INTRODUCTION: A successful vaccination programme forms the cornerstone of controlling coronavirus disease 2019 (COVID-19). The unprecedented speed of COVID-19 vaccine development and lack of long-term data have raised fears regarding its safety and efficacy. Vaccine hesitancy can undermine the uptake, and hence success of the vaccination programme. Given the high complication rates of COVID-19 infections in kidney transplant recipients, it is particularly important to identify and address vaccine hesitancy in this population. METHODS: We conducted a cross-sectional survey among kidney transplant recipients attending transplant clinic between 5 April and 5 May 2021. The survey assessed attitudes towards COVID-19, willingness/hesitancy towards COVID-19 vaccination, vaccination concerns and prompts to vaccination. This was scored on a Likert scale with scores ranging from 'strongly disagree' - 1 point to 'strongly agree' - 5 points. RESULTS: One hundred and one completed responses were captured. Of these, 86% respondents reported to agree or strongly agree to vaccination. This was despite significant concerns of allograft rejection (mean score 4.12, standard deviation [SD] 0.97) and decreased immunosuppressant efficacy (mean score 4.14, SD 0.96) with vaccination. Multivariable model showed a positive association with transplant vintage of ≥ 5 years (median 2.41), lower educational levels of secondary school or less (median 5.82) and healthcare provider advocacy (median 1.88) in predicting vaccine acceptance. CONCLUSIONS Vaccine acceptance rate was high among kidney transplant recipients. Vaccine hesitancy remains a concern in those with a transplant vintage of less than 5 years and those with tertiary educational level. Healthcare provider advocacy is important in improving vaccine acceptance rates.
Humans ; Kidney Transplantation ; Singapore/epidemiology* ; Male ; Cross-Sectional Studies ; Female ; COVID-19 Vaccines ; COVID-19/epidemiology* ; Middle Aged ; Adult ; Transplant Recipients/psychology* ; Patient Acceptance of Health Care/statistics & numerical data* ; Vaccination Hesitancy/psychology* ; Surveys and Questionnaires ; Vaccination/psychology* ; Aged ; SARS-CoV-2

BACKGROUND: Effective interventions during the coronavirus disease 2019 (COVID-19) pandemic require an understanding of patients' knowledge and perceptions that influence their behaviour. Our study assessed knowledge of COVID-19 among kidney transplant recipients and donors, hitherto unevaluated. METHODS: We conducted a cross-sectional survey among 325 kidney transplant recipients and 172 donors between 1 May 2020 and 30 June 2020. The survey questionnaire assessed knowledge levels of COVID-19, sociodemographic data, health status, psychosocial impact of COVID-19 and precautionary behaviours during the pandemic. RESULTS: The mean COVID-19 knowledge score of the study population was 7.5 (standard deviation: 2.2) out of 10. The mean score was significantly higher among kidney recipients compared to kidney donors (7.9 [1.9] vs. 6.7 [2.6]; P <0.001). Younger age (21-49 vs. ≥50 years) and higher education (diploma and higher vs. secondary and lower) were associated with significantly higher knowledge scores in donors, but not among recipients ( P -interactions ≤0.01). In both kidney recipients and donors, financial concerns and/or social isolation were associated with lower knowledge levels. CONCLUSIONS Concerted efforts are needed to improve COVID-19 knowledge in kidney transplant recipients and donors, particularly older donors, donors with lower education and patients with financial concerns or feelings of social isolation. Intensive patient education may mitigate the impact of education levels on COVID-19 knowledge levels.
Humans ; COVID-19/epidemiology* ; Kidney Transplantation ; Middle Aged ; Singapore/epidemiology* ; Male ; Female ; Adult ; Cross-Sectional Studies ; Health Knowledge, Attitudes, Practice ; Transplant Recipients/psychology* ; Surveys and Questionnaires ; Tissue Donors/psychology* ; SARS-CoV-2 ; Young Adult ; Aged ; Pandemics

BACKGROUND: T cell dysfunction, which includes exhaustion, anergy, and senescence, is a distinct T cell differentiation state that occurs after antigen exposure. Although T cell dysfunction has been a cornerstone of cancer immunotherapy, its potential in transplant research, while not yet as extensively explored, is attracting growing interest. Interferon regulatory factor 4 (IRF4) has been shown to play a pivotal role in inducing T cell dysfunction. METHODS: A novel ultra-low-dose combination of Trametinib and Rapamycin, targeting IRF4 inhibition, was employed to investigate T cell proliferation, apoptosis, cytokine secretion, expression of T-cell dysfunction-associated molecules, effects of mitogen-activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR) signaling pathways, and allograft survival in both in vitro and BALB/c to C57BL/6 mouse cardiac transplantation models. RESULTS: In vitro , blockade of IRF4 in T cells effectively inhibited T cell proliferation, increased apoptosis, and significantly upregulated the expression of programmed cell death protein 1 (PD-1), Helios, CD160, and cytotoxic T lymphocyte-associated antigen (CTLA-4), markers of T cell dysfunction. Furthermore, it suppressed the secretion of pro-inflammatory cytokines interferon (IFN)-γ and interleukin (IL)-17. Combining ultra-low-dose Trametinib (0.1 mg·kg -1 ·day -1 ) and Rapamycin (0.1 mg·kg -1 ·day -1 ) demonstrably extended graft survival, with 4 out of 5 mice exceeding 100 days post-transplantation. Moreover, analysis of grafts at day 7 confirmed sustained IFN regulatory factor 4 (IRF4) inhibition, enhanced PD-1 expression, and suppressed IFN-γ secretion, reinforcing the in vivo efficacy of this IRF4-targeting approach. The combination of Trametinib and Rapamycin synergistically inhibited the MAPK and mTOR signaling network, leading to a more pronounced suppression of IRF4 expression. CONCLUSIONS Targeting IRF4, a key regulator of T cell dysfunction, presents a promising avenue for inducing transplant immune tolerance. In this study, we demonstrate that a novel ultra-low-dose combination of Trametinib and Rapamycin synergistically suppresses the MAPK and mTOR signaling network, leading to profound IRF4 inhibition, promoting allograft acceptance, and offering a potential new therapeutic strategy for improved transplant outcomes. However, further research is necessary to elucidate the underlying pharmacological mechanisms and facilitate translation to clinical practice.
Animals ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Interferon Regulatory Factors/metabolism* ; Heart Transplantation/methods* ; T-Lymphocytes/immunology* ; Sirolimus/therapeutic use* ; Pyridones/therapeutic use* ; Graft Survival/drug effects* ; Pyrimidinones/therapeutic use* ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Male ; Signal Transduction/drug effects*

BACKGROUND: The primary limitation to kidney transplantation is organ shortage. Recent progress in gene editing and immunosuppressive regimens has made xenotransplantation with porcine organs a possibility. However, evidence in pig-to-human xenotransplantation remains scarce, and antibody-mediated rejection (AMR) is a major obstacle to clinical applications of xenotransplantation. METHODS: We conducted a kidney xenotransplantation in a brain-dead human recipient using a porcine kidney with five gene edits (5GE) on March 25, 2024 at Xijing Hospital, China. Clinical-grade immunosuppressive regimens were employed, and the observation period lasted 22 days. We collected and analyzed the xenograft function, ultrasound findings, sequential protocol biopsies, and immune surveillance of the recipient during the observation. RESULTS: The combination of 5GE in the porcine kidney and clinical-grade immunosuppressive regimens prevented hyperacute rejection. The xenograft kidney underwent delayed graft function in the first week, but urine output increased later and the single xenograft kidney maintained electrolyte and pH homeostasis from postoperative day (POD) 12 to 19. We observed AMR at 24 h post-transplantation, due to the presence of pre-existing anti-porcine antibodies and cytotoxicity before transplantation; this AMR persisted throughout the observation period. Plasma exchange and intravenous immunoglobulin treatment mitigated the AMR. We observed activation of latent porcine cytomegalovirus toward the end of the study, which might have contributed to coagulation disorder in the recipient. CONCLUSIONS 5GE and clinical-grade immunosuppressive regimens were sufficient to prevent hyperacute rejection during pig-to-human kidney xenotransplantation. Pre-existing anti-porcine antibodies predisposed the xenograft to AMR. Plasma exchange and intravenous immunoglobulin were safe and effective in the treatment of AMR after kidney xenotransplantation.
Transplantation, Heterologous/methods* ; Kidney Transplantation/methods* ; Heterografts/pathology* ; Immunoglobulins, Intravenous/administration & dosage* ; Graft Survival/immunology* ; Humans ; Animals ; Sus scrofa ; Graft Rejection/prevention & control* ; Kidney/pathology* ; Gene Editing ; Species Specificity ; Immunosuppression Therapy/methods* ; Plasma Exchange ; Brain Death ; Biopsy ; Male ; Aged

Organ transplantation, particularly pediatric liver transplantation (LT), has transformed medical practice over the past six decades, providing life-saving interventions for children with end-stage liver disease. This review demonstrated the historical milestones of pediatric organ transplantation, emphasizing Japan's contributions, mainly through the National Center for Child Health and Development. While early transplantation efforts in the 1950s and 1960s faced significant challenges, breakthroughs in preservation methods, immunosuppressive therapies, surgical techniques, and innovations such as living donor LT in Asia have greatly improved success rates. Japan's pediatric LT landscape is distinct, primarily due to its reliance on living donor LT, shaped by cultural and religious influences that have traditionally restricted deceased donor organ donation. This review manuscript discusses Japan's pioneering role in expanding the indications for pediatric LT to include rare conditions such as inherited metabolic disorders and hepatoblastoma. It highlights recent innovations such as hyper-reduced lateral segment grafts, machine perfusion, and minimally invasive surgery that have further improved outcomes. International collaboration has facilitated the sharing of expertise, advancing pediatric liver transplantation practice worldwide. Despite these achievements, challenges remain, particularly in light of Japan's declining birth rate, which threatens the sustainability of pediatric transplant services. This review emphasizes the need for centralized transplant facilities, greater awareness of brain-dead organ donation, and continued medical advances to ensure that pediatric LT remains a viable, life-saving option for future generations.
Humans ; Liver Transplantation/trends* ; Japan ; Child ; Living Donors

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

Liver transplantation is an effective treatment for end-stage liver disease. Liver transplantation is technically complex and associated with significant trauma. In recent years,minimally invasive surgical techniques,such as laparoscopy and robotic surgery,have rapidly developed and been widely applied across various surgical fields. Minimally invasive surgery offers advantages including reduced trauma,less bleeding,and faster postoperative recovery,and has become a mainstream trend in surgical development. In the field of liver transplantation,laparoscopic and robotic donor hepatectomy techniques for living donor liver transplantation have made significant progress. However, due to difficulties in exposing the anastomotic sites of the donor liver and challenges in vascular anastomosis,the application of minimally invasive techniques in donor liver implantation has progressed relatively slowly. With advancements in laparoscopic and robotic surgical techniques and related instruments,laparoscopic donor liver implantation has gradually become feasible. Currently,multiple liver transplant centers worldwide have begun to progressively perform laparoscopic or robot-assisted liver transplantation in recipients,demonstrating potential advantages in reducing surgical trauma and accelerating postoperative recovery. However,there is currently a lack of guidelines or consensus on the application of minimally invasive surgery in liver transplant recipients. Therefore,Branch of Organ Transplantation of Chinese Medical Association,Surgery Group of Chinese Society of Surgery of Chinese Medical Association,and Branch of Organ Transplant Physicians of Chinese Medical Doctor Association invited experts in the field to discuss clinical issues. Combining published guidelines,consensus statements,and research advancements,they formulated the "Technical guidelines for minimally invasive surgery in liver transplant recipients（2025）", aiming to provide reasonable guidance and references for clinical practitioners in the field of liver transplantation.
Humans ; Liver Transplantation/methods* ; Minimally Invasive Surgical Procedures/methods* ; Laparoscopy ; Robotic Surgical Procedures ; Practice Guidelines as Topic

OBJECTIVE: To explore the effectiveness of multi-segment inverted Y-shaped vein transplantation using the anterior lateral malleolar venous network for repair of amputated palm injury distal to the superficial palmar arch. METHODS: Between September 2018 and July 2023, 5 patients with amputated palm injury distal to the superficial palmar arch were treated. There were 3 males and 2 females with an average age of 35.4 years (range, 29-52 years). The time from injury to admission was 1-6 hours (mean, 3.2 hours). The multi-segment inverted Y-shaped vein transplantation in the anterior lateral malleolar venous network were used to repair the common and proper palmar digital arteries; the another anterior lateral malleolar venous network was used to repair the dorsal vein of the hand. The soft tissue defect of dorsal hand in 1 patient was repaired with the pedicled ilioinguinal flap, and the wound at the donor site was directly sutured. Postoperative treatment included anti-infection therapy, antispasmodic therapy, and thrombosis prevention measures. RESULTS: The partial necrosis of the fingertip of the thumb occurred in 1 case, and the marginal necrosis of the abdominal flap after operation occurred in 1 case. The remaining fingers showed good blood supply with normal tension. The incision at donor site of the abdominal flap healed by first intention. All patients were followed up 8-41 months (median, 19 months). At last follow-up, the hand contour was satisfactory; the grasping function, opposition function, and proprioception recovered, and two-point discrimination ranged from 5 to 7 mm (mean, 6 mm). According to the upper extremity function evaluation criteria issued by Hand Surgery Society of the Chinese Medical Association, the functional outcomes were excellent in 3 cases, good in 1 case, and fair in 1 case. CONCLUSION The multi-segment inverted Y-shaped vein transplantation using the anterior lateral malleolar venous network for repairing defects in the common and proper palmar digital arteries distal to the superficial palmar arch offers advantages such as superficial location, flexible harvesting, and high compatibility. This technique has demonstrated favorable outcomes in complex transmetacarpal amputation reconstruction.
Humans ; Adult ; Male ; Female ; Hand Injuries/surgery* ; Middle Aged ; Plastic Surgery Procedures/methods* ; Veins/transplantation* ; Surgical Flaps/blood supply* ; Hand/surgery* ; Treatment Outcome ; Soft Tissue Injuries/surgery*

OBJECTIVE: To review the nomenclature, functional unit construction, technical essentials, and prevention and treatment of complications of functional perforator flaps, so as to provide references for the structural and functional reconstruction of composite tissue defects. METHODS: By retrieving and analyzing domestic and foreign literature on anatomical research, technical innovation and clinical application of functional design and application of perforator flaps, combined with the clinical practice of our team, the methods for harvesting and integrating functional units of perforator flaps were summarized. RESULTS: Functional perforator flap refers to a perforator flap that, on the basis of perforator blood supply, carries one or more tissue functional units (such as muscles, nerves, lymphatic vessels, lymph nodes, bones, mucous membranes, joints or articular cartilages, etc.) with sufficient blood supply located in the supra-fascia and/or sub-fascia, and is used to reconstruct one or more functions of the recipient site. The design and transfer of functional perforator flaps should not only meet the needs of precise coverage of the wound, but also reconstruct the functions of the recipient site such as muscle contraction, flap sensation, lymphatic drainage, blood flow bridging, bone growth, glandular secretion or joint movement, while avoiding iatrogenic dysfunction in the donor site. CONCLUSION Functional perforator flaps have broken through the limitation of "wound coverage" and realize the integrated reconstruction of "structure-function-aesthetics".
Humans ; Perforator Flap/blood supply* ; Plastic Surgery Procedures/methods* ; Soft Tissue Injuries/surgery* ; Tissue and Organ Harvesting/methods* ; Skin Transplantation/methods*

OBJECTIVE: To evaluate the effectiveness of functional perforator flaps utilizing the superficial circumflex iliac artery as a vascular pedicle, as well as chimeric iliac bone flaps, in the reconstruction of composite tissue defects in the hand and foot. METHODS: A retrospective review of the clinical data from 13 patients suffering from severe hand or foot injuries, treated between May 2019 and January 2025, was conducted. The cohort comprised 8 males and 5 females, with ages ranging from 31 to 67 years (mean, 48.5 years). The injuries caused by mechanical crush incidents (n=9) and traffic accidents (n=4). The distribution of injury sites included 8 cases involving the hand and 5 cases involving the foot. Preoperatively, all patients exhibited bone defects ranging from 2.0 to 6.5 cm and soft tissue defects ranging from 10 to 210 cm². Reconstruction was performed using functional perforator flaps based on the superficial circumflex iliac artery and chimeric iliac bone flaps. The size of iliac bone flaps ranged from 2.5 cm×1.0 cm×1.0 cm to 7.0 cm×2.0 cm×1.5 cm, while the size of the soft tissue flaps ranged from 4 cm×3 cm to 15 cm×8 cm. In 1 case with a significant hand defect, a posterior interosseous artery perforator flap measuring 10.0 cm×4.5 cm was utilized as an adjunct. Likewise, an anterolateral thigh perforator flap measuring 25 cm×7 cm was combined in 1 case involving a foot defect. All donor sites were primarily closed. Postoperative flap survival was monitored, and bone healing was evaluated through imaging examination. Functional outcomes were assessed based on the location of the defects: for hand injuries, grip strength, pinch strength, and flap two-point discrimination were measured; for foot injuries, the American Orthopaedic Foot & Ankle Society (AOFAS) score, visual analogue scale (VAS) score, Maryland Foot Score, plantar pressure distribution and gait symmetry index (GSI) were evaluated. RESULTS: All flaps survived completely, with primary healing observed at both donor and recipient sites. All patients were followed up 6-18 months (mean, 12.2 months). No significant flap swelling or deformity was observed. Imaging examination showed a bone callus crossing rate of 92.3% (12/13) at 3 months after operation, and bone density recovered to more than 80% of the healthy side at 6 months. The time required for bone flap integration ranged from 2 to 6 months (mean, 3.2 months). One patient with a foot injury exhibited hypertrophic scarring at the donor site; however, no major complication, such as infection or bone nonunion, was noted. At 6 months after operation, grip strength in 8 patients involving the hand recovered to 75%-90% of the healthy side (mean, 83.2%), while pinch strength recovered to 70%-85% (mean, 80%). Flap two-point discrimination ranged from 8 to 12 mm, approaching the sensory capacity of the healthy side (5-8 mm). Among the 5 patients involving the foot, the AOFAS score at 8 months was 80.5±7.3, VAS score was 5.2±1.6. According to the Maryland Foot Score, 2 cases were rated as excellent and 3 as good. Gait analysis at 6 months after operation showed GSI above 90%, with plantar pressure distribution closely resembling that of the contralateral foot. CONCLUSION The use of functional perforator flaps based on the superficial circumflex iliac artery, combined with chimeric iliac bone flaps, provides a reliable vascular supply and effective functional restoration for the simultaneous repair of composite bone and soft tissue defects in the hand or foot. This technique represents a viable and effective reconstructive option for composite tissue defects in these anatomical regions.
Humans ; Male ; Middle Aged ; Female ; Perforator Flap/transplantation* ; Adult ; Plastic Surgery Procedures/methods* ; Hand Injuries/surgery* ; Aged ; Retrospective Studies ; Foot Injuries/surgery* ; Ilium/transplantation* ; Iliac Artery/surgery* ; Soft Tissue Injuries/surgery* ; Bone Transplantation/methods* ; Treatment Outcome