Stem cell-based brain repair is a promising emergent therapy for Parkinson's disease based on years of foundational research using human fetal donors as a cell source.Unlike current therapeutic options for patient...Stem cell-based brain repair is a promising emergent therapy for Parkinson's disease based on years of foundational research using human fetal donors as a cell source.Unlike current therapeutic options for patients,this approach has the potential to provide longterm stem cell–derived reconstruction and restoration of the dopaminergic input to denervated regions of the brain allowing for restoration of certain functions to patients.The ultimate clinical success of stem cell–derived brain repair will depend on both the safety and efficacy of the approach and the latter is dependent on the ability of the transplanted cells to survive and differentiate into functional dopaminergic neurons in the Parkinsonian brain.Because the pre-clinical literature suggests that there is considerable variability in survival and differentiation between studies,the aim of this systematic review was to assess these parameters in human stem cell-derived dopaminergic progenitor transplant studies in animal models of Parkinson's disease.A defined systematic search of the PubMed database was completed to identify relevant studies published up to March 2024.After screening,76 articles were included in the analysis from which 178 separate transplant studies were identified.From these,graft survival could be assessed in 52 studies and differentiation in 129 studies.Overall,we found that graft survival ranged from<1% to 500% of cells transplanted,with a median of 51%of transplanted cells surviving in the brain;while dopaminergic differentiation of the cells ranged from 0% to 46% of cells transplanted with a median of 3%.This systematic review suggests that there is considerable scope for improvement in the differentiation of stem cell-derived dopaminergic progenitors to maximize the therapeutic potential of this approach for patients.展开更多
Behavioral recovery using(viable)peripheral nerve allografts to repair ablation-type(segmental-loss)peripheral nerve injuries is delayed or poor due to slow and inaccurate axonal regeneration.Furthermore,such peripher...Behavioral recovery using(viable)peripheral nerve allografts to repair ablation-type(segmental-loss)peripheral nerve injuries is delayed or poor due to slow and inaccurate axonal regeneration.Furthermore,such peripheral nerve allografts undergo immunological rejection by the host immune system.In contrast,peripheral nerve injuries repaired by polyethylene glycol fusion of peripheral nerve allografts exhibit excellent behavioral recovery within weeks,reduced immune responses,and many axons do not undergo Wallerian degeneration.The relative contribution of neurorrhaphy and polyethylene glycol-fusion of axons versus the effects of polyethylene glycol per se was unknown prior to this study.We hypothesized that polyethylene glycol might have some immune-protective effects,but polyethylene glycol-fusion was necessary to prevent Wallerian degeneration and functional/behavioral recovery.We examined how polyethylene glycol solutions per se affect functional and behavioral recovery and peripheral nerve allograft morphological and immunological responses in the absence of polyethylene glycol-induced axonal fusion.Ablation-type sciatic nerve injuries in outbred Sprague–Dawley rats were repaired according to a modified protocol using the same solutions as polyethylene glycol-fused peripheral nerve allografts,but peripheral nerve allografts were loose-sutured(loose-sutured polyethylene glycol)with an intentional gap of 1–2 mm to prevent fusion by polyethylene glycol of peripheral nerve allograft axons with host axons.Similar to negative control peripheral nerve allografts not treated by polyethylene glycol and in contrast to polyethylene glycol-fused peripheral nerve allografts,animals with loose-sutured polyethylene glycol peripheral nerve allografts exhibited Wallerian degeneration for all axons and myelin degeneration by 7 days postoperatively and did not recover sciatic-mediated behavioral functions by 42 days postoperatively.Other morphological signs of rejection,such as collapsed Schwann cell basal lamina tubes,were absent in polyethylene glycol-fused peripheral nerve allografts but commonly observed in negative control and loose-sutured polyethylene glycol peripheral nerve allografts at 21 days postoperatively.Loose-sutured polyethylene glycol peripheral nerve allografts had more pro-inflammatory and less anti-inflammatory macrophages than negative control peripheral nerve allografts.While T cell counts were similarly high in loose-sutured-polyethylene glycol and negative control peripheral nerve allografts,loose-sutured polyethylene glycol peripheral nerve allografts expressed some cytokines/chemokines important for T cell activation at much lower levels at 14 days postoperatively.MHCI expression was elevated in loose-sutured polyethylene glycol peripheral nerve allografts,but MHCII expression was modestly lower compared to negative control at 21 days postoperatively.We conclude that,while polyethylene glycol per se reduces some immune responses of peripheral nerve allografts,successful polyethylene glycol-fusion repair of some axons is necessary to prevent Wallerian degeneration of those axons and immune rejection of peripheral nerve allografts,and produce recovery of sensory/motor functions and voluntary behaviors.Translation of polyethylene glycol-fusion technologies would produce a paradigm shift from the current clinical practice of waiting days to months to repair ablation peripheral nerve injuries.展开更多
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...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.展开更多
Extensive research has investigated the etiology of Crohn’s disease(CD),encompassing genetic predisposition,lifestyle factors,and environmental triggers.Recently,the gut microbiome,recognized as the human body’s sec...Extensive research has investigated the etiology of Crohn’s disease(CD),encompassing genetic predisposition,lifestyle factors,and environmental triggers.Recently,the gut microbiome,recognized as the human body’s second-largest gene pool,has garnered significant attention for its crucial role in the patho-genesis of CD.This paper investigates the mechanisms underlying CD,focusing on the role of‘creeping fat’in disease progression and exploring emerging therapeutic strategies,including fecal microbiota transplantation,enteral nutri-tion,and therapeutic diets.Creeping fat has been identified as a unique patho-logical feature of CD and has recently been found to be associated with dysbiosis of the gut microbiome.We characterize this dysbiotic state by identi-fying key microbiome-bacteria,fungi,viruses,and archaea,and their contributions to CD pathogenesis.Additionally,this paper reviews contemporary therapies,empha-sizing the potential of biological therapies like fecal microbiota transplantation and dietary interventions.By elucidating the complex interactions between host-microbiome dynamics and CD pathology,this article aims to advance our under-standing of the disease and guide the development of more effective therapeutic strategies for managing CD.展开更多
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 believe...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.展开更多
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 ped...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.展开更多
Age-related macular degeneration is a serious neurodegenerative disease of the retina that significantly impacts vision.Unfortunately,the specific pathogenesis remains unclear,and effective early treatment options are...Age-related macular degeneration is a serious neurodegenerative disease of the retina that significantly impacts vision.Unfortunately,the specific pathogenesis remains unclear,and effective early treatment options are consequently lacking.The microbiome is defined as a large ecosystem of microorganisms living within and coexisting with a host.The intestinal microbiome undergoes dynamic changes owing to age,diet,genetics,and other factors.Such dysregulation of the intestinal flora can disrupt the microecological balance,resulting in immunological and metabolic dysfunction in the host,and affecting the development of many diseases.In recent decades,significant evidence has indicated that the intestinal flora also influences systems outside of the digestive tract,including the brain.Indeed,several studies have demonstrated the critical role of the gut-brain axis in the development of brain neurodegenerative diseases,including Alzheimer’s disease and Parkinson’s disease.Similarly,the role of the“gut-eye axis”has been confirmed to play a role in the pathogenesis of many ocular disorders.Moreover,age-related macular degeneration and many brain neurodegenerative diseases have been shown to share several risk factors and to exhibit comparable etiologies.As such,the intestinal flora may play an important role in age-related macular degeneration.Given the above context,the present review aims to clarify the gut-brain and gut-eye connections,assess the effect of intestinal flora and metabolites on age-related macular degeneration,and identify potential diagnostic markers and therapeutic strategies.Currently,direct research on the role of intestinal flora in age-related macular degeneration is still relatively limited,while studies focusing solely on intestinal flora are insufficient to fully elucidate its functional role in age-related macular degeneration.Organ-on-a-chip technology has shown promise in clarifying the gut-eye interactions,while integrating analysis of the intestinal flora with research on metabolites through metabolomics and other techniques is crucial for understanding their potential mechanisms.展开更多
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...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.展开更多
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 disorde...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.展开更多
Transplantation of the left lateral section(LLS)of the liver is now an established practice for treating advanced diffuse and unresectable focal liver diseases in children,with variants of the LLS primarily used in in...Transplantation of the left lateral section(LLS)of the liver is now an established practice for treating advanced diffuse and unresectable focal liver diseases in children,with variants of the LLS primarily used in infants.However,the surgical challenge of matching the size of an adult donor's graft to the volume of a child's abdomen remains significant.This review explores historical developments,various approaches to measuring the required functional liver mass,and techniques to prevent complications associated with large-for-size grafts in infants.展开更多
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 brea...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.展开更多
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...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.展开更多
BACKGROUND In the absence of effective antimicrobials,transplant surgery is not viable,and antirejection immunosuppressants cannot be administered,as resistant infections compromise the life-saving goal of organ trans...BACKGROUND In the absence of effective antimicrobials,transplant surgery is not viable,and antirejection immunosuppressants cannot be administered,as resistant infections compromise the life-saving goal of organ transplantation.AIM To evaluate the efficacy of antimicrobials in preventing resistance in solid organ transplant recipients.METHODS A systematic review was conducted using a search methodology consistent with the preferred reporting items for systematic reviews and meta-analyses.This review included randomized clinical trials that evaluated the efficacy of antimicrobial agents(prophylactic or therapeutic)aimed at preventing antimicrobial resistance.The search strategy involved analyzing multiple databases,including PubMed/MEDLINE,Web of Science,Embase,Scopus,and SciELO,as well as examining gray literature sources on Google Scholar.A comprehensive electronic database search was conducted from the databases’inception until May 2024,with no language restrictions.RESULTS After the final phase of the eligibility assessment,this systematic review ultimate-ly included 7 articles.A total of 2318 patients were studied.The most studied microorganisms were cytomegalovirus,although vancomycinresistant enterococci,Clostridioides difficile,and multidrug-resistant Enterobacterales were also analyzed.The antimicrobials used in the interventions were mainly maribavir,valganciclovir,gancic-lovir,and colistin-neomycin.Of concern,all clinical trials showed significant proportions of resistant microorga-nisms after the interventions,with no statistically significant differences between the groups(mean resistance 13.47%vs 14.39%),except for two studies that demonstrated greater efficacy of maribavir and valganciclovir(mean resistance 22.2%vs 41.1%in the control group;P<0.05).The total reported deaths in three clinical trials were 75,and there were 24 graft rejections in two studies.CONCLUSION All clinical trials reported significant proportions of antimicrobial-resistant microorganisms following interventions.More high-quality randomized clinical trials are needed to corroborate these results.展开更多
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 healt...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.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is a leading cause of cancer-related deaths worldwide.Liver transplantation(LT)offers the most effective treatment.HCC recurrence is the strongest risk factor that decreases pos...BACKGROUND Hepatocellular carcinoma(HCC)is a leading cause of cancer-related deaths worldwide.Liver transplantation(LT)offers the most effective treatment.HCC recurrence is the strongest risk factor that decreases post-LT survival in patients transplanted for HCC.The rate of HCC recurrence is generally reported as 8%-20%in the literature.Many predictors of HCC have already been researched,however,to our knowledge there are no published studies on this topic using Australian data.AIM To determine the rate and identify predictors of HCC recurrence in a contemporary Western Australian LT cohort.METHODS We performed a retrospective cohort study of all liver transplants in patients with HCC at Sir Charles Gairdner Hospital between 2006 and 2021.Data was collected from various health record databases and included recipient demographics,serum biochemistry,radiology,operation notes,explant histopathology and details of recurrence.Overall survival of HCC patients post-LT,stratified for recurrence,was calculated by Kaplan Meier analysis.Univariate and multivariate Cox regression was used to determine predictors of HCC recurrence post-LT.RESULTS Between 1/1/2006 and 12/31/2021,119 patients were transplanted with HCC.8.4%of subjects developed recurrent HCC after LT with median follow-up time of 5.4 years.The median time to recurrence was 2.9 years±0.75 years.When comparing baseline characteristics,a greater proportion of subjects with recurrence had common characteristics on explant histopathology,including>3 viable nodules(P=0.001),vascular invasion(P=0.003)and poorly differentiated HCC(P=0.03).Unadjusted survival curves showed lower 1-year,3-year,5-year and 10-year survival rates in subjects with HCC recurrence compared to those without HCC recurrence(90%vs 92%,70%vs 88%,42%vs 80%,14%vs 76%,respectively;log rank P<0.001).CONCLUSION HCC recurrence was low at 8.4%in this contemporary Australian cohort,however it significantly impacted post-LT survival.Further studies are required to confirm predictors of recurrence and improve recipient outcomes.展开更多
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 nephr...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.展开更多
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 mode...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.展开更多
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)pla...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.展开更多
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 ...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.展开更多
BACKGROUND Acute liver failure(ALF)is a severe condition characterized by rapid deterioration of liver function in individuals without preexisting liver disease.Liver transplantation(LT)is the most impactful treatment...BACKGROUND Acute liver failure(ALF)is a severe condition characterized by rapid deterioration of liver function in individuals without preexisting liver disease.Liver transplantation(LT)is the most impactful treatment.Yellow fever(YF)is an infectious disease that primarily affects the liver and has a high mortality rate.However,LT can be a viable option for treating rare cases with extensive liver involvement.However,the criteria for assessing the severity of ALF and determining the indications for transplantation have not been specifically validated for cases caused by YF.AIM To present necessary adjustments to established scoring systems for ALF secondary to YF.METHODS This was an observational,retrospective,single-center study.Fourteen consecutive patients with confirmed ALF due to YF were monitored in the intensive care unit by a specialized liver transplant team during a three-month epidemic outbreak in Brazil.During hospitalization,general supportive therapeutic measures were implemented,and the patients were regularly assessed using the King's College criteria and the Clichy-Villejuif criteria to determine the severity of liver failure.LT is considered a viable measure for patients with signs of end-stage liver failure.RESULTS Eight of 14(57%)patients developed severe neurological alterations within the first 96 hours after hospital admission.Four patients underwent emergency LT,and despite a moderate viral infection of the graft after transplantation,the 5-year survival rate was 50%.Although the King's College criteria and the Clichy-Villejuif criteria are the main scoring systems for ALF,they are insufficient for predicting the risk of mortality in this context,primarily because of low serum bilirubin levels in the final stage of the disease and significant disparities between coagulation abnormalities and patient severity.CONCLUSION To ensure good applicability in cases of YF-induced ALF,the authors suggest adaptations to the King's College and Clichy-Villejuif criteria.展开更多
基金supported by research grants from the Michael J Fox Foundation for Parkinson’s Research(grant numbers:17244 and 023410)Science Foundation Ireland(Grant Numbers:19/FFP/6554)(to ED)。
文摘Stem cell-based brain repair is a promising emergent therapy for Parkinson's disease based on years of foundational research using human fetal donors as a cell source.Unlike current therapeutic options for patients,this approach has the potential to provide longterm stem cell–derived reconstruction and restoration of the dopaminergic input to denervated regions of the brain allowing for restoration of certain functions to patients.The ultimate clinical success of stem cell–derived brain repair will depend on both the safety and efficacy of the approach and the latter is dependent on the ability of the transplanted cells to survive and differentiate into functional dopaminergic neurons in the Parkinsonian brain.Because the pre-clinical literature suggests that there is considerable variability in survival and differentiation between studies,the aim of this systematic review was to assess these parameters in human stem cell-derived dopaminergic progenitor transplant studies in animal models of Parkinson's disease.A defined systematic search of the PubMed database was completed to identify relevant studies published up to March 2024.After screening,76 articles were included in the analysis from which 178 separate transplant studies were identified.From these,graft survival could be assessed in 52 studies and differentiation in 129 studies.Overall,we found that graft survival ranged from<1% to 500% of cells transplanted,with a median of 51%of transplanted cells surviving in the brain;while dopaminergic differentiation of the cells ranged from 0% to 46% of cells transplanted with a median of 3%.This systematic review suggests that there is considerable scope for improvement in the differentiation of stem cell-derived dopaminergic progenitors to maximize the therapeutic potential of this approach for patients.
基金supported by grants from the Lone Star Paralysis Foundation,NIH R01NS081063Department of Defense award W81XWH-19-2-0054 to GDB+2 种基金supported by University of Wyoming Startup funds,Department of Defense grant W81XWH-17-1-0402the University of Wyoming Sensory Biology COBRE under National Institutes of Health(NIH)award number 5P20GM121310-02the National Institute of General Medical Sciences of the NIH under award number P20GM103432 to JSB。
文摘Behavioral recovery using(viable)peripheral nerve allografts to repair ablation-type(segmental-loss)peripheral nerve injuries is delayed or poor due to slow and inaccurate axonal regeneration.Furthermore,such peripheral nerve allografts undergo immunological rejection by the host immune system.In contrast,peripheral nerve injuries repaired by polyethylene glycol fusion of peripheral nerve allografts exhibit excellent behavioral recovery within weeks,reduced immune responses,and many axons do not undergo Wallerian degeneration.The relative contribution of neurorrhaphy and polyethylene glycol-fusion of axons versus the effects of polyethylene glycol per se was unknown prior to this study.We hypothesized that polyethylene glycol might have some immune-protective effects,but polyethylene glycol-fusion was necessary to prevent Wallerian degeneration and functional/behavioral recovery.We examined how polyethylene glycol solutions per se affect functional and behavioral recovery and peripheral nerve allograft morphological and immunological responses in the absence of polyethylene glycol-induced axonal fusion.Ablation-type sciatic nerve injuries in outbred Sprague–Dawley rats were repaired according to a modified protocol using the same solutions as polyethylene glycol-fused peripheral nerve allografts,but peripheral nerve allografts were loose-sutured(loose-sutured polyethylene glycol)with an intentional gap of 1–2 mm to prevent fusion by polyethylene glycol of peripheral nerve allograft axons with host axons.Similar to negative control peripheral nerve allografts not treated by polyethylene glycol and in contrast to polyethylene glycol-fused peripheral nerve allografts,animals with loose-sutured polyethylene glycol peripheral nerve allografts exhibited Wallerian degeneration for all axons and myelin degeneration by 7 days postoperatively and did not recover sciatic-mediated behavioral functions by 42 days postoperatively.Other morphological signs of rejection,such as collapsed Schwann cell basal lamina tubes,were absent in polyethylene glycol-fused peripheral nerve allografts but commonly observed in negative control and loose-sutured polyethylene glycol peripheral nerve allografts at 21 days postoperatively.Loose-sutured polyethylene glycol peripheral nerve allografts had more pro-inflammatory and less anti-inflammatory macrophages than negative control peripheral nerve allografts.While T cell counts were similarly high in loose-sutured-polyethylene glycol and negative control peripheral nerve allografts,loose-sutured polyethylene glycol peripheral nerve allografts expressed some cytokines/chemokines important for T cell activation at much lower levels at 14 days postoperatively.MHCI expression was elevated in loose-sutured polyethylene glycol peripheral nerve allografts,but MHCII expression was modestly lower compared to negative control at 21 days postoperatively.We conclude that,while polyethylene glycol per se reduces some immune responses of peripheral nerve allografts,successful polyethylene glycol-fusion repair of some axons is necessary to prevent Wallerian degeneration of those axons and immune rejection of peripheral nerve allografts,and produce recovery of sensory/motor functions and voluntary behaviors.Translation of polyethylene glycol-fusion technologies would produce a paradigm shift from the current clinical practice of waiting days to months to repair ablation peripheral nerve injuries.
基金supported in part by NIH R01 NS100531,R01 NS103481NIH R21NS130241(to LD)+3 种基金Merit Review Award I01 BX002356,I01 BX003705 from the U.S.Department of Veterans AffairsIndiana Spinal Cord and Brain Injury Research Foundation(No.19919)Mari Hulman George Endowment Funds(to XMX)Indiana Spinal Cord&Brain Injury Research Fund from ISDH(to NKL and LD)。
文摘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.
文摘Extensive research has investigated the etiology of Crohn’s disease(CD),encompassing genetic predisposition,lifestyle factors,and environmental triggers.Recently,the gut microbiome,recognized as the human body’s second-largest gene pool,has garnered significant attention for its crucial role in the patho-genesis of CD.This paper investigates the mechanisms underlying CD,focusing on the role of‘creeping fat’in disease progression and exploring emerging therapeutic strategies,including fecal microbiota transplantation,enteral nutri-tion,and therapeutic diets.Creeping fat has been identified as a unique patho-logical feature of CD and has recently been found to be associated with dysbiosis of the gut microbiome.We characterize this dysbiotic state by identi-fying key microbiome-bacteria,fungi,viruses,and archaea,and their contributions to CD pathogenesis.Additionally,this paper reviews contemporary therapies,empha-sizing the potential of biological therapies like fecal microbiota transplantation and dietary interventions.By elucidating the complex interactions between host-microbiome dynamics and CD pathology,this article aims to advance our under-standing of the disease and guide the development of more effective therapeutic strategies for managing CD.
文摘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.
文摘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.
基金supported by the National Natural Science Foundation of China,No.82171080Nanjing Medical Science and Technology Development Project,No.YKK23264Postgraduate Research&Practice Innovation Program of Jiangsu Province,Nos.JX10414151,JX10414152(all to KL)。
文摘Age-related macular degeneration is a serious neurodegenerative disease of the retina that significantly impacts vision.Unfortunately,the specific pathogenesis remains unclear,and effective early treatment options are consequently lacking.The microbiome is defined as a large ecosystem of microorganisms living within and coexisting with a host.The intestinal microbiome undergoes dynamic changes owing to age,diet,genetics,and other factors.Such dysregulation of the intestinal flora can disrupt the microecological balance,resulting in immunological and metabolic dysfunction in the host,and affecting the development of many diseases.In recent decades,significant evidence has indicated that the intestinal flora also influences systems outside of the digestive tract,including the brain.Indeed,several studies have demonstrated the critical role of the gut-brain axis in the development of brain neurodegenerative diseases,including Alzheimer’s disease and Parkinson’s disease.Similarly,the role of the“gut-eye axis”has been confirmed to play a role in the pathogenesis of many ocular disorders.Moreover,age-related macular degeneration and many brain neurodegenerative diseases have been shown to share several risk factors and to exhibit comparable etiologies.As such,the intestinal flora may play an important role in age-related macular degeneration.Given the above context,the present review aims to clarify the gut-brain and gut-eye connections,assess the effect of intestinal flora and metabolites on age-related macular degeneration,and identify potential diagnostic markers and therapeutic strategies.Currently,direct research on the role of intestinal flora in age-related macular degeneration is still relatively limited,while studies focusing solely on intestinal flora are insufficient to fully elucidate its functional role in age-related macular degeneration.Organ-on-a-chip technology has shown promise in clarifying the gut-eye interactions,while integrating analysis of the intestinal flora with research on metabolites through metabolomics and other techniques is crucial for understanding their potential mechanisms.
文摘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.
文摘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.
文摘Transplantation of the left lateral section(LLS)of the liver is now an established practice for treating advanced diffuse and unresectable focal liver diseases in children,with variants of the LLS primarily used in infants.However,the surgical challenge of matching the size of an adult donor's graft to the volume of a child's abdomen remains significant.This review explores historical developments,various approaches to measuring the required functional liver mass,and techniques to prevent complications associated with large-for-size grafts in infants.
文摘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.
文摘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.
文摘BACKGROUND In the absence of effective antimicrobials,transplant surgery is not viable,and antirejection immunosuppressants cannot be administered,as resistant infections compromise the life-saving goal of organ transplantation.AIM To evaluate the efficacy of antimicrobials in preventing resistance in solid organ transplant recipients.METHODS A systematic review was conducted using a search methodology consistent with the preferred reporting items for systematic reviews and meta-analyses.This review included randomized clinical trials that evaluated the efficacy of antimicrobial agents(prophylactic or therapeutic)aimed at preventing antimicrobial resistance.The search strategy involved analyzing multiple databases,including PubMed/MEDLINE,Web of Science,Embase,Scopus,and SciELO,as well as examining gray literature sources on Google Scholar.A comprehensive electronic database search was conducted from the databases’inception until May 2024,with no language restrictions.RESULTS After the final phase of the eligibility assessment,this systematic review ultimate-ly included 7 articles.A total of 2318 patients were studied.The most studied microorganisms were cytomegalovirus,although vancomycinresistant enterococci,Clostridioides difficile,and multidrug-resistant Enterobacterales were also analyzed.The antimicrobials used in the interventions were mainly maribavir,valganciclovir,gancic-lovir,and colistin-neomycin.Of concern,all clinical trials showed significant proportions of resistant microorga-nisms after the interventions,with no statistically significant differences between the groups(mean resistance 13.47%vs 14.39%),except for two studies that demonstrated greater efficacy of maribavir and valganciclovir(mean resistance 22.2%vs 41.1%in the control group;P<0.05).The total reported deaths in three clinical trials were 75,and there were 24 graft rejections in two studies.CONCLUSION All clinical trials reported significant proportions of antimicrobial-resistant microorganisms following interventions.More high-quality randomized clinical trials are needed to corroborate these results.
文摘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.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a leading cause of cancer-related deaths worldwide.Liver transplantation(LT)offers the most effective treatment.HCC recurrence is the strongest risk factor that decreases post-LT survival in patients transplanted for HCC.The rate of HCC recurrence is generally reported as 8%-20%in the literature.Many predictors of HCC have already been researched,however,to our knowledge there are no published studies on this topic using Australian data.AIM To determine the rate and identify predictors of HCC recurrence in a contemporary Western Australian LT cohort.METHODS We performed a retrospective cohort study of all liver transplants in patients with HCC at Sir Charles Gairdner Hospital between 2006 and 2021.Data was collected from various health record databases and included recipient demographics,serum biochemistry,radiology,operation notes,explant histopathology and details of recurrence.Overall survival of HCC patients post-LT,stratified for recurrence,was calculated by Kaplan Meier analysis.Univariate and multivariate Cox regression was used to determine predictors of HCC recurrence post-LT.RESULTS Between 1/1/2006 and 12/31/2021,119 patients were transplanted with HCC.8.4%of subjects developed recurrent HCC after LT with median follow-up time of 5.4 years.The median time to recurrence was 2.9 years±0.75 years.When comparing baseline characteristics,a greater proportion of subjects with recurrence had common characteristics on explant histopathology,including>3 viable nodules(P=0.001),vascular invasion(P=0.003)and poorly differentiated HCC(P=0.03).Unadjusted survival curves showed lower 1-year,3-year,5-year and 10-year survival rates in subjects with HCC recurrence compared to those without HCC recurrence(90%vs 92%,70%vs 88%,42%vs 80%,14%vs 76%,respectively;log rank P<0.001).CONCLUSION HCC recurrence was low at 8.4%in this contemporary Australian cohort,however it significantly impacted post-LT survival.Further studies are required to confirm predictors of recurrence and improve recipient outcomes.
文摘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.
文摘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.
文摘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.
文摘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.
基金Supported by The INCT-CNPq Program,No.465425/2014-3.
文摘BACKGROUND Acute liver failure(ALF)is a severe condition characterized by rapid deterioration of liver function in individuals without preexisting liver disease.Liver transplantation(LT)is the most impactful treatment.Yellow fever(YF)is an infectious disease that primarily affects the liver and has a high mortality rate.However,LT can be a viable option for treating rare cases with extensive liver involvement.However,the criteria for assessing the severity of ALF and determining the indications for transplantation have not been specifically validated for cases caused by YF.AIM To present necessary adjustments to established scoring systems for ALF secondary to YF.METHODS This was an observational,retrospective,single-center study.Fourteen consecutive patients with confirmed ALF due to YF were monitored in the intensive care unit by a specialized liver transplant team during a three-month epidemic outbreak in Brazil.During hospitalization,general supportive therapeutic measures were implemented,and the patients were regularly assessed using the King's College criteria and the Clichy-Villejuif criteria to determine the severity of liver failure.LT is considered a viable measure for patients with signs of end-stage liver failure.RESULTS Eight of 14(57%)patients developed severe neurological alterations within the first 96 hours after hospital admission.Four patients underwent emergency LT,and despite a moderate viral infection of the graft after transplantation,the 5-year survival rate was 50%.Although the King's College criteria and the Clichy-Villejuif criteria are the main scoring systems for ALF,they are insufficient for predicting the risk of mortality in this context,primarily because of low serum bilirubin levels in the final stage of the disease and significant disparities between coagulation abnormalities and patient severity.CONCLUSION To ensure good applicability in cases of YF-induced ALF,the authors suggest adaptations to the King's College and Clichy-Villejuif criteria.