The effectiveness of nirmatrelvir/ritonavir regimen in hospitalized renal transplant patients with prolonged COVID-19 infection: a multicenter clinical experience.

OBJECTIVES: Effectiveness of nirmatrelvir/ritonavir (NR) in kidney transplant recipients (KTRs) infected COVID-19 for more than 5 days has not been evaluated. METHODS: In this multicenter retrospective study, 85 KTRs with COVID-19 were enrolled, including 50 moderate, 21 severe, and 14 critical patients. RESULTS: The median time from onset to starting NR treatment was 14 (IQR, 11-19) days. Before NR treatment, 96.5% patients reduced use of antimetabolites. They also stopped using calcineurin inhibitors (CNI) 12-24 hours before NR treatment, with CNI concentrations well-controlled during NR treatment. The use of intravenous corticosteroids increased with COVID-19 severity. The median time to reach viral negative conversion was 5 (IQR, 4-8) days for all patients. For moderate and severe COVID-19 patients, they had a low rate of ICU admission (1.4%), exacerbation requiring upgraded oxygen therapy (5.6%), and dialysis (2.8%); no intubation and mechanical ventilation, and no deaths were observed. Patients with critical COVID-19 had a low mortality rate (7.1%). CONCLUSIONS: A regimen including NR for clearing SARS-CoV-2 along with reducing immunosuppressants and using intravenous corticosteroids is associated with lower rates of exacerbation and mortality in KTRs who have moderate to critical SARS-CoV-2 infection and the virus still present after 5 days.

A fast and robust iterative genome-editing method based on a Rock-Paper-Scissors strategy.

The production of optimized strains of a specific phenotype requires the construction and testing of a large number of genome modifications and combinations thereof. Most bacterial iterative genome-editing methods include essential steps to eliminate selection markers, or to cure plasmids. Additionally, the presence of escapers leads to time-consuming separate single clone picking and subsequent cultivation steps. Herein, we report a genome-editing method based on a Rock-Paper-Scissors (RPS) strategy. Each of three constructed sgRNA plasmids can cure, or be cured by, the other two plasmids in the system; plasmids from a previous round of editing can be cured while the current round of editing takes place. Due to the enhanced curing efficiency and embedded double check mechanism, separate steps for plasmid curing or confirmation are not necessary, and only two times of cultivation are needed per genome-editing round. This method was successfully demonstrated in Escherichia coli and Klebsiella pneumoniae with both gene deletions and replacements. To the best of our knowledge, this is the fastest and most robust iterative genome-editing method, with the least times of cultivation decreasing the possibilities of spontaneous genome mutations.

Simultaneous pancreas and kidney transplantation for end-stage kidney disease patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

PURPOSE: The indications for patients with type 2 diabetes mellitus (T2DM) combined with end-stage kidney disease (ESKD) undertaking simultaneous pancreas and kidney transplantation (SPK) remain an unresolved issue. This study aimed to systematically review the survival outcomes of SPK among T2DM-ESKD patients. METHODS: Online databases including PubMed, MEDLINE, EMBASE, and the CENTRAL Library, CNKI, Chinese Biomedical Literature Database, and Wan-Fang database were used to locate the studies of ESKD patients with T2DM undertaking SPK up to May 2021. A third reviewer was consulted if there were disagreements. Data were analyzed with STATA (15.0). RESULTS: Nine cohort studies were identified. The pooled 1-year, 3-year, and 5-year patient survival rates of patients with T2DM and ESKD after SPK were 98%, 95%, and 91% respectively. Comparing the treatment effect of SPK between type 1 diabetes mellitus (T1DM) and T2DM, the survival estimates were comparable. For T2DM patients, SPK had a survival advantage compared with KTA. CONCLUSIONS: The synthesized clinical outcomes of T2DM patients with ESKD after SPK were relatively better than KTA, but a subset of T2DM-ESKD patients who would benefit the most from SPK was to be defined. PROSPERO registration number CRD42019118321. Date of registration: 14 Jan 2019 (retrospectively registered).

Metabolic outcomes and renal function after simultaneous kidney/pancreas transplantation compared with kidney transplantation alone for type 2 diabetes mellitus patients.

In this study, we aimed to compare the metabolic outcomes, renal function, and survival outcomes of simultaneous pancreas and kidney transplantation (SPK) and kidney transplantation alone (KTA) among end-stage kidney disease (ESKD) patients with type II diabetes mellitus (T2DM). Patients with ESKD and T2DM who underwent KTA (n = 85) or SPK (n = 71) in a transplant center were retrospectively reviewed. Metabolic profiles, renal function, and survival outcomes were assessed repeatedly at different follow-up time points. Propensity score procedures were applied to enhance between-group comparability. The levels of renal and metabolic outcomes between SPK and KTA over time were examined and analyzed using mixed-model repeated-measures approaches. The median follow-up period was 1.8 years. Compared with KTA, SPK resulted in superior metabolic outcomes and renal function, with lower levels of glycated hemoglobin (HbA1c; P = 0.0055), fasting blood glucose (P < 0.001), triglyceride (P = 0.015), cholesterol (P = 0.0134), low-density lipoprotein (P = 0.0161), and higher estimated glomerular filtration rate (eGFR; P < 0.001). SPK provided better metabolic outcomes and renal function. The survival outcomes of the recipients and grafts were comparable between the two groups.

A prediction model of delayed graft function in deceased donor for renal transplant: a multi-center study from China.

BACKGROUND: Kidneys obtained from deceased donors increase the incidence of delayed graft function (DGF) after renal transplantation. Here we investigated the influence of the risk factors of donors with DGF, and developed a donor risk scoring system for DGF prediction. METHODS: This retrospective study was conducted in 1807 deceased kidney donors and 3599 recipients who received donor kidneys via transplants in 29 centers in China. We quantified DGF associations with donor clinical characteristics. A donor risk scoring system was developed and validated using an independent sample set. RESULTS: The incidence of DGF from donors was 19.0%. Six of the donor characteristics analyzed, i.e., age, cause of death, history of hypertension, terminal serum creatinine, persistence of hypotension, and cardiopulmonary resuscitation (CPR) time were risk factors for DGF. A 49-point scoring system of donor risk was established for DGF prediction and exhibited a superior degree of discrimination. External validation of DGF prediction revealed area under the receiver-operating characteristic (AUC) curves of 0.7552. CONCLUSIONS: Our study determined the deceased donor risk factors related to DGF after renal transplantation pertinent to the Chinese cohort. The scoring system developed here had superior diagnostic significance and consistency and can be used by clinicians to make evidence-based decisions on the quality of kidneys from deceased donors and guide renal transplantation therapy.

Exploration of symptom experience in kidney transplant recipients based on symptoms experience model.

PURPOSE: Kidney transplant recipients suffer from a variety of symptoms, and symptom management is crucial in improving their quality of life (QOL). Accordingly, this study aims to identify the symptoms experienced by kidney transplant recipients and examine the relationship amongst antecedents, symptom experience and QOL of recipients in China. METHODS: A total of 300 kidney transplant recipients were investigated in one of the most first-rate hospitals in China by asking them to fill out a self-designed general questionnaire, the Symptom Experience Scale, the Sense of Coherence Scale (Chinese version), the Revised Life Orientation Test (Chinese version) and the 36-item Short Form Health Survey (Chinese version). RESULTS: Kidney transplant recipients experienced multiple symptoms that were frequent, severe and bothersome. The final model showed significant consistency with the data. In the QOL model, post-transplant time, complications, immunosuppressive agents and sense of coherence explained 30.7% of the variance of symptom experience. Moreover, habitual residence, economic burden, post-transplant time, kidney function, optimism and symptom experience accounted for 70.6% of the variance on QOL. CONCLUSIONS: We can explain the relationship between antecedents, symptom experience and QOL amongst Chinese kidney transplant recipients by using Symptoms Experience Model. Clinicians and caregivers can manage the recipient's symptoms during follow-up from psychological, physical and medication management perspectives. Improving sense of coherence, maintaining optimism and managing symptoms are essential for enhancing QOL.

Phenolic compounds induce ferroptosis-like death by promoting hydroxyl radical generation in the Fenton reaction.

Phenolic compounds are industrially versatile chemicals, also the most ubiquitous pollutants. Recently, biosynthesis and biodegradation of phenols has attracted increasing attention, while phenols' toxicity is a major issue. Here, we evolved phloroglucinol-tolerant Escherichia coli strains via adaptive evolution, and three mutations (ΔsodB, ΔclpX and fetAB overexpression) prove of great assistance in the tolerance improvement. We discover that phloroglucinol complexes with iron and promotes the generation of hydroxyl radicals in Fenton reaction, which leads to reducing power depletion, lipid peroxidation, and ferroptosis-like cell death of E. coli. Besides phloroglucinol, various phenols can trigger ferroptosis-like death in diverse organisms, from bacteria to mammalian cells. Furthermore, repressing this ferroptosis-like death improves phloroglucinol production and phenol degradation by corresponding strains respectively, showing great application potential in microbial degradation or production of desired phenolic compounds, and phloroglucinol-induced ferroptosis suppresses tumor growth in mice, indicating phloroglucinol as a promising drug for cancer treatment.

Predicting Motor Imagery BCI Performance Based on EEG Microstate Analysis.

Motor imagery (MI) electroencephalography (EEG) is natural and comfortable for controllers, and has become a research hotspot in the field of the brain-computer interface (BCI). Exploring the inter-subject MI-BCI performance variation is one of the fundamental problems in MI-BCI application. EEG microstates with high spatiotemporal resolution and multichannel information can represent brain cognitive function. In this paper, four EEG microstates (MS1, MS2, MS3, MS4) were used in the analysis of the differences in the subjects' MI-BCI performance, and the four microstate feature parameters (the mean duration, the occurrences per second, the time coverage ratio, and the transition probability) were calculated. The correlation between the resting-state EEG microstate feature parameters and the subjects' MI-BCI performance was measured. Based on the negative correlation of the occurrence of MS1 and the positive correlation of the mean duration of MS3, a resting-state microstate predictor was proposed. Twenty-eight subjects were recruited to participate in our MI experiments to assess the performance of our resting-state microstate predictor. The experimental results show that the average area under curve (AUC) value of our resting-state microstate predictor was 0.83, and increased by 17.9% compared with the spectral entropy predictor, representing that the microstate feature parameters can better fit the subjects' MI-BCI performance than spectral entropy predictor. Moreover, the AUC of microstate predictor is higher than that of spectral entropy predictor at both the single-session level and average level. Overall, our resting-state microstate predictor can help MI-BCI researchers better select subjects, save time, and promote MI-BCI development.

Quality of life, anxiety and depression symptoms in living related kidney donors: a cross­sectional study.

OBJECTIVES: Few studies have examined the quality of life of living kidney donors in mainland China. The data on anxiety and depression of living kidney donors was also scant. This study aimed to investigate quality of life, anxiety, and depression and identify their influencing factors among living kidney donors in mainland China. METHODS: A cross-sectional study included 122 living kidney donors from a kidney transplantation center in China. The abbreviated World Health Organization Quality of Life questionnaire, Generalized Anxiety Disorder 2-item and Patient Health Questionnaire 2-item were used to assess the quality of life, anxiety and depression symptoms, respectively. RESULTS: Our study found that the physical related quality of life of our donors was poorer than that of the domestic general population. Among 122 donors, 43.4% and 29.5% of them were found to have anxiety and depression symptoms, respectively. Poor health condition of recipient was identified as not only negative factors affecting all domains of quality of life, but also closely related to anxiety and depression of kidney donors. Donors with proteinuria were more likely to have a poor psychological, social related quality of life, as well as anxiety and depression symptoms. CONCLUSIONS: Living kidney donation has an impact on the physical and mental health of donors. Both the physical and mental health of living kidney donors should not be ignored. More attention and support should be given to donors with proteinuria and donors whose relative recipient suffering poor health condition.

Kidney transplant for autosomal dominant polycystic kidney disease: the superiority of concurrent bilateral nephrectomy.

OBJECTIVE: To assess the transplant outcome of patients who underwent concurrent bilateral nephrectomies (CBN) during kidney transplantation (KT) owing to autosomal dominant polycystic kidney disease (ADPKD). METHODS: The study included 67 ADPKD patients, 4 of whom were excluded, and the rest, 63 patients, were divided into two groups: KT with CBN (group A, n = 31) and KT without CBN (group B, n = 32). Demographic factors, transplant-related factors, posttransplant complications and patient survival were compared. RESULTS: There was no statistical difference in demographic or transplant-related factors between the two groups, though group A patients required more operation time (300 ± 30.85 vs. 120 ± 20.78 min, p < 0.01), needed more blood transfusion (4.31 ± 1.05 vs. 1.35 ± 0.23 U, p < 0.01) and had more adjacent organ injury during operation (22.58 vs. 0%, p < 0.01) compared with group B. However, group A patients had better relief from arterial hypertension persistence and lower urinary tract infection postoperation than group B (16/24 vs. 22/24, 6.45 vs. 31.25%, p < 0.05). Patient survival in the two groups was similar at 1 and 5 years (p > 0.05). CONCLUSION: CBN could be safely performed during KT for patients with ADPKD. The patients could benefit from reduction of the operative procedures, better relief from arterial hypertension persistence and lower urinary tract infection posttransplantation.

Epstein-Barr virus-associated monomorphic post-transplant lymphoproliferative disorder after pediatric kidney transplantation: A case report.

BACKGROUND: Post-transplant lymphoproliferative disease (PTLD) is the most common malignant tumor that occurs after kidney transplantation in children, and is associated with Epstein-Barr virus (EBV). CASE SUMMARY: We report a case of PTLD that occurred in a 17-year-old female patient at 5 mo post-transplant. The first symptom was abdominal pain accompanied by fever, nausea, and vomiting. EBV-associated monomorphic PTLD with multiple abdominal nodules was diagnosed by pathology, clinical manifestations, imaging results, and the presence of EB-DNA. After successful treatment with rituximab, the abdominal nodules in the spleen and liver disappeared. CONCLUSION: Early pathological biopsy to confirm the diagnosis is critical to treatment and prognosis. Reducing immunosuppression and rituximab therapy are effective methods for treating PTLD, but need to be initiated as early as possible.

Kidney re-transplantation after living donor graft nephrectomy due to de novo chromophobe renal cell carcinoma: A case report.

BACKGROUND: There are few reported cases of allograft nephrectomy due to malignancy followed by successful renal re-transplantation two years later. In this paper, we report a patient who underwent kidney re-transplantation after living donor graft nephrectomy due to de novo chromophobe renal cell carcinoma (ChRCC) involving the allograft kidney. CASE SUMMARY: A 34-year-old man underwent living kidney transplantation at the age of 22 years for end-stage renal disease. Maintenance immunosuppression consisted of tacrolimus, mycophenolate mofetil (MMF), and prednisone. Six years post-transplantation, at another hospital, ultrasonography revealed a small mass involving the upper pole of the graft. The patient declined further examination and treatment at this point. Seven years and three months post-transplantation, the patient experienced decreasing appetite, weight loss, gross hematuria, fatigue, and oliguria. Laboratory tests showed anemia (hemoglobin level was 53 g/L). Contrast-enhanced computed tomography revealed a large heterogeneous cystic-solid mass involving the upper pole of the renal allograft. Graft nephrectomy was performed and immunosuppressants were withdrawn. Histological and immunohistochemical features of the tumor were consistent with ChRCC. One year after allograft nephrectomy, low doses of tacrolimus and MMF were administered for preventing allosensitization. Two years after allograft nephrectomy, the patient underwent kidney re-transplantation. Graft function remained stable with no ChRCC recurrence in more than 2-years of follow-up. CONCLUSION: De novo ChRCC in kidney graft generally has a good prognosis after graft nephrectomy and withdrawal of immunosuppression. Kidney re-transplantation could be a viable treatment. A 2-year malignancy-free period may be sufficient time before re-transplantation.

Safety and Efficacy of Anti-CD19-Chimeric Antigen Receptor T Cell Combined With Programmed Cell Death 1 Inhibitor Therapy in a Patient With Refractory Post-Transplant Lymphoproliferative Disease: Case Report and Literature Review.

Post-transplant lymphoproliferative disease (PTLD) often exhibits poor prognosis and high mortality, and there are no uniform guidelines for the treatment of this disease. Anti-CD19 chimeric antigen receptor (CAR) T cells show significant efficacy in treatment of relapse/refractory diffuse large B-cell lymphoma (DLBCL). Treatment using anti-CD19-CAR T-cell therapy in PTLD has been limited by immunosuppressants and has not been widely employed. In this study, a refractory post kidney transplant DLBCL patient with a high tumor burden was enrolled in a clinical trial of anti-CD19-CAR T-cell therapy. The tacrolimus dose was not decreased during combination chemotherapy, as the creatinine level of the patient increased. To improve the function of autologous T cells, combination therapy with anti-CD19-CAR T cells and programmed cell death 1 (PD-1) inhibitors was selected. After treatment with the combination therapy, the patient was diagnosed with grade 1 cytokine release syndrome and grade 3 immune effector cell-associated neurotoxicity syndrome. The amplification peak of anti-CD19-CAR T cells reached 9.01% on day 7. With PD-1 inhibitor maintenance therapy, his disease was maintained in partial remission for 18 weeks. However, his tumor suddenly increased in size, and he discontinued the treatment, including radiation therapy. The anti-CD19-CAR T cell and PD-1 inhibitors have a combined effect on PTLD, and this combination therapy needs to be further explored.

Bacterial protein acetylation and its role in cellular physiology and metabolic regulation.

Protein acetylation is an evolutionarily conserved posttranslational modification. It affects enzyme activity, metabolic flux distribution, and other critical physiological and biochemical processes by altering protein size and charge. Protein acetylation may thus be a promising tool for metabolic regulation to improve target production and conversion efficiency in fermentation. Here we review the role of protein acetylation in bacterial physiology and metabolism and describe applications of protein acetylation in fermentation engineering and strategies for regulating acetylation status. Although protein acetylation has become a hot topic, the regulatory mechanisms have not been fully characterized. We propose future research directions in protein acetylation.

Transplant-related Symptom Clusters in Renal Transplant Recipients.

Renal transplant recipients experience multiple symptoms, but complex relationships among these symptoms remain poorly understood. To explore the existence of symptom clusters in renal transplant recipients. A total of 295 renal transplant recipients were recruited in a hospital in Tianjin from October 2017 to January 2018. The participants completed the symptom questionnaire that assessed three symptom dimensions of 62 symptoms. Exploratory factor analysis was performed to identify symptom clusters. Five symptom clusters were extracted through exploratory factor analysis: emotional-sleep symptom cluster, pain-gastrointestinal symptom cluster, immune-related symptom cluster, lack of energy symptom cluster, and visual dysfunction symptom cluster, which explained 50.53% of the variance of symptom experience. Renal transplant recipients experienced a complex series of symptoms, and some symptoms related to one another formed a symptom cluster. Adopting a symptom cluster approach has the potential to remarkably enhance symptom assessment and nursing care for renal transplant recipients.

Human parvovirus B19-associated early postoperative acquired pure red cell aplasia in simultaneous pancreas-kidney transplantation: A case report.

BACKGROUND: Acquired pure red cell aplasia (aPRCA) related to human parvovirus B19 (HPV B19) is rarely reported in simultaneous pancreas-kidney transplantation (SPKT) recipients; there has yet to be a case report of early postoperative infection. In this current study, we report the case of a Chinese patient who experienced the disease in the early postoperative period. CASE SUMMARY: A 63-year-old man, with type 2 diabetes and end-stage renal disease, received a brain dead donor-derived SPKT. Immunosuppression treatment consisted of tacrolimus, prednisone, enteric-coated mycophenolate sodium (EC-MPS), and thymoglobulin combined with methylprednisolone as induction. The hemoglobin (Hb) level declined due to melena at postoperative day (POD) 3, erythropoietin-resistant anemia persisted, and reticulocytopenia was diagnosed at POD 20. The bone marrow aspirate showed decreased erythropoiesis and the presence of giant pronormoblasts at POD 43. Metagenomic next-generation sequencing (mNGS) of a blood sample identified HPV B19 infection at POD 66. EC-MPS was withdrawn; three cycles of intravenous immunoglobulin (IVIG) infusion therapy were administered; and tacrolimus was switched to cyclosporine. The HPV B19-associated aPRCA resolved completely and did not relapse within the 1-year follow-up period. The diminution in mNGS reads was correlated with Hb and reticulocyte count improvements. CONCLUSION: HPV B19-associated aPRCA can occur at an early period after SPKT. An effective therapy regimen includes IVIG infusion and adjustment of the immuno-suppressive regimen. Moreover, mNGS can be used for the diagnosis and to reflect disease progression.

IL-21 Receptor Blockade Shifts the Follicular T Cell Balance and Reduces De Novo Donor-Specific Antibody Generation.

Donor-specific antibodies (DSAs) play a key role in chronic kidney allograft injury. Follicular T helper (Tfh) cells trigger the humoral alloimmune response and promote DSA generation, while T-follicular regulatory (Tfr) cells inhibit antibody production by suppressing Tfh and B cells. Interleukin (IL)-21 exerts a distinct effect on Tfh and Tfr. Here, we studied whether blocking IL-21R with anti-IL-21R monoclonal antibody (αIL-21R) changes the Tfh/Tfr balance and inhibits DSA generation. First, we investigated the impact of αIL-21R on CD4+ T cell proliferation and apoptosis. The results showed that αIL-21R did not have cytotoxic effects on CD4+ T cells. Next, we examined Tfh and regulatory T cells (Tregs) in an in vitro conditioned culture model. Naïve CD4+ T cells were isolated from 3-month-old C57BL/6 mice and cultured in Tfh differentiation inducing conditions in presence of αIL-21R or isotype IgG and differentiation was evaluated by CXCR5 expression, a key Tfh marker. αIL-21R significantly inhibited Tfh differentiation. In contrast, under Treg differentiation conditions, FOXP3 expression was inhibited by IL-21. Notably, αIL-21R rescued IL-21-inhibited Treg differentiation. For in vivo investigation, a fully mismatched skin transplantation model was utilized to trigger the humoral alloimmune response. Consistently, flow cytometry revealed a reduced Tfh/Tfr ratio in recipients treated with αIL-21R. Germinal center response was evaluated by flow cytometry and lectin histochemistry. We observed that αIL-21R significantly inhibited germinal center reaction. Most importantly, DSA levels after transplantation were significantly inhibited by αIL-21R at different time points. In summary, our results demonstrate that αIL-21R shifts the Tfh/Tfr balance toward DSA inhibition. Therefore, αIL-21R may be a useful therapeutic agent to prevent chronic antibody mediated rejection after organ transplantation.

PSMP Is Discriminative for Chronic Active Antibody-Mediated Rejection and Associate With Intimal Arteritis in Kidney Transplantation.

Chronic active antibody-mediated rejection (CAAMR) is an intermediate process that occurs during the development of chronic antibody-mediated rejection (CAMR), which is a key problem associated with the long-term kidney grafts survival. This study investigated the role played by PC3-secreted microprotein (PSMP) in the progression of CAAMR and CAMR. We showed that CAAMR and CAMR patients' allografts dysfunction with declined survival rate, which suggested that earlier diagnosis and treatment of CAAMR might be important to prevent irreversible chronic injury of CAMR progression. We found PSMP was an important factor in the development of chronic antibody-mediated rejection. The PSMP expression increased significantly in CAAMR biopsy samples but not in CAMR and control patients, which distinguished CAAMR patients from CAMR and non-rejection patients. Moreover, our results showed that infiltration of CD68+ macrophages in CAAMR increased, and the correlation between CD68+ macrophages and PSMP expression in CAAMR patients was significant. Additionally, our data also revealed that intimal arteritis (v-lesion) accompanied by increased macrophage infiltration might have contributed to more graft loss in CAAMR, and PSMP expression was significantly associated with the v-lesion score. These results indicated that PSMP played an important role in the recruitment of macrophages and promote intimal arteritis inducing allograft lost in CAAMR progression. In future study PSMP could be a potential histopathological diagnostic biomarker and treatment target for CAAMR in kidney transplantation.

Suture ligation for submucosal hemostasis during hand-sewn side-to-side duodeno-ileostomy in simultaneous pancreas and kidney transplantation.

BACKGROUND: Enteric anastomotic (EA) bleeding is a potentially life-threatening surgical complication associated with enteric anastomosis during simultaneous pancreas and kidney transplantation (SPKT). AIM: To investigate whether suture ligation (SL) for submucosal hemostasis during hand-sewn enteric anastomosis could decrease the morbidity of early EA bleeding in SPKT. METHODS: We compared the outcomes of 134 patients classified into SL (n = 44) and no SL (NSL) groups (n = 90). This study adheres to the declarations of Istanbul and Helsinki and all donors were neither paid nor coerced. RESULTS: During the first postoperative week, the EA bleeding rate in the SL group was lower than that in the NSL group (2.27% vs 15.56%; P = 0.021); no relationship was found between EA bleeding and donor age, mean pancreatic cold ischemia time, platelet count, prothrombin time international normalized rate, activated partial thromboplastin time, and thrombin time. Anastomotic leakage was observed in one case in the SL group at postoperative day (POD) 14 and in one case at POD 16 in the NSL group (P = 0.754). No significant difference was found between the two groups in the patient survival, pancreas graft survival, or kidney graft survival. CONCLUSION: SL for submucosal hemostasis during hand-sewn enteric anastomosis in SPKT can decrease the morbidity of early EA bleeding without increasing the anastomotic leakage rate.