BACKGROUND: Pre-transplant exposure to immune checkpoint inhibitors (ICIs) significantly increases the risk of allograft rejection after liver transplantation (LT); however, whether ICI-related rejection leads to increased graft loss remains controversial. Therefore, this study aimed to investigate the association between ICI-related allograft rejection and perioperative graft loss. METHODS: This was a retrospective analysis of adult liver transplant recipients with early biopsy-proven T-cell-mediated rejection (TCMR) at Liver Transplantation Center of Sun Yat-sen Memorial Hospital from June 2019 to September 2024. The pathological features, clinical characteristics, and perioperative graft survival were analyzed. RESULTS: Twenty-eight patients who underwent early TCMR between June 2019 and September 2024 were included. Based on pre-LT ICI exposure, recipients were categorized into ICI-related TCMR (irTCMR, n = 12) and conventional TCMR (cTCMR, n = 16) groups. Recipients with irTCMR had a higher median Banff rejection activity index (RAI) (6 vs . 5, P = 0.012) and more aggressive tissue damage and inflammation. Recipients with irTCMR showed higher proportion of treatment resistance, achieving a complete resolution rate of only 8/12 compared to 16/16 for cTCMR. Graft loss occurred in 5/12 of irTCMR recipients within 90 days after LT, with no graft loss in cTCMRs recipients. Cox analysis demonstrated that irTCMR with an ICI washout period of <30 days was an independent risk factor for perioperative graft loss (hazard ratio [HR], 6.540; 95% confidence interval [CI], 1.067-40.067, P = 0.042). CONCLUSION IrTCMR is associated with severe pathological features, increased resistance to treatment, and higher graft loss in adult liver transplant recipients.
Humans ; Liver Transplantation/adverse effects* ; Male ; Female ; Middle Aged ; Retrospective Studies ; Graft Rejection/immunology* ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; T-Lymphocytes/drug effects* ; Graft Survival/immunology* ; Aged

Background and aims:Despite growing evidence linking pretransplant exposure to immune checkpoint inhibitors(ICIs)to increased allograft rejection risk after liver transplantation(LT),a lack of comparative studies to definitively establish the correlation between ICI exposure and adverse short-term outcomes after LT exists.This study aimed to analyze the impact of preoperative ICI exposure on short-term post-LT prognosis and allograft rejection risk.Methods:This retrospective cohort study included 121 recipients who underwent LT for hepatocellular carcinoma(HCC)between June 2019 and March 2023.The recipients were categorized into ICI(n=35)and non-ICI(n=86)exposure groups based on pretransplant ICI exposure.Demographics,clinical characteristics,and short-term outcomes were compared between the cohorts.Kaplan-Meier analysis evaluated the impact of ICI exposure on graft survival.Univariate and multivariate logistic regression models assessed the impact of patient characteristics on allograft rejection.Results:Recipients with or without ICI exposure exhibited comparable demographic baseline charac-teristics.The incidences of early allograft dysfunction and biliary and vascular complications were similar between both groups.Post-transplant infection incidence was 37.1％and 20.9％in the ICI and non-ICI groups,respectively(P=0.064).Allograft rejection rates were significantly higher in the ICI group than in the non-ICI group(22.9％vs.5.8％,P=0.015).The ICI group exhibited a higher 90-day post-transplant mortality rate than that of the non-ICI group(14.3％vs.2.3％,P=0.034).Logistic regression analyses demonstrated that allograft rejection independently correlated with 90-day post-transplant mortality,with ICI exposure being an independent risk factor for allograft rejection.In recipients with ICI exposure,a shorter interval between ICIs and LT(washout period)was significantly associated with a higher allograft rejection risk,with the optimal washout period identified as 21 days for predicting 90-day rejection-free survival(P=0.0001).Moreover,in recipients with allograft rejection,the peripheral CD4+/CD8+T cell ratio was much lower in the ICI group than in the non-ICI group.Conclusions:Pretransplant ICI exposure was an independent risk factor for allograft rejection and was significantly associated with 90-day post-transplant mortality after LT for HCC.A ≤21-day washout period was significantly associated with allograft rejection.Future multicenter studies with larger cohorts and prospective designs are essential to validate these findings,confirm causality,and establish standardized clinical guidelines for ICI use before transplantation.Trail registration:ClinicalTrials.gov NCT05913583.

The special natural environment of the plateau brings about great difficulties and challenges to the field medical support.The serious injury treatment group of the field medical team is responsible for the early treatment of the critically injured,which is highly demanding and is more likely to be adversely affected by the plateau environment.Based on the real experiences and current reality,this paper outlines the priorities of work done by the serious injury treatment group on the plateau in terms of personnel selection,professional training,material preparation,site construction,treatment regimens and combat readiness in the hope of providing references for the medical support for China's the military on the plateau.

Fecal microbiota transplantation (FMT) has the potential to rebuild the intestinal microbiome of patients, which can influence the disease course, alleviate symptoms, or even cure the disease. It is seen as a promising breakthrough for treating major chronic diseases that are difficult to manage. Currently, FMT therapy has been clinically studied for over 80 diseases and has led to significant breakthroughs. However, there are still four main challenges: (1) identifying the effective characteristics of donor microbiota and ensuring precise matching between donors and recipients; (2) understanding the pathways and molecular mechanisms by which key FMT bacteria and metabolites improve disease outcomes; (3) studying strain interactions and colonization mechanisms to restore intestinal microbiota balance; and (4) refining the precision of microbiome and functional microbiota transplantation. To address these clinical challenges, this article reviews the latest research both domestically and internationally, outlines the response patterns of FMT therapy, examines the reasons behind FMT failure, and explores future directions for the development of FMT. The aim is to accelerate the scientific and precise advancement of FMT technology in China.

Cognitive dysfunction is a common complication of diabetes mellitus(DM)with a complex pathogenesis that may be closely related to neuropathic changes.Functional magnetic resonance imaging(fMRI)can investigate brain function by measuring changes in brain tissue structure and hemodynamics following enhanced neural activity,potentially facilitating early detection of the brain pathophysiological changes underlying cognitive dysfunction in DM.This paper reviews the application of fMRI technology in the assessment of brain structure and function in diabetic patients,aiming to provide a basis for the early detection,intervention,and research on cognitive impairment in DM.

Cognitive dysfunction is a common complication of diabetes mellitus(DM)with a complex pathogenesis that may be closely related to neuropathic changes.Functional magnetic resonance imaging(fMRI)can investigate brain function by measuring changes in brain tissue structure and hemodynamics following enhanced neural activity,potentially facilitating early detection of the brain pathophysiological changes underlying cognitive dysfunction in DM.This paper reviews the application of fMRI technology in the assessment of brain structure and function in diabetic patients,aiming to provide a basis for the early detection,intervention,and research on cognitive impairment in DM.

Objective:To analyze the characteristics of non-seroconverted cases after rabies vaccination and observe the effect of booster vaccination.Methods:A retrospective collection of data was conducted from March 2022 to March 2023 across 409 rabies vaccination clinics in 27 provinces in China, focusing on cases with rabies virus neutralizing antibody (RVNA) levels less than 0.5 IU/ml after vaccination.Results:A total of 77 cases were identified in whom seroconversion was not observed within 30 days post-vaccination with the rabies vaccine. The gender distribution was 51.9% male and 48.1% female, with ages ranging from 2 to 83 years old. Delayed vaccination was observed in 11 cases (14.3%), and 63 cases (81.8%) received human rabies immunoglobulin (HRIG) injections. None of the cases had a confirmed immunosuppressive disease or taking immunosuppressive drugs, and the body mass index (BMI) distribution ranged from 14.37 to 34.74 kg/m 2. Seventy-six cases seroconverted after 1 to 3 doses of rabies vaccines as a booster vaccination. One case that did not seroconvert after the initial booster vaccination seroconverted after receiving additional 2 doses of vaccine. All patients were followed up for one year, with no cases of rabies reported. Conclusions:The characteristics of cases that failed to seroconvert after the full course of rabies vaccination lacked specificity, and booster vaccination could lead to seroconversion.

Fecal microbiota transplantation (FMT) has the potential to rebuild the intestinal microbiome of patients, which can influence the disease course, alleviate symptoms, or even cure the disease. It is seen as a promising breakthrough for treating major chronic diseases that are difficult to manage. Currently, FMT therapy has been clinically studied for over 80 diseases and has led to significant breakthroughs. However, there are still four main challenges: (1) identifying the effective characteristics of donor microbiota and ensuring precise matching between donors and recipients; (2) understanding the pathways and molecular mechanisms by which key FMT bacteria and metabolites improve disease outcomes; (3) studying strain interactions and colonization mechanisms to restore intestinal microbiota balance; and (4) refining the precision of microbiome and functional microbiota transplantation. To address these clinical challenges, this article reviews the latest research both domestically and internationally, outlines the response patterns of FMT therapy, examines the reasons behind FMT failure, and explores future directions for the development of FMT. The aim is to accelerate the scientific and precise advancement of FMT technology in China.

Objective:To analyze the characteristics of non-seroconverted cases after rabies vaccination and observe the effect of booster vaccination.Methods:A retrospective collection of data was conducted from March 2022 to March 2023 across 409 rabies vaccination clinics in 27 provinces in China, focusing on cases with rabies virus neutralizing antibody (RVNA) levels less than 0.5 IU/ml after vaccination.Results:A total of 77 cases were identified in whom seroconversion was not observed within 30 days post-vaccination with the rabies vaccine. The gender distribution was 51.9% male and 48.1% female, with ages ranging from 2 to 83 years old. Delayed vaccination was observed in 11 cases (14.3%), and 63 cases (81.8%) received human rabies immunoglobulin (HRIG) injections. None of the cases had a confirmed immunosuppressive disease or taking immunosuppressive drugs, and the body mass index (BMI) distribution ranged from 14.37 to 34.74 kg/m 2. Seventy-six cases seroconverted after 1 to 3 doses of rabies vaccines as a booster vaccination. One case that did not seroconvert after the initial booster vaccination seroconverted after receiving additional 2 doses of vaccine. All patients were followed up for one year, with no cases of rabies reported. Conclusions:The characteristics of cases that failed to seroconvert after the full course of rabies vaccination lacked specificity, and booster vaccination could lead to seroconversion.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.