around the world.Key differences pertain to the administration of these organizations,trends in organ donation,and organ allocation policies,which reflect the financial,cultural,and religious diversity across different regions.While a global transplant organization may be out of reach,agreeing on best practices for the benefit of patients is essential.

Lesson learnt from 60 years of liver transplantation:Advancements,challenges,and future directions

Over the past six decades,liver transplantation(LT)has evolved from an experimental procedure into a standardized and life-saving intervention,reshaping the landscape of organ transplantation.Driven by pioneering breakthroughs,technological advancements,and a deepened understanding of immunology,LT has seen remarkable progress.Some of the most notable breakthroughs in the field include advances in immunosuppression,a revised model for end-stage liver disease,and artificial intelligence(AI)-integrated imaging modalities serving diagnostic and therapeutic roles in LT,paired with ever-evolving technological advances.Additionally,the refinement of transplantation procedures,resulting in the introduction of alternative transplantation methods,such as living donor LT,split LT,and the use of marginal grafts,has addressed the challenge of organ shortage.Moreover,precision medicine,guiding personalized immunosuppressive strategies,has significantly improved patient and graft survival rates while addressing emergent issues,such as short-term complications and early allograft dysfunction,leading to a more refined strategy and enhanced postoperative recovery.Looking ahead,ongoing research explores regenerative medicine,diagnostic tools,and AI to optimize organ allocation and posttransplantation car.In summary,the past six decades have marked a transformative journey in LT with a commitment to advancing science,medicine,and patient-centered care,offering hope and extending life to individuals worldwide.

Interplay between creeping fat and gut microbiota: A brand-new perspective on fecal microbiota transplantation in Crohn's disease

Inflammatory bowel disease,particularly Crohn's disease(CD),has been linked to modifications in mesenteric adipose tissue(MAT)and the phenomenon known as"creeping fat"(CrF).The presence of CrF is believed to serve as a predictor for early clinical recurrence following surgical intervention in patients with CD.Notably,the incorporation of the mesentery during ileocolic resection for CD has been correlated with a decrease in surgical recurrence,indicating the significant role of MAT in the pathogenesis of CD.While numerous studies have indicated that dysbiosis of the gut microbiota is a critical factor in the development of CD,the functional implications of translocated microbiota within the MAT of CD patients remain ambiguous.This manuscript commentary discusses a recent basic research conducted by Wu et al.In their study,intestinal bacteria from individuals were transplanted into CD model mice,revealing that fecal microbiota trans-plantation(FMT)from healthy donors alleviated CD symptoms,whereas FMT from CD patients exacerbated these symptoms.Importantly,FMT was found to affect intestinal permeability,barrier function,and the levels of proinflammatory factors and adipokines.Collectively,these findings suggest that targeting MAT and CrF may hold therapeutic potential for patients with CD.However,the study did not evaluate the composition of the intestinal microbiota of the donors or the subsequent alterations in the gut microbiota.Overall,the gut microbiota plays a crucial role in the histopathology of CD,and thus,targeting MAT and CrF may represent a promising avenue for treatment in this patient population.

Human leukocyte antigen and donor-specific antibodies in liver transplantation

In this article,we comment on an article published in a recent issue of the World Journal of Gastroenterology.We specifically focus on the roles of human leukocyte antigen(HLA)and donor-specific antibodies(DSAs)in pediatric liver transpl-antation(LT),as well as the relationship between immune rejection after LT and DSA.Currently,LT remains the standard of care for pediatric patients with end-stage liver disease or severe acute liver failure.However,acute and chronic re-jection continues to be a significant cause of graft dysfunction and loss.HLA mismatch significantly reduces graft survival and increases the risk of acute rejection.Among them,D→R one-way mismatch at three loci was significantly related to graft-versus-host disease incidence after LT.The adverse impact of HLA-DSAs on LT recipients is already established.Therefore,the evaluation of HLA and DSA is crucial in pediatric LT.

Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury

Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal cord.Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury.We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal directions.Such Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder functions.Importantly,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord injury.These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

Expanding role of antibodies in kidney transplantation

The role of antibodies in kidney transplant(KT)has evolved significantly over the past few decades.This role of antibodies in KT is multifaceted,encompassing both the challenges they pose in terms of antibody-mediated rejection(AMR)and the opportunities for improving transplant outcomes through better detection,prevention,and treatment strategies.As our understanding of the immunological mechanisms continues to evolve,so too will the approaches to managing and harnessing the power of antibodies in KT,ultimately leading to improved patient and graft survival.This narrative review explores the multifaceted roles of antibodies in KT,including their involvement in rejection mechanisms,advancements in desensitization protocols,AMR treatments,and their potential role in monitoring and improving graft survival.

Fecal microbiota transplantation in allergic diseases

Microorganisms such as bacteria,fungi,viruses,parasites living in the human intestine constitute the human intestinal microbiota.Dysbiosis refers to composi-tional and quantitative changes that negatively affect healthy gut microbiota.In recent years,with the demonstration that many diseases are associated with dysbiosis,treatment strategies targeting the correction of dysbiosis in the treat-ment of these diseases have begun to be investigated.Faecal microbiota trans-plantation(FMT)is the process of transferring faeces from a healthy donor to another recipient in order to restore the gut microbiota and provide a therapeutic benefit.FMT studies have gained popularity after probiotic,prebiotic,symbiotic studies in the treatment of dysbiosis and related diseases.FMT has emerged as a potential new therapy in the treatment of allergic diseases as it is associated with the maintenance of intestinal microbiota and immunological balance(T helper 1/T helper 2 cells)and thus suppression of allergic responses.In this article,the definition,application,safety and use of FMT in allergic diseases will be discussed with current data.

Literature study on traditional Chinese medicine syndromes after renal transplantation

BACKGROUND Kidney transplantation is the most effective means to treat patients with renal failure,but its postoperative problems such as rejection reactions,immunosuppressant poisoning,chronic transplant kidney nephropathy,etc.still have not been effectively solved.This study searched for literature on traditional Chinese medicine(TCM)syndromes after kidney transplantation in China,conducted statistical analysis of the results,and sought to identify the underlying patterns.AIM To understand the TCM syndromes after renal transplantation and associated rules and provide a theoretical basis for further clinical research.METHODS The literature pertaining to TCM syndromes in renal transplantation,published in the China National Knowledge Infrastructure,Wanfang database,and WIP database from 1970 to 2021,was meticulously searched and comprehensively and statistically analyzed.RESULTS Following the established inclusion and exclusion criteria,13 studies were selected for analysis.Post-renal transplantation,no significant discrepancy was noted among the groups based on the location of TCM viscera.However,when categorized according to TCM pathogenic factors,the groups with spleen and kidney yang deficiency,as well as liver and kidney yin deficiency,exhibited a statistically significant difference in the frequency.CONCLUSION Currently,the research on TCM syndromes pertaining to renal transplantation is in its nascent phase.It is imperative to conduct a multicentric,large-scale survey of TCM syndromes subsequent to renal transplantation in the ensuing years.

Future of non-invasive graft evaluation:A systematic review of proteomics in kidney transplantation

BACKGROUND Despite the developments in the field of kidney transplantation,the already existing diagnostic techniques for patient monitoring are considered insufficient.Protein biomarkers that can be derived from modern approaches of proteomic analysis of liquid biopsies(serum,urine)represent a promising innovation in the monitoring of kidney transplant recipients.AIM To investigate the diagnostic utility of protein biomarkers derived from proteomics approaches in renal allograft assessment.METHODS A systematic review was conducted in accordance with PRISMA guidelines,based on research results from the PubMed and Scopus databases.The primary focus was on evaluating the role of biomarkers in the non-invasive diagnosis of transplant-related com-plications.Eligibility criteria included protein biomarkers and urine and blood samples,while exclusion criteria were language other than English and the use of low resolution and sensitivity methods.The selected research articles,were categorized based on the biological sample,condition and methodology and the significantly and reproducibly differentiated proteins were manually selected and extracted.Functional and network analysis of the selected proteins was performed.RESULTS In 17 included studies,58 proteins were studied,with the cytokine CXCL10 being the most investigated.Biological pathways related to immune response and fibrosis have shown to be enriched.Applications of biomarkers for the assessment of renal damage as well as the prediction of short-term and long-term function of the graft were reported.Overall,all studies have shown satisfactory diagnostic accuracy of proteins alone or in combination with conventional methods,as far as renal graft assessment is concerned.CONCLUSION Our review suggests that protein biomarkers,evaluated in specific biological fluids,can make a significant contribution to the timely,valid and non-invasive assessment of kidney graft.

Machine learning in solid organ transplantation:Charting the evolving landscape

BACKGROUND Machine learning(ML),a major branch of artificial intelligence,has not only demonstrated the potential to significantly improve numerous sectors of healthcare but has also made significant contributions to the field of solid organ transplantation.ML provides revolutionary opportunities in areas such as donorrecipient matching,post-transplant monitoring,and patient care by automatically analyzing large amounts of data,identifying patterns,and forecasting outcomes.AIM To conduct a comprehensive bibliometric analysis of publications on the use of ML in transplantation to understand current research trends and their implications.METHODS On July 18,a thorough search strategy was used with the Web of Science database.ML and transplantation-related keywords were utilized.With the aid of the VOS viewer application,the identified articles were subjected to bibliometric variable analysis in order to determine publication counts,citation counts,contributing countries,and institutions,among other factors.RESULTS Of the 529 articles that were first identified,427 were deemed relevant for bibliometric analysis.A surge in publications was observed over the last four years,especially after 2018,signifying growing interest in this area.With 209 publications,the United States emerged as the top contributor.Notably,the"Journal of Heart and Lung Transplantation"and the"American Journal of Transplantation"emerged as the leading journals,publishing the highest number of relevant articles.Frequent keyword searches revealed that patient survival,mortality,outcomes,allocation,and risk assessment were significant themes of focus.CONCLUSION The growing body of pertinent publications highlights ML's growing presence in the field of solid organ transplantation.This bibliometric analysis highlights the growing importance of ML in transplant research and highlights its exciting potential to change medical practices and enhance patient outcomes.Encouraging collaboration between significant contributors can potentially fast-track advancements in this interdisciplinary domain.

Success of intravenous immunoglobulin and steroids in managing severe COVID-19 following lung transplantation:A case report

BACKGROUND Coronavirus disease 2019(COVID-19)pneumonia with severe septic shock and acute respiratory distress syndrome(ARDS)are critical illnesses for patients following transplant.Intravenous immunoglobulin(IVIG)plays a role in both immune support and inflammation control,especially in immunocompromised patients.This case report describes the first successful experience using IVIG and pulse steroids to manage this critical condition following lung transplantation.CASE SUMMARY A 65-year-old male patient reported a history of chronic obstructive pulmonary disease and poor lung function and received bilateral sequential lung transplantations.Postoperatively,he developed COVID-19 pneumonia,severe septic shock,and ARDS.He recovered from this critical condition after empirical antibiotics administration and veno-venous extracorporeal membrane oxygenation,in addition to IVIG and pulse steroids.CONCLUSION IVIG is a valuable adjunct in managing severe sepsis in lung transplant recipients after COVID-19 infection.We aim,for the first time,to report the success of such a management approach for COVID-19 ARDS and sepsis in the post-lung transplant setting.With further investigations,this is a starting point for wider analysis of such an approach in this setting and consequently helps guide clinical practice for such a challenging patient population moving forward.

Advances in the treatment of autism spectrum disorder:Wharton jelly mesenchymal stem cell transplantation

BACKGROUND Autism spectrum disorder(ASD)is a complex neurodevelopmental disorder with multifaceted origins.In recent studies,neuroinflammation and immune dysregulation have come to the forefront in its pathogenesis.There are studies suggesting that stem cell therapy may be effective in the treatment of ASD.AIM To evolve the landscape of ASD treatment,focusing on the potential benefits and safety of stem cell transplantation.METHODS A detailed case report is presented,displaying the positive outcomes observed in a child who underwent intrathecal and intravenous Wharton’s jelly-derived mesenchymal stem cells(WJ-MSCs)transplantation combined with neurorehabilitation.RESULTS The study demonstrates a significant improvement in the child’s functional outcomes(Childhood Autism Rating Scale,Denver 2 Developmental Screening Test),especially in language and gross motor skills.No serious side effects were encountered during the 2-year follow-up.CONCLUSION The findings support the safety and effectiveness of WJ-MSC transplantation in managing ASD.

Physiology and health assessment,risk balance,and model for endstage liver disease scores:Postoperative outcome of liver transplantation

BACKGROUND Liver transplantation aims to increase the survival of patients with end-stage liver diseases and improve their quality of life.The number of organs available for transplantation is lower than the demand.To provide fair organ distribution,predictive mortality scores have been developed.AIM To compare the Acute Physiology and Chronic Health Evaluation IV(APACHE IV),balance of risk(BAR),and model for end-stage liver disease(MELD)scores as predictors of mortality.METHODS Retrospective cohort study,which included 283 adult patients in the postoperative period of deceased donor liver transplantation from 2014 to 2018.RESULTS The transplant recipients were mainly male,with a mean age of 58.1 years.Donors were mostly male,with a mean age of 41.6 years.The median cold ischemia time was 3.1 hours,and the median intensive care unit stay was 5 days.For APACHE IV,a mean of 59.6 was found,BAR 10.7,and MELD 24.2.The 28-day mortality rate was 9.5%,and at 90 days,it was 3.5%.The 28-day mortality prediction for APACHE IV was very good[area under the curve(AUC):0.85,P<0.001,95%CI:0.76-0.94],P<0.001,BAR(AUC:0.70,P<0.001,95%CI:0.58–0.81),and MELD(AUC:0.66,P<0.006,95%CI:0.55-0.78),P<0.008.At 90 days,the data for APACHE IV were very good(AUC:0.80,P<0.001,95%CI:0.71–0.90)and moderate for BAR and MELD,respectively,(AUC:0.66,P<0.004,95%CI:0.55–0.77),(AUC:0.62,P<0.026,95%CI:0.51–0.72).All showed good discrimination between deaths and survivors.As for the best value for liver transplantation,it was significant only for APACHE IV(P<0.001).CONCLUSION The APACHE IV assessment score was more accurate than BAR and MELD in predicting mortality in deceased donor liver transplant recipients.

Effects of early postnatal gastric and colonic microbiota transplantation on piglet gut health

Background Diarrhea is a major cause of reduced growth and mortality in piglets during the suckling and weaning periods and poses a major threat to the global pig industry.Diarrhea and gut dysbiosis may in part be prevented via improved early postnatal microbial colonization of the gut.To secure better postnatal gut colonization,we hypothesized that transplantation of colonic or gastric content from healthy donors to newborn recipients would prevent diarrhea in the recipients in the post-weaning period.Our objective was to examine the impact of transplanting colonic or gastric content on health and growth parameters and paraclinical parameters in recipient single-housed piglets exposed to a weaning transition and challenged with enterotoxigenic Escherichia coli(ETEC).Methods Seventy-two 1-day-old piglets were randomized to four groups:colonic microbiota transplantation(CMT,n=18),colonic content filtrate transplantation(CcFT,n=18),gastric microbiota transplantation(GMT,n=18),or saline(CON,n=18).Inoculations were given on d 2 and 3 of life,and all piglets were milk-fed until weaning(d 20)and shortly after challenged with ETEC(d 24).We assessed growth,diarrhea prevalence,ETEC concentration,organ weight,blood parameters,small intestinal morphology and histology,gut mucosal function,and microbiota composition and diversity.Results Episodes of diarrhea were seen in all groups during both the milk-and the solid-feeding phase,possibly due to stress associated with single housing.However,CcFT showed lower diarrhea prevalence on d 27,28,and 29 compared to CON(all P<0.05).CcFT also showed a lower ETEC prevalence on d 27(P<0.05).CMT showed a higher alpha diversity and a difference in beta diversity compared to CON(P<0.05).Growth and other paraclinical endpoints were similar across groups.Conclusion In conclusion,only CcFT reduced ETEC-related post-weaning diarrhea.However,the protective effect was marginal,suggesting that higher doses,more effective modalities of administration,longer treatment periods,and better donor quality should be explored by future research to optimize the protective effects of transplantation.

Incidence, risk factors and clinical outcome of multidrug-resistant organisms after heart transplantation

BACKGROUND Transplant recipients commonly harbor multidrug-resistant organisms(MDROs),as a result of frequent hospital admissions and increased exposure to antimi-crobials and invasive procedures.AIM To investigate the impact of patient demographic and clinical characteristics on MDRO acquisition,as well as the impact of MDRO acquisition on intensive care unit(ICU)and hospital length of stay,and on ICU mortality and 1-year mortality post heart transplantation.METHODS This retrospective cohort study analyzed 98 consecutive heart transplant patients over a ten-year period(2013-2022)in a single transplantation center.Data was collected regarding MDROs commonly encountered in critical care.RESULTS Among the 98 transplanted patients(70%male),about a third(32%)acquired or already harbored MDROs upon transplantation(MDRO group),while two thirds did not(MDRO-free group).The prevalent MDROs were Acinetobacter baumannii(14%),Pseudomonas aeruginosa(12%)and Klebsiella pneumoniae(11%).Compared to MDRO-free patients,the MDRO group was characterized by higher body mass index(P=0.002),higher rates of renal failure(P=0.017),primary graft dysfunction(10%vs 4.5%,P=0.001),surgical re-exploration(34%vs 14%,P=0.017),mechanical circulatory support(47%vs 26%P=0.037)and renal replacement therapy(28%vs 9%,P=0.014),as well as longer extracorporeal circulation time(median 210 vs 161 min,P=0.003).The median length of stay was longer in the MDRO group,namely ICU stay was 16 vs 9 d in the MDRO-free group(P=0.001),and hospital stay was 38 vs 28 d(P=0.006),while 1-year mortality was higher(28%vs 7.6%,log-rank-χ2:7.34).CONCLUSION Following heart transplantation,a predominance of Gram-negative MDROs was noted.MDRO acquisition was associated with higher complication rates,prolonged ICU and total hospital stay,and higher post-transplantation mortality.

How to apply ex-vivo split liver transplantation safely and feasibly: A three-step approach

BACKGROUND Given the current organ shortage crisis,split liver transplantation(SLT)has emerged as a promising alternative for select end-stage liver disease patients.AIM To introduce an ex-vivo liver graft splitting approach and evaluate its safety and feasibility in SLT.METHODS A retrospective analysis was conducted on the liver transplantation data from cases performed at our center between April 1,2022,and May 31,2023.The study included 25 SLT cases and 81 whole liver transplantation(WLT)cases.Total ex-vivo liver splitting was employed for SLT graft procurement in three steps.Patient outcomes were determined,including liver function parameters,postoperative complications,and perioperative mortality.Group comparisons for categorical variables were performed using theχ²-test.RESULTS In the study,postoperative complications in the 25 SLT cases included hepatic artery thrombosis(n=1)and pulmonary infections(n=3),with no perioperative mortality.In contrast,among the 81 patients who underwent WLT,complications included perioperative mortality(n=1),postoperative pulmonary infections(n=8),abdominal infection(n=1),hepatic artery thromboses(n=3),portal vein thrombosis(n=1),and intra-abdominal bleeding(n=5).Comparative analysis demonstrated significant differences in alanine aminotransferase(176.0 vs 73.5,P=0.000)and aspartate aminotransferase(AST)(42.0 vs 29.0,P=0.004)at 1 wk postoperatively,and in total bilirubin(11.8 vs 20.8,P=0.003)and AST(41.5 vs 26.0,P=0.014)at 2 wk postoperatively.However,the overall incidence of complications was comparable between the two groups(P>0.05).CONCLUSION Our findings suggest that the total ex-vivo liver graft splitting technique is a safe and feasible approach,especially under the expertise of an experienced transplant center.The approach developed by our center can serve as a valuable reference for other transplantation centers.

Relative carcinogenicity of tacrolimus vs mycophenolate after solid organ transplantation and its implications for liver transplant care

BACKGROUND De novo malignancy is a leading cause of late morbidity and mortality in liver transplant recipients.Cumulative immunosuppression has been shown to contribute to post-transplant malignancy(PTM)risk.There is emerging evidence on the differential carcinogenic risk profile of individual immunosuppressive drugs,independent of the net effect of immunosuppression.Calcineurin inhibitors such as tacrolimus may promote tumourigenesis,whereas mycophenolic acid(MPA),the active metabolite of mycophenolate mofetil,may limit tumour progression.Liver transplantation(LT)is relatively unique among solid organ transplantation in that immunosuppression monotherapy with either tacrolimus or MPA is often achievable,which makes careful consideration of the risk-benefit profile of these immunosuppression agents particularly relevant for this cohort.However,there is limited clinical data on this subject in both LT and other solid organ transplant recipients.AIM To investigate the relative carcinogenicity of tacrolimus and MPA in solid organ transplantation.METHODS A literature search was conducted using MEDLINE and Embase databases using the key terms“solid organ transplantation”,“tacrolimus”,“mycophenolic acid”,and“carcinogenicity”,in order to identify relevant articles published in English between 1st January 2002 to 11th August 2022.Related terms,synonyms and explosion of MeSH terms,Boolean operators and truncations were also utilised in the search.Reference lists of retrieved articles were also reviewed to identify any additional articles.Excluding duplicates,abstracts from 1230 records were screened by a single reviewer,whereby 31 records were reviewed in detail.Full-text articles were assessed for eligibility based on pre-specified inclusion and exclusion criteria.RESULTS A total of 6 studies were included in this review.All studies were large population registries or cohort studies,which varied in transplant era,type of organ transplanted and immunosuppression protocol used.Overall,there was no clear difference demonstrated between tacrolimus and MPA in de novo PTM risk following solid organ transplantation.Furthermore,no study provided a direct comparison of carcinogenic risk between tacrolimus and MPA monotherapy in solid organ transplantation recipients.CONCLUSION The contrasting carcinogenic risk profiles of tacrolimus and MPA demonstrated in previous experimental studies,and its application in solid organ transplantation,is yet to be confirmed in clinical studies.Thus,the optimal choice of immunosuppression drug to use as maintenance monotherapy in LT recipients is not supported by a strong evidence base and remains unclear.

Insight into the history and trends of liver transplantation for echinococcosis:A bibliometric analysis

BACKGROUND Liver transplantation(LT)has demonstrated favorable efficacy in managing endstage alveolar echinococcosis.Nevertheless,the current research focal points and advancement trends remain ambiguous.AIM To map the research landscape to underscore critical areas of focus,influential studies,and future directions of LT for echinococcosis treatment.METHODS Publications on LT for echinococcosis treatment published between 1900 and 2023 were searched in the Web of Science database and analyzed using bibliometrics.RESULTS A total of 14 countries/regions,75 institutions,and 499 authors have published research articles,with China,Turkey,and France being the three most productive countries.The four institutions with the most contributions were Sichuan University,Xinjiang Medical University,the University de Franche Comte,and Inonu University.The three authors who contributed the most were Wen Hao,Wang Wentao,and Bresson Hadni Solange.The four most common keywords were alveolar echinococcosis,LT,ex-vivo liver resection and autotransplantation,and echinococcosis multilocularies.CONCLUSION Our study found that the treatment of complications after LT for echinococcosis treatment and the preoperative surgical plan based on the anatomical relationship between the lesion and the blood vessel are early research hotspots.Recent research focuses on the treatment of complications after ex-vivo liver resection and autotransplantation,especially vascular complications.

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.