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

Objective:To evaluate the clinical feasibility of subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation following transvenous lead extraction (TLE).Methods:This was a retrospective study. Consecutive patients who underwent S-ICD implantation at Peking University People′s Hospital between June 2015 and October 2023 were enrolled. Patients were divided into the TLE group and the newly implanted group based on whether they received TLE prior to S-ICD implantation. Baseline characteristics, S-ICD indication, defibrillation threshold test results, complications, and postoperative follow-up data were collected and compared between the two groups.Results:A total of 27 patients were included, aged (49.2±14.2) years, including 19 males. There were 12 patients in the TLE group and 15 in the newly implanted group. Compared with the TLE group, patients in the newly implanted group were younger ((43.3±13.7) years vs. (55.6±12.0) years, P=0.013). The main S-ICD indication in the TLE group was high infection risk (9/12), whereas in the newly implanted group it was younger age (11/15). All patients underwent successful S-ICD implantation, with 18 patients completing defibrillation threshold testing (all successful). Additionally, the TLE group had longer follow-up duration than the newly implanted group (42 (19, 60) months vs. 12 (3, 28) months, P=0.001). No complications or deaths occurred during follow-up, with normal device function in both groups. A total of 17 ventricular tachycardia or fibrillation events were recorded, of which 7 met defibrillation criteria and all received effective therapy. Conclusion:S-ICD demonstrates safety and efficacy as a therapeutic option for patients after TLE, with comparable device functionality and follow-up outcomes to patients with newly implanted S-ICD.

With the increasing numbers of implanted cardiovascular implantable electronic devices(CIED),the issue of lead management has become increasingly prominent.Currently,there is controversy on the management of redundant lead.In clinical practices such as CIED device upgrades,choosing to abandon redundant leads can avoid the risks associated with lead extraction.However,the strategy may increase the risks of future CIED infections,venous occlusions,and the risks of future lead extraction.On the other hand,choosing to remove redundant leads might expose patients to risks associated with lead extraction.Therefore,the management regarding redundant lead need to balance the risks of abandonment and extraction strategies.This article discusses the current strategies for redundant lead management and their potential risks.

With the increasing numbers of implanted cardiovascular implantable electronic devices(CIED),the issue of lead management has become increasingly prominent.Currently,there is controversy on the management of redundant lead.In clinical practices such as CIED device upgrades,choosing to abandon redundant leads can avoid the risks associated with lead extraction.However,the strategy may increase the risks of future CIED infections,venous occlusions,and the risks of future lead extraction.On the other hand,choosing to remove redundant leads might expose patients to risks associated with lead extraction.Therefore,the management regarding redundant lead need to balance the risks of abandonment and extraction strategies.This article discusses the current strategies for redundant lead management and their potential risks.

Objective:To evaluate the clinical feasibility of subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation following transvenous lead extraction (TLE).Methods:This was a retrospective study. Consecutive patients who underwent S-ICD implantation at Peking University People′s Hospital between June 2015 and October 2023 were enrolled. Patients were divided into the TLE group and the newly implanted group based on whether they received TLE prior to S-ICD implantation. Baseline characteristics, S-ICD indication, defibrillation threshold test results, complications, and postoperative follow-up data were collected and compared between the two groups.Results:A total of 27 patients were included, aged (49.2±14.2) years, including 19 males. There were 12 patients in the TLE group and 15 in the newly implanted group. Compared with the TLE group, patients in the newly implanted group were younger ((43.3±13.7) years vs. (55.6±12.0) years, P=0.013). The main S-ICD indication in the TLE group was high infection risk (9/12), whereas in the newly implanted group it was younger age (11/15). All patients underwent successful S-ICD implantation, with 18 patients completing defibrillation threshold testing (all successful). Additionally, the TLE group had longer follow-up duration than the newly implanted group (42 (19, 60) months vs. 12 (3, 28) months, P=0.001). No complications or deaths occurred during follow-up, with normal device function in both groups. A total of 17 ventricular tachycardia or fibrillation events were recorded, of which 7 met defibrillation criteria and all received effective therapy. Conclusion:S-ICD demonstrates safety and efficacy as a therapeutic option for patients after TLE, with comparable device functionality and follow-up outcomes to patients with newly implanted S-ICD.

Objective To investigate the application value of quantitative relaxation parameters based on synthetic MRI technology in the differential diagnosis of parotid gland tumors.Methods Conventional MRI and synthetic MRI data of 59 patients with patho-logically confirmed parotid gland tumors were analyzed retrospectively.T1,T2,and proton density(PD)values of the tumor were extracted from T1,T2 and PD mapping.The differences in quantitative relaxation parameters of pleomorphic adenomas,Warthin tumors,and malignant tumors were further compared.Diagnostic performance of each quantitative relaxation parameter was assessed and com-pared via receiver operating characteristic(ROC)curve and DeLong test.Results T2 value was significantly higher in pleomorphic adenomas than that in malignant tumors(P<0.05).The T1,T2,and PD values of pleomorphic adenomas and malignant tumors were significantly higher than those of Warthin tumors(P<0.05).The area under the curve(AUC)of the T2 value in differentia-ting pleomorphic adenomas from malignant tumors was 0.794.The AUC for T1 value(0.939)in differentiating Warthin tumors from malignant tumors was significantly higher than that of T2(0.873,P=0.341)and PD(0.927,P=0.891)values,without sta-tistically significant difference.The AUC for T2 value(0.968)in differentiating pleomorphic adenomas from Warthin tumors was significantly higher than that of T1(0.931,P=0.360)and PD(0.876,P=0.120)values,without statistically significant difference.Conclusion Quantitative relaxation parameters based on synthetic MRI technology may contribute to differentiating pleomorphic adenomas,Warthin tumors,and malignant tumors of the parotid gland.

Objective To observe the changes in functional connectivity(FC)of raphe nucleus in patients with first-episode depression complicated with suicidal ideation(SI).Methods Ninety-eight first-episode depression patients were prospectively enrolled and assigned into SI group(n=56)or non SI group(n=42)based on complicated with SI or not,while 47 healthy volunteers were recruited as control group.Resting-state functional MRI was performed.FC between dorsal raphe nucleus(DRN),median raphe nucleus(MRN)and the whole brain were analyzed and compared among 3 groups and between each 2 groups,and the correlations of FC of different brain regions with clinical data of SI group were explored.Results Compared with control group,FC between DRN and left cerebellum and left putamen in SI group and non SI group decreased(all P＜0.05),between MRN and right inferior temporal gyrus increased but between MRN and left inferior frontal gyrus,right superior occipital gyrus,left inferior parietal lobule,left putamen decreased(all P＜0.05).FC between DRN and left putamen in SI group was higher than that in non SI group(P＜0.05).FC between MRN and right central posterior gyrus of SI group increased compared with that in the rest 2 groups(both P＜0.05).FC between MRN and left putamen in SI group was positively correlated with body mass score of Hamilton depression scale-24(HAMD-24)(rs=0.297,P=0.026).Conclusion Abnormal changes of FC between raphe nucleus and cortex,also between raphe nucleus and subcortical area occurred,and FC between MRN and left putamen positively correlated with body mass score of HAMD-24 in patients with first-episode depression complicated with SI.

Objective:To explore the early differential diagnosis method by comparing the clinical characteristics of acquired immunodeficiency syndrome (AIDS) patients complicated with tuberculous meningitis (TBM) and cryptococcus neoformans meningitis (CNM).Methods:The AIDS patients admitted to Guangzhou Eighth People′s Hospital, Guangzhou Medical University from January 2011 to February 2022 and diagnosed with combined TBM and CNM after discharge respectively were included. A retrospective study was performed to analyze the clinical features of 21 AIDS patients complicated with TBM (TBM group) and 54 AIDS patients with CNM (CNM group) (all cases were confirmed by etiology). The data of meningitis-related symptoms and signs, blood routine test, CD4 + T lymphocyte counts, imaging characteristics and cerebrospinal fluid examination at admission were collected and analyzed. Statistical analysis was performed by using independent sample t test, rank sum test or chi-square test. Results:The age of patients in the TBM group was (44.6±12.9) years old, which was older than that of patients in the CNM ((37.6±12.6) years old), the difference was statistically significant ( t=-2.15, P=0.035). Forty-eight cases (88.89%) and seven cases (12.96%) in the CNM group experienced headaches and consciousness disorders respectively, with statistically significant differences compared to those in the TBM group (13 cases (61.90%) and nine cases (42.86%), respectively) ( χ2=7.25, P=0.007 and χ2=8.05, P=0.005, respectively). The proportion of leukopenia was 27.78%(15/54), and proportion of thrombocytopenia was 16.67%(9/54) in the CNM group, which were higher than those in the TBM group (4.76%(1/21) and 0(0/21), respectively), and the differences were statistically significant ( χ2=4.77, P=0.029 and χ2=3.98, P=0.042, respectively). The CD4 + T lymphocyte count in the TBM group was 74.0(92.0)/μL, which was higher than 19.5(56.5)/μL in the CNM group, and the difference was statistically significant ( Z=-2.87, P=0.009). The CNM group had 46 cases (85.19%) with cerebrospinal fluid pressure >180 mmH 2O(1 mmH 2O=0.009 8 kPa) and 24 cases (44.44%) with cerebrospinal fluid pressure >330 mmH 2O, which were significantly higher than those in the TBM group with seven cases (33.33%) and four cases (19.05%), respectively, and the differences were statistically significant ( χ2=19.61, P<0.001 and χ2=4.17, P=0.041, respectively). Fifty-two point three eight percent (11/21) of patients in the TBM group had a white blood cell counts>200×10 6/L in the cerebrospinal fluid, which was higher than that in the CNM group (1.85%(1/54)), with a statistically significant difference ( χ2=27.23, P<0.001). The white blood cell counts, protein and adenosine deaminase levels in the cerebrospinal fluid of TBM group were significantly higher than those in the CNM group (200.00(579.50)×10 6/L vs 17.50(66.25)×10 6/L, 1 863(2 858) mg/L vs 672 (513) mg/L and 6.60 (8.55) U/L vs 1.95(2.60) U/L, respectively), and the cerebrospinal fluid chloride level was lower than that in the CNM group ((107.71±8.22) mmol/L vs (115.99±6.55) mmol/L), and all the differences were statistically significant ( Z=4.11, P<0.001, Z=21.23, P=0.008, Z=2.09, P=0.040 and t=4.57, P<0.001, respectively). There was no significant difference in cerebrospinal fluid glucose between the TBM group and the CNM group ((1.86±1.22) mmol/L vs (2.34±1.05) mmol/L, t=-1.72, P=0.090). The proportion of patients with bilateral lung lesions in the TBM group was higher than that in the CNM group, and the difference was statistically significant (100.00%(21/21) vs 40.74% (22/54), χ2=-6.53, P=0.011). Conclusions:Patients with AIDS complicated with TBM are more likely to have consciousness disorders, inflammatory response in the cerebrospinal fluid, and more bilateral lung lesions. In contrast, patients with AIDS complicated with CNM are more frequently to experience severe headache and significant elevation of cerebrospinal fluid pressure, leukopenia and thrombocytopenia, and lower peripheral blood CD4 + T lymphocyte counts.

Objective:To investigate the clinical efficacy of transfer of a free segment of the proximal second toe interphalangeal joint composite tissue flap in reconstruction of defects of interphalangeal joint of fingers, and simultaneously reconstruct the donor site defect left with the second toe by a transfer of a pedicled bone flap of the fibular proximal great toe.Methods:From December 2020 to April 2023, a total of 9 patients with interphalangeal joint defects of fingers were treated in the Department of Hand Microsurgery of Shunde Heping Surgery Hospital. The patients were 7 males and 2 females, aged 18-55 years old, with an average age of 31 years old. Firstly, transfers of a free segment of the proximal second toe interphalangeal joint composite tissue flap were performed to reconstruct the defects of finger joints. Simultaneously in the surgery, transfers of the fibular pedicled bone flap of the proximal great toe were conducted to reconstruct the donor site defects left in the second toe. Patients were instructed with appropriate postoperative functional exercises. K-wires were removed at 8-12 weeks after surgery. Outpatient visits, telephone and WeChat follow-ups were conducted to evaluate the appearance and functional recovery of the reconstructed interphalangeal joints and donor feet. Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association, Vancouver Scar Scale (VSS) and American Orthopedic Foot and Ankle Society (AOFAS) foot function scoring standards were employed in the evaluation.Results:Postoperative follow-up lasted for 6 to 30 months. All of the 9 interphalangeal joint composite tissue flaps in the fingers survived with complete and good appearance. Function of the reconstructed interphalangeal joints of the fingers recovered well. According to the Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association, the average score achieved 12 points, with 6 patients of excellent, 2 of good and 1 of fair. After surgery, the appearance and function of the donor great toes and second toes all recovered well. The average score of the scars in donor second toe evaluated by VSS was 4 points. All the donor feet were kept with 5 toes, with full, intact and good in appearance. According to the AOFAS foot function scoring standard, the average score achieved 95 points, and were excellent.Conclusion:Application of transfer of free proximal segment of interphalangeal joint composite tissue flap of the second toe in reconstruction of the interphalangeal joint defect of a finger, and simultaneously reconstruct the defect left with the donor second toe with a fibular proximal great toe flap pedicled with bone tissue can achieve good clinical efficacy in reconstruction of the defects of interphalangeal joint of fingers, restore the function of the interphalangeal joint of fingers and the appearance and function of the donor foot.