To investigate the efficacy and safety of glucocorticoids combined with cyclophosphamide (CTX) and rituximab (RTX) in elderly patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis with renal involvement.

BACKGROUND: Chronic kidney disease (CKD)-associated anemia (CKD-anemia) is associated with poor survival, and hemoglobin targets are often not achieved with current therapies. Phase 3 trials have demonstrated the treatment efficacy of roxadustat for CKD-anemia. This phase 4 study aims to evaluate the long-term (52-week) safety and effectiveness of roxadustat in a broad real-world patient population with CKD-anemia with and without dialysis in China. METHODS: This Phase 4 multicenter, open-label, prospective study, conducted from 24 November 2020 to 11 November 2022, evaluated the long-term safety and effectiveness of roxadustat for CKD-anemia in China. Patients aged ≥18 years with CKD-anemia with or without dialysis were included. The initial oral dose was 70-120 mg (weight-based followed by dose adjustment) over 52 weeks. The primary endpoint was safety based on adverse events (AEs). The secondary endpoints were hemoglobin changes from baseline and the proportion of patients who achieved mean hemoglobin ≥100 g/L. Effectiveness evaluable populations 1 (EE1) and EE2 included roxadustat-naïve and previously roxadustat-treated patients, respectively. The safety analysis set (SAF) included all patients who received ≥1 occasion. RESULTS: The EE1, EE2, and SAF populations included 1804, 193, and 2021 patients, respectively. In the SAF, the mean age was 50 ± 14 years, and 1087 patients (53.8%) were male. Mean baseline hemoglobin was 96.9 ± 14.0 g/L in EE1 and 100.3 ± 12.9 g/L in EE2. In EE1, the mean (95% confidence interval) hemoglobin changes from baseline over weeks 24-36 and 36-52 were 14.2 (13.5-14.9) g/L and 14.3 (13.5-15.0) g/L, respectively. Over weeks 24-36 and 36-52, 83.3% and 86.1% of patients in EE1 and 82.7% and 84.7% in EE2 achieved mean hemoglobin ≥100 g/L, respectively. In the SAF, 1643 (81.3%) patients experienced treatment-emergent AEs (TEAEs). Overall, 219 (10.8%) patients experienced drug-related TEAEs. Thirty-eight (1.9%) patients died of TEAEs (unrelated to the study drug). Vascular access thrombosis was uncommon. CONCLUSIONS: Roxadustat (52 weeks) increased hemoglobin and maintained the treatment target in Chinese patients with CKD-anemia with acceptable safety, supporting its use in real-world settings. REGISTRATION Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2100046322; CDE ( www.chinadrugtrials.org.cn ) CTR20201568.
Humans ; Male ; Female ; Anemia/etiology* ; Middle Aged ; Renal Insufficiency, Chronic/complications* ; Glycine/adverse effects* ; Isoquinolines/adverse effects* ; Aged ; Prospective Studies ; Adult ; Hemoglobins/metabolism* ; Treatment Outcome ; China ; Registries ; East Asian People

Background/Aims: Liver cirrhosis involves chronic inflammation and progressive fibrosis.Among various immune cells, CD8+ T cells are considered a major contributor to hepatic inflammation and fibrosis. However, the exact molecular pathways governing CD8+ T-cell-mediated effects in cirrhosis remain unclear. Methods: This study analyzed transcriptomic and single-cell sequencing data to elucidate CD8+ T-cell heterogeneity and implications in cirrhosis. Results: Weighted gene co-expression analysis of bulk RNA-seq data revealed an association between cirrhosis severity and activated T-cell markers like HLA and chemokine genes. Furthermore, single-cell profiling uncovered eight CD8+ T-cell subtypes, notably, effector memory (Tem) and exhausted (Tex) T cells. Tex cells, defined by PDCD1, LAG3, and CXCL13 expression, were increased in cirrhosis, while Tem cells were decreased. Lineage tracing and differential analysis highlighted CXCL13+ Tex cells as a terminal, exhausted subtype of cells with roles in PD-1 signaling, glycolysis, and T-cell regulation. CXCL13+ Tex cells displayed T-cell exhaustion markers like PDCD1, HAVCR2, TIGIT, and TNFRSF9. Functional analysis implicated potential roles of these cells in immunosuppression. Finally, a CXCL13+ Tex-cell gene signature was found that correlated with cirrhosis severity and poorer prognosis of liver cancer. Conclusions In summary, this comprehensive study defines specialized CD8+ T-cell subpopulations in cirrhosis, with CXCL13+ Tex cells displaying an exhausted phenotype associated with immune dysregulation and advanced disease. Key genes and pathways regulating these cells present potential therapeutic targets.

Objective:To construct an assessment model for operational quality of medical equipment by adopting Driving Force-Pressure-State-Impact-Response(DPSIR)model,and analyze its application value in operational management for medical equipment.Methods:The DPSIR model was adopted to formulate 20 evaluation indicators from five dimensions:driving force,pressure,state,influence and response.The evaluation indicators were evaluated by using composite weight method.According to the evaluation results,the management process of medical equipment was improved to achieve the optimal allocation for medical equipment.A total of 442 medical equipment in clinical use at Nanjing Brain Hospital from January 2022 to December 2023 were selected,and they were randomly divided into a conventional management mode group(221 equipment)and an assessment model mode group for operational quality of medical equipment by using DPSIR(221 equipment,model management mode group).The management quality of equipment operation,management efficiency and safety of using equipment between the two management modes were compared.A self-made questionnaire was used to investigate the satisfaction scores of managers for equipment,clinicians and clinical nurses on the clinical services of the equipment under the two management modes.Results:The scores of the standardization degrees of equipment operation,cleaning and disinfection,maintenance and repairing fault of adopting the model management mode were respectively(93.25±4.69),(93.47±5.36),(91.48±4.59)and(93.44±4.98),all of which were higher than those of adopting the conventional management mode,and the differences were statistically significant(t=15.489,12.920,10.905,16.354,P<0.05).The average utilization rate,stability rate of quality,and effective rate of diagnosis and treatment of the equipment of adopting the model management mode were(92.36±3.65)%,(90.58±4.36)%and(93.47±4.69)%,all of which were higher than those of adopting the conventional management mode,and the differences were statistically significant(t=12.376,10.726,11.721,P<0.05).The satisfaction scores of managers for equipment,clinicians and nurses for adopting the model management mode were higher than those of adopting the conventional management mode,and the differences were statistically significant(t=12.376,10.726,11.721,P<0.05).The incidence rates of corresponding infections,pressure-related injuries and risks caused by operation problems of equipment in adopting the model management mode were significantly lower than those in adopting the conventional management mode,and the differences were statistically significant(x2=12.280,15.000,14.141,P<0.05).Conclusion:The assessment model based on DPSIR for operational quality of medical equipment can enhance the management efficiency for medical equipment,and improve the satisfaction of users in using equipment,and raise the quality and level of management for equipment.

Objective:To evaluate the efficacy and safety of rituximab (RTX) in the treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (AAGN).Methods:This was a single-center, retrospective and single-arm study. The clinical data of AAGN patients who received RTX induction therapy at the First Affiliated Hospital of Zhejiang University School of Medicine from April 2016 to July 2021 and had a follow-up period of more than 6 months were collected. The follow-up was up to June 2022. The Birmingham Vasculitis Activity Score (BVAS) from 2003 was used to assess vasculitis activity. The treatment regimen for RTX was once every 1 to 2 weeks, with 375 mg/m 2 each time. For some patients, the dose was adjusted according to the immune status before medication. The clinical outcomes, renal remission, recurrence and safety was analyzed. Kaplan-Meier method was used to analyze the cumulative renal remission rate. Results:A total of 43 AAGN patients were included in the study, with age of (57.6±16.6) years, 19 males (44.2%) and 34 (79.1%) newly treated patients. There were 34 patients (79.1%) with positive myeloperoxidase-ANCA and 8 patients (18.6%) with positive proteinase 3-ANCA. The dosage of RTX used at the 12-month follow-up was 600 (500, 1 200) mg. At 6 months of follow-up, 32 patients (74.4%) achieved renal remission, and renal remission time was 5.0 (3.3, 5.8) months. Three patients (7.0%) progressed to end-stage renal disease, and two patients (4.7%) died. Compared with patients without renal remission, patients with renal remission had lower baseline serum creatinine ( Z=-2.853, P=0.004), serum uric acid ( t=-2.861, P=0.007), urine protein/urine creatinine ratio ( Z=-2.130, P=0.033) and proportion of methylprednisolone pulse therapy ( χ 2=5.002, P=0.025), and higher estimated glomerular filtration rate ( Z=-2.728, P=0.006). At 12 months of follow-up, 33 patients (76.7%) achieved renal remission, and the cumulative renal remission rate was 82.4%. Two patients (4.7%) had renal recurrence, 5 patients (11.6%) progressed to end-stage renal disease, and 3 patients (7.0%) died. Infection (4 patients, including 2 severe infections) was the main adverse event, all of which occurred within 6 months of RTX treatment. Conclusions:The clinical remission rate and safety of RTX in the treatment of AAGN are both relatively high.

Objective:To compare the differences of long-term survival rates between hemodialysis (HD) and peritoneal dialysis (PD) in the oldest old end-stage renal disease (ESRD) patients, and analyze the influencing factors of mortality.Methods:It was a retrospective cohort study. The clinical data from the oldest old patients (≥80 years old) who underwent HD or PD for the first time and maintained dialysis treatment for ≥3 months in the Zhejiang Dialysis Registration System from January 1, 2008 to December 31, 2021 were collected. The follow-up endpoint was until the patients' death or December 31, 2022. The propensity score matching method was used to match groups. Kaplan-Meier method and log-rank test were used to compare the differences of long-term survival rates between the two groups. Cox regression analysis was used to analyze the risk factors of mortality.Results:A total of 5 880 the oldest old dialysis patients were included in this study, with 5 363 patients in the initial HD group and 517 patients in the initial PD group. After matching, there were 517 patients in the HD group and 517 patients in the PD group. The median survival time of HD group before matching was 39.9 months, with 1-year, 3-year, and 5-year survival rates of 85.4%, 54.9%, and 30.0%, respectively. The median survival time of PD group was 32.9 months, with 1-year, 3-year, and 5-year survival rates of 82.5%, 47.1%, and 22.3%, respectively. After matching, the median survival time of HD group was 40.3 months, and the 1-year, 3-year, and 5-year survival rates were 86.1%, 57.8%, and 29.1%, respectively. The survival rate of PD group remained unchanged. The difference of 1-year survival rate between the two groups was not statistically significant, but the 2-year, 3-year, 4-year, 5-year, and overall survival rates in HD group were higher than those in PD group (Log‐rank test, χ2=4.897, P=0.027; χ2=9.693, P=0.002; χ2=10.194, P=0.001; χ2=7.868, P=0.005; χ2=12.510, P<0.001). Multivariate Cox regression analysis showed that HD (HD/PD, HR=0.794, 95% CI 0.669-0.943, P=0.009), increasing age ( HR=1.069, 95% CI 1.038-1.110, P<0.001), comorbidity with chronic obstructive pulmonary disease ( HR=1.510, 95% CI 1.065-2.139, P=0.021) and serum albumin <35 g/L ( HR=1.393, 95% CI 1.165-1.665, P<0.001) were independent correlated factors of mortality. Conclusions:There is no significant difference in the 1-year survival rate between HD and PD groups. The survival rate for more than 1 year in HD patients is higher than that in PD patients. HD is an independent protective factor of survival, and increasing age, comorbidities of chronic obstructive pulmonary disease, and serum albumin <35 g/L are independent risk factors affecting the survival in the oldest old dialysis patients.

Objective:To evaluate the efficacy and safety of rituximab (RTX) in the treatment of idiopathic membranous nephropathy (IMN), explore the influencing factors of the therapeutic effect and construct a nomogram model for predicting the therapeutic effect.Methods:A single retrospective study was conducted in IMN patients in the First Affiliated Hospital of Zhejiang University School of Medicine from January 2017 to December 2022. All patients received monotherapy with RTX and were followed up for at least 12 months. RTX regimen adopted a B-cell guided regimen to achieve 0 cells/μl of peripheral blood CD19+ B cells through multiple administrations, followed by monitoring every 2?3 months and adding doses as needed to maintain this state. The complete response rate, partial response rate, and composite response rate at 6 months, 12 months and the end of follow up were analyzed. Logistic stepwise regression and R language were applied to construct a nomogram model for efficacy prediction. The receiver operating characteristic (ROC) curve, calibration curve and Hosmer-Lemeshow test were used to internally validate the nomogram model.Results:A total of 147 IMN patients were included in the study, with age of 56 (47, 65) years, 99 (67.4%) males. There were 69 (46.9%) newly treated patients, 78 (53.1%) retreatment patients. The follow-up time was 14.4 (12.0, 15.0) months. The total RTX dose was 1 800 (1 200, 2 400) mg. The composite response rates at 6 months, 12 months and the end of the follow-up were 36.7% (54/147), 59.9% (88/147) and 63.3% (93/147), respectively. The complete remission rates at 6 months, 12 months and the end of the follow-up were 6.1% (9/147), 13.6% (20/147) and 19.7% (29/147), respectively. Logistic stepwise regression analysis showed that age ≥ 65 years ( OR=0.335, 95% CI 0.135?0.833), retreatment ( OR=0.333, 95% CI 0.144?0.771), high cholesterol ( OR=0.716, 95% CI 0.577?0.888), high serum creatinine ( OR=0.978, 95% CI 0.963?0.993) and B-cell reconstruction within 6 months ( OR=0.273, 95% CI 0.115?0.645) were independent correlated factors affecting composite remission. Based on these factors, a nomogram model for predicting the therapeutic effect of RTX in IMN patients was constructed. The ROC curve indicated that the accuracy of this model in predicting composite remission was good ( AUC=0.814, 95% CI 0.744-0.883). The calibration curve showed that the predicted composite response rate had a good fit with the actual response rate (Hosmer-Lemeshow test χ2=11.917, P=0.155). Conclusions:RTX has good efficacy and safety as a monotherapy for IMN patients. The constructed nomogram prediction model has high discrimination and accuracy to predict the efficacy of RTX treatment for IMN.

This was a single-center retrospective case series study. This study evaluated the efficacy and safety of percutaneous covered stent endovascular exclusion under digital subtraction angiography (DSA) for removing dialysis catheters misplaced in arteries. The clinical data from 7 patients treated in the First Affiliated Hospital of Zhejiang University School of Medicine from January 2012 to October 2023 were analyzed. All patients had dialysis catheters confirmed to be misplaced in arteries via chest CT, X-ray radiography or computed tomography angiography. Percutaneous covered stent endovascular exclusion under DSA was used to remove the catheters. The results showed that except for one elderly patient died during waiting for surgery, the remaining 6 patients achieved satisfactory outcomes with no postoperative bleeding. There was no related complication observed during a 6-month follow-up. Arterial misplacement of dialysis catheters is a serious complication requiring prompt removal. Percutaneous covered stent endovascular exclusion under DSA offers a minimally invasive, effective, and safe approach with a high technical success rate and a low complication rate, making it a viable surgical option for similar clinical cases.

Objective:To investigate the effect of pre-dialysis blood pressure (Pre-BP) on all-cause and cardiovascular disease (CVD) mortality in patients on maintenance hemodialysis (MHD).Methods:This single-center, retrospective cohort study enrolled patients undergoing first-time hemodialysis between January 1, 2007, and June 30, 2021, from the dialysis registry of the First Affiliated Hospital, Zhejiang University School of Medicine. General information and laboratory parameters were collected. Pre-dialysis systolic blood pressure (Pre-SBP) and pre-dialysis diastolic blood pressure (Pre-DBP) were calculated and averaged at 4-6 months after dialysis. The mean Pre-SBP and Pre-DBP values were used as continuous variables, and restricted cubic spline (RCS) curves were used to assess the relationship between Pre-BP and mortality risk. Patients were subsequently divided into six groups for Pre-DBP and six groups for Pre-SBP combined with Pre-DBP. Survival analyses were performed using the Kaplan-Meier method. All-cause and CVD mortality were compared between groups using the log-rank test. Multivariate Cox regression models were used to analyze the associations between Pre-BP and all-cause and CVD mortality.Results:A total of 1 213 patients were enrolled. By the end of follow-up, 175 patients (14.4%) had died, of whom 62 (35.4%) died from CVD. Kaplan-Meier survival curves showed that the Pre-DBP<65 mmHg group (1 mmHg=0.133 kPa) had a significantly lower cumulative survival rate ( χ2=90.52, P<0.001) and a significantly higher CVD mortality rate ( χ2=35.54, P<0.001) than the other groups. The combined Pre-SBP and Pre-DBP analysis showed that the Pre-SBP≥150 mmHg and Pre-DBP<80 mmHg groups had a significantly lower cumulative survival rate ( χ2=45.58, P<0.001) and a significantly higher CVD mortality rate ( χ2=30.13, P<0.001) than the other groups. Multivariate Cox regression model analysis showed that compared with other groups, the risk of MHD all-cause mortality was increased in the Pre-DBP<65 mmHg group and the Pre-SBP≥150 mmHg and Pre-DBP<80 mmHg group [ HR (95% CI)=1.927 (1.195-3.109), 3.298 (1.567-6.939), both P<0.05]. Conclusion:In patients undergoing MHD, Pre-DBP<65 mmHg or Pre-SBP≥150 mmHg and Pre-DBP<80 mmHg were independent risk factors for all-cause mortality, with a low cumulative survival rate and a high risk of CVD mortality.